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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 796. Отображено 100.
05-01-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120003247A1
Автор:
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 1109.-. (canceled)111. The antibody-drug conjugate of claim 110 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.112. The antibody-drug conjugate of claim 111 , wherein p is 2 to 5.113. The antibody-drug conjugate of claim 110 , wherein p is 2 to 8.114. The antibody-drug conjugate of claim 110 , wherein p is 2 to 5.121. The antibody-drug conjugate of claim 110 , wherein w is 2.122. The antibody-drug conjugate of claim 121 , wherein Wis -valine-citrulline-.123. The antibody-drug conjugate of claim 110 , wherein Wis 5-aminovaleric acid claim 110 , homo phenylalanine lysine claim 110 , tetraisoquinolinecarboxylate lysine claim 110 , cyclohexylalanine lysine claim 110 , isonepecotic acid lysine claim 110 , beta-alanine lysine claim 110 , glycine serine valine glutamine and isonepecotic acid.129. The antibody-drug conjugate of claim 110 , wherein Z is —O— or —NH—.130. The antibody-drug conjugate of claim 129 , wherein Z is —O— and Ris —H claim 129 , methyl or t-butyl.131. The antibody-drug conjugate of claim 130 , wherein Ris —H.132. The antibody-drug conjugate of claim 110 , wherein R claim 110 , Rand Rare independently isopropyl or sec-butyl and Ris —H.133. The antibody-drug conjugate of claim 110 , wherein Rand Rare each methyl claim 110 , and Ris —H.134. The antibody-drug conjugate of claim 110 , wherein each occurrence of Ris —OCH.135. The antibody-drug conjugate of claim 110 , wherein Rand Rare each isopropyl claim 110 , Rand Rare each methyl claim 110 , Ris —H claim 110 , Ris sec-butyl claim 110 , each occurrence of Ris —OCH claim 110 , and Ris —H.136. The antibody-drug conjugate of claim 110 , wherein Ris H claim 110 , C-Calkyl claim 110 , or ...

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Номер записи: 1
05-01-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120003248A1
Автор: Doronina Svetlana O., Ebens Allen J., Kline Toni Beth, Polakis Paul, Senter Peter D., Sliwkowski Mark X., Spencer Susan D., Toki Brian E.
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 154.-. (canceled)56. The antibody-drug conjugate of claim 55 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.57. The antibody-drug conjugate of claim 56 , wherein p is 2 to 5.58. The antibody-drug conjugate of claim 55 , wherein p is 2 to 8.59. The antibody-drug conjugate of claim 55 , wherein p is 2 to 5.67. The antibody-drug conjugate of claim 55 , wherein the antibody is a monoclonal antibody.69. A pharmaceutical composition comprising an effective amount of the antibody-drug conjugate of and a pharmaceutically acceptable diluent claim 55 , carrier or excipient. This application is a continuation of U.S. patent application Ser. No. 11/833,961, filed Aug. 3, 2007 which is a division of U.S. application Ser. No. 10/983,340, filed Nov. 25, 2004, which claims the benefit of U.S. Provisional Patent Application No. 60/622,455, filed Oct. 27, 2004; U.S. Provisional Patent Application No. 60/598,899, filed Aug. 4, 2004; U.S. Provisional Patent Application No. 60/557,116, filed Mar. 26, 2004; and U.S. Provisional Patent Application No. 60/518,534, filed Nov. 6, 2003; the disclosures of which are incorporated by reference herein.Some of the subject matter in this application was made by or on behalf of Seattle Genetics, Inc. and Genentech, Inc. as a result of activities undertaken within the scope of a joint research agreement effective on or before the date the claimed invention was made.The present invention is directed to a Drug Compound and more particularly to Drug-Linker-Ligand Conjugates, Drug-Linker Compounds, and Drug-Ligand Conjugates, to compositions including the same, and to methods for using the same to treat cancer, an autoimmune disease ...

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Номер записи: 2
02-02-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120027783A1
Автор: Doronina Svetlana O., Ebens Allen J., Kline Toni Beth, Polakis Paul, Senter Peter D., Sliwkowski Mark X., Spencer Susan D., Toki Brian E.
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 2. The antibody-drug conjugate compound of claim 1 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.3. The antibody-drug conjugate compound of claim 1 , wherein p is 1 to 4.4. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 8.5. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 5.11. The antibody-drug conjugate compound of claim 1 , wherein w is an integer ranging from 2 to 12.12. The antibody-drug conjugate compound of claim 11 , wherein w is 2.13. The antibody-drug conjugate compound of wherein W claim 12 , is -valine-citrulline-.14. The antibody-drug conjugate compound of wherein A is maleimidocaproyl and a is 1.15. The antibody-drug conjugate compound of wherein Y is p-aminobenzyloxycarbonyl (PAB) and y is 1.17. The antibody-drug conjugate compound of claim 1 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:15 that is expressed on the cell surface.18. The antibody-drug conjugate compound of claim 17 , wherein the antibody is a humanized antibody.19. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a monoclonal antibody.20. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a chimeric antibody.21. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a humanized antibody.22. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a Fab fragment.24. The antibody-drug conjugate compound of claim 23 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:15 that is expressed on the cell surface.25. The antibody-drug conjugate compound of claim 24 , wherein the antibody is a humanized ...

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Номер записи: 3
02-02-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120027784A1
Автор: Doronina Svetlana O., Ebens Allen J., Kline Toni Beth, Polakis Paul, Senter Peter D., Sliwkowski Mark X., Spencer Susan D., Toki Brian E.
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 2. The antibody-drug conjugate compound of claim 1 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.3. The antibody-drug conjugate compound of claim 1 , wherein p is 1 to 4.4. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 8.5. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 5.11. The antibody-drug conjugate compound of claim 1 , wherein w is an integer ranging from 2 to 12.12. The antibody-drug conjugate compound of claim 11 , wherein w is 2.13. The antibody-drug conjugate compound of wherein W claim 12 , is -valine-citrulline-.14. The antibody-drug conjugate compound of wherein A is maleimidocaproyl and a is I.15. The antibody-drug conjugate compound of wherein Y is p-aminobenzyloxycarbonyl (PAB) and y is 1.17. The antibody-drug conjugate compound of claim 1 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:27 that is expressed on the cell surface.18. The antibody-drug conjugate compound of claim 17 , wherein the antibody is a humanized antibody.19. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a monoclonal antibody.20. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a chimeric antibody.21. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a humanized antibody.22. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a Fab fragment.24. The antibody-drug conjugate compound of claim 23 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:27 that is expressed on the cell surface.25. The antibody-drug conjugate compound of claim 24 , wherein the antibody is a humanized ...

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Номер записи: 4
09-02-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120034246A1
Автор:
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 2. The antibody-drug conjugate compound of claim 1 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.3. The antibody-drug conjugate compound of claim 1 , wherein p is 1 to 4.4. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 8.5. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 5.11. The antibody-drug conjugate compound of claim 1 , wherein w is an integer ranging from 2 to 12.12. The antibody-drug conjugate compound of claim 11 , wherein w is 2.13. The antibody-drug conjugate compound of wherein Wis -valine-citrulline-.14. The antibody-drug conjugate compound of wherein A is maleimidocaproyl and a is 1.15. The antibody-drug conjugate compound of wherein Y is p-aminobenzyloxycarbonyl (PAB) and y is 1.17. The antibody-drug conjugate compound of claim 1 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:5 that is expressed on the cell surface.18. The antibody-drug conjugate compound of claim 17 , wherein the antibody is a humanized antibody.19. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a monoclonal antibody.20. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a chimeric antibody.21. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a humanized antibody.22. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a Fab fragment.24. The antibody-drug conjugate compound of claim 23 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:5 that is expressed on the cell surface.25. The antibody-drug conjugate compound of claim 24 , wherein the antibody is a humanized antibody.26. ...

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Номер записи: 5
09-02-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120034247A1
Автор:
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 2. The antibody-drug conjugate compound of claim 1 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.3. The antibody-drug conjugate compound of claim 1 , wherein p is 1 to 4.4. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 8.5. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 5.11. The antibody-drug conjugate compound of claim 1 , wherein w is an integer ranging from 2 to 12.12. The antibody-drug conjugate compound of claim 11 , wherein w is 2.13. The antibody-drug conjugate compound of wherein Wis -valine-citrulline-.14. The antibody-drug conjugate compound of wherein A is maleimidocaproyl and a is 1.15. The antibody-drug conjugate compound of wherein Y is p-aminobenzyloxycarbonyl (PAB) and y is 1.17. The antibody-drug conjugate compound of claim 1 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:35 that is expressed on the cell surface.18. The antibody-drug conjugate compound of claim 17 , wherein the antibody is a humanized antibody.19. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a monoclonal antibody.20. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a chimeric antibody.21. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a humanized antibody.22. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a Fab fragment.24. The antibody-drug conjugate compound of claim 23 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:35 that is expressed on the cell surface.25. The antibody-drug conjugate compound of claim 24 , wherein the antibody is a humanized antibody.26 ...

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Номер записи: 6
09-02-2012 дата публикации

IDENTIFYING MATERIAL FROM A BREAST DUCT

Номер: US20120034644A1
Автор:
Принадлежит: Atossa Genetics, Inc.

Methods and systems for identifying material from a breast duct using one or more markers that can be identified in ductal fluid retrieved from the breast are provided. 128-. (canceled)29. A method of predicting the likelihood of breast cancer recurrence or identifying viable treatment regimen in a human patient comprising:measuring, using an analytical instrument, the expression levels of one or more RNA transcripts, one or more proteins, or a combination thereof, in a ductal fluid sample (a) obtained from at least one duct of a breast of the patient and (b) transformed to a form suitable for use with the analytical instrument, whereinsaid one or more RNA transcripts are selected from the group consisting of a growth factor receptor, HER2, estrogen receptor, progesterone receptor, Bcl2, a protein that participates in a transcriptional activation pathway, Ki67, a cyclin, a cathepsin L, a peptide form of a factor from a growth factor, glutathione S-transferase, a macrophage inflammatory protein, BAG-1, a protein that participates in an aptoptosis pathway, a macrophage inflammatory protein, an actin binding protein, stromelysin-3 or their expression products, or a combination thereof; andcomparing the presence or absence of levels of one or more in expression of said one or more RNA transcripts, or their expression products, or a combination thereof, to a normal control, wherein levels over normal controls indicate a likelihood of breast cancer recurrence and wherein levels at or below a normal indicates a viable treatment regimen.30. The method of claim 29 , wherein said ductal fluid sample contains cells.31. The method of claim 30 , further comprising analyzing the cytology of cells in said sample.32. The method of claim 31 , wherein the presence of tumor cells indicates a likelihood of breast cancer recurrence.33. The method of claim 31 , wherein the absence of tumor cells indicates an efficacious treatment regimen.34. The method of claim 29 , wherein the fluid ...

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Номер записи: 7
23-02-2012 дата публикации

Humanized Anti-CD70 Binding Agents and Uses Thereof

Номер: US20120045436A1
Автор:
Принадлежит: Seattle Genetics, Inc.

Disclosed are CD70 binding agents, such as humanized anti-CD70 antibodies and fragments and derivatives, that exert a cytotoxic, cytostatic or immunomodulatory on CD70 expressing cells, as well as pharmaceutical compositions and kits comprising the antibody, fragment or derivative. Also disclosed are methods for the treatment of CD70-expressing cancers and immunological disorders, comprising administering to a subject the CD70 binding agents or pharmaceutical compositions. 138-. (canceled)39. A method for treating a cancer in a human subject , comprising administering to the subject having a CD70 expressing cancer an effective amount of a humanized antibody or antigen binding fragment , comprising:{'sub': H', 'H', 'H, '(i) a humanized heavy chain comprising the three CDRs from SEQ ID NO:2 and a variable region framework sequence of human germline V1-2 or V1-18 and exon J-6, provided that any of positions 1146, H67, 1168, H69, H70, 1171, H80, H81, H82, H82A and 1191 (Kabat numbering) can be occupied by the amino acid occupying the corresponding position from SEQ ID NO:2, and'}(ii) a humanized light chain comprising the three CDRs from SEQ ID NO:22 and a variable region framework sequence of human germline Vκ exon B3 and Jκ exon Jκ−1, provided that any of positions L25 and L33 can be occupied by the amino acid occupying the corresponding position from SEQ ID NO:22.40. The method of claim 39 , wherein position H46 is occupied by the amino acid occupying the corresponding position from SEQ ID NO:2.41. The method of claim 39 , wherein at least one of positions H46 claim 39 , H67 claim 39 , H68 claim 39 , H69 claim 39 , H70 claim 39 , H71 claim 39 , H80 claim 39 , H81 claim 39 , H82 claim 39 , H82A and H91 (Kabat numbering) in the humanized heavy chain variable region is occupied by the residue occupying the corresponding position in SEQ ID NO:2.42. The method of claim 39 , wherein at least one of positions L25 and L33 in the humanized light chain variable region is ...

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Номер записи: 8
03-05-2012 дата публикации

Beta-Glucuronide-Linker Drug Conjugates

Номер: US20120107332A1
Автор:
Принадлежит: Seattle Genetics, Inc.

Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided. 1. (canceled)3. (canceled)4. The method of claim 2 , wherein the Ligand Unit is an antibody.5. The method of claim 4 , wherein the antibody is a humanized or chimeric antibody or an antigen binding fragment of an antibody.6. (canceled)7. (canceled)8. The method of claim 2 , wherein w is 1.13. (canceled)14. (canceled)16. (canceled)18. The method of claim 2 , wherein p is 2 to 6.19. The method of claim 18 , wherein p is 2 to 4.22. The method of claim 2 , wherein D is cytotoxic claim 2 , cytostatic or immunomodulatory drug.23. The method of claim 2 , wherein a is 1 or 2.24. The method of claim 2 , wherein Y is a carbonyl group (—CO)— or a p-aminobenzyl alcohol group whose phenylene portion is substituted with Qwherein Q is C-Calkyl claim 2 , —O—(C-Calkyl) claim 2 , -halogen claim 2 , -nitro or -cyano; and m is an integer ranging from 0-4.26. The method of any one of claim 2 , further comprising administering an effective amount of an additional anticancer agent or an immunosuppressant agent.27. The method of any one of claim 2 , wherein the ligand drug conjugate compound is in a formulation further comprising a pharmaceutically acceptable diluent claim 2 , carrier or excipient.2832.-. (canceled)33. The method of claim 39 , wherein the cytotoxic drug is an auristatin.34. (canceled)35. The method of claim 27 , wherein the ligand drug conjugate compound is formulated in a unit dosage injectable form.36. The method of claim 22 , wherein the cytotoxic drug is a DNA replication inhibitor.37. The method of claim 22 , wherein the cytotoxic drug is a DNA minor groove binder.38. The method of claim 22 , wherein the cytotoxic drug is an alkylating agent.39. The method of claim 22 , wherein the cytotoxic drug is an antitubulin agent.4047.-. (canceled)48. The method of claim 39 , wherein the antitubulin agent is a maytansinoid.49. (canceled)50. (canceled) This ...

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Номер записи: 9
07-06-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120141508A1
Автор: Doronina Svetlana O., Ebens Allen J., Kline Toni Beth, Polakis Paul, Senter Peter D., Sliwkowski Mark X., Spencer Susan D., Toki Brian E.
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 2. The antibody-drug conjugate compound of claim 1 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.3. The antibody-drug conjugate compound of claim 1 , wherein p is 1 to 4.4. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 8.5. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 5.11. The antibody-drug conjugate compound of claim 1 , wherein w is an integer ranging from 2 to 12.12. The antibody-drug conjugate compound of claim 11 , wherein w is 2.13. The antibody-drug conjugate compound of wherein Wis -valine-citrulline-.14. The antibody-drug conjugate compound of wherein A is maleimidocaproyl and a is 1.15. The antibody-drug conjugate compound of wherein Y is PAB and y is 1.17. The antibody-drug conjugate compound of claim 1 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:4 that is expressed on the cell surface.18. The antibody-drug conjugate compound of claim 17 , wherein the antibody is a humanized antibody.19. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a monoclonal antibody.20. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a chimeric antibody.21. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a humanized antibody.22. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a Fab fragment.24. The antibody-drug conjugate compound of claim 23 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:4 that is expressed on the cell surface.25. The antibody-drug conjugate compound of claim 24 , wherein the antibody is a humanized antibody.26. The antibody-drug conjugate ...

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Номер записи: 10
07-06-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120141509A1
Автор: Doronina Svetlana O., Ebens Allen J., Kline Toni Beth, Polakis Paul, Senter Peter D., Sliwkowski Mark X., Spencer Susan D., Toki Brian E.
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 2. The antibody-drug conjugate compound of claim 1 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.3. The antibody-drug conjugate compound of claim 1 , wherein p is 1 to 4.4. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 8.5. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 5.11. The antibody-drug conjugate compound of claim 1 , wherein w is an integer ranging from 2 to 12.12. The antibody-drug conjugate compound of claim 11 , wherein w is 2.13. The antibody-drug conjugate compound of wherein Wis -valine-citrulline-.14. The antibody-drug conjugate compound of wherein A is maleimidocaproyl and a is 1.15. The antibody-drug conjugate compound of wherein Y is PAB and y is 1.17. The antibody-drug conjugate compound of claim 1 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:6 that is expressed on the cell surface.18. The antibody-drug conjugate compound of claim 17 , wherein the antibody is a humanized antibody.19. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a monoclonal antibody.20. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a chimeric antibody.21. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a humanized antibody.22. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a Fab fragment.24. The antibody-drug conjugate compound of claim 23 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:6 that is expressed on the cell surface.25. The antibody-drug conjugate compound of claim 24 , wherein the antibody is a humanized antibody.26. The antibody-drug conjugate ...

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Номер записи: 11
07-06-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120141510A1
Автор:
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 2. The antibody-drug conjugate compound of claim 1 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.3. The antibody-drug conjugate compound of claim 1 , wherein p is 1 to 4.4. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 8.5. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 5.11. The antibody-drug conjugate compound of claim 1 , wherein w is an integer ranging from 2 to 12.12. The antibody-drug conjugate compound of claim 11 , wherein w is 2.13. The antibody-drug conjugate compound of wherein Wis -valine-citrulline-.14. The antibody-drug conjugate compound of wherein A is maleimidocaproyl and a is 1.15. The antibody-drug conjugate compound of wherein Y is PAB and y is 1.17. The antibody-drug conjugate compound of claim 1 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:17 that is expressed on the cell surface.18. The antibody-drug conjugate compound of claim 17 , wherein the antibody is a humanized antibody.19. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a monoclonal antibody.20. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a chimeric antibody.21. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a humanized antibody.22. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a Fab fragment.24. The antibody-drug conjugate compound of claim 23 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:17 that is expressed on the cell surface.25. The antibody-drug conjugate compound of claim 24 , wherein the antibody is a humanized antibody.26. The antibody-drug ...

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Номер записи: 12
14-06-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120148608A1
Автор: Doronina Svetlana O., Ebens Allen J., Kline Toni Beth, Polakis Paul, Senter Peter D., Sliwkowski Mark X., Spencer Susan D., Toki Brian E.
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 2. The antibody-drug conjugate compound of claim 1 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.3. The antibody-drug conjugate compound of claim 1 , wherein p is 1 to 4.4. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 8.5. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 5.11. The antibody-drug conjugate compound of claim 1 , wherein w is an integer ranging from 2 to 12.12. The antibody-drug conjugate compound of claim 11 , wherein w is 2.13. The antibody-drug conjugate compound of wherein Wis -valine-citrulline-.14. The antibody-drug conjugate compound of wherein A is maleimidocaproyl and a is 1.15. The antibody-drug conjugate compound of wherein Y is PAB and y is 1.17. The antibody-drug conjugate compound of claim 1 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:3 that is expressed on the cell surface.18. The antibody-drug conjugate compound of claim 17 , wherein the antibody is a humanized antibody.19. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a monoclonal antibody.20. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a chimeric antibody.21. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a humanized antibody.22. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a Fab fragment.24. The antibody-drug conjugate compound of claim 23 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:3 that is expressed on the cell surface.25. The antibody-drug conjugate compound of claim 24 , wherein the antibody is a humanized antibody.26. The antibody-drug conjugate ...

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Номер записи: 13
14-06-2012 дата публикации

MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS

Номер: US20120148610A1
Автор: Doronina Svetlana O., Ebens Allen J., Kline Toni Beth, Polakis Paul, Senter Peter D., Sliwkowski Mark X., Spencer Susan D., Toki Brian E.
Принадлежит: Seattle Genetics, Inc.

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo. 2. The antibody-drug conjugate compound of claim 1 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.3. The antibody-drug conjugate compound of claim 1 , wherein p is 1 to 4.4. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 8.5. The antibody-drug conjugate compound of claim 1 , wherein p is 2 to 5.11. The antibody-drug conjugate compound of claim 1 , wherein w is an integer ranging from 2 to 12.12. The antibody-drug conjugate compound of claim 11 , wherein w is 2.13. The antibody-drug conjugate compound of wherein W claim 12 , is -valine-citrulline-.14. The antibody-drug conjugate compound of wherein A is maleimidocaproyl and a is 1.15. The antibody-drug conjugate compound of wherein Y is PAB and y is 1.17. The antibody-drug conjugate compound of claim 1 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:9 that is expressed on the cell surface.18. The antibody-drug conjugate compound of claim 17 , wherein the antibody is a humanized antibody.19. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a monoclonal antibody.20. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a chimeric antibody.21. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a humanized antibody.22. The antibody-drug conjugate compound of claim 1 , wherein the antibody is a Fab fragment.24. The antibody-drug conjugate compound of claim 23 , wherein the antibody binds to a portion of the polypeptide of SEQ ID NO:9 that is expressed on the cell surface.25. The antibody-drug conjugate compound of claim 24 , wherein the antibody is a humanized antibody.26. The antibody- ...

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Номер записи: 14
14-06-2012 дата публикации

NUCLEIC ACID MOLECULES AND USES THEREOF

Номер: US20120149761A1
Автор: Quay Steven C.
Принадлежит: Atossa Genetics, Inc.

Provided in this application are formulations of double stranded RNA molecules and Krebs Cycle analogs that improving ribonuclease stability, reducing off-target effects of a double stranded siRNA molecule, or of reducing interferon responsiveness of a double stranded siRNA molecule using such dsRNA. Also disclosed are methods of treating a primary tumor or a metastasis by contacting circulating tumor cells, a primary tumor, or a metastasis with a described formulation. 1. A formulation , comprising:(a) an RNAi molecule comprising at least on: locked nucleic acid (LNA), unlocked nucleic acid (UNA), bridged nucleic acid (BNA), glycerol nucleic acid (GNA), or a combination thereof; and(b) an RNAi carrier.2. The formulation of claim 1 , wherein the carrier provides for one or more of the following: stability for shortened duplexes claim 1 , reduction or prevention of sense strand loading claim 1 , reduction or prevention of seed region microRNA adverse side effects and reduction of non-specific immunoactivation.3. The formulation of claim 1 , wherein the RNAi carrier is a di-lipid amino acid (DILA).4. The formulation of claim 1 , wherein the RNAi carrier is a Krebs Cycle analog.5. The formulation of claim 1 , wherein the RNAi carrier is a Krebs Cycle analog and wherein the Krebs Cycle analog reduces or prevents cytotoxicity.6. A formulation claim 1 , comprising:(a) an RNAi molecule; and(b) a Krebs Cycle analog RNAi carrier.7. The formulation of claim 6 , wherein the RNA or RNA analog comprises a locked nucleic acid (LNA) claim 6 , an unlocked nucleic acid (UNA) claim 6 , a bridged nucleic acid (BNA) claim 6 , a glycerol nucleic acid (GNA) claim 6 , or a combination thereof.8. A formulation claim 6 , comprising:(a) an RNAi molecule comprising at least on: locked nucleic acid (LNA), unlocked nucleic acid (UNA), bridged nucleic acid (BNA), glycerol nucleic acid (GNA), or a combination thereof; and(b) a Krebs Cycle analog RNAi carrier.9. A formulation claim 6 , comprising ...

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Номер записи: 15
19-07-2012 дата публикации

Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation

Номер: US20120183997A1
Автор: Brian Toki, Dennis R. Benjamin, Django Sussman, Patrick J. Burke, Scott C. Jeffrey, Stephen C. Alley
Принадлежит: Seattle Genetics Inc

The invention provides methods and compositions for preparing antibodies and antibody derivatives with reduced core fucosylation.

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Номер записи: 16
23-08-2012 дата публикации

SYSTEMS AND METHODS FOR BREAST CANCER DETECTION AND RISK ASSESSMENT

Номер: US20120214245A1
Автор:
Принадлежит: Atossa Genetics, Inc.

The invention relates to a simple screening test for neoplasia, a precancerous condition, or cancer of the breast. A method is described whereby a breast cancer marker is detected in breast fluid. In a particular embodiment, the method involves treating samples of breast fluids with an aldehyde detecting reagent without any prewashing. The appearance in breast fluids of a marker that is detected by an aldehyde detecting reagent, such as a Schiff's reagent, correlates very well with the disease status of the breast cancer subjects from which the fluids were obtained. Screening test kits are also provided. 1. A method of screening a patient for breast cancer or for elevated breast cancer risk , comprising:providing a solid support configured to receive a volume of breast aspirate fluid from the patient;wherein the volume of breast aspirate fluid is obtained from a breast duct of a patient;wherein the volume of breast aspirate fluid is obtained at least in part by the application of suction within or along the breast of the patient;wherein the solid support comprises an aldehyde detecting agent; anddetecting a change in a detectable property produced by contacting the volume of breast aspirate fluid to the aldehyde detecting reagent on the solid support;wherein the volume of breast aspirate fluid does not undergo pretreatment or modification before being placed on the solid support.2. The method of claim 1 , wherein the solid support comprises a pad.3. The method of claim 1 , wherein the detectable property comprises at least one of:color, spectral properties, spectral absorption, fluorescence, chemi-luminescence, mass spectral properties or chromatographic properties.4. The method of claim 1 , wherein the aldehyde detecting reagent comprises Schiff's reagent.5. The method of claim 1 , wherein the aldehyde marker comprises low molecular weight aldehydes that are soluble in water.6. The method of claim 1 , wherein the volume of breast aspirate fluid is additionally ...

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Номер записи: 17
04-10-2012 дата публикации

Treatment of B-Cell Cancers With Anti-CD70 Antibody-Drug Conjugates

Номер: US20120251559A1
Автор:
Принадлежит: Seattle Genetics, Inc.

Disclosed are anti-CD70 antibodies and derivatives thereof conjugated to cytotoxic therapeutic agents, as well as pharmaceutical compositions and kits comprising the antibody- and antibody derivative-drug conjugates. Also disclosed are methods, for the treatment of a CD70-expressing cancer, comprising administering to a subject the disclosed pharmaceutical compositions. 1. A method for the treatment of a CD70-expressing cancer of a B-cell lineage in a human subject , the method comprising:administering to the subject, in an amount effective for the treatment thereof, an antibody-drug conjugate comprising an antibody that specifically binds to CD70, wherein:(i) the drug is a cytotoxic agent, and(ii) the antibody-drug conjugate is internalized into cells, where it exerts a therapeutic effect.2. The method of claim 1 , wherein the antibody is a humanized antibody.3. The method of claim 1 , wherein the antibody is a chimeric antibody.4. The method of claim 1 , wherein the antibody is multivalent.5. The method of claim 1 , wherein the cytotoxic agent is selected from the group consisting of an auristatin claim 1 , a DNA minor groove binding agent claim 1 , a DNA minor groove alkylating agent claim 1 , an enediyne claim 1 , a duocarmycin claim 1 , a maytansinoid claim 1 , and a vinca alkaloid.6. The method of claim 1 , wherein the cytotoxic agent is an anti-tubulin agent.7. The method of claim 6 , wherein the cytotoxic agent is AFP or MMAE.8. The method of claim 1 , wherein the antibody is conjugated to the cytotoxic agent via a linker.9. The method of claim 8 , wherein the linker is cleavable under intracellular conditions.10. The method of claim 9 , wherein the cleavable linker is cleavable by an intracellular protease.11. The method of claim 10 , wherein the linker comprises a dipeptide.12. The method of claim 11 , wherein the dipeptide is val-cit or phe-lys.13. The method of claim 9 , wherein the cleavable linker is hydrolyzable at a pH of less than 5.5.14. The method ...

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Номер записи: 18
15-11-2012 дата публикации

Anti-CD70 Antibody-Drug Conjugates and Their Use for the Treatment of Cancer and Immune Disorders

Номер: US20120288512A1
Автор: Law Che-Leung, Pestano Linda A., Scholler Nathalie, Wahl Alan F.
Принадлежит: Seattle Genetics, Inc.

Disclosed are anti-CD70 antibodies and derivatives thereof conjugated to cytotoxic, immunosuppressive, or other therapeutic agents, as well as pharmaceutical compositions and kits comprising the antibody- and antibody derivative-drug conjugates. Also disclosed are methods, for the treatment of CD70-expressing cancers and immunological disorders, comprising administering to a subject the disclosed pharmaceutical compositions. 1. A method for the treatment of an immunological disorder in a subject , wherein the immune disorder is mediated by cells that express CD70 , the method comprising:administering to the subject, in an amount effective for the treatment, an antibody-drug conjugate comprising an antibody that binds CD70 and is conjugated to a cytotoxic agent, wherein the antibody-drug conjugate is internalized into immune cells that express CD70, where it exerts a therapeutic effect.2. The method of claim 1 , wherein the antibody competes for binding to CD70 with a monoclonal antibody that comprises:(a) a heavy chain variable region having the amino acid sequence set forth in residues 20-137 of SEQ ID NO:2, and a light chain variable region having the amino acid sequence set forth in residues 21-132 of SEQ ID NO:12, or(b) a heavy chain variable region having the amino acid sequence set forth in residues 20-137 of SEQ ID NO:22, and a light chain variable region having the amino acid sequence set forth in residues 21-132 SEQ ID NO:32.3. The method of claim 2 , wherein the antibody is a humanized claim 2 , or chimeric antibody.4. The method of claim 2 , wherein the antibody is multivalent.5. The method of claim 1 , wherein the antibody is a chimeric or humanized antibody and(a) comprises H1, H2, H3, L1, L2 and L3 complementarity determining regions having, respectively, the amino acid sequences set forth in SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10; SEQ ID NO:16, SEQ ID NO:18, and SEQ ID NO:20; or(b) comprises H1, H2, H3, L1, L2 and L3 complementarity determining ...

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Номер записи: 19
22-11-2012 дата публикации

CD19 Binding Agents and Uses Thereof

Номер: US20120294853A1
Автор: Benjamin Dennis, Carter Paul, CERVENY Charles G., Francisco Leigh, Gerber Hans Peter, McDonagh Charlotte
Принадлежит: Seattle Genetics, Inc.

This invention, inter alia, relates to CD19 binding agents and methods of using such CD19 binding agents for treating disease. 1. A method for treating a CD19-associated disorder in a mammalian subject comprising administering an antibody or antigen-binding fragment that specifically binds to human CD19 in an amount effective to treat the disorder in the mammalian subject; the antibody or antigen-binding fragment comprising a heavy chain variable region amino acid sequence as set forth in SEQ ID NO:29 with 0 , 1 or 2 substitutions relative to SEQ ID NO:9 and a light chain variable region amino acid sequence as set forth in SEQ ID NO:30 with 0 , 1 or 2 substitutions relative to SEQ ID NO:17; wherein the antibody or antigen-binding fragment binds to CD19 with a dissociation constant of 1×10M.2. The method of claim 1 , wherein the CD19-associated disorder is a CD19 expressing cancer.3. The method of claim 1 , wherein the heavy chain variable region has the amino acid sequence of SEQ ID NO:9.4. The method of claim 1 , wherein the light chain variable region has the amino acid sequence of SEQ ID NO:24.5. The method of claim 1 , wherein the antibody comprises a human IgG constant region and is administered.6. The method of claim 5 , wherein the isotype of the IgG constant region is IgG1 claim 5 , IgG2 claim 5 , or IgG1V1.7. The method of claim 1 , wherein the antibody or antigen-binding fragment is conjugated to an anti-tubulin agent.8. The method of claim 7 , wherein the anti-tubulin agent is an auristatin.9. The method of claim 1 , wherein the antibody or antigen-binding fragment as a ligand-drug conjugate compound claim 1 , wherein the ligand drug conjugate compound is of the following formula:{'br': None, 'sub': 'p', 'L-(LU-D)\u2003\u2003(I)'}or a pharmaceutically acceptable salt or solvate thereof;wherein:L is a ligand unit wherein the ligand unit is the antibody or antigen-binding fragment; and(LU-D) is a Linker unit-Drug unit moiety, wherein:LU- is a Linker unit, ...

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Номер записи: 20
22-11-2012 дата публикации

Anti-CD70 Antibody and Its Use for the Treatment and Prevention of Cancer and Immune Disorders

Номер: US20120294863A1
Автор: Law Che-Leung, McEarchern Julie, Wahl Alan F.
Принадлежит: Seattle Genetics, Inc.

Disclosed are CD70 binding agents, such as anti-CD70 antibodies and derivatives, that induce a cytotoxic, cytostatic or immunomodulatory without conjugation to a therapeutic agents as well as pharmaceutical compositions and kits comprising the antibody or derivative. Also disclosed are methods for the treatment and prevention of CD70-expressing cancers and immunological disorders comprising administering the CD70 binding agents to a subject. 1. A method for the treatment of a CD70-expressing Hodgkin's lymphoma in a subject , comprising:administering to the subject an effective amount of an antibody having an antigen-binding region that binds to CD70 and at least one effector domain mediating at least an ADCC, ADCP or CDC response in the subject, wherein the antibody exerts a cytostatic or cytotoxic effect in the absence of conjugation to a therapeutic agent and wherein the antibody is not conjugated to a therapeutic agent.2. The method of claim 1 , wherein the antibody is a chimeric claim 1 , humanized claim 1 , or fully human antibody.3. The method of claim 2 , wherein the antibody is a humanized antibody.4. The method of claim 3 , wherein the humanized antibody comprises an effector domain of a human IgM or IgG antibody.5. The method of claim 4 , wherein the IgG antibody is of the human IgG1 subtype.6. The method of claim 2 , wherein the antibody is a chimeric antibody.7. The method of claim 6 , wherein the chimeric antibody comprises an effector domain of a human IgM or IgG antibody.8. The method of claim 7 , wherein the IgG antibody is of the human IgG1 subtype.9. The method of claim 2 , wherein the antibody comprises a human constant region.10. The method of claim 1 , wherein the antibody comprises H1 claim 1 , H2 claim 1 , H3 claim 1 , L1 claim 1 , L2 and L3 complementarity-determining regions having claim 1 , respectively claim 1 , the amino acid sequences set forth in SEQ ID NO:6 claim 1 , SEQ ID NO:8 claim 1 , SEQ ID NO:10; SEQ ID NO:16 claim 1 , SEQ ID NO: ...

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Номер записи: 21
20-12-2012 дата публикации

METHODS FOR SCREENING ANTIBODIES

Номер: US20120322686A1
Автор: Benjamin Dennis, Lyon Robert, Ryan Maureen
Принадлежит: Seattle Genetics, Inc.

The invention provides methods for making antibody conjugates for use in antibody screening assays and antibody conjugates produced by the claimed methods. 1. A method for making antibody conjugates for use in antibody screening assays comprising the steps of:providing a first and second antibody-containing sample wherein the first and second antibody-containing sample vary with respect to antibody quantity and antibody sequence provided that substantially all of the antibody present in the first sample is of the same sequence and substantially all of the antibody present in the second sample is of the same sequence;immobilizing the antibodies on a solid support to provide a first and second sample comprising immobilized antibodies;fully reducing the reducible disulfide bonds of the immobilized antibodies to provide a first sample comprising reduced immobilized antibodies and second sample comprising reduced immobilized antibodies, wherein the reduction is selective for the reducible disulfide bonds;reacting the reduced immobilized antibodies with capping agent, drug or drug-linker, and optionally a detection agent to provide immobilized antibody conjugates, wherein the capping agent, drug or drug-linker, and optional detection agent selectively react with reactive thiols, the capping agent, drug or drug-linker, and optional detection agent are provided in molar excess, and the ratio of capping agent, drug or drug linker, and optional detection agent is selected so as to achieve a desired level of drug loading; andeluting the antibody conjugates to provide a first and second antibody drug conjugate composition.2. The method of wherein the reducible disulfide bonds are the naturally occurring interchain disulfide bonds of the antibody.3. The method of wherein the antibody in the first and second antibody-containing sample have the same number of reducible disulfide bonds and the reduced immobilized antibodies are contacted with the same ratio of capping agent claim 1 ...

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Номер записи: 22
24-01-2013 дата публикации

Combination Therapy With Antibody-Drug Conjugates

Номер: US20130022627A1
Автор: Gerber Hans-Peter, Oflazoglu Ezogelin, Sievers Eric
Принадлежит: Seattle Genetics, Inc.

Methods for the treatment of Hodgkin's lymphoma comprising administering both a chemotherapeutic regimen and an antibody-drug conjugate compound to a subject in need thereof are provided. 1. A method for treating Hodgkin lymphoma in a subject , the method comprising administering to a subject in need thereof gemcitabine and an antibody-drug conjugate compound , wherein said antibody-drug conjugate compound is an anti-CD30 antibody conjugated to an auristatin compound thereby treating Hodgkin lymphoma in the patient.2. The method of wherein said antibody-drug conjugate compound is delivered over a treatment cycle wherein the total dose over the treatment cycle is from 0.1 mg/kg to 3.2 mg/kg of the subject's body weight.3. The method of wherein said antibody-drug conjugate compound is delivered over a treatment cycle wherein the total dose over the treatment cycle is from about 0.6 mg/kg to about 3.2 mg/kg of the subject's body weight.4. The method of wherein the antibody-drug conjugate compound is delivered as a split dose over the treatment cycle.5. The method of wherein the antibody-drug conjugate compound is delivered as a single dose over the treatment cycle.6. The method of wherein the treatment cycle is three weeks.7. The method of wherein the treatment cycle is four weeks.8. The method of wherein the antibody-drug conjugate compound is administered in a dose range of 0.4 to 1 mg/kg of the subject's body weight per dose.9. The method of wherein gemcitabine is administered in a dose range of 500 mg/mto 1500 mg/mper dose.10. The method of wherein the antibody-drug conjugate compound and gemcitabine are administered during a treatment cycle of three or four weeks and no additional anti-cancer agents are administered during the treatment cycle.11. (canceled)12. The method of wherein said subject is suffering from advanced stage Hodgkin lymphoma.13. The method of wherein said subject has relapsed or refractory Hodgkin lymphoma.14. The method of wherein the antibody- ...

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Номер записи: 23
07-03-2013 дата публикации

Pyrrolobenzodiazepines used to treat proliferative diseases

Номер: US20130059800A1
Автор: Arnaud Tiberghien, Luke Masterson, Patrick Burke, Peter Senter, Philip Wilson Howard, Scott Jeffrey
Принадлежит: Seattle Genetics Inc, SPIROGEN DEVELOPMENTS SÀRL

Pyrrolobenzodiazepine dimers I having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds.

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Номер записи: 24
28-03-2013 дата публикации

IDENTIFYING MATERIAL FROM A BREAST DUCT

Номер: US20130078650A1
Автор: HUNG David T.
Принадлежит: Atossa Genetics, Inc.

Methods and systems for identifying material from a breast duct using one or more markers that can be identified in ductal fluid retrieved from the breast are provided. 128-. (canceled)29. A method of predicting the likelihood of breast cancer recurrence or identifying viable treatment regimen in a human patient comprising:obtaining a ductal fluid sample from at least one duct of a breast of the patient;transforming said sample to a form suitable for analysis of protein in an analytical instrument;measuring, using immunohistochemistry, ELISA, protein probe labeling, polypeptide probe labeling, peptide probe labeling, or a combination thereof, in an analytical instrument, the expression levels of one or more proteins in said transformed sample, whereinsaid one or more proteins are selected from the group consisting of a growth factor receptor, HER2, estrogen receptor, progesterone receptor, Bcl2, a protein that participates in a transcriptional activation pathway, Ki67, a cyclin, a cathepsin L, a peptide form of a factor from a growth factor, glutathione S-transferase, a macrophage inflammatory protein, BAG-1, a protein that participates in an-apoptosis pathway, a macrophage inflammatory protein, an actin binding protein, stromelysin-3, or a combination thereof; andcomparing the presence or absence of levels of one or more in expression of said one or more proteins to a normal control, wherein levels over normal controls indicate a likelihood of breast cancer recurrence and wherein levels at or below a normal indicates a viable treatment regimen.30. The method of claim 29 , wherein said ductal fluid sample contains cells.31. The method of claim 30 , further comprising analyzing the cytology of cells in said sample.32. The method of claim 31 , wherein the presence of tumor cells indicates a likelihood of breast cancer recurrence.33. The method of claim 31 , wherein the absence of tumor cells indicates an efficacious treatment regimen.34. The method of claim 29 , ...

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Номер записи: 25
09-05-2013 дата публикации

METHODS OF BREAST CANCER DETECTION

Номер: US20130115629A1
Автор: Chen Shu-Chih, Quay Steven C.
Принадлежит: Atossa Genetics, Inc.

Methods of diagnosing breast cancers are provided. The methods include analyzing the expression patterns of biomarkers in a plurality of cells to distinguish between invasive and non-invasive cancers, usual and atypical hyperplasias, and basal-like breast cancers. Breast cancers are diagnosed based upon different combinations of the biomarkers found in nipple aspirate fluid. 122.-. (canceled)23. A method of classifying a breast cancer , comprising:a) contacting a cell of a nipple aspirate fluid sample absorbed onto an absorbent paper with antibodies that bind to CK5, CK14, CK7, CK18, and p63, wherein the absorbent paper is sized to cover a nipple;b) detecting binding of one or more of the antibodies to said cell; andc) classifying the cancer based upon the binding pattern of the primary antibodies;wherein the cell derived from the nipple aspirate fluid (NAF) sample is not a tissue.24. The method of claim 23 , wherein the absorbent paper is from about 1.0 to about 3.0 inches in diameter and from about 0.01 to about 0.1 inches thick.25. The method of claim 23 , wherein detecting binding of the one or more antibodies further comprises staining the cells with a stain selected from among horseradish peroxidase claim 23 , alkaline phosphatase claim 23 , diaminobenzidine claim 23 , Fast Red claim 23 , hematoxylin claim 23 , eosin and a combination thereof.26. The method of claim 23 , further comprising washing the absorbent paper and collecting the effluent.27. The method of claim 23 , wherein the absorbent paper comprises microcellulose claim 23 , mixed cellulose ester claim 23 , or nitrocellulose.28. The method of claim 23 , wherein the absorbent paper is a device as illustrated in .29. The method of claim 23 , further comprising classifying the breast cancer as basal-like if an anti-CK5 antibody claim 23 , an anti-CK14 antibody claim 23 , and optionally an anti-p63 claim 23 , primary antibody binds to the cell.30. The method of claim 23 , further comprising classifying ...

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Номер записи: 26
16-05-2013 дата публикации

Methods of combining metagenome and the metatranscriptome in multiplex profiles

Номер: US20130121968A1
Автор: Quay Steven C.
Принадлежит: Atossa Genetics, Inc.

The present invention describes changes in bacterial gastrointestinal, cutaneous and nasal microbiota associated various mammalian medical conditions. Described are diagnostic tests that arise from combining phylogenetic information about the families, genus, and species of the microbiome and their relative abundance with the metabolic information contained in the metatranscriptome to determine the presence and absence of a disease or medical condition. Provided are compositions of bacteria, co-cultures of bacteria and a carrier for use in treating the disclosed medical conditions. The described compositions restore or correct disease- or medical condition-related imbalances in the microbiome profile with culture-conditioned formulations in which the transcriptome activity of the administered organisms is optimized. Alternatively, formulations of metabolites that drive changes in the metatranscriptome native to the mammal that treat disease or a medical condition or restore health are taught. 1. A method of diagnosing the presence or absence of a medical condition in a mammal comprising:a. isolating and quantifying at least a portion of 16S ribosomal RNA of a sample from said patient to determine a metagenomic profile;b. isolating and quantifying at least a portion of messenger RNA of said sample to determine a metatranscriptome profile; andc. comparing, using a general purpose computer, a multiplex profile of a metatranscriptome profile and a metagenomic profile to a multiplex profile of a population of patients diagnosed with said medical condition to determine the presence or absence of the medical condition.2. The method claim 1 , further comprising combining the metagenomic and metatranscriptome profiles into the multiplex profile using a general purpose computer.3. The method of claim 1 , wherein said medical condition is a cancer claim 1 , an infection claim 1 , an inflammatory disease claim 1 , an autoimmune disease claim 1 , a hormonal disease claim 1 , a ...

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Номер записи: 27
16-05-2013 дата публикации

MONOMETHYLVALINE COMPOUNDS HAVING PHENYLALANINE SIDE-CHAIN MODIFICATIONS AT THE C-TERMINUS

Номер: US20130123465A1
Автор: Doronina Svetlana O., Kline Toni Beth
Принадлежит: Seattle Genetics, Inc.

Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) are provided having C-terminal phenylalanine residue side chain replacements or modifications which are provided alone or attached to ligands through various linkers. The related conjugates can target specific cell types to provide therapeutic benefit. 216.-. (canceled)1821.-. (canceled)2427.-. (canceled)29. A compound of claim 28 , having the formula:{'br': None, 'L-LU-D'}or a pharmaceutically acceptable salt or solvate thereof.32. The compound of having the formula:{'br': None, 'sub': 'p', 'Ab-(D).'}33. The compound of claim 31 , wherein the antibody is attached to the drug moiety through a cysteine residue of the antibody.34. The compound of wherein p is 2 to 5.35. The compound of wherein p is 2 to 8.36. (canceled)45. The compound of wherein w is an integer ranging from 2 to 12.46. The compound of wherein w is 2.47. The compound of wherein Wis -valine-citrulline-.48. (canceled)49. (canceled)50. The compound of claim 31 , wherein the antibody is a monoclonal antibody.51. The compound of claim 31 , wherein the antibody is a bispecific antibody.52. The compound of claim 31 , wherein the antibody is a chimeric antibody.53. The compound of claim 31 , wherein the antibody is a humanized antibody.54. The compound of claim 31 , wherein the antibody is an antibody fragment.55. The compound of claim 54 , wherein the antibody fragment is a Fab fragment.56114.-. (canceled) This application claims the benefit of U.S. Provisional Application No. 60/697,767, filed Jul. 7, 2005; the disclosure of which is incorporated by reference herein.The present invention is directed to Drug Compounds, to Drug-Linker-Ligand Conjugates, Drug-Linker Compounds, and Drug-Ligand Conjugates; as well as to compositions including the same, and to methods for using the same to treat cancer, an autoimmune disease, an infectious disease and other pathological conditions. The invention also relates to methods of using Antibody-Drug Conjugate ...

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Номер записи: 28
23-05-2013 дата публикации

METHODS OF INHIBITION OF PROTEIN FUCOSYLATION IN VIVO USING FUCOSE ANALOGS

Номер: US20130129784A1
Автор: Alley Stephen, Benjamin Dennis, Senter Peter
Принадлежит: Seattle Genetics, Inc.

The invention provides methods and compositions for the inhibition of fucosylation of proteins, including antibodies, in vivo by administration of a fucose analog. 3. The method of claim 1 , wherein the mammal has cancer or an autoimmune disorder.4. (canceled)5. The method of claim 3 , further comprising administering cancer-associated antigen or an antigenic fragment thereof as an immunogen.6. The method of claim 1 , wherein each of R-Ris independently selected from the group consisting of —OH claim 1 , —OC(O)H claim 1 , —OC(O)C-Calkyl claim 1 , —OC(O)C-Calkenyl claim 1 , —OC(O)C-Calkynyl claim 1 , —OC(O)aryl claim 1 , —OC(O)heterocycle claim 1 , —OC(O)C-Calkylene(aryl) claim 1 , —OC(O)C-Calkenylene(aryl) claim 1 , —OC(O)C-Calkynylene(aryl) claim 1 , —OC(O)C-Calkylene(heterocycle) claim 1 , —OC(O)C-Calkenylene(heterocycle) claim 1 , —OC(O)C-Calkynylene(heterocycle) claim 1 , —OC(O)CHO(CHCHO)CHand —OC(O)CHCHO(CHCHO)CH; and Ris selected from the group consisting of —C≡CH claim 1 , —C≡CCH claim 1 , —CHC≡CH claim 1 , —C(O)OCH claim 1 , —CH(OAc)CH claim 1 , —CN claim 1 , —CHCN claim 1 , —CHX (wherein X is F claim 1 , Br claim 1 , Cl or I) and methoxiran.7. The method of claim 1 , wherein each of R-Ris independently selected from the group consisting of —OH—OC(O)H and —OC(O)C-Calkyl.8. The method of claim 7 , wherein each of R-Ris independently selected from the group consisting of —OH and —OAc.9. The method of claim 1 , wherein Ris selected from the group consisting of —C≡CH and —C═CCH.10. (canceled)11. The method of claim 1 , wherein Ris —CHX claim 1 , wherein X is F claim 1 , Br claim 1 , Cl or I.12. (canceled)13. (canceled)14. The method of claim 1 , wherein Ris —CHX claim 1 , wherein X is F.15. (canceled)16. (canceled)17. (canceled)18. (canceled)20. The method of claim 19 , wherein Ris F.21. The method of claim 19 , wherein Ris F.22. The method of claim 19 , wherein Ris F.23. The method of claim 19 , wherein Rand Rare each F.24. The method of claim 19 , wherein Rand ...

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Номер записи: 29
20-06-2013 дата публикации

NOVEL AURISTATIN DERIVATIVES AND USE THEREOF

Номер: US20130157960A1
Автор: GOLFIER Sven, Krenz Ursula, LERCHEN Hans-Georg, SCHUHMACHER Joachim, STELTE-LUDWIG Beatrix
Принадлежит: Seattle Genetics, Inc.

The present application relates to novel derivatives of monomethylauristatin F, to processes for preparing these derivatives, to the use of these derivatives for treating and/or preventing diseases, and also to the use of these derivatives for preparing medicaments for treating and/or preventing diseases, more particularly hyperproliferative and/or angiogenic disorders such as, for example, cancerous disorders. Such treatments may be practised as a monotherapy or else in combination with other medicaments or further therapeutic measures. 68.-. (canceled)10. The medicament of in combination with one or more further active compounds.11. (canceled) The present application relates to novel derivatives of monomethylauristatin F, to processes for preparing these derivatives, to the use of these derivatives for treating and/or preventing diseases, and also to the use of these derivatives for preparing medicaments for treating and/or preventing diseases, more particularly hyperproliferative and/or angiogenic disorders such as, for example, cancerous disorders. Such treatments may be practised as a monotherapy or else in combination with other medicaments or further therapeutic measures.Cancerous disorders are the consequence of uncontrolled cell growth in a wide variety of tissues. In many cases the new cells penetrate existing tissue (invasive growth), or they metastase into remote organs. Cancerous disorders occur in a wide variety of organs, and the diseases often progress in a tissue-specific manner. The designation “cancerous disorder” as a generic term therefore describes a large group of defined diseases of different organs, tissues and cell types.Early-stage tumours may be able to be removed by surgical and radiotherapeutic measures. Metastasized tumours can generally only be given palliative therapy by means of chemotherapeutic agents. The objective in that case is to achieve the optimum combination of improving quality of life and prolonging remaining lifetime.The ...

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Номер записи: 30
15-08-2013 дата публикации

Synergistic Effects Between Auristatin-Based Antibody Drug Conjugates And Inhibitors Of The PI3K-AKT mTOR Pathway

Номер: US20130209496A1
Автор: Che-Leung Law, Julie A. Mcearchern, Timothy S. Lewis
Принадлежит: Seattle Genetics Inc

The present invention is directed to methods for treating cancer comprising administering to a subject in need thereof an auristatin-based antibody drug conjugate and an inhibitor of the PI3K-AKT-mTOR pathway.

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Номер записи: 31
21-11-2013 дата публикации

CD33 Antibodies And Use Of Same To Treat Cancer

Номер: US20130309223A1
Автор: Django Sussman, Maureen Ryan, May Kung Sutherland, Patrick Burke, Scott Jeffrey
Принадлежит: Seattle Genetics Inc

The invention provides murine, chimeric, and humanized antibodies that specifically bind to CD33. The antibodies are useful for treatment and diagnoses of various cancers as well as detecting CD33.

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Номер записи: 32
26-12-2013 дата публикации

METHOD AND SYSTEM FOR SORTING DATA IN A CLOUD-COMPUTING ENVIRONMENT AND OTHER DISTRIBUTED COMPUTING ENVIRONMENTS

Номер: US20130346425A1
Автор: Bruestle Jeremy J.
Принадлежит: Spiral Genetics Inc.

The current document is directed to a method and system for data processing in cloud-computing environments and other distributed-computing environments. Implementations of a merge sort suitable for the sorting of data within cloud-computing environments and other distributed-computing environments are disclosed. These implementations takes advantage of the massive parallelism available in cloud-computing environments as well as take into consideration numerous constraints regarding data-storage and data-retrieval operations in a cloud-computing environment. The implementations provide a type of data-sorting method and system that iteratively carries out highly parallel merge-sort operations that can be effectively applied over a range of data-set sizes up to extremely large data sets. 1. A merge-sort system comprising:a distributed computing environment, implemented on multiple physical computer systems, that provides computational resources for execution of tasks and that provides a virtual data-storage subsystem for storing and retrieving data objects; and receive an indication of a number of data objects stored within the distributed computing environment, each data object including multiple records, each record comprising a key and a data value,', 'distribute tasks, each task associated with a data object, to computational resources within the distributed computing environment where the tasks are executed, each task sorting the records of the data object associated with the task by key value, and', 'distribute tasks, each task associated with a subset of the data objects, to computational resources within the distributed computing environment where the tasks are executed, each task merge sorting the records of the subset of the data objects associated with the task by key value.', 'while a range of key values in any data object of the number of data objects overlaps with a range of key values in any other data object of the number of data objects,'}], 'computer ...

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Номер записи: 33
30-01-2014 дата публикации

BETA-GLUCURONIDE-LINKER DRUG CONJUGATES

Номер: US20140031535A1
Автор: Jeffrey Scott
Принадлежит: Seattle Genetics, Inc.

Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided. 7. The drug linker conjugate of claim 1 , wherein the Drug Unit is a DNA minor groove binder.8. The drug linker conjugate of claim 1 , wherein the Drug Unit is an alkylating agent.9. The drug linker conjugate of claim 1 , wherein the Drug Unit is an antitubulin agent.10. The drug linker conjugate of claim 1 , wherein the Drug Unit is a maytansinoid.11. The drug linker conjugate of claim 1 , wherein the Drug Unit is an auristatin. This application is a Divisional of U.S. patent application Ser. No. 13/274,212, filed Oct. 14, 2011; which is a divisional of U.S. patent application Ser. No. 11/996,009, which was filed under 35 U.S.C. §371 as a national stage application of International Application No. PCT/US2006/027925, filed Jul. 18, 2006; which claims the benefit of U.S. Provisional Patent Application Nos. 60/700,422, filed Jul. 18, 2005, and 60/779,076, filed Mar. 4, 2006; the disclosures of which are incorporated by reference herein in their entirety and for all purposes.Monoclonal antibody therapies are gaining momentum as adjunct and front-line treatments for cancer. Successes of mAb therapies like AVASTIN (anti-VEGF) for colon cancer, RITUXAN (Rituximab; anti-CD20) for Non-Hodgkin's Lymphoma and HERCEPTIN (anti-Her2) for breast cancer have demonstrated that unconjugated antibodies can improve patient survival without the incidence of significantly increased toxicity.Monoclonal antibodies (mAb) can be conjugated to a therapeutic agent to form an antibody drug conjugate (ADC). ADCs can exhibit increased efficacy, as compared to an unconjugated antibody. The linkage of the antibody to the drug can be direct, or indirect via a linker. One of components believed to be important for developing effective and well-tolerated ADCs is the composition and stability of the linker. For some types of ADCs, the linker desirably provides serum stability, yet ...

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Номер записи: 34
30-01-2014 дата публикации

METHODS AND COMPOSITIONS FOR MAKING ANTIBODIES AND ANTIBODY DERIVATIVES WITH REDUCED CORE FUCOSYLATION

Номер: US20140031536A1
Автор: ALLEY STEPHEN C., Benjamin Dennis R., Burke Patrick J., Jeffrey Scott C., Sussman Django, Toki Brian
Принадлежит: Seattle Genetics, Inc.

The invention provides methods and compositions for preparing antibodies and antibody derivatives with reduced core fucosylation. 2. The culture medium of wherein Ris selected from the group consisting of —C≡CH claim 1 , —C≡CCH claim 1 , C(O)OCH claim 1 , —CHCN claim 1 , and —CHBr.3. The culture medium of wherein Ris —C≡CH and R-Ris —OAc.4. The culture medium of claim 1 , which is free of added animal protein.5. The culture medium of claim 1 , which is free of serum.6. The culture medium of claim 1 , which is free of added fucose.7. The culture medium of claim 1 , which is a powder.8. The culture medium of claim 1 , which is a liquid.9. The culture medium of claim 1 , wherein each of R-Ris independently selected from the group consisting of —OH and —OC(O)C-Calkyl.10. The culture medium of claim 1 , wherein each of R-Ris independently selected from the group consisting of —OH and —OAc.11. The culture medium of claim 1 , wherein Ris selected from the group consisting of —C≡CH and —C≡CCH.12. The culture medium of claim 1 , wherein Ris —C(O)OCH claim 1 , —CHCN claim 1 , or —CHBR.13. The culture medium of wherein the effective amount is an amount of the analog that is sufficient to decrease fucose incorporation into a complex N-glycoside-linked sugar chain of an antibody or antibody derivative by at least 90%.14. The culture medium of claim 1 , which:(i) is free of added animal protein;(ii) is free of serum;(iii) is free of added fucose; and(iv) is a powder or a liquid.15. The culture medium of claim 13 , which:(i) is free of added animal protein;(ii) is free of serum;(iii) is free of added fucose; and(iv) is a powder or a liquid.16. The culture medium of wherein the effective amount is an amount of the analog that is sufficient to decrease fucose incorporation into a complex N-glycoside-linked sugar chain of an antibody or antibody derivative by at least 90%.17. The culture medium of wherein the antibody or antibody derivative is a humanized or human antibody or ...

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Номер записи: 35
20-02-2014 дата публикации

Auristatin drug linker conjugates

Номер: US20140050746A1
Автор: Peter Senter, Svetlana Doronina, Timothy Bovee
Принадлежит: Seattle Genetics Inc

Drug Linker compounds and Drug Linker Ligand conjugates are provided that have auristatins linked via the C-terminus. The conjugates show efficacy without the need for a self-immolative group to release the drug.

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Номер записи: 36
20-03-2014 дата публикации

N-CARBOXYALKYLAURISTATINS AND USE THEREOF

Номер: US20140080763A1
Автор: EL SHEIKH Sherif, GNOTH Mark, LERCHEN Hans-Georg, SCHUHMACHER Joachim, STELTE-LUDWIG Beatrix
Принадлежит: Seattle Genetics, Inc.

The present application relates to new derivatives, substituted on the N terminus by a carboxyalkyl group, of monomethylauristatin E and monomethylauristatin F, to processes for preparing these derivatives, to the use of these derivatives for treating and/or preventing diseases, and to the use of these derivatives for producing medicaments for treating and/or preventing diseases, more particularly hyperproliferative and/or angiogenic disorders such as cancer disorders, for example. Such treatments may be applied as a monotherapy or else in combination with other medicaments or further therapeutic measures. 57.-. (canceled)8. A pharmaceutical composition comprising a compound as defined in or a salt or solvate thereof and further comprising one or more inert claim 1 , non-toxic claim 1 , pharmaceutically suitable excipients.9. The pharmaceutical composition of claim 9 , further comprising one or more additional active ingredients.10. (canceled)11. A method for the treatment and/or prevention of cancer or tumor conditions in humans or animals claim 1 , said method comprising administering to a subject an effective amount of at least one compound as defined in .12. A method for treatment and/or prevention of cancer or tumor diseases in humans or animals claim 8 , said method comprising administering to a subject an effective amount of at least one pharmaceutical composition of . The present patent application relates to novel derivatives of monomethylauristatin E and monomethylauristatin F, substituted with a carboxyalkyl group on the N terminus, methods of synthesis of these derivatives, use of these derivatives for treatment and/or prevention of diseases and use of these derivatives for production of pharmaceutical drugs for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic diseases, such as the various forms of cancer, for example. Such treatments may be in the form of monotherapy or in combination with other drugs or other ...

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Номер записи: 37
27-03-2014 дата публикации

Variant Target Binding Agents and Uses Thereof

Номер: US20140086942A1
Автор: Carter Paul, Sussman Django
Принадлежит: Seattle Genetics, Inc.

The present invention provides variant target binding agents and methods relating to the use of such binding agents for the prophylaxis or treatment of cancers and immunological disorders. The variant target binding agent is conjugated to a therapeutic agent that exerts a cytotoxic, cytostatic, or immunomodulatory effect on target cells. 1. A method of treating a cancer in a subject , comprising administering to the subject an effective amount of a variant target binding agent conjugate , the variant target binding agent comprising:a binding region comprising an antibody Fv region or an antigen binding fragment thereof that specifically binds to a target antigen on a cancer cell;at least a portion of a Fc region of a human immunoglobulin IgG1 constant region comprising an introduced cysteine residue at amino acid position 239, that is S239C, according to the EU index as set forth in Kabat;a therapeutic agent conjugated directly or via a linker to the introduced cysteine residue, wherein the therapeutic agent exerts a cytotoxic effect on a cancer cell expressing the target antigen.2. The method of claim 1 , wherein the binding region specifically binds to CD30 claim 1 , CD33 claim 1 , or CD70.3. The method of claim 1 , wherein the therapeutic agent is conjugated to the introduced cysteine residue via a linker.4. The method of claim 3 , wherein the therapeutic agent is conjugated to the introduced cysteine residue via a maleimide group of the linker.5. The method of wherein the variant target binding agent is an intact antibody conjugated to a therapeutic agent.6. The method of wherein the variant target binding agent is an intact antibody conjugated to a therapeutic agent.7. The method of claim 1 , wherein the therapeutic agent is a DNA minor groove binding agent.8. The method of claim 7 , wherein the DNA minor groove binding agent is a DNA minor groove alkylating agent.9. The method of claim 1 , wherein the therapeutic agent is an anti-tubulin agent.10. The method ...

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Номер записи: 38
02-01-2020 дата публикации

Glycan-interacting compounds and methods of use

Номер: US20200000932A1
Автор: Daniel T. Dransfield, David A. Eavarone, Jillian M. PRENDERGAST
Принадлежит: Seattle Genetics Inc

Methods of treating cancer are provided that include administering glycan-interacting antibodies. Included are anti-sialyl Tn antigen antibodies and related compositions and formulations suitable to achieve desirable bioactivity, bioavailability, and toxicity levels.

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Номер записи: 39
02-01-2020 дата публикации

BCMA ANTIBODIES AND USE OF SAME TO TREAT CANCER AND IMMUNOLOGICAL DISORDERS

Номер: US20200002431A1
Автор: FELDHAUS Michael, Ryan Maureen, Sussman Django, Westendorf Lori
Принадлежит: Seattle Genetics, Inc.

The invention provides humanized antibodies that specifically bind to BCMA. The antibodies are useful for treatment and diagnoses of various cancers and immune disorders as well as detecting BCMA. 1. A humanized , chimeric or veneered antibody , which is a humanized , chimeric or veneered form of an antibody deposited as ATCC PTC-6937.2. The antibody of claim 1 , comprising a mature heavy chain variable region having at least 90% sequence identity to hSG16.17 VH3 (SEQ ID NO: 13) and a mature light chain variable region having at least 90% sequence identity to hSG16.17 VK2 (SEQ ID NO: 19).3. The antibody of claim 2 , comprising a mature heavy chain variable region having at least 95% sequence identity to hSG16.17 VH3 (SEQ ID NO: 13) and a mature light chain variable region having at least 95% sequence identity to hSG16.17 VK2 (SEQ ID NO: 19).4. The antibody of claim 1 , comprising the three Kabat CDRs (SEQ ID NOs: 60-62) of hSG16.17 VH3 (SEQ ID NO: 13) and three Kabat CDRs (SEQ ID NOs: 90-92) of hSG16.17 VK2 (SEQ ID NO: 19) provided that position H58 can be occupied by N or K claim 1 , position H60 can be occupied by A or N claim 1 , position H61 can be occupied by Q or E claim 1 , position H62 can be occupied by K or N claim 1 , position H64 can be occupied by Q or K claim 1 , position H65 can be occupied by G or T claim 1 , position L24 can be occupied by R or L claim 1 , and position L53 can be occupied by S or R.5. The antibody of comprising the three Kabat CDRs (SEQ ID NOs: 60-62) of hSG16.17 VH3 (SEQ ID NO: 13) and three Kabat CDRs (SEQ ID NOs: 90-92) of hSG16.17 VK2 (SEQ ID NO: 19).6. The antibody of claim 1 , wherein positions H20 claim 1 , H48 claim 1 , H69 claim 1 , H71 claim 1 , H73 claim 1 , H76 claim 1 , H80 claim 1 , H88 claim 1 , H91 and H93 are occupied by L claim 1 , I claim 1 , M claim 1 , A claim 1 , K claim 1 , N claim 1 , V claim 1 , A claim 1 , F claim 1 , and T respectively claim 1 , and positions L46 claim 1 , L48 and L87 are occupied by V ...

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Номер записи: 40
07-01-2021 дата публикации

Humanized Anti-CD70 Binding Agents and Uses Thereof

Номер: US20210002380A1
Автор: Carter Paul, McDonagh Charlotte
Принадлежит: Seattle Genetics, Inc.

Disclosed are CD70 binding agents, such as humanized anti-CD70 antibodies and fragments and derivatives, that exert a cytotoxic, cytostatic or immunomodulatory on CD70 expressing cells, as well as pharmaceutical compositions and kits comprising the antibody, fragment or derivative. Also disclosed are methods for the treatment of CD70-expressing cancers and immunological disorders, comprising administering to a subject the CD70 binding agents or pharmaceutical compositions. 138-. (canceled)39. A method for treating diffuse large B-cell lymphomas in a human subject , comprisingadministering to a subject having diffuse large B-cell lymphoma an effective amount of a humanized antibody or antigen binding fragment, comprising:{'sub': H', 'H', 'H, '(i) a humanized heavy chain comprising the three CDRs from SEQ ID NO:2 and a variable region framework sequence of human germline V1-2 or V1-18 and exon J-6, provided that any of positions H46, H67, H68, H69, H70, H71, H80, H81, H82, H82A and H91 (Kabat numbering) can be occupied by the amino acid occupying the corresponding position from SEQ ID NO:2; and'}{'sub': χ', 'χ', 'χ, '(ii) a humanized light chain comprising the three CDRs from SEQ ID NO:22 and a variable region framework sequence of human germline V exon B3 and J exon J-1, provided that any of positions L25 and L33 can be occupied by the amino acid occupying the corresponding position from SEQ ID NO:22.'}40. The method of claim 39 , wherein position H46 is occupied by the amino acid occupying the corresponding position from SEQ ID NO:2.41. The method of claim 39 , wherein at least one of positions H46 claim 39 , H67 claim 39 , H68 claim 39 , H69 claim 39 , H70 claim 39 , H71 claim 39 , H80 claim 39 , H81 claim 39 , H82 claim 39 , H82A and H91 (Kabat numbering) in the humanized heavy chain variable region is occupied by the residue occupying the corresponding position in SEQ ID NO:2.42. The method of claim 39 , wherein at least one of positions L25 and L33 in the ...

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Номер записи: 41
07-01-2016 дата публикации

Detection and Treatment of Pancreatic, Ovarian and Other CD70 Positive Cancers

Номер: US20160003847A1
Автор: Ryan Maureen, Smith Maria Leia
Принадлежит: Seattle Genetics, Inc.

The application provides methods of diagnosis, prognosis, prophylaxis and treatment of ovarian, pancreatic and other cancers using antibodies that specifically bind to denatured CD70. 1. A monoclonal antibody that specifically binds to denatured human CD70 on a sample of formalin fixed , paraffin-embedded cells or tissues that express human CD70 , wherein the monoclonal antibody comprises three heavy chain complementarity determining regions (CDRs): heavy chain CDR1 , heavy chain CDR2 , and heavy chain CDR3 , wherein the heavy chain CDRs are identical to the heavy chain CDRs of the antibody SG-21.5D12; and three light chain CDRs: light chain CDR1 , light chain CDR2 , and light chain CDR3 , wherein the light chain CDRs are identical to the light chain CDRs of the antibody SG-21.5D12 , and wherein the antibody SG-21.5D12 is produced by the hybridoma deposited with the ATCC and assigned Accession No. PTA-8734.2. The monoclonal antibody of claim 1 , which is a chimeric or humanized antibody.3. The monoclonal antibody of claim 1 , that is antibody SG-21.5D12 as produced by the hybridoma deposited with the ATCC and assigned Accession No. PTA-8734.4. The monoclonal antibody of claim 1 , comprising the heavy chain variable region of the antibody SG-21.5D12 and the light chain variable region of the antibody SG-21.5D12.5. A diagnostic kit claim 1 , comprising the monoclonal antibody of .6. A method of detecting expression of CD70 in a tissue sample of a patient claim 1 , comprisingobtaining a tissue sample of pancreas, ovary, lung, larynx, pharynx, breast, or skin from the patient;fixing the tissue sample and denaturing CD70 in the tissue sample, wherein the sample is fixed in formalin and embedded in paraffin;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting the fixed tissue sample with the monoclonal antibody of ; and'}detecting binding of the monoclonal antibody to the fixed tissue sample to determine whether CD70 is expressed in the sample.7. A combination ...

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Номер записи: 42
14-01-2021 дата публикации

HYDROPHOBIC AURISTATIN F COMPOUNDS AND CONJUGATES THEREOF

Номер: US20210008099A1
Автор: Doronina Svetlana O., Moquist Philip
Принадлежит: Seattle Genetics, Inc.

Ligand Drug Conjugates of hydrophobically-modified auristatin F compounds that exhibit cytotoxic activities towards targeted cells, including abnormal cells such as cancer cells, that are MDR+ while also exhibiting bystander activities towards nearby cells having lower expression of the moeity targeted by the Conjugate. 2. The compound of claim 1 , wherein Ris methyl and Ris hydrogen claim 1 ,3. The compound of claim 1 , wherein Ris hydrogen and Ar is phenyl.4. The compound of claim 1 , wherein Ris methyl; Ris hydrogen; and Ar is phenyl.5. The compound of any one of to claim 1 , wherein Ris a saturated C-Calkyl claim 1 , an unsaturated C-Calkyl or a carbocyclyl-alkyl- of up to 9 total carbon atoms.6. The compound of any one of to claim 1 , wherein Ris a branched C-Calkyl claim 1 , in particular a branched C-Calkyl claim 1 , or Ris —(C-Calkylene)-X—R claim 1 , wherein X is a carbamate functional group and Ris t-butyl or CHC═CH.7. The compound of claim 6 , wherein R has the formula of —(CH)—N(R)—C(═O)-t-Bu wherein Ris hydrogen or —CH.9. The compound of any one of to claim 6 , wherein Ris —CHCHCH(CH)CHC(CH) claim 6 , —CHCHCHCHN(CH)—C(═O)—O-t-Bu claim 6 , —CHCHCHN(CH)—C(═O)—O-t-Bu or —CHCHCHNH—C(═O)—O-t-Bu.10. The compound of any one of to claim 6 , wherein{'sup': '1', 'sub': 2', '2', '2', '2', '3, 'Ris —CHCHCHCHN(CH)—C(═O)-t-Bu.'}22. The Ligand Drug Conjugate composition of or claim 6 , wherein L is an antibody Ligand Unit of an intact antibody or an antigen-binding fragment thereof claim 6 , that is capable of selectively binding to a cancer cell antigen claim 6 ,in particular, the antibody Ligand Unit is of an intact chimeric, humanized or human antibody.23. The Ligand Drug Conjugate composition of claim 22 , wherein subscript p ranges from about 2 to about 12 claim 22 , or from about 2 to about 10 claim 22 , or from about 2 to about 8 claim 22 , in particular claim 22 , subscript p is about 2 claim 22 , about 4 or about 8. The invention relates to hydrophobic ...

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Номер записи: 43
14-01-2021 дата публикации

Glycan-Interacting Compounds and Methods of Use

Номер: US20210011021A1
Автор: Behrens Jeffrey, da Silva Ana Paula Galvao, DeSander Julie, Eavarone David A., Ghaderi Darius, Meetze Kristan, Prendergast Jillian M., Zhang Mai
Принадлежит: Seattle Genetics, Inc.

The present invention provides glycan-interacting antibodies and methods for producing glycan-interacting antibodies useful in the treatment and prevention of human disease, including cancer. Such glycan-interacting antibodies include monoclonal antibodies, derivatives, and fragments thereof as well as compositions and kits comprising them. Further provided are methods of using glycan-interacting antibodies to target cells and treat disease.

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Номер записи: 44
17-01-2019 дата публикации

CONJUGATES OF QUATERNIZED TUBULYSIN COMPOUNDS

Номер: US20190015517A1
Автор: Burke Patrick J., Courter Joel
Принадлежит: Seattle Genetics, Inc.

Compounds and compositions are disclosed in which a quaternized drug unit is linked to a targeting ligand unit from which a tertiary amine-containing drug is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as cancer or an autoimmune disease using the compounds and compositions of the invention are also disclosed. 34.-. (canceled)9. (canceled)11. (canceled)15. The Ligand Drug Conjugate composition of wherein Ris —CHCHor CH—CH═CH.16. (canceled)17. The Ligand Drug Conjugate composition of claim 13 , wherein{'sup': 2A', '2B', '3, 'sub': 2', '3', '2', '2', '2', '3', '2', '3', '3, 'Ris —CHCH, —CH—CH═CHor —CHC(CH)═CH, Ris —CH, Ris —CHand subscript u is 0, or'}{'sup': 2A', '2B', '3', '7B, 'sub': 2', '3', '2', '2', '2', '3', '2', '3', '3, 'Ris —CHCHor —CH—CH═CH, or —CHC(CH)═CH, Ris —CH, Ris —CHand subscript u is 1, wherein Ris —OH.'}19. (canceled)21. (canceled)26. The Ligand Drug Conjugate composition of claim 24 , wherein Ris saturated C-Calkyl or unsaturated C-Calkyl claim 24 , wherein saturated C-Calkyl is —CH claim 24 , —CHCH claim 24 , —CHCHCHand unsaturated C-Calkyl is —CHCH═CHor —CH(CH)CH═CH.27. The Ligand Drug Conjugate composition of wherein Ris —C(O)CH claim 25 , —CHCHor —CHCH═CH.2829.-. (canceled)32. (canceled)36. (canceled)38. (canceled)40. (canceled)42. (canceled)4445.-. (canceled)47. (canceled)5053.-. (canceled)55. (canceled)57. (canceled)61. (canceled)62. The Drug Linker compound of wherein Ris —C(O)CH claim 60 , —CHCHor —CHCH═CH.6364.-. (canceled)67. (canceled)70. (canceled)7273.-. (canceled)77. (canceled)81. (canceled)86. (canceled)88. (canceled)91. (canceled)93. A formulation comprising a Ligand Drug Conjugate of and one or more excipients.94. The formulation of wherein the formulation is a pharmaceutically acceptable formulation or a precursor thereof claim 93 , whereinthe Ligand Drug Conjugate is present in the pharmaceutically acceptable formulation or precursor thereof in an ...

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Номер записи: 45
21-01-2021 дата публикации

Glycan Analysis and Profiling

Номер: US20210017213A1
Автор: Ana Paula Galvao Da Silva, Darius Ghaderi, Jeffrey BEHRENS, Jillian M. PRENDERGAST, Julie DESANDER, Mai ZHANG
Принадлежит: Seattle Genetics Inc

The invention provides methods and tools, for example, glycan arrays, for the analysis of glycans and anti-glycan antibodies. Embodiments of the invention may be used to detect proteins, antibodies, diseases and/or pathogenic agents. In other embodiments, methods of the invention are used to develop or optimize arrays and antibodies.

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Номер записи: 46
17-04-2014 дата публикации

Variant Target Binding Agents and Uses Thereof

Номер: US20140105922A1
Автор: Carter Paul, Sussman Django
Принадлежит: Seattle Genetics, Inc.

The present invention provides variant target binding agents and methods relating to the use of such binding agents for the prophylaxis or treatment of cancers and immunological disorders. The variant target binding agent is conjugated to a therapeutic agent that exerts a cytotoxic, cytostatic, or immunomodulatory effect on target cells. 1. A variant target binding agent conjugate , comprising:a binding region that comprises an antibody Fv region or an antigen binding fragment thereof that specifically binds to a target antigen, wherein the target antigen is CD33;at least a portion of a Fc region of a human immunoglobulin IgG1 constant region, comprising an introduced cysteine residue at amino acid position 239, that is S239C, according to the EU index as set forth in Kabat; anda therapeutic agent conjugated directly or via a linker to the introduced cysteine residue, wherein the therapeutic agent exerts a cytotoxic or cytostatic effect on a cell that expresses CD33.2. The variant target binding agent of claim 1 , wherein the therapeutic agent is conjugated to the introduced cysteine residue via a linker.3. The variant target binding agent of claim 2 , wherein the therapeutic agent is conjugated to the introduced cysteine residue via a maleimide group of the linker.4. The variant target binding agent conjugate of claim 2 , wherein the therapeutic agent is a cytotoxic agent that exerts a cytotoxic effect on a cell that expresses CD33.5. The variant target binding agent conjugate of claim 4 , wherein the cytotoxic agent is a DNA minor groove binding agent.6. The variant target binding agent of claim 5 , wherein the DNA minor groove binding agent is a DNA minor groove alkylating agent.7. The variant target binding agent conjugate of claim 3 , wherein the therapeutic agent is a cytotoxic agent that exerts a cytotoxic effect on a cell that expresses CD33.8. The variant target binding agent conjugate of claim 7 , wherein the cytotoxic agent is a DNA minor groove binding ...

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Номер записи: 47
26-01-2017 дата публикации

Humanized Anti-CD70 Binding Agents and Uses Thereof

Номер: US20170022282A1
Автор: Charlotte Mcdonagh, Paul Carter
Принадлежит: Seattle Genetics Inc

Disclosed are CD70 binding agents, such as humanized anti-CD70 antibodies and fragments and derivatives, that exert a cytotoxic, cytostatic or immunomodulatory on CD70 expressing cells, as well as pharmaceutical compositions and kits comprising the antibody, fragment or derivative. Also disclosed are methods for the treatment of CD70-expressing cancers and immunological disorders, comprising administering to a subject the CD70 binding agents or pharmaceutical compositions.

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Номер записи: 48
24-01-2019 дата публикации

BCMA ANTIBODIES AND USE OF SAME TO TREAT CANCER AND IMMUNOLOGICAL DISORDERS

Номер: US20190023801A1
Автор: FELDHAUS Michael, Ryan Maureen, Sussman Django, Westendorf Lori
Принадлежит: Seattle Genetics, Inc.

The invention provides humanized antibodies that specifically bind to BCMA. The antibodies are useful for treatment and diagnoses of various cancers and immune disorders as well as detecting BCMA. 1. A humanized antibody the specifically binds to the human BCMA protein , the antibody comprising a mature heavy chain variable region having at least 90% sequence identity to hSG16.17 VH3 (SEQ ID NO: 13) and a mature light chain variable region having at least 90% sequence identity to hSG16.17 VK2 (SEQ ID NO: 19).2. The antibody of claim 1 , comprising a mature heavy chain variable region having at least 95% sequence identity to hSG16.17 VH3 (SEQ ID NO: 13) and a mature light chain variable region having at least 95% sequence identity to hSG16.17 VK2 (SEQ ID NO: 19).3. The antibody of claim 1 , comprising the three Kabat CDRs (SEQ ID NOs: 60-62) of hSG16.17 VH3 (SEQ ID NO: 13) and three Kabat CDRs (SEQ ID NOs: 90-92) of hSG16.17 VK2 (SEQ ID NO: 19) provided that position H58 can be occupied by N or K claim 1 , position H60 can be occupied by A or N claim 1 , position H61 can be occupied by Q or E claim 1 , position H62 can be occupied by K or N claim 1 , position H64 can be occupied by Q or K claim 1 , position H65 can be occupied by G or T claim 1 , position L24 can be occupied by R or L claim 1 , and position L53 can be occupied by S or R.4. The antibody of comprising the three Kabat CDRs (SEQ ID NOs: 60-62) of hSG16.17 VH3 (SEQ ID NO: 13) and three Kabat CDRs (SEQ ID NOs: 90-92) of hSG16.17 VK2 (SEQ ID NO: 19).5. The antibody of claim 1 , wherein positions H20 claim 1 , H48 claim 1 , H69 claim 1 , H71 claim 1 , H73 claim 1 , H76 claim 1 , H80 claim 1 , H88 claim 1 , H91 and H93 are occupied by L claim 1 , I claim 1 , M claim 1 , A claim 1 , K claim 1 , N claim 1 , V claim 1 , A claim 1 , F claim 1 , and T respectively claim 1 , and positions L46 claim 1 , L48 and L87 are occupied by V claim 1 , V and F respectively.6. The antibody of claim 1 , wherein the mature heavy ...

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Номер записи: 49
02-02-2017 дата публикации

STABLE FORMULATIONS FOR ANTI-CD19 ANTIBODIES AND ANTIBODY-DRUG CONJUGATES

Номер: US20170028062A1
Автор: Amsberry Kent, Jiang Shan
Принадлежит: Seattle Genetics, Inc.

This disclosure provides optimized formulations for CD19 antibodies and antibody-drug conjugates (ADCs) 1. A stable formulation of an anti-CD19 antibody comprising a phosphate buffer , wherein the anti-CD19 antibody comprises a light chain variable region of SEQ ID NO:1 and a heavy chain variable region of SEQ ID NO:2 , wherein the phosphate buffer has a pH value between 5.0 and 7.0.2. The stable formulation of claim 1 , wherein the phosphate buffer is a sodium phosphate buffer.3. The stable formulation of claim 1 , wherein the phosphate buffer is a potassium phosphate buffer.4. The stable formulation of claim 1 , wherein the phosphate buffer has a pH between 5.5 and 6.5.5. The stable formulation of claim 1 , wherein the phosphate buffer has a pH of about 6.0.6. The stable formulation of claim 1 , wherein the anti-CD19 antibody is conjugated to a cytotoxic agent.7. The stable formulation of claim 6 , wherein the cytotoxic agent is an auristatin.8. The stable formulation of claim 7 , wherein the cytotoxic agent is monomethylauristatin F (MMAF).9. (canceled)10. The stable formulation of claim 6 , further comprising a surfactant.11. The stable formulation of claim 10 , wherein the surfactant is polysorbate 80.12. The stable formulation of claim 11 , wherein the polysorbate 80 concentration is between 0.01% and 0.05% weight/volume.13. The stable formulation of claim 12 , wherein the polysorbate 80 concentration is about 0.02%.14. The stable formulation of claim 10 , further comprising a bulking agent.15. The stable formulation of claim 14 , wherein the bulking agent is a sugar.16. The stable formulation of claim 15 , wherein the bulking agent is a member selected from the group consisting of sucrose and trehalose.17. The stable formulation of claim 15 , wherein the sugar concentration is between 10 mg/ml and 75 mg/ml.18. The stable formulation of claim 16 , wherein the sugar is sucrose.19. The stable formulation of claim 18 , wherein the sucrose concentration is about ...

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Номер записи: 50
29-01-2015 дата публикации

NOVEL BINDER-DRUG CONJUGATES (ADCS) AND USE THEREOF

Номер: US20150030618A1
Автор: BEIER Rudolf, Borkowski Sandra, Bruder Sandra, EL SHEIKH Sherif, GOLFIER Sven, Greven Simone, Harrenga Axel, HEISLER Iring, JÖRIßEN Hannah, Kopitz Charlotte C., LERCHEN Hans-Georg, LINDEN Lars, Mahlert Christoph, PETRUL Heike, SCHUHMACHER Joachim, STELTE-LUDWIG Beatrix, THIERAUCH Karl-Heinz, WILLUDA Jörg
Принадлежит: Seattle Genetics, Inc.

The present application relates to new binder-drug conjugates (ADCs) of N,N-dialkylauristatins that are directed against the target C4.4a, to active metabolites of these ADCs, to processes for preparing these ADCs, to the use of these ADCs for treating and/or preventing illnesses, and also to the use of these ADCs for producing medicaments for treating and/or preventing illnesses, more particularly hyperproliferative and/or angiogenic diseases such as, for example, cancer diseases. Such treatments may be practised as a monotherapy or else in combination with other medicaments or further therapeutic measures. 1. (canceled)46-. (canceled)14. (canceled)16. (canceled)18. (canceled)20. (canceled)23. Binder-drug conjugate according to claim 2 , where the binder binds to a cancer target molecule2428-. (canceled)29. Binder-drug conjugate according to claim 2 , where the binder is an antibody or an antigen-binding antibody fragment thereof or an antibody mimetic.30. Binder-drug conjugate according to claim 29 , where the antibody is a monoclonal antibody.31. (canceled)32. Binder-drug conjugate according to claim 29 , where the antibody is an intact or a modified intact antibody and wherein the antibody is a human claim 29 , humanized or chimeric antibody.33. Binder-drug conjugate according to claim 29 , where the antibody is an antibody of the IgG class.3449-. (canceled)52. (canceled)53. A medicament comprising the binder-drug conjugate of in combination with a pharmaceutically acceptable excipient.54. The medicament of claim 53 , further comprising one or more anti-hyperproliferative claim 53 , cytostatic claim 53 , or cytotoxic substances.55. A method for the treatment of cancer in a human or animal subject comprising administering to said subject the binder-drug conjugate of .56. A method for the treatment of cancer in a human or animal subject comprising administering to said subject the medicament of . This application is a continuation-in-part of International ...

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Номер записи: 51
01-02-2018 дата публикации

Combination therapy using a cd19-adc and vincristine

Номер: US20180028681A1
Автор: Che-Leung Law, Ivan STONE
Принадлежит: Seattle Genetics Inc

This invention relates to treatment of acute lymphoblastic leukemia.

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Номер записи: 52
24-04-2014 дата публикации

METHODS AND SYSTEMS FOR IDENTIFYING, FROM READ SYMBOL SEQUENCES, VARIATIONS WITH RESPECT TO A REFERENCE SYMBOL SEQUENCE

Номер: US20140114584A1
Автор: Bruestle Jeremy J.
Принадлежит: Spiral Genetics Inc.

The current document is directed to automated methods and processor-controlled systems for assembling short read symbol sequences into longer assembled symbol sequences that are aligned and compared to a reference symbol sequence in order to determine differences between the longer assembled symbol sequences and the reference sequence. These methods and systems are applied to process electronically stored symbol-sequence data. While the symbol-sequence data may represent genetic-code data, the automated methods and processor-controlled systems may be more generally applied to various different symbol-sequence data. In certain implementations, redundancy in read symbol sequences is used to preprocess the read symbol sequences to identify and correct symbol errors. In certain implementations, those corrected read symbol sequences that exactly match subsequences of the reference symbol sequence are identified and removed from subsequent processing steps, to simply the identification of differences between the longer assembled symbol sequences and the reference sequence. 1. A variant-symbol-sequence detection system comprising:one or more processors;one or more data-storage devices; and receive a set of read symbol sequences generated from multiple copies of an initial symbol sequence,', 'k-merize the read symbol sequences to generate a set of unique k-mers, each unique k-mer of the set associated with a k-mer quality score;', 'filter the set of unique k-mers to remove k-mers likely to contain erroneous symbols in order to generate a set of legitimate k-mers;', 'correct erroneous symbols within the read symbol sequences using the set of legitimate k-mers to generate a set of corrected read symbol sequences;', 'filter the set of corrected read symbol sequences to remove corrected read symbol sequences that exactly match subsequences within a reference symbol sequence to generate a set of variant read symbol sequences; and', 'assemble the variant read symbol sequences ...

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Номер записи: 53
30-01-2020 дата публикации

WEEKLY DOSING REGIMENS FOR ANTI-CD30 VC-PAB-MMAE ANTIBODY DRUG-CONJUGATES

Номер: US20200030405A1
Автор: Kennedy Dana, Sievers Eric
Принадлежит: Seattle Genetics, Inc.

Methods for the treatment of CD30-expressing cancers are provided. The methods comprise administering to a subject in need thereof a weekly dose of from about 0.8 mg/kg to about 1.8 mg/kg of an antibody-drug conjugate compound having formula (I); or a pharmaceutically acceptable salt thereof; wherein: mAb is an anti-CD30 antibody unit, S is a sulfur atom of the antibody, A- is a Stretcher unit, and p is from about 3 to about 5. 125-. (canceled)26. A method for treating a CD30-expressing hematologic cancer in a human subject , the method comprising administering to a human subject in need thereof a dose of a pharmaceutical composition comprising (i) cAC10-MC-vc-PAB-MMAE antibody-drug conjugate , and (ii) a pharmaceutically acceptable carrier , wherein the administered dose of cAC10-MC-vc-PAB-MMAE antibody-drug conjugate is 1.8 mg/kg of the human subject's body weight and the pharmaceutical composition is administered every three weeks , wherein the pharmaceutical composition is administered by intravenous infusion to the human subject.27. The method of claim 26 , wherein the average number of MMAE molecules per cAC10 antibody of the cAC10-MC-vc-PAB-MMAE antibody-drug conjugate in the pharmaceutical composition is about 4.28. The method of claim 26 , wherein the CD30-expressing hematologic cancer is Hodgkin Lymphoma.29. The method of claim 28 , wherein the average number of MMAE molecules per cAC10 antibody of the cAC10-MC-vc-PAB-MMAE antibody-drug conjugate in the pharmaceutical composition is about 4.30. The method of claim 26 , wherein the CD30-expressing hematologic cancer is anaplastic large cell lymphoma.31. The method of claim 30 , wherein the average number of MMAE molecules per cAC10 antibody of the cAC10-MC-vc-PAB-MMAE antibody-drug conjugate in the pharmaceutical composition is about 4.32. The method of claim 26 , wherein the pharmaceutical composition is administered for 2 or more 21-day treatment cycles.33. The method of claim 32 , wherein the ...

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Номер записи: 54
30-01-2020 дата публикации

ANTIBODIES TO INTEGRIN AVB6 AND USE OF SAME TO TREAT CANCER

Номер: US20200031938A1
Автор: Ryan Maureen, Sussman Django
Принадлежит: Seattle Genetics, Inc.

The invention provides antibodies that specifically bind to integrin αvβ6. The antibodies are useful for treatment and diagnoses of various cancers as well as detecting αvβ6. 1. A humanized antibody that specifically binds to the human integrin αvβ6 wherein the antibody comprises a mature heavy chain region having a heavy chain variable region having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 11 or 22 , and a light chain variable region having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 25.2. The antibody of claim 1 , comprising a mature heavy chain region having a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 11 or 22 claim 1 , and a mature light chain variable region having the amino acid sequence set forth in SEQ ID NO: 25.3. The antibody of wherein the mature heavy chain variable region is fused to a heavy chain constant region and the mature light chain variable region is fused to a light chain constant region.4. The antibody of claim 3 , wherein the heavy chain constant region is a mutant form of a natural human constant region which has reduced binding to an Fc gamma receptor relative to the natural human constant region.5. The antibody of claim 3 , wherein the heavy chain constant region is of IgG1 isotype.6. The antibody of claim 1 , wherein the antibody is conjugated to a cytotoxic or cytostatic agent.7. The antibody of claim 6 , wherein the cytotoxic agent is vcMMAE or mcMMAF.8. A method of treating a patient having pancreatic cancer or head and neck cancer claim 1 , comprising administering to the patient an effective regime of an antibody of .9. A pharmaceutical composition comprising an antibody of .10. An isolated polynucleotide comprising a sequence encoding a heavy chain variable region and a light chain variable region as defined in .11. An isolated vector comprising the polynucleotide of .12. An isolated host cell comprising the vector ...

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Номер записи: 55
09-02-2017 дата публикации

METHODS OF INHIBITION OF PROTEIN FUCOSYLATION IN VIVO USING FUCOSE ANALOGS

Номер: US20170035790A1
Автор: Alley Stephen, Benjamin Dennis, Senter Peter
Принадлежит: Seattle Genetics, Inc.

The invention provides methods and compositions for the inhibition of fucosylation of proteins, including antibodies, in vivo by administration of a fucose analog. 159-. (canceled)61. The method of claim 64 , wherein each of R claim 64 , R claim 64 , and Ris independently selected from the group consisting of —OH and OAc claim 64 , Ris F claim 64 , Rand Rare each H claim 64 , and Ris CH.62. The method of wherein the fucose analog is 2-deoxy-2-fluorofucose.63. The method of wherein the fucose analog is 2-deoxy-2-fluorofucose peracetate.64. The method of further comprising administering a tumor-associated antigen or an antigenic fragment thereof as an immunogen.65. The method of further comprising administering a chemotherapeutic agent.66. The method of wherein the cancer is breast cancer.67. The method of wherein the cancer is lung cancer.68. The method of wherein the cancer is renal cell carcinoma.69. The method of wherein administration is oral administration.70. The method of wherein administration of the therapeutically effective amount is in the form of one or more dosage units.72. The pharmaceutical composition of claim 71 , wherein each of R claim 71 , R claim 71 , and Ris independently selected from the group consisting of —OH and —OAc claim 71 , Ris F claim 71 , Rand Rare each H claim 71 , and Ris CH.73. The pharmaceutical composition of wherein the fucose analog is 2-deoxy-2-fluorofucose.74. The pharmaceutical composition of wherein the fucose analog is 2-deoxy-2-fluorofucose peracetate.75. The pharmaceutical composition of claim 71 , wherein the composition is suitable for oral administration. This application claims the benefit of U.S. Provisional Application No. 61/371,116, filed Aug. 5, 2010, the disclosure of which is incorporated by reference herein.L-fucose, also referred to as 6-deoxy-L-galactose, is a monosaccharide that is a component of some N- and O-linked glycans and glycolipids in animals. (See Becker and Lowe, Glycobiology 13:41R-51R (2003).) ...

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Номер записи: 56
11-02-2016 дата публикации

ACTIVATED CARBON FILTRATION FOR PURIFICATION OF BENZODIAZEPINE ADCS

Номер: US20160039870A1
Автор: Meyer Damon, Sun Michael
Принадлежит: Seattle Genetics, Inc.

Disclosed are methods of purifying mixtures comprising benzoidiazepine antibody-drug conjugates. 1. A method of removing benzodiazepine drug-related impurities from a mixture comprising benzodiazepine ADCs and benzodiazepine drug-related impurities comprising passing the mixture through an activated charcoal filter.2. The method of further comprising the steps of (i) contacting an antibody with a benzodiazepine drug-linker under conditions sufficient to form a mixture comprising benzodiazepine ADCs claim 1 , and (ii) contacting the mixture with a quenching agent to form quenched benzodiazepine drug-linkers.3. The method of further comprising the steps of (i) contacting an antibody conjugated to a linker with a benzodiazepine drug under conditions sufficient to form a mixture comprising benzodiazepine ADCs and benzodiazepine drug-related impurities.4. The method of wherein the benzodiazepine drug-related impurities are quenched drug-linkers.5. The method of wherein the benzodiazepine drug-related impurities are unconjugated drugs.6. The method of wherein the activated charcoal is attached to a solid support.7. The method of wherein filtration is via single pass filtration or recirculation through a single filter.8. The method of wherein filtration is via multiple discrete filtrations through a single filter.9. The method of wherein filtration is via recirculation through a single filter when there is 10 g or less benzodiazepine ADC in the mixture and filtration is via single pass filtration when there is greater than 10 g benzodiazepine ADC in the mixture.10. The method of wherein there is greater than about 20 g benzodiazepine ADC in the mixture and filtration is via single pass filtration.11. The method of wherein the flux is between about 3 L/min/mand 20 L/min/m.12. The method of wherein the flux is between about 6 L/min/mand 20 L/min/m.13. (canceled)14. The method of wherein filtration is via recirculation through a single filter and wherein the mixture ...

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Номер записи: 57
12-02-2015 дата публикации

METHODS OF USING MONOMETHYLVALINE COMPOSITIONS HAVING PHENYLALANINE CARBOXY MODIFICATIONS AT THE C-TERMINUS

Номер: US20150044238A1
Автор: Doronina Svetlana O, Jeffrey Scott, Kline Toni Beth, Meyer Damon, Senter Peter D
Принадлежит: Seattle Genetics, Inc.

Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) having a carboxylic acid equivalent at the C-terminal phenylalanine were prepared and attached to ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand-drug conjugates were active in vitro and in vivo in inhibiting cell proliferation and are represented by the general structure of 2. The method of wherein Wis -phenylalanine-lysine-.3. The method of wherein Wis —N-methyl valine-citrulline-.5. The method of wherein Rof Formula A is selected from the group consisting of H claim 4 , C-Calkyl claim 4 , C-Ccarbocyclyl claim 4 , X-aryl claim 4 , X—(C-C-carbocyclyl) and X—C-C-heterocyclyl.6. The method of claim 4 , wherein Rof Formula A is C-Calkyl or benzyl.7. The method of claim 4 , wherein Rof Formula A is H.8. The method of claim 4 , wherein Rof Formula A is benzyl.38. The method of wherein the antibody is AC10 claim 1 , S2C6 claim 1 , BR96 claim 1 , 1F5 claim 1 , 1F6 claim 1 , M195 and 2F2.39. The method of wherein the patient is a human.40. The method of claim 1 , further comprising administering an effective amount of an additional anticancer agent.41. The method of wherein the amount of the Antibody-Drug Conjugate composition administered to the patient is in the range of about 0.1 to about 10 mg/kg of patient weight claim 1 , wherein the administered Antibody-Drug Conjugate composition is in a pharmaceutically acceptable formulation.42. The method of wherein said formulation of the Antibody-Drug Conjugate composition is administered at about three week intervals.43. The method of wherein said formulation of the Antibody-Drug Conjugate composition is administered parenterally or intravenously. This application is a divisional application of, and claims priority under 35 U.S.C. §121, to pending U.S. patent application Ser. No. 11/994,459 filed on May 19, 2008, which is a national phase application of, and claims priority under 35 USC §365(c), to international patent ...

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Номер записи: 58
06-02-2020 дата публикации

Anti-TIGIT Antibodies

Номер: US20200040082A1
Автор: BEERS Courtney, Peterson Scott, PIASECKI Julia C., Prinz Bianka
Принадлежит: Seattle Genetics, Inc.

Isolated antibodies or antigen-binding portions that bind to human TIGIT (T-cell immunoreceptor with Ig and ITIM domains) are provided. In some embodiments, the antibody or antigen-binding portion thereof has a binding affinity (K) for human TIGIT of less than 5 nM. In some embodiments, the anti-TIGIT antibody blocks binding of CD155 and/or CD112 to TIGIT. 166.-. (canceled)67. An isolated antibody or antigen-binding portion thereof that binds to human TIGIT (T-cell immunoreceptor with Ig and ITIM domains) , wherein the antibody or antigen-binding portion thereof comprises a heavy chain CDR1 , CDR2 , and CDR3 and a light chain CDR1 , CDR2 , and CDR3 comprising the sequences of:(a) SEQ ID NOs: 58, 60, 62, 67, 69, and 71, respectively; or(b) SEQ ID NOs: 224, 225, 62, 67, 69, and 71, respectively; or(c) SEQ ID NOs: 226, 227, 228, 67, 69, and 71, respectively; or(d) SEQ ID NOs: 224, 229, 230, 67, 69, and 71, respectively; or(e) SEQ ID NOs: 224, 227, 230, 67, 69, and 71, respectively.68. The isolated antibody or antigen-binding portion thereof of claim 67 , wherein the antibody is a monoclonal antibody.69. The isolated antibody or antigen-binding portion thereof of claim 67 , wherein the antibody or antigen-binding portion thereof is humanized.70. The isolated antibody or antigen-binding portion thereof of claim 69 , wherein the antibody or antigen-binding portion thereof is an IgG1 antibody.71. The isolated antibody or antigen-binding portion thereof of claim 67 , wherein the antigen-binding portion thereof is a Fab claim 67 , a F(ab′) claim 67 , a scFv claim 67 , or a bivalent scFv.72. The isolated antibody or antigen-binding portion thereof of claim 67 , comprising a heavy chain variable region comprising an amino acid sequence that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:55 claim 67 , SEQ ID NO:246 claim 67 , SEQ ID NO:247 claim 67 , SEQ ID NO:248 claim 67 , or SEQ ID NO:249 and a light chain variable region comprising an amino acid ...

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Номер записи: 59
18-02-2016 дата публикации

CYCLODEXTRIN AND ANTIBODY-DRUG CONJUGATE FORMULATIONS

Номер: US20160045615A1
Автор: Jiang Shan, Li Hui, Meyer Damon, Wallace Mary
Принадлежит: Seattle Genetics, Inc.

Disclosed are formulations, including both liquid and lyophilized formulations, comprising a benzodiazepine anti-body-drug conjugate (ADC) and a cyclodextrin. Also disclosed are methods of purifying mixtures comprising benzodiazepine anti-body-drug conjugates and process drug-related impurities. 1. A method for removing benzodiazepine drug-related impurities from a mixture comprising benzodizepine ADCs and benzodiazepine drug-related impurities comprising subjecting the mixture to tangential flow filtration while maintaining a concentration of at least about 1% w/v cylodextrin in the mixture.2. The method of wherein the cyclodextrin is present in the mixture at the start of tangential flow filtration.3. The method of wherein the cyclodextrin is added to the mixture prior to any substantial removal of benzodiazepine drug-related impurities and cyclodextrin is thereafter maintained at a concentration of at least about 1% w/v in the mixture.4. (canceled)5. (canceled)6. The method of wherein the tangential flow filtration is constant volume diafiltration.7. The method of wherein the tangential flow filtration device comprises a pump claim 1 , a filtration holder having an inlet claim 1 , a filtrate outlet claim 1 , a retentate outlet claim 1 , an ultrafiltration membrane having a pore size of about 50 Kd or smaller that separates the filtration holder into an upstream compartment and a downstream compartment such that all filtrate must enter the inlet and pass through the ultrafiltration membrane before exiting the filtration holder through the filtrate outlet claim 1 , a sample reservoir for holding the conjugation reaction mixture claim 1 , and a buffer reservoir in fluid communication with the sample reservoir and wherein the buffer in the buffer reservoir comprises at least about 1% w/v cylodextrin claim 1 , at least about 2% w/v cylodextrin claim 1 , or at least about 3% w/v cylodextrin.8. The method of wherein the buffer replaces the filtration volume at the same ...

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Номер записи: 60
18-02-2021 дата публикации

CD33 ANTIBODIES AND USE OF SAME TO TREAT CANCER

Номер: US20210047404A1
Автор: Burke Patrick, Jeffrey Scott, Ryan Maureen, Sussman Django, Sutherland May Kung
Принадлежит: Seattle Genetics, Inc.

The invention provides murine, chimeric, and humanized antibodies that specifically hind to CD33. The antibodies are useful for treatment and diagnoses of various cancers as well as detecting CD33. 117-. (canceled)18. A method of treating a patient having or at risk of having a cancer that expresses CD33 , comprising administering to the patient an effective regime of an antibody-drug conjugate comprising an antibody that specifically binds to a human CD33 protein , wherein the antibody comprises a mature heavy chain variable region comprising three heavy chain complementarity determining regions (CDRs) comprising SEQ ID NOS:19-21 respectively , and a mature light chain variable region comprising three light chain CDRs comprising SEQ ID NOS:22-24 respectively.19. The method of claim 18 , wherein the cancer is acute myeloid leukemia (AML) claim 18 , myelodysplastic syndrome (MDS) claim 18 , acute promyelocytic leukemia (APL) claim 18 , chronic myelogenous leukemia (CIVIL) claim 18 , chronic myelomonocytic leukemia (CMML) claim 18 , a chronic myeloproliferative disorders claim 18 , precursor B-cell acute lymphoblastic leukemia (preB-ALL) claim 18 , precursor T-cell acute lymphoblastic leukemia (preT-ALL) claim 18 , multiple myeloma (MM) claim 18 , mast cell disease claim 18 , or myeloid Sarcoma.2044-. (canceled)45. A method of treating a patient having acute myeloid leukemia (AML) claim 18 , comprising administering to the patient an effective regime of an antibody that specifically binds to a human CD33 protein claim 18 , wherein the antibody comprises a mature heavy chain variable region comprising three heavy chain complementarity determining regions (CDRs) comprising SEQ ID NOS:19-21 respectively claim 18 , and a mature light chain variable region comprising three light chain CDRs comprising SEQ ID NOS:22-24 respectively.46. The method of claim 45 , wherein the antibody is conjugated to a cytotoxic or cytostatic agent.47. The method of claim 46 , wherein the ...

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Номер записи: 61
27-02-2020 дата публикации

Methods of inhibition of protein fucosylation in vivo using fucose analogs

Номер: US20200061091A1
Автор: Dennis Benjamin, Peter Senter, Stephen Alley
Принадлежит: Seattle Genetics Inc

The invention provides methods and compositions for the inhibition of fucosylation of proteins, including antibodies, in vivo by administration of a fucose analog.

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Номер записи: 62
27-02-2020 дата публикации

VARIANT TARGET BINDING AGENTS AND USES THEREOF

Номер: US20200062857A1
Автор: Carter Paul, Sussman Django
Принадлежит: Seattle Genetics, Inc.

The present invention provides variant target binding agents and methods relating to the use of such binding agents for the prophylaxis or treatment of cancers and immunological disorders. The variant target binding agent is conjugated to a therapeutic agent that exerts a cytotoxic, cytostatic, or immunomodulatory effect on target cells. 147-. (canceled)48. A variant target binding agent that is an antibody drug conjugate ,comprising:an antibody having a binding region that specifically binds to a target antigen and at least a portion of a Fc region of a human immunoglobulin (IgG1) constant region, the Fc region having an introduced cysteine residue at position 239, that is S239C; anda therapeutic agent that exerts a cytotoxic, cytostatic orimmunomodulatory effect on a cell expressing the target antigen, wherein the therapeutic agent is conjugated to the introduced cysteine residue of the antibody via a cleavable linker.49. The antibody drug conjugate of claim 48 , wherein the therapeutic agent is a cytotoxic agent.50. The antibody drug conjugate of claim 48 , wherein the therapeutic agent is an auristatin claim 48 , a DNA minor groove binding agent claim 48 , a DNA minor groove alkylating agent claim 48 , an enediyne claim 48 , a lexitropsin claim 48 , a duocarmycin claim 48 , a taxane claim 48 , a puromycin claim 48 , a dolastatin claim 48 , a maytansinoid claim 48 , or a vinca alkaloid.51. The antibody drug conjugate of claim 50 , wherein the therapeutic agent is a DNA minor groove alkylating agent.52. The antibody drug conjugate of claim 48 , wherein the therapeutic agent is a cytotoxic drug claim 48 , and wherein the cytotoxic drug is conjugated to the introduced cysteine residue as a maleimide derivatized cytotoxic drug.53. The antibody drug conjugate of claim 48 , wherein the cleavable linker is a peptide linker cleavable by an intracellular protease.54. The antibody drug conjugate of claim 48 , wherein the cleavable linker is a disulfide linker.55. The ...

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Номер записи: 63
27-02-2020 дата публикации

Anti-TIGIT Antibodies

Номер: US20200062859A1
Автор: BEERS Courtney, Gardai Shyra, Peterson Scott, PIASECKI Julia C., Prinz Bianka
Принадлежит: Seattle Genetics, Inc.

Isolated antibodies that bind to human TIGIT (T-cell immunoreceptor with Ig and ITIM domains) are provided. In some embodiments, the antibody has a binding affinity (K) for human TIGIT of less than 5 nM. In some embodiments, the anti-TIGIT antibody blocks binding of CD155 and/or CD112 to TIGIT. In some embodiments, the antibodies are afucosylated. 1184.-. (canceled)185. An isolated antibody that binds to human TIGIT (T-cell immunoreceptor with Ig and ITIM domains) , wherein the antibody comprises a heavy chain CDR1 , CDR2 , and CDR3 and a light chain CDR1 , CDR2 , and CDR3 comprising the sequences of:(a) SEQ ID NOs: 58, 60, 62, 67, 69, and 71, respectively; or(b) SEQ ID NOs: 224, 225, 62, 67, 69, and 71, respectively; or(c) SEQ ID NOs: 226, 227, 228, 67, 69, and 71, respectively; or(d) SEQ ID NOs: 224, 229, 230, 67, 69, and 71, respectively; or(e) SEQ ID NOs: 224, 227, 230, 67, 69, and 71, respectively.186. The isolated antibody of claim 185 , wherein the antibody is a monoclonal antibody.187. The isolated antibody of claim 185 , wherein the antibody is humanized.188. The isolated antibody of claim 187 , wherein the antibody is an IgG1 antibody.189. The isolated antibody of claim 185 , wherein the antigen-binding portion thereof is a Fab claim 185 , a F(ab′) claim 185 , a scFv claim 185 , or a bivalent scFv.190. The isolated antibody of claim 185 , comprising a heavy chain variable region comprising an amino acid sequence that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:55 claim 185 , SEQ ID NO:246 claim 185 , SEQ ID NO:247 claim 185 , SEQ ID NO:248 claim 185 , or SEQ ID NO:249 and a light chain variable region comprising an amino acid sequence that has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:64.191. The isolated antibody of claim 185 , comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:55 claim 185 , SEQ ID NO:246 claim 185 , SEQ ID NO:247 claim 185 , SEQ ID NO:248 ...

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Номер записи: 64
27-02-2020 дата публикации

PREPARING ANTIBODIES FROM CHO CELL CULTURES FOR CONJUGATION

Номер: US20200063180A1
Автор: Beam Kevin, Hayes Bradley, Lyon Robert, Meyer Damon, Valliere-Douglass John
Принадлежит: Seattle Genetics, Inc.

The invention is based in part on the observation that a CHO cell oxidizing enzyme, particularly QSOX1, can survive a seemingly rigorous antibody purification process to reduce subsequent conjugation efficiency of the antibody to a drug. Whether the oxidizing enzyme survives the purification procedure depends on which purification techniques are employed which can vary from one antibody to another. With knowledge that contamination with a CHO cell oxidizing enzyme is a potential problem for subsequent conjugation, a suitable purification scheme can be devised for any antibody that eliminates or at least reduces CHO oxidizing enzyme(s) to an acceptable level. 1. A method of producing a conjugated antibody , comprising:(a) obtaining a preparation of antibody;(b) testing the preparation for the presence of a CHO cell sulfhydryl oxidizing enzyme selected from at least one of quiescin Q6 sulfhydryl oxidase 1 (QSOX1), Q6 sulfhydryl oxidase 2 (QSOX2), and Augmenter of Liver Regeneration (ALR);(c) if the enzyme is detected at a detectable level in step (b), performing a purification step to remove the enzyme to a non-detectable level, wherein the purification step is selected from a step of (i) loading the preparation on a protein A column with a salt wash, (ii) performing depth filtration, (iii) using anion exchange with a quaternary ammonium ion column, and (iv) performing phenyl membrane filtration;(d) if the enzyme is not detected at a detectable level in step (b) or (c), proceeding to step (d); and(e) conjugating the at least partially purified antibody via one or more sulfhydryl groups to a drug to produce the conjugated antibody.2. The method of claim 1 , wherein the CHO cell sulfhydryl oxidizing enzyme is QSOX1.3. The method of claim 1 , wherein the testing comprises identifying a band of 65-75 kDa on a gel.4. The method of claim 3 , wherein the band is identified by western blot or silver stain.5. The method of claim 1 , wherein the testing comprises a functional ...

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Номер записи: 65
14-03-2019 дата публикации

COMBINATIONS OF PBD-BASED ANTIBODY DRUG CONJUGATES WITH BCL-2 INHIBITORS

Номер: US20190076549A1
Автор: Arthur William, Biechele Travis, Rohm Rory, Thurman Robert
Принадлежит: Seattle Genetics, Inc.

This invention relates to treatment of cancer using antibody drug conjugates that comprise PBD molecules in combination with Bcl-2 inhibitors. 1. A method of treating cancer in a subject in need of such treatment , the method comprising the step of administering an antibody drug conjugate (ADC) and a Bcl-2 inhibitor , wherein the ADC comprises a PBD cytotoxic agent and an antibody that specifically binds to a protein expressed by a cancer cell in the subject , wherein the Bcl-2 inhibitor is selected from the group consisting of ABT-199 and ABT-263.2. The method of claim 1 , wherein the antibody binds specifically to a protein selected from the group consisting of CD33 claim 1 , CD123 claim 1 , CD19 claim 1 , CD352 claim 1 , and CD70.4. The method of claim 1 , wherein the Bcl-2 inhibitor is ABT-199.5. The method of claim 4 , wherein the Bcl-2 inhibitor is ABT-263.6. The method of claim 3 , wherein the antibody specifically binds to a human CD33 protein.7. The method of claim 6 , wherein the antibody is h2H12.8. The method of claim 7 , wherein the Bcl-2 inhibitor is ABT-199.9. The method of claim 3 , wherein the antibody specifically binds to a human CD123 protein.10. The method of claim 9 , wherein the antibody is h7G3.11. The method of claim 10 , wherein the Bcl-2 inhibitor is ABT-199.12. A method of treating cancer in a subject in need of such treatment claim 10 , the method comprising the step of administering an antibody drug conjugate (ADC) and a Bcl-2 inhibitor claim 10 , wherein the cancer is a CD33 positive cancer claim 10 , wherein the ADC comprises a PBD cytotoxic agent conjugated to an h2H12 antibody claim 10 , and wherein the Bcl-2 inhibitor is selected from the group consisting of ABT-199 and ABT-263.13. The method of claim 12 , wherein the Bcl-2 inhibitor is ABT-199.15. The method of claim 12 , wherein the CD33-positive cancer is selected from the group consisting of acute myeloid leukemia and myelodysplastic syndrome.16. A method of treating cancer in ...

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Номер записи: 66
29-03-2018 дата публикации

Sensory Apparatus for Detection of Peripheral Neuropathy

Номер: US20180085056A1
Автор: Youngblood Danya Joy
Принадлежит: Seattle Genetics, Inc.

A texture ring system is configured to aid individuals in detecting the symptoms of peripheral neuropathy. The system includes planar components that each have a differently textured surface, and a connector component that secures the planar components together in a circular ring. 1. A texture ring system comprising:a plurality of planar components, each planar component comprising a textured surface that is tactually distinct from the textured surface of another of the plurality of planar components; anda connector component configured to secure the plurality of planar components, the connector component comprising a circular ring.2. The texture ring system of claim 1 , one of the textured surfaces comprising ribbed lines claim 1 , a rock salt pattern claim 1 , a fishnet pattern claim 1 , a concave bump pattern claim 1 , a convex bump pattern claim 1 , a checkered pattern claim 1 , or a sandpaper pattern.3. The texture ring system of claim 1 , the planar component comprising an oblong shape claim 1 , a circular shape claim 1 , or a rectangular shape.4. The texture ring system of claim 1 , the planar component further comprising a circular inner component claim 1 , the circular inner component comprising the textured surface.5. The texture ring system of claim 1 , the planar component further comprising an opening claim 1 , the opening configured to be threaded through the circular ring for securing the planar component to the connector component.6. The texture ring system of claim 1 , wherein each planar component is between 2 and 3 inches in length and between 1 and 2 inches in width.7. The texture ring system of claim 1 , wherein each planar component is composed of plastic.8. The texture ring system of claim 1 , wherein the connector component is composed of metal.9. A texture ring system comprising:three plastic planar components, each planar component comprising an oblong shape, and each planar component comprising a circular inner component having a textured ...

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Номер записи: 67
21-03-2019 дата публикации

COMBINATION THERAPY USING A LIV1-ADC AND A CHEMOTHERAPEUTIC

Номер: US20190085091A1
Автор: KOSTIC ANA, Li Fu, Sussman Django
Принадлежит: Seattle Genetics, Inc.

The invention provides methods of treating a subject having or at risk of cancer by administering a LIV-1 antibody drug conjugate and a chemotherapeutic. 1. A method for treating a subject having or at risk of cancer , the method comprising administering to the subject a LIV-1 antibody drug conjugate (LIV-1-ADC) and a chemotherapeutic , wherein the LIV-1-ADC comprises a humanized hLIV22 antibody conjugated to a vcMMAE (valine-citrulline-monomethyl auristatin E) , and wherein the chemotherapeutic is one of carboplatin , doxorubicin , and paclitaxel.2. The method of claim 1 , wherein the subject has breast cancer.3. The method of claim 2 , wherein the breast cancer is triple negative breast cancer claim 2 , triple positive breast cancer claim 2 , HER2-positive breast cancer claim 2 , or hormone receptor positive cancer.4. The method of claim 3 , wherein the subject has triple negative breast cancer.5. The method of claim 1 , wherein the subject has prostate cancer claim 1 , ovarian cancer claim 1 , endometrial cancer claim 1 , pancreatic cancer claim 1 , lung cancer claim 1 , a cervical cancer claim 1 , a melanoma claim 1 , or squamous cell carcinoma.6. The method of claim 1 , wherein the LIV-1-ADC is administered at a dosage between 1.5 mg/kg and 4 mg/kg of the subject's body weight.7. The method of claim 1 , wherein the LIV-1-ADC is administered at a dosage of 2.5 mg/kg of the subject's body weight.8. The method of claim 1 , wherein the LIV-1-ADC is administered once every 3 weeks.9. The method of claim 1 , wherein the LIV-1-ADC is administered by intravenous injection.10. The method of claim 1 , wherein the chemotherapeutic is carboplatin claim 1 , and wherein the carboplatin is administered at a dosage between 200 mg/mand 750 mg/m.11. The method of claim 1 , wherein the chemotherapeutic is carboplatin claim 1 , and wherein the carboplatin is administered by intravenous injection.12. The method of claim 1 , wherein the chemotherapeutic is doxorubicin claim 1 , and ...

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Номер записи: 68
05-04-2018 дата публикации

CD48 ANTIBODIES AND CONJUGATES THEREOF

Номер: US20180092984A1
Автор: Gordon Kristine, LEWIS TIMOTHY, Westendorf Lori
Принадлежит: Seattle Genetics, Inc.

The invention provides murine, chimeric, and humanized antibodies that specifically bind to CD48 and conjugates thereof. 1. A chimeric or humanized antibody that specifically binds to the human CD48 protein , wherein the antibody comprises heavy chain CDR sequences of SEQ ID NOs:3-5 and light chain CDR sequences of SEQ ID NOs:6-8 , and wherein the antibody exhibits higher binding affinity to the human CD48 protein , as compared to a murine antibody that specifically binds to the human CD48 protein and comprises heavy chain CDR sequences of SEQ ID NOs:3-5 and light chain CDR sequences of SEQ ID NOs:6-8.2. The antibody of claim 1 , wherein the chimeric or humanized antibody exhibits at least 2-fold higher binding affinity for the human CD48 protein claim 1 , as compared to the murine antibody.3. The antibody of claim 1 , wherein the antibody is a humanized antibody.4. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable region of SEQ ID NO:1.5. The antibody of claim 1 , wherein the antibody comprises a light chain variable region of SEQ ID NO:2.6. (canceled)7. The antibody of claim 1 , wherein the antibody is conjugated to a drug-linker wherein a cytotoxic drug is attached to a linker.9. A humanized antibody that specifically binds to the human CD48 protein claim 1 , wherein the antibody comprises a heavy chain variable region of SEQ ID NO:1 and a light chain variable region of SEQ ID NO:2.10. The antibody of claim 9 , wherein the antibody is conjugated to a drug-linker wherein a cytotoxic drug is attached to a linker.12. (canceled)15. The antibody of wherein n ranges from 8 to 14.1617-. (canceled)18. The antibody of wherein Ris —CHor —CHCHCOH.2029-. (canceled)30. The antibody of wherein attachment of the drug-linker to the antibody is via the cysteine residues of the interchain disulfide bonds of the antibody.31. A composition comprising a population of the antibody of wherein the average drug load of the antibodies in the composition is 8 ...

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Номер записи: 69
26-06-2014 дата публикации

Humanized Anti-CD70 Binding Agents and Uses Thereof

Номер: US20140178936A1
Автор: Carter Paul, McDonagh Charlotte
Принадлежит: Seattle Genetics, Inc.

Disclosed are CD70 binding agents, such as humanized anti-CD70 antibodies and fragments and derivatives, that exert a cytotoxic, cytostatic or immunomodulatory on CD70 expressing cells, as well as pharmaceutical compositions and kits comprising the antibody, fragment or derivative. Also disclosed are methods for the treatment of CD70-expressing cancers and immunological disorders, comprising administering to a subject the CD70 binding agents or pharmaceutical compositions. 138-. (canceled)39. An isolated polynucleotide encoding a humanized heavy chain variable region comprising the three CDRs from SEQ ID NO:2 and a variable region framework sequence of human germline V1-2 or V1-18 and exon J-6 , provided that any of positions H46 , H67 , H68 , H69 , H70 , H71 , H80 , H81 , H82 , H82A and H91 (Kabat numbering) can be occupied by the amino acid occupying the corresponding position from SEQ ID NO:2.40. The isolated polynucleotide of claim 39 , further encoding a human IgG constant region.41. The isolated polynucleotide of claim 40 , wherein the IgG constant region is IgG1 or IgG3.42. The isolated polynucleotide of claim 40 , wherein the humanized heavy chain variable region and the human IgG constant region together comprise the amino acid sequence corresponding to residues 20-467 of SEQ ID NO:16 or residues 20-467 of SEQ ID NO:20.43. The isolated polynucleotide of claim 42 , comprising the nucleotide sequence of nucleotides 58-1401 of SEQ ID NO:15 or nucleotides 58-1401 of SEQ ID NO:19.44. The isolated polynucleotide of claim 39 , wherein position H46 is occupied by the amino acid occupying the corresponding position from SEQ ID NO:2.45. The isolated polynucleotide of claim 39 , wherein at least one of positions H46 claim 39 , H67 claim 39 , H68 claim 39 , H69 claim 39 , H70 claim 39 , H71 claim 39 , H80 claim 39 , H81 claim 39 , H82 claim 39 , H82A and H91 (Kabat numbering) in the humanized heavy chain variable region is occupied by the residue occupying the ...

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Номер записи: 70
10-07-2014 дата публикации

Humanized anti-cd40 antibodies

Номер: US20140193405A1
Автор: Leonard G. Presta, Lori Y. O'connell, Svetlana O. Doronina
Принадлежит: Genentech Inc, Seattle Genetics Inc

Provided are humanized anti-CD40 antibodies and antigen-binding fragments and methods for treating disease characterized by expression of CD40 antigen.

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Номер записи: 71
09-04-2020 дата публикации

DETECTION AND TREATMENT OF CD30+ CANCERS

Номер: US20200110091A1
Автор: ALBERTSON Tina, Smith Maria L.
Принадлежит: Seattle Genetics, Inc.

The application provides methods of diagnosis, prognosis, prophylaxis and treatment of CD30 cancers. 116-. (canceled)17. A method of treating a CD30 positive cancer , comprisingadministering an effective regimen of a CD30-directed therapy to a patient having a cancer selected from ovarian carcinoma, melanoma, triple negative breast cancer, anaplastic thyroid carcinoma, pancreatic carcinoma small cell lung cancer, squamous cell carcinoma of the lung, skin squamous cell carcinoma anal squamous cell carcinoma endometrial carcinoma, carcinoma of unknown primary origin, genitourinary squamous cell carcinoma, gynecologic carcinosarcoma, Leydig cell tumor and Sertoli cell tumor, having detectable expression of CD30, wherein the CD30-directed therapy is an antibody or antibody drug conjugate.18. The method of claim 17 , wherein the CD30-directed therapy is an antibody having effector function.19. The method of claim 17 , wherein the CD30-directed therapy is an antibody drug conjugate.20. The method of claim 19 , wherein the antibody drug conjugate is brentuximab vedotin.21. The method of claim 17 , wherein CD30 expression is detected in at least 10% of malignant or abnormal cells in a sample of the cancer.22. (canceled)23. The method of wherein at least 50% of the malignant or atypical cells in the sample express CD30.2429-. (canceled)30. The method of claim 17 , wherein the patient has ovarian serous carcinoma.31. The method of claim 17 , wherein the patient has melanoma.32. The method of claim 17 , wherein the patient has squamous cell carcinoma.33. The method of claim 17 , wherein the patient has triple negative breast cancer.34. The method of claim 17 , wherein the patient has anaplastic thyroid carcinoma.35. The method of claim 17 , wherein the patient has undifferentiated pancreatic carcinoma or adenocarcinoma.36. The method of claim 17 , wherein the patient has small cell lung cancer.37. The method of claim 17 , wherein the patient has anal squamous cell carcinoma.38 ...

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Номер записи: 72
25-04-2019 дата публикации

COMBINATIONS OF CD33 ANTIBODY DRUG CONJUGATES WITH HYPOMETHYLATING AGENTS

Номер: US20190117787A1
Автор: "OMeara Megan", FELDMAN Eric J., Kennedy Dana
Принадлежит: Seattle Genetics, Inc.

This invention relates to treatment of cancer using a CD33 antibody drug conjugate in combination with hypomethylating agents. 1. A method of treating CD33 expressing acute myeloid leukemia (AML) in a subject in need of such treatment , the method comprising the step of administering a hypomethylating agent and 10 μg/kg of a CD33 antibody drug conjugate (ADC) , wherein the CD33-ADC comprises a humanized 2H12 antibody and a PBD cytotoxic agent , and wherein the hypomethylating agent is selected from the group consisting of 5-azacytidine and 5-aza-2-deoxycytidine.3. The method of claim 1 , wherein the hypomethylating agent is 5-azacytidine.4. The method of claim 3 , wherein the 5-azacytidine is administered at a concentration between 50-100 mg/m.5. The method of claim 3 , wherein the 5-azacytidine is administered at a concentration of about 75 mg/m.6. The method of claim 4 , wherein the 5-azacytidine is administered at a concentration of 75 mg/m.7. The method of claim 1 , wherein the hypomethylating agent is 5-aza-2-deoxycytidine.8. The method of claim 7 , wherein the 5-aza-2-deoxycytidine is administered at a concentration between 15-25 mg/m.9. The method of claim 7 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of about 20 mg/m.10. The method of claim 7 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of 20 mg/m.11. The method of claim 1 , wherein the subject is 75 years or older.12. A method of treating CD33-expressing secondary acute myeloid leukemia (AML) in a subject in need of such treatment claim 1 , the method comprising the step of administering a hypomethylating agent and between 20-40 μg/kg of a CD33 antibody drug conjugate (ADC) claim 1 , wherein the CD33-ADC comprises a humanized 2H12 antibody and a PBD cytotoxic agent claim 1 , and wherein the hypomethylating agent is 5-aza-2-deoxycytidine.14. The method of claim 12 , wherein the 5-aza-2-deoxycytidine is administered at a concentration of about 20 mg/m.15. ...

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Номер записи: 73
16-04-2020 дата публикации

Selective reduction of proteins

Номер: US20200115438A1
Автор: Damon L. Meyer
Принадлежит: Seattle Genetics Inc

The present invention provides a method for making uncapped cysteine protein preparations, including uncapped engineered cysteine antibody preparations. The methods include, inter alia, contacting a reducing agent with engineered cysteine antibody molecules, each of the antibody molecules having at least one capped engineered cysteine residue and at least one interchain disulfide bond and reacting the reducing agent with the antibody molecules under conditions sufficient to uncap engineered cysteine residues and form cap byproducts. The method also includes removing the cap byproduct during the reduction reaction. Substantially all of the interchain disulfide bonds present in the antibody molecules prior to reduction are retained following reduction. Antibody conjugates and methods for preparing antibody conjugates using uncapped antibody preparations are also described.

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Номер записи: 74
07-08-2014 дата публикации

Monomethylvaline compounds capable of conjugation to ligands

Номер: US20140220047A1
Автор: Brian E. Toki, Peter D. Senter, Svetlana O. Doronina, Toni Beth Kline
Принадлежит: Seattle Genetics Inc

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.

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Номер записи: 75
18-05-2017 дата публикации

DOSAGE AND ADMINISTRATION OF NON-FUCOSYLATED ANTI-CD40 ANTIBODIES

Номер: US20170137528A1
Автор: Gardai Shyra, Law Che-Leung, Manley Thomas John, Neff-LaFord Haley, Peng Stanford, Yang Jing
Принадлежит: Seattle Genetics, Inc.

This invention relates methods of using a non-fucosylated anti-CD40 antibody for treatment of cancer and chronic infectious diseases. 1. A method of treating cancer , the method comprising the steps of administering an anti-CD40 antibody to a patient in need of such treatment ,wherein the anti-CD40 antibody comprises the heavy chain variable region of SEQ ID NO:1 and the light chain variable region of SEQ ID NO:2, and a human constant region; wherein the constant region has an N-glycoside-linked sugar chain at residue N297 according to the EU index as set forth in Kabat and less than 5% of the N-glycoside-linked sugar chains comprise a fucose residue; andwherein the anti-CD40 antibody is administered at a dose level between 0.1-2000 μg/kg patient body weight.2. The method of claim 1 , wherein the dose level is between 10-1000 μg/kg.3. The method of claim 1 , wherein the dose level is between 50-800 μg/kg.4. The method of claim 1 , wherein the dose level is between 75-600 μg/kg.5. The method of claim 1 , wherein the dose level is between 100-500 μg/kg.6. The method of claim 1 , wherein the dose level is a range selected from the group consisting of 100-300 μg/kg claim 1 , 300-500 μg/kg claim 1 , 500-700 μg/kg claim 1 , 700-900 μg/kg claim 1 , and 900-1100 μg/kg.7. The method of claim 1 , wherein the dose level is a range selected from the group consisting of 100-150 μg/kg claim 1 , 150-200 μg/kg claim 1 , 200-250 μg/kg claim 1 , 250-300 μg/kg claim 1 , 300-350 μg/kg claim 1 , 350-400 μg/kg claim 1 , 400-450 μg/kg claim 1 , 450-500 μg/kg claim 1 , 500-550 μg/kg claim 1 , 550-600 μg/kg claim 1 , 600-650 μg/kg claim 1 , 650-700 μg/kg claim 1 , 700-750 μg/kg claim 1 , 750-800 μg/kg claim 1 , 800-850 μg/kg claim 1 , 850-900 μg/kg claim 1 , 900-950 μg/kg claim 1 , 950-1000 μg/kg claim 1 , 1000-1050 μg/kg claim 1 , and 1050-1100 μg/kg.8. The method of claim 1 , wherein the dose level is a member of the group consisting of about 60 μg/kg claim 1 , about 100 μg/kg claim 1 , ...

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Номер записи: 76
07-08-2014 дата публикации

NUCLEIC ACID MOLECULES AND USES THEREOF

Номер: US20140221461A1
Автор: Quay Steven C.
Принадлежит: Atossa Genetics, Inc.

Provided in this application are formulations of double stranded RNA molecules and Krebs Cycle analogs that improving ribonuclease stability, reducing off-target effects of a double stranded siRNA molecule, or of reducing interferon responsiveness of a double stranded siRNA molecule using such dsRNA. Also disclosed are methods of treating a primary tumor or a metastasis by contacting circulating tumor cells, a primary tumor, or a metastasis with a described formulation. 1. A formulation , comprising:(a) an RNAi molecule comprising at least on: locked nucleic acid (LNA), unlocked nucleic acid (UNA), bridged nucleic acid (BNA), glycerol nucleic acid (GNA), or a combination thereof; and(b) an RNAi carrier.2. The formulation of claim 1 , wherein the carrier provides for one or more of the following: stability for shortened duplexes claim 1 , reduction or prevention of sense strand loading claim 1 , reduction or prevention of seed region microRNA adverse side effects and reduction of non-specific immunoactivation.3. The formulation of claim 1 , wherein the RNAi carrier is a di-lipid amino acid (DILA).4. The formulation of claim 1 , wherein the RNAi carrier is a Krebs Cycle analog.5. The formulation of claim 1 , wherein the RNAi carrier is a Krebs Cycle analog and wherein the Krebs Cycle analog reduces or prevents cytotoxicity.6. A formulation claim 1 , comprising:(a) an RNAi molecule; and(b) a Krebs Cycle analog RNAi carrier.7. The formulation of claim 6 , wherein the RNA or RNA analog comprises a locked nucleic acid (LNA) claim 6 , an unlocked nucleic acid (UNA) claim 6 , a bridged nucleic acid (BNA) claim 6 , a glycerol nucleic acid (GNA) claim 6 , or a combination thereof.8. A formulation claim 6 , comprising:(a) an RNAi molecule comprising at least on: locked nucleic acid (LNA), unlocked nucleic acid (UNA), bridged nucleic acid (BNA), glycerol nucleic acid (GNA), or a combination thereof; and(b) a Krebs Cycle analog RNAi carrier.9. A formulation claim 6 , comprising ...

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Номер записи: 77
09-05-2019 дата публикации

COMBINATION OF CD33 ANTIBODY DRUG CONJUGATES WITH CHEMOTHERAPEUTIC AGENTS

Номер: US20190134215A1
Автор: Feldman Eric, Kennedy Dana
Принадлежит: Seattle Genetics, Inc.

This invention relates to treatment of cancer using a CD33 antibody drug conjugate in combination with chemotherapeutic agents. 1. An induction-consolidation method of treating CD33 expressing acute myeloid leukemia (AML) in a subject in need of such treatment , the method comprising the step of administering cytarabine , an anthracycline antibiotic , and 10 μg/kg of a CD33 antibody drug conjugate (ADC) , wherein the CD33-ADC comprises a humanized 2H12 antibody and a PBD cytotoxic agent.3. The method of claim 1 , wherein the anthracycline antibiotic is daunorubicin.4. The method of claim 1 , wherein the anthracycline antibiotic is idarubicin.5. The method of claim 1 , wherein the CD33-ADC is administered at a concentration of about 10 μg/kg.6. The method of claim 1 , wherein the CD33-ADC is administered at a concentration of about 10 μg/kg.7. The method of claim 1 , wherein the induction-consolidation method is followed by a maintenance treatment.8. The method of claim 7 , wherein the maintenance treatment is administration of the CD33-ADC at a concentration of about 5 μg/kg.9. An induction method of treating CD33 expressing acute myeloid leukemia (AML) in a subject in need of such treatment claim 7 , the method comprising the step of administering cytarabine claim 7 , an anthracycline antibiotic claim 7 , and a CD33 antibody drug conjugate (ADC) claim 7 , wherein the CD33-ADC comprises a humanized 2H12 antibody and a PBD cytotoxic agent claim 7 , and wherein in 20 μg/kg of the CD33-ADC is administered on day one of a seven-day induction cycle and 10 μg/kg of the CD33-ADC is administered on day four of a seven-day induction cycle.11. The method of claim 9 , wherein the anthracycline antibiotic is daunorubicin and is administered at 60 mg/m/day on induction days 1-3.12. The method of claim 9 , wherein the cytarabine is administered at 100 mg/m/day on induction days 1-7.13. The method of claim 9 , wherein the humanized 2H12 antibody comprises a light chain variable ...

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Номер записи: 78
28-05-2015 дата публикации

CD33 ANTIBODIES AND USE OF SAME TO TREAT CANCER

Номер: US20150147316A1
Автор: Burke Patrick, Jeffrey Scott, Ryan Maureen, Sussman Django, Sutherland May Kung
Принадлежит: Seattle Genetics, Inc.

The invention provides murine, chimeric, and humanized antibodies that specifically bind to CD33. The antibodies are useful for treatment and diagnoses of various cancers as well as detecting CD33. 1. An isolated antibody that specifically binds to the human CD33 protein , wherein the antibody comprises three heavy chain complementarity determining regions (CDRs): heavy chain CDR1 consisting of SEQ ID NO:19 , heavy chain CDR2 consisting of SEQ ID NO:20 , and heavy chain CDR3 consisting of SEQ ID NO:21; and three light chain CDRs: light chain CDR1 consisting of SEQ ID NO:22 , light chain CDR2 consisting of SEQ ID NO:23 , and light chain CDR3 consisting of SEQ ID NO:24.2. The antibody of claim 1 , wherein the antibody is selected from a murine antibody claim 1 , a chimeric antibody claim 1 , and a humanized antibody.3. The antibody of claim 2 , wherein the antibody is a humanized 2H12 antibody.4. The humanized antibody of claim 3 , wherein the antibody comprises a mature heavy chain variable region having an amino acid sequence at least 90% identical to SEQ ID NO:18 provided that position H48 is occupied by I claim 3 , position H66 is occupied by K claim 3 , position H67 is occupied by A claim 3 , position H69 is occupied by L claim 3 , position H71 is occupied by A claim 3 , and position H94 is occupied by S and a mature light chain variable region at least 90% identical to SEQ ID NO:8 provided position L22 is occupied by N claim 3 , position L46 is occupied by T claim 3 , position L69 is occupied by Q claim 3 , and position L71 by Y claim 3 , as determined by the Kabat numbering system.5. The humanized antibody of claim 3 , comprising a mature heavy chain variable region having an amino acid sequence at least 95% identical to SEQ ID NO:18 and a mature light chain variable region at least 95% identical to SEQ ID NO:8.6. The humanized antibody of claim 3 , wherein the mature heavy chain variable region is fused to a heavy chain constant region and the mature light ...

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Номер записи: 79
28-05-2015 дата публикации

N-CARBOXYALKYL-AURISTATIN AND USE THEREOF

Номер: US20150148298A1
Автор: EL SHEIKH Sherif, Gnoth Jean Mark, GOLFIER Sven, Krenz Ursula, LERCHEN Hans-Georg, SCHUHMACHER Joachim, Stelet-Ludwig Beatrix
Принадлежит: Seattle Genetics, Inc.

The present application relates to new derivatives of monomethylauristatin F, substituted on the N terminus by a carboxyalkyl group, processes for preparing these derivatives, their use for the treatment and/or prevention of diseases and to produce medication for the treatment and/or prevention of diseases, particularly hyperproliferative and/or angiogenic disorders such as cancer disorders, for example. Such treatments can occur as monotherapies or in combination with other medication or further therapeutic measures. 6. Compound as defined in to for treatment and/or prevention of diseases.7. Compound as defined in one of the to for use in a procedure to treat and/or prevent cancer and tumor diseases.8. Use of a compound as defined in one of the to for production of drug to treat and/or prevent cancer and tumor diseases.9. Drug which contains a compound as defined in one of the to , in combination with one or more inert , non-toxic , pharmaceutically suitable agents.10. Drug which contains a compound as defined in one of the to , in combination with one or more substances.11. Drug as per or for treatment and/or prevention of cancer and tumor diseases.12. Method for treatment and/or prevention of cancer and tumor diseases in humans or animals using an effective amount of at least one compound as defined in one of the to , or of a drug as defined in one of the to . The present application relates to new derivatives of monomethylauristatin F, substituted on the N terminus by a carboxyalkyl group, processes for preparing these derivatives, their use for the treatment and/or prevention of diseases and to produce medication for the treatment and/or prevention of diseases, particularly hyper proliferative and/or antigenic disorders such as cancer disorders, for example. Such treatments can occur as monotherapies or in combination with other medication or further therapeutic measures.Cancer disorders are the result of uncontrolled cell growths in a wide variety of tissues. ...

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Номер записи: 80
28-08-2014 дата публикации

INTACT MASS DETERMINATION OF PROTEIN CONJUGATED AGENT COMPOUNDS

Номер: US20140242624A1
Автор: SALAS Oscar, VALLIERE-DOUGLASS John Fay
Принадлежит: Seattle Genetics, Inc.

The present invention provides methods and systems for the rapid determination of the intact mass of non-covalently associated antibody heavy chains (HC) and light chains (LC) which result from the attachment of drug conjugates to interchain cysteine residues. By analyzing the antibody-drug conjugate (ADC) using native desalting conditions, the intact-bivalent structure of the ADC, which ordinarily would decompose as a consequence of denaturing chromatographic conditions typically used for LCMS, is maintained. The mass of the desalted ADC is subsequently determined using desolvation and ionization ESI-MS conditions. The methods described herein provide for direct measurement of the intact mass of an ADC conjugated at interchain cysteine residues. The methods described herein also provide for the relative quantitation of the individual ADC species. 1. A method for detecting a mass of a protein agent conjugate compound comprising:(a) providing a non covalently associated and non denatured protein agent conjugate compound in a volatile salt and free of a non-volatile salt;(b) introducing the protein agent conjugate compound into a mass spectrometer; and(c) directly establishing the mass of the protein agent conjugate compound by mass spectrometry.2. The method of further comprising applying a separation media under non denaturing conditions for the protein agent conjugate compound to effect separation of the protein agent conjugate compound from a matrix claim 1 , whereby the protein agent conjugate compound is substantially non-denatured.3. The method of further comprising eluting from the separation media the non denatured protein agent conjugate compound.4. The method of wherein the non denaturing conditions comprises a mass spectrometry compatible volatile SEC buffer.5. The method of wherein the volatile salt comprises ammonium formate claim 1 , ammonium acetate claim 1 , or ammonium carbonate.6. The method of wherein the matrix comprises a non-volatile salt claim ...

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Номер записи: 81
08-06-2017 дата публикации

PREPARING ANTIBODIES FROM CHO CELL CULTURES FOR CONJUGATION

Номер: US20170159099A1
Автор: Beam Kevin, Hayes Bradley, Lyon Robert, Meyer Damon, Valliere-Douglass John
Принадлежит: Seattle Genetics, Inc.

The invention is based in part on the observation that a CHO cell oxidizing enzyme, particularly QSOX1, can survive a seemingly rigorous antibody purification process to reduce subsequent conjugation efficiency of the antibody to a drug. Whether the oxidizing enzyme survives the purification procedure depends on which purification techniques are employed which can vary from one antibody to another. With knowledge that contamination with a CHO cell oxidizing enzyme is a potential problem for subsequent conjugation, a suitable purification scheme can be devised for any antibody that eliminates or at least reduces CHO oxidizing enzyme(s) to an acceptable level. 1. A method of producing a conjugated antibody , comprising:(a) performing at least one purification step of a purification scheme to obtain at least a partially purified preparation of an antibody from a culture of CHO cells expressing the antibody;(b) testing the preparation for presence of a CHO cell oxidizing enzyme;(c) if an unacceptable level of the enzyme is detected as present in the preparation of step (b), repeating steps (a) and (b) with a different purification step;(d) if an acceptable level or no CHO cell oxidizing enzyme is detected as present in the preparation of step (b), performing at least one purification step resulting in the acceptable level or no detected CHO cell oxidizing enzyme on the same culture or a second culture of CHO cells expressing the antibody to obtain at least a partially purified preparation of antibody.2. The method of claim 1 , further comprising step (e) conjugating the at least partially purified antibody via one or more sulfhydryl groups to a drug to produce the conjugated antibody.3. The method of claim 1 , wherein the CHO cell oxidizing enzyme is QSOX1.4. The method of wherein the second culture in step (d) is a larger culture by volume than the culture in step (a).5. The method of claim 4 , wherein the second culture in step (d) is at least 1000 times larger by ...

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Номер записи: 82
21-06-2018 дата публикации

ANTI-NTB-A ANTIBODIES AND RELATED COMPOSITIONS AND METHODS

Номер: US20180169257A1
Автор: Law Che-Leung, LEWIS TIMOTHY, Sussman Django, Westendorf Lori
Принадлежит: Seattle Genetics, Inc.

Disclosed are antibodies, including antibody drug conjugates, that specifically bind to NTB-A. Also disclosed are methods for using the anti-NTB-A antibodies to detect or modulate activity of (e.g., inhibit proliferation of) an NTB-A-expressing cell, as well as for diagnoses or treatment of diseases or disorders (e.g., cancer) associated with NTB-A-expressing cells, such as multiple myeloma, non-Hodgkin lymphoma and acute myeloid leukemia. 1. An antibody that specifically binds to the human NTB-A protein wherein the antibody comprises the three heavy chain complementarity determining regions of SEQ ID NO:3 and the 3 light chain CDRs of SEQ ID NO:13 wherein the CDRs are as defined by Kabat.2. (canceled)3. The antibody of claim 1 , wherein the CDRs are Kabat CDRs.4. The antibody of that is a humanized claim 1 , chimeric or veneered antibody.5. The antibody of claim 1 , comprising a mature heavy chain region having at least 80% sequence identity to SEQ ID NO:8 and a mature light chain variable region having at least 80% sequence identity to SEQ ID NO:18.6. The antibody of claim 5 , which is a humanized antibody comprising a mature heavy chain variable region having at least 90% sequence identity with SEQ ID NO:8 and a mature light chain variable region having at least 90% sequence identity with SEQ ID NO:18.7. The antibody of claim 6 , wherein the mature heavy chain variable region has at least 95% sequence identity with SEQ ID NO:8 and the mature light chain variable region has at least 95% sequence identity with SEQ ID NO:18.8. The antibody of wherein H2 is occupied by I claim 5 , H38 is occupied by R or K claim 5 , H44 is occupied by D or G claim 5 , H46 is occupied by K or E claim 5 , H68 is occupied by V or A claim 5 , H73 is occupied by K claim 5 , H76 is occupied by N or S claim 5 , H91 is occupied by Y or F claim 5 , L1 is occupied by Q or E claim 5 , L5 is occupied by S or T claim 5 , L21 is occupied by M or L claim 5 , L46 is occupied by P claim 5 , L47 is ...

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Номер записи: 83
21-06-2018 дата публикации

Cd123 antibodies and conjugates thereof

Номер: US20180169261A1
Автор: Django Sussman, Lori WESTENDORF, May Kung Sutherland
Принадлежит: Seattle Genetics Inc

The invention provides murine, chimeric, and humanized antibodies that specifically bind to CD123 and conjugates thereof.

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Номер записи: 84
06-06-2019 дата публикации

DRUG CONJUGATES WITH SELF-STABILIZING LINKERS HAVING IMPROVED PHYSIOCHEMICAL PROPERTIES

Номер: US20190167806A1
Автор: Moquist Philip
Принадлежит: Seattle Genetics, Inc.

Compounds and compositions are disclosed in which a Drug Unit is linked to a targeting Ligand Unit through a self-stabilizing Linker Unit from which a drug compound or active drug moiety is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as cancer or an autoimmune disease using the compounds and compositions of the invention are also disclosed. 8. The Ligand-Drug Conjugate composition of claim 1 , wherein BU and Rtogether with the carbon atom to which both are attached claim 1 , define an optionally substituted spiro C-Cheterocyclo having a skeletal secondary or tertiary basic nitrogen atom claim 1 , wherein the skeletal basic nitrogen atom is attributable to BU claim 1 , wherein the basic nitrogen atom is optionally protonated.10. The Ligand-Drug Conjugate composition of claim 9 , wherein subscript P is 1 and subscript Q is 1 claim 9 , 2 or 3 or subscript P is 2 and Q is 1 or 2.11. The Ligand-Drug Conjugate composition of claim 10 , wherein subscript P is 1 claim 10 , subscript Q is 1.12. The Ligand-Drug Conjugate composition of wherein BU and Rtogether with the carbon atom to which both are attached define an optionally substituted spiro C-Ccarbocyclo having exocyclic substitution by a primary claim 1 , secondary or tertiary amine or by an optionally substituted C-C-aminoalkyl claim 1 , wherein the basic nitrogen atom of the amine or aminoalkyl is attributable to BU and is optionally protonated.14. The Ligand-Drug Conjugate composition of claim 6 , wherein W is a Peptide Cleavable Unit comprised of a dipeptide wherein the C-terminus of the dipeptide is covalently bonded to J wherein the dipeptide provides for a recognition site for a regulatory or lysosomal protease for cleavage by said protease of the W-J bond within a compound of the Ligand Drug Conjugate composition so as to initiate release of D or D as a biologically active compound or derivative thereof from that Ligand Drug Conjugate ...

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Номер записи: 85
30-06-2016 дата публикации

Humanized Antibodies To LIV-1 And Use Of Same To Treat Cancer

Номер: US20160185858A1
Автор: Arthur William, Nesterova Albina, Smith Maria Leia, Sussman Django
Принадлежит: Seattle Genetics, Inc.

The invention provides humanized antibodies that specifically bind to LIV-1. The antibodies are useful for treatment and diagnoses of various cancers as well as detecting LIV-1. 119-. (canceled)20. A humanized antibody comprising a mature heavy chain variable region having an amino acid sequence at least 90% identical to HB (SEQ ID NO:10) and a mature light chain variable region at least 90% identical to LB (SEQ ID NO:5).21. The humanized antibody of claim 20 , comprising a mature heavy chain variable region having an amino acid sequence at least 95% identical to HB and a mature light chain variable region at least 95% identical to LB.22. The humanized antibody of claim 20 , provided that position H29 claim 20 , H30 and H76 are occupied by I claim 20 , E and N claim 20 , and L36 is occupied by Y.23. The humanized antibody of any of claim 20 , provided that any difference in the variable region frameworks of the mature heavy chain variable region and SEQ ID NO:10 are selected from the group consisting of H27 occupied by F claim 20 , H28 occupied by N claim 20 , H48 occupied by I claim 20 , H66 occupied by K claim 20 , H67 occupied by A claim 20 , H71 occupied by A claim 20 , H76 occupied by N claim 20 , H93 occupied by N claim 20 , H94 occupied by V claim 20 , L37 occupied by L claim 20 , L39 occupied by K claim 20 , L45 occupied by K claim 20 , and L46 occupied by L.24. The humanized antibody of any of claim 20 , wherein the 3 CDRs of the mature heavy chain variable region are those of SEQ ID NO. 10 and the 3 CDRs of the mature light chain variable region are those of SEQ ID NO:15.25. The humanized antibody of any of claim 20 , wherein the mature heavy chain variable region is fused to a heavy chain constant region and the mature light chain variable region is fused to a light chain constant region.26. The humanized antibody of any of claim 20 , wherein the heavy chain constant region is a mutant form of natural human constant region which has reduced binding to an ...

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Номер записи: 86
29-06-2017 дата публикации

OPTIMAL DOSING OF A CD19-ANTIBODY DRUG CONJUGATE

Номер: US20170182178A1
Автор: ALBERTSON Tina, HAN TAE, ZHAO Baiteng
Принадлежит: Seattle Genetics, Inc.

Methods of optimal dosing of CD19-antibody drug conjugates are disclosed. 1. A method of treating a subject having acute lymphoblastic leukemia , the method comprising the steps ofa) administering a loading dose of a CD19-antibody drug conjugate, wherein the CD19-antibody drug conjugate (CD19-ADC) is a humanized BU12 antibody conjugated to an mcMMAF molecule, followed byb) administering a maintenance dose the CD19-antibody drug conjugate, wherein the maintenance dose of the CD19-antibody drug conjugate is 2.0 mg/kg body weight and is administered every three weeks.2. The method of claim 1 , wherein the patient has a high disease burden and is sensitive to treatment with the CD19 ADC.3. The method of claim 2 , wherein the loading dose is 2.0 mg/kg body weight and is administered on days one and eight of a three week cycle.4. The method of claim 3 , wherein the loading dose is administered for one three week cycle.5. The method of claim 3 , wherein the loading dose is administered for two three week cycles.6. The method of claim 3 , wherein the loading dose is administered for between one and four three week cycles.7. The method of claim 3 , wherein the maintenance dose is administered for multiple three week cycles.8. The method of claim 3 , wherein the maintenance dose is administered for between one and ten three week cycles.9. A method of treating a subject having acute lymphoblastic leukemia claim 3 , the method comprising the step of administering a fixed dose of a CD19-antibody drug conjugate claim 3 , wherein the CD19-antibody drug conjugate (CD19-ADC) is a humanized BU12 antibody conjugated to an mcMMAF molecule claim 3 , wherein the dose intensity is about 1 mg/kg/week.10. The method of claim 9 , wherein the fixed dose is 1.6 mg/kg body weight and is administered on days one and seven of a three week cycle.11. The method of claim 9 , wherein the fixed dose is 2.2 mg/kg body weight and is administered every two weeks.12. The method of claim 9 , wherein the ...

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Номер записи: 87
07-07-2016 дата публикации

NEW BINDER-DRUG CONJUGATES (ADCS) AND USE THEREOF

Номер: US20160193359A1
Автор: BEIER Rudolf, Borkowski Sandra, Bruder Sandra, EL SHEIKH Sherif, GOLFIER Sven, Greven Simone, Harrenga Axel, HEISLER Iring, JÖRIßEN Hannah, Kopitz Charlotte C., LERCHEN Hans-Georg, LINDEN Lars, Mahlert Christoph, PETRUL Heike, SCHUHMACHER Joachim, STELTE-LUDWIG Beatrix, THIERAUCH Karl-Heinz, WILLUDA Jörg
Принадлежит: Seattle Genetics, Inc.

The present application relates to new binder-drug conjugates (ADCs) of N,N-dialkylauristatins that are directed against the target C4.4a, to active metabolites of these ADCs, to processes for preparing these ADCs, to the use of these ADCs for treating and/or preventing illnesses, and also to the use of these ADCs for producing medicaments for treating and/or preventing illnesses, more particularly hyperproliferative and/or angiogenic diseases such as, for example, cancer diseases. Such treatments may be practised as a monotherapy or else in combination with other medicaments or further therapeutic measures. 10. (canceled)13. Compounds of the formulae (XXXa) and (XXXI) according to selected from the following group:N-[6-(3-{[(2R)-2-amino-2-carboxyethyl]sulphanyl}-2,5-dioxopyrrolidin-1-yl)hexyl]-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide,N-[6-(3-{[(2R)-2-amino-2-carboxyethyl]sulphanyl}-2,5-dioxopyrrolidin-1-yl)hexyl]-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-3-(1H-indol-3-yl)-1-(1,2-oxazinan-2-yl)-1-oxopropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide,N-(6-{[(5S)-5-amino-5-carboxypentyl]amino}-6-oxohexyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-3-{1H-indol-3-yl)-1-(1,2-oxazinan-2-yl)-1-oxopropan-2-yl]amino)}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide trifluoroacetate, N-(6-{[(5S)-5-amino-5-carboxypentyl]amino}-6-oxohexyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino})-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide,and also their salts, solvates and solvates of the salts.16. Binder-drug conjugates according to of the general ...

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Номер записи: 88
06-07-2017 дата публикации

BETA-GLUCURONIDE-LINKER DRUG CONJUGATES

Номер: US20170189540A9
Автор: Jeffrey Scott
Принадлежит: Seattle Genetics, Inc.

Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided. 7. The drug linker conjugate of claim 1 , wherein the Drug Unit is a DNA minor groove binder.8. The drug linker conjugate of claim 1 , wherein the Drug Unit is an alkylating agent.9. The drug linker conjugate of claim 1 , wherein the Drug Unit is an antitubulin agent.10. The drug linker conjugate of claim 1 , wherein the Drug Unit is a maytansinoid.11. The drug linker conjugate of claim 1 , wherein the Drug Unit is an auristatin. This application is a Divisional of U.S. patent application Ser. No. 13/274,212, filed Oct. 14, 2011; which is a divisional of U.S. patent application Ser. No. 11/996,009, which was filed under 35 U.S.C. §371 as a national stage application of International Application No. PCT/US2006/027925, filed Jul. 18, 2006; which claims the benefit of U.S. Provisional Patent Application Nos. 60/700,422, filed Jul. 18, 2005, and 60/779,076, filed Mar. 4, 2006; the disclosures of which are incorporated by reference herein in their entirety and for all purposes.Monoclonal antibody therapies are gaining momentum as adjunct and front-line treatments for cancer. Successes of mAb therapies like AVASTIN (anti-VEGF) for colon cancer, RITUXAN (Rituximab; anti-CD20) for Non-Hodgkin's Lymphoma and HERCEPTIN (anti-Her2) for breast cancer have demonstrated that unconjugated antibodies can improve patient survival without the incidence of significantly increased toxicity.Monoclonal antibodies (mAb) can be conjugated to a therapeutic agent to form an antibody drug conjugate (ADC). ADCs can exhibit increased efficacy, as compared to an unconjugated antibody. The linkage of the antibody to the drug can be direct, or indirect via a linker. One of components believed to be important for developing effective and well-tolerated ADCs is the composition and stability of the linker. For some types of ADCs, the linker desirably provides serum stability, yet ...

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Номер записи: 89
06-07-2017 дата публикации

Beta-glucuronide-linker drug conjugates

Номер: US20170189542A1
Автор: Scott Jeffrey
Принадлежит: Seattle Genetics Inc

Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided.

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Номер записи: 90
20-06-2019 дата публикации

CD47 Antibodies and Uses Thereof for Treating Cancer

Номер: US20190185561A1
Автор: Carosino Christopher, FELDHAUS Michael, Gardai Shyra, Leung-Law Che, Levengood Matthew, TRANG Vivian, Westendorf Lori
Принадлежит: Seattle Genetics, Inc.

Humanized antibodies, including masked antibodies that specifically bind to CD47 are provided. Methods for using anti-CD47 antibodies, including masked antibodies, to modulate activity of (e.g., inhibit proliferation of) a CD47-expressing cell, as well as for the treatment of one or more diseases or disorders (e.g., cancer) associated with CD47-expressing cells, are provided. 1. A humanized antibody or antigen-binding fragment thereof that specifically binds human CD47 , the antibody or antigen-binding fragment comprising a light chain variable region and a heavy chain variable region , wherein the heavy chain variable region comprises HCDR1 selected from SEQ ID NOs: 16 , 19 , 21 , and 23; HCDR2 selected from SEQ ID NOs: 17 , 20 , 22 , and 24; and HCDR3 of SEQ ID NO: 18; wherein the light chain variable region comprises LCDR1 selected from SEQ ID NOs: 31 and 34; LCDR2 selected from SEQ ID NOs: 32 and 35; and LCDR3 selected from SEQ ID NOs: 33 and 36; wherein the heavy chain variable region comprises an amino acid sequence with at least 90% identity to an amino acid sequence selected from SEQ ID NOs: 2 , 3 , 4 , 5 , 6 , 7 and 8; and wherein the light chain variable region comprises an amino acid sequence with at least 80% , identity to an amino acid sequence selected from SEQ ID NOs: 10 , 11 , 12 , 13 , 14 and 15.3. The humanized antibody or antigen-binding fragment thereof of claim 1 , wherein the heavy chain variable region comprises HCDR1 claim 1 , HCDR2 claim 1 , and HCDR3 selected from: SEQ ID NOs: 16 claim 1 , 17 claim 1 , and 18; SEQ ID NOs: 19 claim 1 , 20 claim 1 , and 18; SEQ ID NOs: 21 claim 1 , 22 claim 1 , and 18; SEQ ID NOs: 16 claim 1 , 20 claim 1 , and 18; and SEQ ID NOs: 23 claim 1 , 24 claim 1 , and 18.4. The humanized antibody or antigen-binding fragment thereof of claim 1 , wherein the light chain variable region comprises LCDR1 claim 1 , LCDR2 claim 1 , and LCDR3 selected from SEQ ID NOs: 31 claim 1 , 32 claim 1 , and 33; SEQ ID NOs: 31 claim 1 , ...

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Номер записи: 91
27-06-2019 дата публикации

Bcma antibodies and use of same to treat cancer and immunological disorders

Номер: US20190194338A1
Автор: Django Sussman, Lori WESTENDORF, Maureen Ryan, Michael Feldhaus
Принадлежит: Seattle Genetics Inc

The invention provides humanized antibodies that specifically bind to BCMA. The antibodies are useful for treatment and diagnoses of various cancers and immune disorders as well as detecting BCMA.

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Номер записи: 92
19-07-2018 дата публикации

TRANSPAPILLARY METHODS AND COMPOSITIONS FOR TREATING BREAST DISORDERS

Номер: US20180200206A1
Автор: Quay Steven C.
Принадлежит: ATOSSA GENETICS INC.

Methods and treatments are taught for the treatment of breast disorders, including proliferative breast disease, breast cancer, and increased breast density. The methods and compositions deliver efficacious formulations of chemical and/or biological treatment medicaments to the breast via a transpapillary route. 1. A method of delivering a composition comprising endoxifen or a pharmaceutically acceptable salt thereof to a breast duct of an individual in need thereof , comprising:(a) contacting the composition contained within a treatment chamber of a device with a nipple of a breast; and(b) applying positive pressure on the composition.2. The method of claim 1 , wherein the composition is forced into 1 to 5 breast ducts claim 1 , preferably claim 1 , into 4 to 8 breast ducts claim 1 , and more preferably claim 1 , into 7 to 11 breast ducts.3. The method of claim 1 , wherein the individual has a breast disorder.4. The method of claim 3 , wherein the breast disorder is proliferative breast disease claim 3 , breast cancer claim 3 , or increased breast density.5. The method of claim 3 , wherein the proliferative breast disease is atypical ductal hyperplasia or atypical lobular hyperplasia.6. The method of claim 4 , wherein the breast is cancer ductal carcinoma in situ claim 4 , lobular carcinoma in situ claim 4 , invasive (or infiltrating) ductal carcinoma claim 4 , invasive (or infiltrating) lobular carcinoma claim 4 , or inflammatory breast cancer.7. The method of claim 4 , wherein the breast cancer is ER+ breast cancer claim 4 , HER2+ breast cancer claim 4 , or triple-negative breast cancer.8. The method of claim 4 , wherein the breast cancer is adenoid cystic (or adenocystic) carcinoma claim 4 , low-grade adenosquamous carcinoma claim 4 , medullary carcinoma claim 4 , mucinous (or colloid) carcinoma claim 4 , papillary carcinoma claim 4 , tubular carcinoma claim 4 , metaplastic carcinoma claim 4 , or micropapillary carcinoma.9. The method of claim 1 , wherein the ...

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Номер записи: 93
25-06-2020 дата публикации

QUATERNIZED NICOTINAMIDE ADENINE DINUCLEOTIDE SALVAGE PATHWAY INHIBITOR CONJUGATES

Номер: US20200197524A1
Автор: Lyon Robert, Neumann Christopher Scott, Olivas Kathleen, WANG Kung-Pern
Принадлежит: Seattle Genetics, Inc.

Compounds and compositions are disclosed in which a NAMPT Drug Unit is conjugated to a targeting Ligand Unit through quaternization by a Linker Unit from which a NAMPT inhibitor compound or derivative thereof is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as those of cancer or an autoimmune disease, using the compounds and compositions of the invention are also disclosed. 3. The Ligand Drug Conjugate composition of claim 2 , wherein the NAMPT Head (H) Unit is a pyridine mimetic and His that Unit in which a skeletal aromatic nitrogen atom of the pyridine mimetic is quaternized.4. The Ligand Drug Conjugate composition of claim 2 , wherein the Donor Acceptor (DA) Unit is comprised of an optionally substituted amide functional group or bioisostere thereof claim 2 , or wherein H-DA is a nicotinamide mimetic and H-DA is that mimetic in which a skeletal nitrogen atom of the 5- or 6-membered nitrogen-containing partially unsaturated or heteroaromatic ring system of H is quaternized.19. The Ligand-Drug Conjugate composition of claim 13 , wherein the Ligand Unit is an intact antibody or antigen binding fragment thereof claim 13 , thereby defining an antibody Ligand Unit of an antibody drug conjugate (ADC) claim 13 , wherein the moiety targeted by the antibody Ligand Unit is an accessible cell-surface antigen of abnormal cells that is capable of cellular internalization when bound to ADC compound of the composition and is present in greater copy number on the abnormal cells in comparison to normal cells distant from the site of the abnormal cells claim 13 ,or wherein the Ligand Unit is a cognate ligand of an accessible cell-surface receptor on abnormal cell that is capable of cellular internalization when bound to a Ligand Drug Conjugate compound of the composition, and wherein the receptor is present in greater copy number on the abnormal cells in comparison to normal cells,or wherein the Ligand ...

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Номер записи: 94
03-08-2017 дата публикации

Hydrophilic antibody-drug conjugates

Номер: US20170216391A1
Автор: Peter Senter, Robert Lyon, Svetlana Doronina
Принадлежит: Seattle Genetics Inc

Hydrophilic Linkers, Drug-Linker compounds, Drug-Ligand Conjugate compounds and Ligand-Linkers and methods of making and using the same are provided.

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Номер записи: 95
16-08-2018 дата публикации

Targeted pyrrolobenzodiazapine conjugates

Номер: US20180228916A1
Автор: Patrick Burke, Peter Senter, Philip Wilson Howard, Scott Jeffrey
Принадлежит: MedImmune Ltd, Seattle Genetics Inc

Provided are Conjugate comprising PBDs conjugated to a targeting agent and methods of using such PBDs.

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Номер записи: 96
17-08-2017 дата публикации

CYCLODEXTRIN AND ANTIBODY-DRUG CONJUGATE FORMULATIONS

Номер: US20170232112A1
Автор: Jiang Shan, Li Hui, Meyer Damon, Wallace Mary
Принадлежит: Seattle Genetics, Inc.

Disclosed are formulations, including both liquid and lyophilized formulations, comprising a benzodiazepine antibody-drug conjugate (ADC) and a cyclodextrin. Also disclosed are methods of purifying mixtures comprising benzodiazepine antibody-drug conjugates and process drug-related impurities. 1. A liquid pharmaceutical formulation , wherein the formulation is an aqueous solution comprising:a benzodiazepine ADC at a concentration of from about 1 mg/mL to about 3 mg/mL;a cyclodextrin, wherein the cyclodextrin is hydroxypropyl beta cyclodextrin or sulfobutylether beta cyclodextrin at a concentration of from about 6% w/v to about 10% w/v;a lyoprotectant, wherein the lyoprotectant is a sugar at a concentration of about 4% to about 8%;a buffer, wherein the buffer is TRIS at a concentration of about 50 mM; andwherein the pH of the aqueous solution is from about 7 to about 7.5.2. The liquid pharmaceutical formulation of claim 1 , wherein the concentration of the benzodiazepine ADC within the aqueous solution is about 1 mg/mL.3. The liquid pharmaceutical formulation of claim 1 , wherein the lyoprotectant is sucrose claim 1 , wherein the concentration of sucrose within the aquesous solution is about 6% w/v.4. The liquid pharmaceutical formulation of claim 1 , wherein claim 1 , wherein the cyclodextrin is hydroxypropyl beta cyclodextrin claim 1 , wherein the concentration of hydroxypropyl beta cyclodextrin within the aqueous solution is about 6% w/v.5. The liquid pharmaceutical formulation of wherein the aqueous solution has no more than 0.1 μM benzodiazepine drug-related impurites.6. The liquid pharmaceutical formulation of claim 1 , wherein the aqueous solution comprises:benzodiazepine ADC at a concentration of about 1 mg/mL or about 3 mg/mL;hydroxypropyl beta cyclodextrin at a concentration of about 6% w/v;sucrose as the lyoprotectant at a concentration of about 6% w/v; andTRIS buffer at a concentration of about 50 mM;wherein the pH of the aqueous solution is about 7.3; ...

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Номер записи: 97
25-07-2019 дата публикации

WEEKLY DOSING REGIMENS FOR ANTI-CD30 VC-PAB-MMAE ANTIBODY DRUG-CONJUGATES

Номер: US20190224268A1
Автор: Kennedy Dana, Sievers Eric
Принадлежит: Seattle Genetics, Inc.

Methods for the treatment of CD30-expressing cancers are provided. The methods comprise administering to a subject in need thereof a weekly dose of from about 0.8 mg/kg to about 1.8 mg/kg of an antibody-drug conjugate compound having formula (I); or a pharmaceutically acceptable salt thereof; wherein: mAb is an anti-CD30 antibody unit, S is a sulfur atom of the antibody, A− is a Stretcher unit, and p is from about 3 to about 5. 225-. (canceled)125-. (canceled)26. A method for treating a CD30-expressing hematologic cancer in a human subject , the method comprising administering to a subject in need thereof a dose of a pharmaceutical composition comprising cAC10-MC-vc-PAB-MMAE antibody-drug conjugate , wherein the administered dose of cAC10-MC-vc-PAB-MMAE antibody-drug conjugate is 1.8 mg/kg of the subject's body weight and the pharmaceutical composition is administered every three weeks as a monotherapy , wherein the pharmaceutical composition is administered for two or more 21-day treatment cycles.27. The method of claim 26 , wherein the average number of MMAE molecules per cAC10 antibody of the cAC10-MC-vc-PAB-MMAE antibody-drug conjugate in the pharmaceutical composition is about 4.28. The method of claim 26 , wherein the CD30-expressing hematologic cancer is Hodgkin Lymphoma.29. The method of claim 28 , wherein the average number of MMAE molecules per cAC10 antibody of the cAC10-MC-vc-PAB-MMAE antibody-drug conjugate in the pharmaceutical composition is about 4.30. The method of claim 26 , wherein the CD30-expressing hematologic cancer is anaplastic large cell lymphoma.31. The method of claim 30 , wherein the average number of MMAE molecules per cAC10 antibody of the cAC10-MC-vc-PAB-MMAE antibody-drug conjugate in the pharmaceutical composition is about 4.32. The method of claim 26 , wherein the pharmaceutical composition is administered for 3 or more treatment cycles.33. The method of claim 26 , wherein the pharmaceutical composition is administered for 5 or ...

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Номер записи: 98
16-07-2020 дата публикации

PROCESS FOR THE PREPARATION OF GLUCURONIDE DRUG-LINKERS AND INTERMEDIATES THEREOF

Номер: US20200222553A1
Автор: Choudhury Anusuya, Doubleday Wendel, Mao Yunyu, Moquist Philip
Принадлежит: Seattle Genetics, Inc.

The present invention provides improved processes for the preparation of drug-linkers with a β-glucuronide cleavable unit, as well as intermediates thereof. 4. The method of , or , wherein the Grignard reagent has the formula of RMgX and the alkoxy magnesium halide has the formula of ROMgX , wherein Re is C-Calkyl and X is I , Br , or C1.5. The method of claim 4 , wherein the Grignard reagent is MeMgI or MeMgCl.6. The method of claim 5 , wherein the alkoxy magnesium halide is MeOMgI or MeOMgCl.7. The method of any one of to claim 5 , wherein the alcohol-containing solvent comprises a C-Calcohol.8. The method of claim 7 , wherein the alcohol-containing solvent further comprises THF.9. The method of claim 8 , wherein the solvent is a 1:1 (v/v) mixture of methanol and THF.10. The method claim 2 , wherein the first deprotecting agent for removal of Zis an aqueous-containing solution of LiOH.12. The method of any one of embodiments 1 to 11 claim 2 , wherein said Grignard reagent or alkoxy magnesium halide contacting and said deprotecting agent contacting to remove Zare done sequentially in one pot.13. The method of any one of to claim 2 , wherein D is a PBD Drug Unit.16. The method of or claim 2 , wherein R is selected from the group consisting of H claim 2 , OH and OR.17. The method of or claim 2 , wherein R is a Calkyloxy group.18. The method of or claim 2 , wherein R is —OCH.19. The method of any one of to claim 2 , wherein Y and Y′ are O.20. The method of any one of to claim 2 , wherein R is H.21. The method of any one of to claim 2 , wherein R is selected from the group consisting of H and halo.22. The method of claim 14 , wherein Ar is phenylene; Xis selected from the group consisting of —O— claim 14 , —S— and —NH—; and Qis a single bond.23. The method of claim 15 , wherein Ar is phenylene claim 15 , Xis selected from the group consisting of —O— claim 15 , —S— claim 15 , and —NH— claim 15 , Q—CH— and Qis —CH—.24. The method of or claim 15 , wherein Xis NH.25. The ...

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Номер записи: 99
03-09-2015 дата публикации

NOVEL BINDER-DRUG CONJUGATES (ADCs) AND USE OF SAME

Номер: US20150246136A1
Автор: BEIER Rudolf, Borkowski Sandra, Bruder Sandra, GOLFIER Sven, Greven Simone, Harrenga Axel, HEISLER Iring, JÖRIßEN Hannah, Kopitz Charlotte C., LERCHEN Hans-Georg, LINDEN Lars, Mahlert Christoph, PETRUL Heike, SCHUHMACHER Joachim, SHEIKH Sherif El, STELTE-LUDWIG Beatrix, THIERAUCH Karl-Heinz, WILLUDA Jörg
Принадлежит: Seattle Genetics, Inc.

The present patent application relates to novel binder-drug conjugates (ADCs) of N,N-dialkylauristatins directed against the target epidermal growth factor receptor (EGFR, gene ID 1956), effective metabolites of these ADCs, methods for producing these ADCs, use of these ADCs for treatment and or prevention of diseases as well as the use of these ADCs to produce pharmaceutical drugs for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic diseases such as cancer, for example. Such treatments may be administered as monotherapy or in combination with other pharmaceutical drugs or other therapeutic measures. 36-. (canceled)13. A compound of formula (XXXa) or (XXXI) selected from the group consisting of:N-[6-(3-{[(2R)-2-amino-2-carboxyethyl]sulfanyl}-2,5-dioxopyrrolidin-1-yl)hexyl]-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide,N-[6-(3-{[(2R)-2-amino-2-carboxyethyl]sulfanyl}-2,5-dioxopyrrolidin-1-yl)hexyl]-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-3-(1H-indol-3-yl)-1-(1,2-oxazinan-2-yl)-1-oxopropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide,N-(6-{[(5S)-5-amino-5-carboxypentyl]amino}-6-oxohexyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-3-(1H-indol-3-yl)-1-(1,2-oxazinan-2-yl)-1-oxopropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide trifluoroacetate, andN-(6-{[(5S)-5-amino-5-carboxypentyl]amino}-6-oxohexyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide,as well as their salts, solvates, and solvates of the salts.16. Binder-drug conjugates ...

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Номер записи: 100