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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 42532. Отображено 100.
12-01-2012 дата публикации

Natriuretic activities

Номер: US20120010142A1

This document provides methods and material related to natriuretic polypeptides. For example, substantially pure polypeptides having a natriuretic peptide activity, nucleic acids encoding polypeptides having a natriuretic peptide activity, host cells containing such nucleic acids, and methods for inducing a natriuretic or diuretic activity within a mammal are provided.

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19-01-2012 дата публикации

Anti-polyethylene glycol antibody expressing cell quantify any free polyethylene glycol and polyethylene glycol-derivatized molecules

Номер: US20120015380A1
Принадлежит: KAOHSIUNG MEDICAL UNIVERSITY

In this invention, anti-PEG antibodies or anti-methoxyl-PEG (anti-CH 3 O-PEG) antibodies were expressed on cell surface which can collocate with a biotinylated anti-PEG antibody (AGP4-Biotin) or biotinylated PEG (PEG-Biotin) to develop a cell-based sandwich ELISA or a cell-based competition ELISA, respectively. Both of these two methods could sensitively quantify free PEG and PEG-modified macromolecules (proteins, nanoparticles and liposomes) as sensitive as nano-gram level.

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26-01-2012 дата публикации

Methods and compositions for liver cancer therapy

Номер: US20120020961A1

The present disclosure provides methods of treating liver cancer and preventing liver cancer recurrence with anti-progastrin antibodies, methods of monitoring treatment efficacy of anti-progastrin therapy for liver cancer, and compositions useful therefore.

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26-01-2012 дата публикации

Antibodies against fatty acid synthase

Номер: US20120020978A1
Автор: Patrick J. Muraca
Принадлежит: Nuclea Biotechnologies Inc

The present invention relates to antibodies that immunospecifically bind to FAS and certain FAS related proteins. The invention encompasses human and humanized forms of the antibodies and their use in treating cancers and other proliferative disorders. The invention also relates to FAS-derived peptides useful for preparing the antibodies. Methods and compositions for detecting, diagnosing, treating or ameliorating a disease or disorder, especially cancer and other proliferative disorders using the present antibodies also are disclosed.

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26-01-2012 дата публикации

DOPAMINERGIC NEURON PROLIFERATIVE PROGENITOR CELL MARKER Nato3

Номер: US20120021417A1
Принадлежит: Eisai R&D Management Co Ltd

The present invention is a probe, a primer, and an antibody, for detecting a dopaminergic neuron proliferative progenitor cell. According to the present invention, there is provided a polynucleotide probe and a polynucleotide primer for use in the detection or selection of a dopaminergic neuron proliferative progenitor cell, which can hybridize with a polynucleotide consisting of a nucleotide sequence of a Nato3 gene, or a complementary sequence thereto, and an antibody against a Nato3 protein, or a part thereof for use in the detection or selection of a dopaminergic neuron proliferative progenitor cell.

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16-02-2012 дата публикации

Antibody fusion-mediated plant resistance against Oomycota

Номер: US20120042416A1

The present invention relates to fusion proteins comprising anti-Oomycotic proteins or peptides linked to an antibody or fragment thereof specifically recognising an epitope of an Oomycota. The invention is also directed to polynucleotides coding for the fusion proteins. The embodiments of the present invention are particularly useful for the protection of plants against Oomycota. The invention therefore comprises transgenic plants expressing the fusion proteins of the present invention.

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23-02-2012 дата публикации

TREATMENT OF CELIAC DISEASE WITH IgA

Номер: US20120045517A1
Принадлежит: Individual

A process for inhibiting symptoms of a subject with celiac disease is provided that includes administration of monoclonal-, or polyclonal-, monomeric, dimeric, or polymeric IgA. Joining secretory component to the IgA limits oral administration degradation. Formulating agents are mixed with the monomeric, dimeric, or polymeric IgA to yield a dosing form of a capsule, tablet, and a suppository. The therapeutic is amenable to enrobement directly through microencapsulation or the dosing form is coated with an enteric coating.

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01-03-2012 дата публикации

Anti-vegf-c antibodies and methods using same

Номер: US20120052566A9
Принадлежит: F Hoffmann La Roche AG

The invention provides VEGF-C antagonists, such as anti-VEGF-C antibodies, and their use in the prevention and treatment of tumor progression.

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15-03-2012 дата публикации

Monoclonal Antibodies to Hepatocyte Growth Factor

Номер: US20120064066A1
Автор: Kyung Jin Kim, Yi-Chi Su
Принадлежит: Galaxy Biotech LLC

The present invention is directed toward a neutralizing monoclonal antibody to hepatocyte growth factor, a pharmaceutical composition comprising same, and methods of treatment comprising administering such a pharmaceutical composition to a patient.

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15-03-2012 дата публикации

Aminoacyl trna synthetases for modulating hematopoiesis

Номер: US20120064082A1
Принадлежит: aTyr Pharma Inc

Hematopoietic-modulating compositions are provided comprising aminoacyl-tRNA synthetase polypeptides, including active fragments and/or variants thereof, as well as compositions comprising related agents such as antibodies and other binding agents. Also provided are methods of using such compositions in the treatment of conditions that benefit from the modulation of hematopoiesis.

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15-03-2012 дата публикации

assay for detecting vitamin d and antibodies therefor

Номер: US20120064533A1
Принадлежит: Axis Shield Diagnostics Ltd

A molecule which recognises holo-DBP but which does not recognise apo-DBP or has relatively low affinity thereto.

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22-03-2012 дата публикации

Lenalidomide and Thalidomide Immunoassays

Номер: US20120071632A1
Принадлежит: Individual

Novel conjugates and immunogens derived from lenalidomide and antibodies generated by these immunogens are useful in immunoassays for the quantification and monitoring of thalidomide and lenalidomide in biological fluids.

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22-03-2012 дата публикации

Prevention and treatment of blood coagulation-related disases

Номер: US20120073002A1
Принадлежит: Chugai Pharmaceutical Co Ltd

Provided herein is an animal having a persistent hypercoagulable state by implanting a cell, for example a tumor cell, in which the gene of human tissue factor is implanted to an experimental animal such as a mouse and then growing the cell, thereby persistently supplying human tissue factor to the experimental animal. This animal model is useful for research and development of therapeutic agents for diseases having a persistent hypercoagulable state. Also provided are preventive or therapeutic agents for diseases having a persistent hypercoagulable state, a hypercoagulable state resulting from infections, venous thrombosis, arterial thrombosis, and diseases resulting from the hypertrophy of vascular media, the agent comprising an antibody against human tissue factor (human TF) as an active ingredient.

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29-03-2012 дата публикации

Method for removing viruses from high concentration monoclonal antibody solution

Номер: US20120077963A1
Принадлежит: Asahi Kasei Medical Co Ltd

An object of the present invention is to provide a method for removing even small viruses from a high concentration monoclonal antibody solution using a membrane, and thus for recovering the antibody within a short time at high yield in the form of a filtrate. The present invention provides a method for producing a preparation containing a monoclonal antibody, which comprises a step of removing viruses by filtering viruses in a monoclonal antibody solution using a virus-removing membrane, wherein (1) the monomer content of the monoclonal antibody accounts for 90% or more; (2) the monoclonal antibody concentration in the monoclonal antibody solution ranges from 20 mg/ml to 100 mg/ml; (3) the monoclonal antibody solution contains at least a basic amino acid; and (4) the parvovirus removal rate of the virus-removing membrane satisfies the following conditions: LRV (Log Reduction Value: logarithmic reduction value) ≧4.

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19-04-2012 дата публикации

Anti-vegf-d antibodies

Номер: US20120093811A1
Принадлежит: Vegenics Pty Ltd

The invention relates to an isolated antibody that specifically binds vascular endothelial growth factor-D (VEGF-D) and to a humanized antibody that specifically binds VEGF-D.

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19-04-2012 дата публикации

Nucleotide repeat expansion-associated polypeptides and uses thereof

Номер: US20120094299A1
Автор: Laura P.W. Ranum, Tao Zu
Принадлежит: University of Minnesota

Isolated polypeptides that are endogenously expressed from nucleotide repeat expansions are disclosed. In some cases, the polypeptides include polypeptide repeats. In some cases, the polypeptide repeats include at least five contiguous repeats of a single amino acid. In other cases, the repeats include at least six contiguous amino acids of a tetra- or penta-amino acid repeat block.

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10-05-2012 дата публикации

Hydroxycholesterol immunoassay

Номер: US20120115169A1
Принадлежит: Enzo Life Sciences Inc

Provided is a derivative of 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol. Also provided is a protein conjugated to the above derivative. Further provided is an antibody composition comprising antibodies that specifically bind to 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol. Additionally, a method of making antibodies that specifically bind to 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol is provided. Also, a method of assaying for 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol is provided. Additionally provided is a kit for detecting 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol. A method of detecting an enzyme or enzymes utilized in phase II drug metabolism is also provided. Also, a method of detecting an enzyme that synthesizes 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol is provided. Further provided is a method of evaluating progression of multiple sclerosis in a patient. Also provided is a method of determining whether a treatment for multiple sclerosis in a patient is effective. Further, a method of evaluating progression of Huntington's disease in a patient is provided. Additionally provided is a method of determining whether a treatment for Huntington's disease in a patient is effective.

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17-05-2012 дата публикации

Anti-estrogen and immune modulator combinations for treating breast cancer

Номер: US20120121620A1
Автор: David A. Sirbasku
Принадлежит: Individual

Compositions for treating cancers of mucosal tissues including breast, prostate, ovary, colon are disclosed which include various combinations of new or conventional anti-estrogen compounds, aromatase inhibitors, immune modulators, immune inhibitors, immune inhibitor mimicking compounds and steroid or thyroid hormones. Methods of predicting susceptibility of a cancer of mucosal origin to treatment with a composition containing an immune inhibitor or an immune inhibitor mimicking compound are also disclosed. Preferred methods include identifying in a specimen of cancer cells the presence of a Poly-Ig (Fe) receptor or Poly-Ig-like (Fc) receptor capable of binding to an immune inhibitor or an immune inhibitor mimicking compound and of mediating immune inhibition of cancer cell growth.

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24-05-2012 дата публикации

Fc VARIANTS THAT EXTEND ANTIBODY HALF-LIFE

Номер: US20120128663A1
Автор: Gregory A. Lazar
Принадлежит: Xencor Inc

The invention relates generally to compositions and methods for altering the serum half-life in vivo of an antibody.

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24-05-2012 дата публикации

Diagnosis and treatment of cancer using anti-tmprss11e antibody

Номер: US20120128678A1

[Problem to be Solved] An object of the present invention is to provide novel means for the treatment and diagnosis of cancer. [Solution] The present inventors have obtained a monoclonal antibody against TMPRSS11E and found that this antibody binds to a native form of TMPRSS11E, and TMPRSS11E is highly expressed on the cell membranes of cancer cell lines in flow cytometry. This antibody exhibits antibody-dependent cell-mediated cytotoxicity activity (ADCC activity) and antitumor effect based on internalization activity and is promising as a therapeutic target. Moreover, this antibody has neutralization activity against protease activity and is also expected to have effect brought about by the inhibition of TMPRSS11E functions.

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31-05-2012 дата публикации

Compositions and methods for using multispecific-binding proteins comprising an antibody-receptor combination

Номер: US20120134993A1
Принадлежит: Zymogenetics Inc

Disclosed are bispecific binding proteins comprising a antibody/soluble receptor bispecific binding protein that reduces the biological activity of both VEGF-A and FGF. The FGF binding moieties are generally soluble FGFR3 or FGFR2. An Fc polypeptide is fused to the C-terminus of the FGF binding moiety and VEGF-A binding moiety are polypeptides fused using peptide or polypeptide linker sequences, and can be expressed as single bispecific binding protein. The bispecific antibody/soluble receptor binding proteins can be used to treat cancers characterized by solid tumor growth as well as other diseases.

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07-06-2012 дата публикации

Antibodies and Methods of Use Thereof

Номер: US20120141373A1
Принадлежит: UNIVERSITY OF CALIFORNIA

The disclosure relates to protease-binding agent specific for a protease. The agent may be an antibody capable of specifically binding and inhibiting a protease, such as a P1-Arg-specific protease. The disclosure also provides methods of producing, and compositions comprising the subject agent. Methods and kits related to the protease-binding agent find use in protection against, detection, diagnosing, treating cancer and infections due to pathogens containing active proteases.

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14-06-2012 дата публикации

method of producing an antibody using a cancer cell

Номер: US20120151611A1
Принадлежит: Individual

The present invention aims to provide a method for antibody preparation. The present invention is directed to a method for preparing an antibody-producing cell, which comprises the following steps: (1) transplanting metastatic cancer cells capable of expressing a target antigen into a non-human animal to ensure engraftment of the cancer cells in the animal; (2) immunizing the animal with the target antigen; and (3) collecting the antibody-producing cell from the immunized animal; as well as a method for preparing an antibody, which comprises collecting the antibody from the antibody-producing cell prepared by the above method.

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21-06-2012 дата публикации

Antibody identifying an antigen-bound antibody and an antigen-unbound antibody, and method for preparing the same

Номер: US20120157663A1

The present invention relates to an antibody that recognizes a first antibody, the antibody specifically recognizing one of a free first antibody and an antigen-binding first antibody. More specifically, the above antibody is a domino antibody that specifically recognizes and binds to an antigen-binding first antibody, or an antibody-unlocking antibody that specifically recognizes and binds to a free first antibody.

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12-07-2012 дата публикации

Bystander immune suppression as a predictor for response to a vaccine

Номер: US20120177581A1
Принадлежит: Individual

The present invention relates to antigen-specific immune regulatory response. Methods for detecting an antigen-specific immune regulatory response, methods for selecting candidate vaccine recipients, and methods for improved vaccination strategies are presented.

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12-07-2012 дата публикации

Monoclonal antibody capable of binding to heparin-binding epidermal growth factor-like growth factor

Номер: US20120177649A1
Принадлежит: Kyowa Hakko Kirin Co Ltd

Medicaments for treating diseases related to HB-EGF escalation are in demand. The present invention provides a monoclonal antibody or an antibody fragment thereof which binds to a cell membrane-bound HB-EGF, a membrane type HB-EGF and a secretory HB-EGF.

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12-07-2012 дата публикации

Vegf antagonist formulations

Номер: US20120178683A1
Принадлежит: Regeneron Pharmaceuticals Inc

Formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided including a pre-lyophilized formulation, a reconstituted lyophilized formulation, and a stable liquid formulation. Preferably, the fusion protein has the sequence of SEQ ID NO:4.

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19-07-2012 дата публикации

Aldehyde-Tagged Immunoglobulin Polypeptides and Methods of Use Thereof

Номер: US20120183566A1
Принадлежит: Redwood Bioscience Inc

The present disclosure provides aldehyde-tagged immunoglobulin (Ig) polypeptides that can be converted by a formylglycine-generating enzyme to produce a 2-formylglycine (FGly)-modified Ig polypeptide. An FGly-modified Ig polypeptide can be covalently and site-specifically bound to a moiety of interest to provide an Ig conjugate. The disclosure also encompasses methods of production of such aldehyde-tagged Ig polypeptides, FGly-modified Ig polypeptides, and Ig conjugates, as well as methods of use of same.

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19-07-2012 дата публикации

Bispecific death receptor agonistic antibodies

Номер: US20120184718A1
Принадлежит: ROCHE GLYCART AG

The present invention relates to bispecific antibodies comprising a first antigen binding site specific for a death receptor and a second antigen binding site specific for a second antigen, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

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02-08-2012 дата публикации

Human domain antibodies against components of the human insulin-like growth factor (igf) system

Номер: US20120195897A1

The invention provides antibodies or antibody fragments that bind to insulin-like growth factor (IGF) 1 receptor (IGF-1R) or IGF-2, as well as method of using the antibodies for inhibiting the IGF-mediated signaling pathway, inhibiting IGF-1R signaling, and treating cancer. The invention also provides a method of detecting the presence of IGF-1R or IGF-2 in a sample using the inventive antibodies and antibody fragments.

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09-08-2012 дата публикации

Constructs and libraries comprising antibody surrogate light chain sequences

Номер: US20120202713A1
Принадлежит: Sea Lane Biotechnologies LLC

The invention concerns constructs and libraries comprising antibody surrogate light chain sequences. In particular, the invention concerns constructs comprising VpreB sequences, optionally partnered with another polypeptide, such as, for example, antibody heavy chain variable domain sequences, and libraries containing the same.

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16-08-2012 дата публикации

Modified Variable Domain Molecules And Methods For Producing And Using Same

Номер: US20120207673A1
Автор: Daniel Christ, Kip Dudgeon
Принадлежит: GARVAN INSTITUTE OF MEDICAL RESEARCH

The present disclosure provides an isolated protein comprising an antibody heavy chain variable region (V H ) comprising a negatively charged amino acid at position 28 and/or 31 and/or 32 and/or 33 and/or 35 according to the numbering system of Kabat, the protein capable of binding specifically to an antigen.

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16-08-2012 дата публикации

Motif-Specific and Context-Independent Antibodies That Specifically Bind to a Cleaved Caspase Motif or a Sumoylated Lysine-Containing Motif

Номер: US20120208985A1
Принадлежит: Cell Signaling Technology Inc

There is provided a motif-specific, context-independent antibody that specifically binds a recurring, modified motif consisting of (i) at least one sumoylated lysine residue, and (ii) one or more degenerate amino acids bound by a peptide bond to said sumoylated lysine residue, said antibody specifically binding said motif in a plurality of non-homologous peptides or proteins within an organism in which it recurs. Also provided is a motif-specific, context-independent antibody that specifically binds a recurring, modified motif consisting of (i) a C-terminal aspartic acid residue, and (ii) one or more degenerate amino acids bound by a peptide bond to said C-terminal aspartic acid residue, said antibody specifically binding said motif in a plurality of non-homologous peptides or proteins within an organism in which it recurs.

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23-08-2012 дата публикации

Doxorubicin immunoassay

Номер: US20120214184A1
Принадлежит: Individual

Novel conjugates of doxorubicin and novel doxorubicin immunogens derived from the 13 and 14 positions of doxorubicin and antibodies generated by these doxorubicin linked immunogens all of which are useful in immunoassays for the quantification and monitoring of doxorubicin in biological fluids.

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30-08-2012 дата публикации

Fc Region-Containing Polypeptides That Exhibit Improved Effector Function Due To Alterations Of The Extent Of Fucosylation, And Methods For Their Use

Номер: US20120219551A1
Принадлежит: Macrogenics Inc

The present invention relates to Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and to methods of using such polypeptides for treating or preventing cancer and other diseases. The Fc region-containing polypeptides of the present invention are preferably immunoglobulins (e.g., antibodies), in which the Fc region comprises at least one amino acid substitution relative to the corresponding amino acid sequence of a wild type Fc region, and which is sufficient to attenuate post-translational fucosylation and mediate improved binding to an activating Fc receptor and reduced binding to an inhibitory Fc receptor. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by FcγR is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by FcγR is desired (e.g., inflammation, autoimmune disease).

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30-08-2012 дата публикации

Prophylaxis Against Cancer Metastasis

Номер: US20120219561A1
Принадлежит: InGeneron Inc, University of Texas System

This document provides prophylactic methods for reducing cancer metastasis by targeting LCN2, MMP9, and CX-CR4.

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20-09-2012 дата публикации

Antibody Substituting for Function of Blood Coagulation Factor VIII

Номер: US20120237517A1
Принадлежит: Chugai Pharmaceutical Co Ltd

The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

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04-10-2012 дата публикации

Peptides capable of binding to serum proteins and compounds, constructs and polypeptides comprising the same

Номер: US20120253008A1
Принадлежит: Ablynx NV

The present invention relates to amino acid sequences that are capable of binding to serum proteins; to compounds, proteins, polypeptides, fusion proteins or constructs comprising or essentially consisting of such amino acid sequences; to nucleic acids that encode such amino acid sequences, compounds, proteins, polypeptides, fusion proteins or constructs; to compositions, and in particular pharmaceutical compositions, that comprise such amino acid sequences, compounds, proteins, polypeptides, fusion proteins or constructs; and to uses of such amino acid sequences, compounds, proteins, polypeptides, fusion proteins or constructs.

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11-10-2012 дата публикации

Antibodies Directed to Angiopoietin-1 and Angiopoietin-2 and Uses Thereof

Номер: US20120258122A1
Принадлежит: Boone Thomas C, Oliner Jonathan D

Disclosed are specific binding agents, such as fully human antibodies, that bind to angiopoietin 1 and/or angiopoietin-2. Also disclosed are heavy chain fragments, light chain fragments, and CDRs of the antibodies, as well as methods of making and using the antibodies.

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25-10-2012 дата публикации

Expression Vectors and Cell Lines Expressing Vascular Endothelial Growth Factor D, and Method of Treating Melanomas

Номер: US20120270781A1
Принадлежит: Vegenics Pty Ltd

This invention relates to expression vectors comprising VEGF-D and its biologically active derivatives, cell lines stably expressing VEGF-D and its biologically active derivatives, and to a method of making a polypeptide using these expression vectors and host cells. The invention also relates to a method for treating and alleviating melanomas or tumors expressing VEGF-D and various diseases.

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01-11-2012 дата публикации

Vhh for application in tissue repair, organ regeneration, organ replacement and tissue engineering

Номер: US20120276103A1

The present invention relates to a VHH which binds to a growth factor or is an antagonist for a growth factor, or binds to an implant.

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01-11-2012 дата публикации

5.9 kDa PEPTIDE IMMUNOASSAY METHOD

Номер: US20120276562A1
Принадлежит: Nitto Boseki Co Ltd

Disclosed is an immunoassay method whereby a 5.9 kDa peptide which results from the degradation of the α-E chain and α chain of human fibrinogens and which is used as a peptide marker for diagnosing hepatic disease can be specifically assayed in a biological sample containing contaminating peptides by bringing antibodies that recognize the N terminal of said peptide marker and antibodies that recognize the C terminal of said peptide marker into contact with said peptide marker, forming immune complexes of said peptide marker and the two antibodies, and immunoassaying the obtained immune complexes.

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22-11-2012 дата публикации

Reporter vector presenting extracellular binding capacity to metallic compounds

Номер: US20120295274A1
Принадлежит: Individual

According to one embodiment, a reporter vector presenting an extracellular binding capacity to metallic compounds contains a nucleotide sequence exhibiting a promoter activity depending on a specific condition, a nucleotide sequence encoding a metallic compound-binding peptide presented extracellularly, and a nucleotide sequence encoding transcription termination signals.

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29-11-2012 дата публикации

Plasmodium vivax Hybrid Circumsporozoite Protein and Vaccine

Номер: US20120301497A1
Принадлежит: Individual

Described in this application is a synthetic P. vivax circumsporozoite protein useful as a diagnostic reagent, for antibody production, and as a vaccine protective against infection with any strain of P. vivax.

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20-12-2012 дата публикации

Anti-c4.4a antibodies and uses thereof

Номер: US20120321619A1
Принадлежит: Bayer Intellectual Property GmbH

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for the membrane-anchored, 29 kDa C4.4a polypeptide, which is over expressed in several tumors, e.g. lung, colorectal, pancreas, prostate, renal and breast cancer. These antibodies, accordingly, can be used to treat these and other disorders and conditions. Antibodies of the invention also can be used in the diagnostics field, as well as for further investigating the role of C4.4a in the progression of disorders associated with cancer. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.

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20-12-2012 дата публикации

Adam6 Mice

Номер: US20120322108A1
Принадлежит: Regeneron Pharmaceuticals Inc

Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

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20-12-2012 дата публикации

Anti-Rhesus D Recombinant Polyclonal Antibody and Methods of Manufacture

Номер: US20120322690A1
Принадлежит: Symphogen AS

The invention relates to a method for manufacturing an anti-RhD recombinant polyclonal antibody composition (anti-RhD rpAb). The method comprises obtaining a collection of cells transfected with a library of anti-RhD antibody expression vectors, wherein each cell in the collection is capable of expressing from a VH and VL comprising nucleic acid segment, one member of the library, which encodes a distinct member of anti-RhD recombinant polyclonal antibody composition and is located at the same site in the genome of individual cells in said collection. The cells are cultured under suitable conditions for expression of the recombinant polyclonal antibody, which is obtained from the cells or culture supernatant. Nucleic acid segments encoding the anti-RhD rpAb are introduced into the cells by transfection with a library of vectors for site-specific integration. The method is suitable for manufacturing anti-RhD rpAb, thereby making available a superior replacement of plasma-derived prophylactic and therapeutic immunoglobulin products.

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10-01-2013 дата публикации

Methods and Compositions for Regulating Musashi Function

Номер: US20130011404A1
Принадлежит: University of Arkansas

The invention generally features compositions and methods for detecting and regulating cell proliferation, potentiation, and differentiation in a population of cells. In particular, compositions and methods are provided for modulating the activity of Musashi proteins. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

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31-01-2013 дата публикации

Vascular endothelial cell growth factor antagonists

Номер: US20130028911A1
Принадлежит: Genentech Inc

The present invention provides human vascular endothelial cell growth factor (hVEGF) antagonists, including monoclonal antibodies, hVEGF receptors, and hVEGF variants that are useful for the treatment of age-related macular degeneration, and other diseases and disorders characterized by undesirable or excessive neovascularization.

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14-02-2013 дата публикации

Compositions and Methods for Preventing and Treating Cancer via Modulating UBE1L, ISG215 and/or UBP43

Номер: US20130041016A1
Принадлежит: Dartmouth College

Compositions and methods of using compositions that induce UBE1L or a ubiquitin-like protein ISG15, or inhibit a deconjugase UBP43 to degrade oncogenic proteins and enhance apoptosis of cancer (neoplastic) or pre-cancerous (pre-neoplastic) cells are provided. Methods for the prevention or treatment of cancer via administration of these compositions are also provided.

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28-02-2013 дата публикации

Plasma Carboxypeptidase B as a Predictor for Disease Severity and Response

Номер: US20130052186A1

Compositions and methods are provided for prognostic classification of individuals into groups that are informative of the individual's likelihood of developing severe disease associated with undesirable complement activation. Individuals having one or both alleles for a more stable or active carboxypeptidase B variant have a reduced propensity for developing severe disease. The presence of the protective variant may be identified through any suitable method.

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28-02-2013 дата публикации

Substituted benzofurans, benzothiophenes, benzoselenophenes and indoles and their use as tubulin polymerisation inhibitors

Номер: US20130053351A1
Принадлежит: Bionomics Ltd

The present invention relates generally to substituted benzofurans, benzothiophenes, and indoles and their use as tubulin polymerisation inhibitors.

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21-03-2013 дата публикации

RADIOACTIVE METAL-LABELED ANTI-CADHERIN ANTIBODY

Номер: US20130071324A1
Принадлежит:

An object of the present invention is to provide a radioactive metal anti-cadherin antibody which is highly accumulated specifically in cancer tissue. Another object is to provide a cancer therapeutic agent having high anti-cancer effect and safety and a cancer diagnostic agent. The radioactive metal-labeled anti-cadherin antibody is obtained by binding a radioactive metallic element to an anti-cadherin antibody via a metal-chelating reagent. 1. A radioactive metal-labeled anti-cadherin antibody , obtained by a process comprising binding a radioactive metallic element to an anti-cadherin antibody via a metal-chelating reagent.2. The radioactive metal-labeled anti-cadherin antibody of claim 1 , wherein the anti-cadherin antibody is capable of binding to a region comprising residues 1 to 655 of SEQ ID NO: 2.3. The radioactive metal-labeled anti-cadherin antibody of claim 1 , wherein the anti-cadherin antibody is a monoclonal antibody.4. The radioactive metal-labeled anti-cadherin antibody of claim 1 , wherein the anti-cadherin antibody is selected from the group consisting of a chimeric antibody claim 1 , a humanized antibody claim 1 , and a human antibody.5. The radioactive metal-labeled anti-cadherin antibody of claim 1 , wherein the anti-cadherin antibody is a monoclonal antibody a recombinant antibody claim 1 , or a fragment thereof produced by an antibody-producing cell of an accession number of NITE BP-897 claim 1 , NITE BP-898 claim 1 , NITE BP-899 claim 1 , NITE BP-1034 claim 1 , NITE BP-1035 claim 1 , NITE BP-1036 claim 1 , NITE BP-1037 claim 1 , NITE BP-1038 claim 1 , NITE BP-1039 claim 1 , NITE BP-1040 claim 1 , NITE BP-1041 claim 1 , NITE BP-1042 claim 1 , NITE BP-1043 claim 1 , NITE BP-1044 claim 1 , NITE BP-1045 claim 1 , NITE BP-1046 claim 1 , NITE BP-1047 claim 1 , NITE BP-1048 claim 1 , NITE BP-1049 claim 1 , or NITE BP-1050.6. The radioactive metal-labeled anti-cadherin antibody of claim 1 , wherein the anti-cadherin antibody is a monoclonal antibody ...

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21-03-2013 дата публикации

1B20 PCSK9 ANTAGONISTS

Номер: US20130071379A1
Принадлежит:

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure. 1. An isolated PCSK9-specific antagonist which comprises:(a) a heavy chain variable region comprising a CDR3 domain comprising SEQ ID NO: 17 or an equivalent thereof, said equivalent characterized as having one or more conservative amino acid substitutions in the CDR3 domain; and/or(b) a light chain variable region comprising a CDR3 domain comprising SEQ ID NO: 7 or an equivalent thereof, said equivalent characterized as having one or more conservative amino acid substitutions in the CDR3 domain;wherein said PCSK9-specific antagonist antagonizes PCSK9's inhibition of cellular LDL uptake.2. The PCSK9-specific antagonist of wherein the CDR3 domain(s) are in a human germline region in the CDR3 region thereof.3. The PCSK9-specific antagonist of that binds to human PCSK9 with an equilibrium dissociation constant (K) of less than 1200 nM.4. The PCSK9-specific antagonist of that binds to human PCSK9 with a Kof less than 500 nM.5. The PCSK9-specific antagonist of that binds to human PCSK9 with a Kof less than 100 nM.6. The PCSK9-specific antagonist of that binds to human PCSK9 with a Kof less than 5 nM.7. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an ICof less than 500 nM.8. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an ICof less than ...

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21-03-2013 дата публикации

PHARMACEUTICAL COMPOSITION FOR TREATING AND/OR PREVENTING CANCER

Номер: US20130071398A1
Принадлежит: Toray Industries, Inc.

According to the present invention, a cancer antigen protein to be specifically expressed on the surfaces of cancer cells is identified and thus the use of an antibody targeting the cancer antigen protein as an agent for treating and/or preventing cancer is provided. Specifically, the present invention provides a pharmaceutical composition for treating and/or preventing a cancer, which comprises an antibody or a fragment thereof as an active ingredient having immunological reactivity with a partial polypeptide of CAPRIN-1, which is represented by any of even-numbered sequences of SEQ ID NOS: 2 to 30, wherein the polypeptide has the amino acid sequence represented by SEQ ID NO: 37 or an amino acid sequence having 80% or more sequence identity with the amino acid sequence represented by SEQ ID NO: 37. 1. A pharmaceutical composition for treating and/or preventing a cancer , comprising an antibody or a fragment thereof as an active ingredient that has immunological reactivity with a partial polypeptide of CAPRIN-1 , wherein CAPRIN-1 is represented by any of the even-numbered sequences of SEQ ID NOS: 2 to 30 , and wherein the partial polypeptide comprises the amino acid sequence represented by SEQ ID NO: 37 or an amino acid sequence having 80% or more sequence identity with the amino acid sequence of SEQ ID NO: 37.2. The pharmaceutical composition according to claim 1 , wherein the cancer is breast cancer claim 1 , brain tumor claim 1 , leukemia claim 1 , lymphoma claim 1 , lung cancer claim 1 , mastocytoma claim 1 , renal cancer claim 1 , uterine cervix cancer claim 1 , bladder cancer claim 1 , esophageal cancer claim 1 , gastric cancer claim 1 , or colorectal cancer.3. The pharmaceutical composition according to claim 1 , wherein the antibody is a monoclonal antibody or a polyclonal antibody.4. The pharmaceutical composition according to claim 1 , wherein the antibody is a human antibody claim 1 , humanized antibody claim 1 , chimeric antibody claim 1 , single chain ...

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21-03-2013 дата публикации

LINGO binding molecules and Pharmaceutical Use Thereof

Номер: US20130071400A1
Принадлежит: NOVARTIS AG

The present invention provides a binding molecule which is capable of binding to the rat, cynomolgus monkey and human LINGO polypeptide, a polynucleotide encoding such binding molecule; an expression vector comprising said polynucleotide; an expression system comprising a polynucleotide capable of producing a binding molecule; an isolated host cell which comprises an expression system as defined above; the use of such binding molecule as a pharmaceutical, especially in the treatment to promote axonal regeneration/plasticity; a pharmaceutical composition comprising said binding molecule; and a method of treatment of diseases associated with axonal degeneration and demyelination. 1. A binding molecule which is capable of binding to the protein according to SEQ ID NO: 1 , SEQ ID NO: 2 , or SEQ ID NO: 3 , with a dissociation constant <1000 nM.2. A binding molecule according to which binds to one or more of the sequences chosen form the group consisting of SEQ ID NO: 46-51.3. A binding molecule according to which is capable of disinhibiting spinal cord myelin at a concentration of less than 20 nM.4. A binding molecule according to claim 1 , which is capable of increasing the mean neurite length per cell of rat cerebellar granule cells grown on a substrate of adult rat spinal cord myelin by at least 20%.5. A binding molecule according to claim 1 , which comprises one or more amino acid sequences chosen from the group consisting of SEQ ID NO: 12-17 or SEQ ID NO: 18-23.6. A binding molecule according to claim 5 , which comprises at least one antigen binding site chosen from the group consisting of;a sequence which is at least 50% homologous to SEQ ID NO: 5 or SEQ ID NO: 7, and;a sequence which is at least 50% homologous to SEQ ID NO: 4 or SEQ ID NO: 6, or a direct equivalent thereof.7. A binding molecule according to claim 6 , which comprises a first sequence which is at least 50% homologous to SEQ ID NO: 5 or SEQ ID NO: 7 claim 6 , and a second sequence which is at least ...

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21-03-2013 дата публикации

METHODS OF TREATING DIABETES AND COMPOSITIONS CAPABLE OF SAME

Номер: US20130071401A1
Автор: Bram Yaron, Gazit Ehud
Принадлежит: Ramot at Tel-Aviv University Ltd.

A composition of matter is disclosed which comprises isolated oligomers of human islet amyloid polypeptide (IAPP). Antibodies recognizing same are also disclosed. Use of the composition of matter and the antibodies are also disclosed. 1. A composition of matter comprising isolated oligomers of human islet amyloid polypeptide (IAPP).2. The composition of matter of claim 1 , wherein said oligomers comprise dimers and/or trimers.3. The composition of matter of claim 1 , wherein said oligomers have a molecular weight between 4 kDa and 90 kDa.4. The composition of matter of claim 1 , wherein the composition is devoid of fibrils of IAPP.5. The composition of matter of claim 1 , further comprising sodium dodecyl sulfate (SDS).6. The composition of matter of claim 1 , wherein said oligomers have an alpha helical conformation.7. The composition of matter of claim 1 , wherein said oligomers are crosslinked.8. The composition of matter of claim 1 , wherein said oligomers are non-crosslinked.9. The composition of matter of claim 8 , wherein said oligomers consist of dimers and/or trimers.10. The composition of matter of claim 1 , being stable for up to 7 days.11. A method of generating a composition of matter comprising isolated oligomers of human islet amyloid polypeptide (IAPP) claim 1 , the method comprising:(a) dissolving human IAPP in an agent that eliminates structured forms of IAPP;(b) removing said agent; and(c) redissolving said non-structured form of IAPP in a solvent and an anionic surfactant, thereby generating the composition of matter.12. The method of claim 11 , wherein said agent is selected from the group consisting of 1 claim 11 ,1 claim 11 ,1 claim 11 ,3 claim 11 ,3 claim 11 ,3 hexafluoro-2-propanol (HFIP) claim 11 , trifluoroethanol (TFE) claim 11 , and trifluoroacetic acid (TFA).13. The method of claim 11 , wherein said solvent is selected from the group consisting of sodium hydroxide claim 11 , potassium hydroxide claim 11 , ammonium hydroxide claim 11 , ...

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21-03-2013 дата публикации

Sulfur-Containing Amino Acid Derivative

Номер: US20130071863A1
Принадлежит: AJINOMOTO CO., INC.

The present invention provides a method of measuring an endogenous low-molecular-weight compound specifically and conveniently with high sensitivity. Using the particular sulfur-containing amino acid derivative, a method of measuring an endogenous low-molecular-weight compound specifically and conveniently with high sensitivity can be provided. 2. The derivative according to claim 1 , wherein Y is a group bound to an endogenous low-molecular-weight compound claim 1 , and Z is selected from the group consisting of a hydrogen atom and a high-molecular-weight-imparting group.3. The derivative according to claim 1 , wherein Y is an endogenous low-molecular-weight compound reactive group claim 1 , and Z is a labeling compound modifying group.4. The derivative according to claim 1 , wherein the immunoresponsive hydrophobic group has a cyclic structure.5. The derivative according to claim 4 , wherein the immunoresponsive hydrophobic group is selected from the group consisting of a 9-fluorenylmethyloxycarbonyl (Fmoc) group and a quinolinylaminocarbonyl group.6. The derivative according to claim 1 , wherein the endogenous low-molecular-weight compound reactive group is selected from the group consisting of an aldehyde group claim 1 , an N-succinimidyl group claim 1 , a halogen group claim 1 , an isothiocyanate group claim 1 , and a maleimido group.7. The derivative according to claim 1 , wherein the high-molecular-weight-imparting group or labeling compound modifying group is bound via a linker.8. A reagent for measuring an endogenous low-molecular-weight compound claim 1 , which comprises the sulfur-containing amino acid derivative according to .9. The reagent according to claim 8 , wherein the endogenous low-molecular-weight compound is an amino acid.10. A method of producing an antibody which is able to recognize an endogenous low-molecular-weight compound claim 2 , comprising immunizing an animal with an antigen comprising the sulfur-containing amino acid derivative ...

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21-03-2013 дата публикации

Secreted Protein Acidic and Rich in Cysteine (SPARC) Protein SRM Assay

Номер: US20130072581A1
Принадлежит:

The current disclosure provides for specific peptides from the Secreted Protein Acidic and Rich in Cysteine (SPARC) protein and the derived ionization characteristics of those peptides that are advantageous for quantifying SPARC directly in formalin fixed biological samples by the method of Selected Reaction Monitoring (SRM) mass spectrometry. Such fixed biological samples include: formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and formalin fixed and paraffin embedded tissue culture cells. SPARC protein is quantitated in biological samples by the method of SRM/MRM mass spectrometry by quantitating one or more of the peptides described herein. The peptides can be quantitated if they reside in a modified or an unmodified form. Examples of potentially modified forms of SPARC peptides include those bearing phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence. 1. A method for measuring the level of the Secreted Protein Acidic and Rich in Cysteine (SPARC) protein in a biological sample , comprising detecting and/or quantifying the amount of one or more modified or unmodified SPARC fragment peptides in a protein digest prepared from said biological sample using mass spectrometry; and calculating the level of modified or unmodified SPARC protein in said sample; andwherein said level is a relative level or an absolute level.20. The method of claim , further comprising the step of fractionating said protein digest prior to detecting and/or quantifying the amount of one or more modified or unmodified SPARC fragment peptides.34-. (canceled)5. The method of claim 1 , wherein said protein digest comprises a protease digest.68-. (canceled)9. The method of claim 1 , wherein the SPARC fragment peptide comprises an amino acid sequence as set forth as SEQ ID NO:1 claim 1 , SEQ ID NO:2 claim 1 , SEQ ID NO:3 claim 1 , SEQ ID NO:4 claim 1 , SEQ ID ...

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21-03-2013 дата публикации

Antibodies to Alpha Synuclein

Номер: US20130072663A1
Принадлежит: Elan Pharmaceuticals, Inc.

The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals. 135-. (canceled)36. An antibody that specifically binds to a fragment of alpha-synuclein , wherein the fragment is amino acids 1-119 or 1-122 of SEQ ID NO:1; without specifically binding to full-length alpha synuclein.37. The antibody of or that is a human antibody.38. The antibody of or that is a humanized antibody.39. The antibody of or that is a mnoclonal antibody.40. The antibody of or having human isotype IgG1.41. The antibody of designated 12C6 or 7G8.4252-. (canceled)53. An antibody that specifically binds to a fragment of alpha-synuclein claim 36 , wherein the fragment is amino acids 120-140 or 123-140 of SEQ ID NO:1; without specifically binding to full-length alpha synuclein. The present application is a continuation of U.S. application Ser. No. 12/040,739, filed Feb. 29, 2008, which is a continuation of U.S. application Ser. No. 11/194,115, now U.S. Pat. No. 7,358,331, filed Jul. 29, 2005, which is a continuation-in-part of U.S. application Ser. No. 10/969,335, now U.S. Pat. No. 7,306,945, filed Oct. 19, 2004, which is a continuation-in-part of U.S. application Ser. No. 10/850,570 filed May 19, 2004, which claims the benefit under 35 USC §119(e) of U.S. ...

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21-03-2013 дата публикации

HUMAN MONOCLONAL ANTIBODY HAVING FAT-REDUCING EFFECT

Номер: US20130072664A1
Автор: Vollmers Heinz Peter
Принадлежит: PATRYS LIMITED

Purified polypeptide is proposed, the amino acid sequence of which is essentially identical to the amino acid sequence of SEQ ID NO:1 and SEQ ID NO:3, the polypeptide binding low density lipoproteins (LDL) and/or oxidized LDL (oxLDL), in particular LDL cholesterol and/or oxidized LDL cholesterol (oxLDL cholesterol). 126-. (canceled)27. A purified polypeptide comprising an amino acid sequence which is at least 90% identical to the amino acid sequence of SEQ ID NO:1 and/or SEQ ID N0:3 , wherein the polypeptide or fragments of the polypeptide binds the low density lipoproteins (LDL) and/or oxidized LDL (oxLDL) , in particular LDL cholesterol and/or oxidized LDL cholesterol (oxLDL cholesterol).28. The purified polypeptide of claim 27 , wherein the binding of the polypeptide or of the fragments of the polypeptide to low density lipoproteins (LDL) and very low density lipoproteins (VLDL) claim 27 , and to the respective oxidized forms (ox LDL and oxVLDL) is stronger than the binding to high density lipoproteins (HDL).29. The polypeptide of claim 27 , wherein the polypeptide or fragments of the polypeptide and the low density lipoproteins (LDL) and/or oxidized low density lipoproteins (oxLDL) that occur in human and animal bodies have complementary carbohydrate structures.30. The purified polypeptide of claim 27 , wherein the polypeptide is an antibody or a functional fragment thereof.31. The purified polypeptide of claim 30 , wherein the polypeptide is a functional fragment of one of the following groups comprising V claim 30 , V claim 30 , F claim 30 , Fc claim 30 , Fab claim 30 , Fab' claim 30 , and F(ab′).32. The purified polypeptide of claim 31 , wherein the amino acid sequence of the variable region of the light chain (V) is essentially identical to SEQ ID NO:1 and/or the amino acid sequence of the variable region of the heavy chain (V) is essentially identical to SEQ ID NO:3.33. The purified polypeptide of claim 31 , wherein the nucleic acid sequence of the variable ...

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21-03-2013 дата публикации

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Номер: US20130072665A1
Принадлежит:

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described. 1. (canceled)2. An antibody that binds specifically to PCSK9 , wherein the antibody binds to PCSK9 with a higher affinity at pH 7.4 than at pH 6.0.3. The antibody of claim 2 , wherein the antibody binds to PCSK9 with a lower Kat pH 7.4 than at pH 6.0.4. The antibody of claim 2 , wherein the antibody binds to PCSK9 with a ratio of a Kat pH 6.0 to a Kat pH 7.4 that is at least about 2:1.5. The antibody of claim 2 , wherein the antibody binds to PCSK9 with a ratio of a Kat pH 6.0 to a Kat pH 7.4 that is at least about 3:1.6. The antibody of claim 2 , wherein the antibody binds to PCSK9 with a lower kat pH 7.4 than at pH 6.0.7. The antibody of claim 2 , wherein the antibody binds to PCSK9 with a ratio of a kat pH 6.0 to a kat pH 7.4 that is at least about 2:1.8. An antibody that binds specifically to PCSK9 claim 2 , wherein the antibody binds to PCSK9 with a higher affinity at pH 7.4 than at pH 5.5.9. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a lower Kat pH 7.4 than at pH 5.5.10. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a ratio of a Kat pH 5.5 to a Kat pH 7.4 that is at least about 2:1.11. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a ratio of a Kat pH 5.5 to a Kat pH 7.4 that is at least about 3:1.12. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a ratio of a Kat pH 5.5 to a Kat pH 7.4 that is at least about 4:1.13. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a lower kat pH 7.4 than at pH 5.5.14. The antibody of claim 8 , wherein the antibody binds to PCSK9 with a ratio ...

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21-03-2013 дата публикации

Compositions and Methods for Brown Fat Induction and Activity Using FNDC5

Номер: US20130074199A1
Принадлежит: Dana-Farber Cancer Institute, Inc.

The invention provides compositions and methods for brown fat induction and activity through modulation of Fndc5 activity and/or expression. Also provided are methods for preventing or treating metabolic disorders in a subject through modulation of Fndc5 activity and/or expression. Further provided are methods for identifying compounds that are capable of modulating Fndc5 activity and/or expression. 1. An isolated polypeptide which:a) comprises amino acid residues 73-140 of SEQ ID NO:2 but which lacks an Fndc5 signal peptide;b) comprises amino acid residues 30-140 of SEQ ID NO:2 but which does not encode the full-length amino acid sequence of an Fndc5 protein; orc) comprises amino acid residues 29-140 of SEQ ID NO:2 but which does not encode the full-length amino acid sequence of an Fndc5 protein.2. The isolated polypeptide of claim 1 , which comprises amino acid residues 73-140 of SEQ ID NO:2 claim 1 , but which lacks an Fndc5 signal peptide.3. The isolated polypeptide of claim 2 , which lacks the C-terminal residue of SEQ ID NO:2.4. The isolated polypeptide of claim 1 , which comprises amino acid residues 30-140 of SEQ ID NO:2 and which does not encode the full-length amino acid sequence of an Fndc5 protein.5. The isolated polypeptide of claim 1 , which comprises amino acid residues 29-140 of SEQ ID NO:2 but which does not encode the full-length amino acid sequence of an Fndc5 protein.6. The isolated polypeptide of claim 1 , having a molecular weight of about 20 kilodaltons.7. The isolated polypeptide of claim 6 , wherein the molecular weight is as determined by gel electrophoresis under deglycosylated claim 6 , reduced claim 6 , and denatured conditions.8. The isolated polypeptide of claim 2 , which comprises amino acid residues 29-140 of SEQ ID NO:2.9. The isolated polypeptide of claim 2 , which comprises amino acid residues 30-140 of SEQ ID NO:2.10. The isolated polypeptide of claim 1 , wherein the polypeptide lacks an Fndc5 hydrophobic domain.11. The isolated ...

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28-03-2013 дата публикации

METHODS FOR DETECTING AND REGULATING ALOPECIA AREATA AND GENE COHORTS THEREOF

Номер: US20130078244A1
Принадлежит:

The invention provides for methods for controlling hair growth by administering a HLDGC modulating compound to a subject. The invention further provides for a method for screening compounds that bind to and modulate polypeptides encoded by HLDGC genes. The invention also provides methods of detecting the presence of or a predisposition to a hair-loss disorder in a human subject as well as methods of treating such disorders. 1. A method for detecting the presence of or a predisposition to a hair-loss disorder in a human subject , the method comprising:(a) obtaining a biological sample from a human subject; and(b) detecting whether or not there is an alteration in the level of expression of an mRNA or a protein encoded by a HLDGC gene in the subject as compared to the level of expression in a subject not afflicted with a hair-loss disorder.2. A method for detecting the presence of or a predisposition to a hair-loss disorder in a human subject , the method comprising:(a) obtaining a biological sample from a human subject; and(b) detecting the presence of one or more nucleotide polymorphisms (SNPs) in a chromosome region containing a HLDGC gene in the subject, wherein the SNP is selected from the SNPs listed in Table 2.3. The method of claim 1 , wherein the detecting comprises determining whether mRNA expression or protein expression of the HLDGC gene is increased or decreased as compared to expression in a normal sample.4. The method of claim 1 , wherein the detecting comprises determining in the sample whether expression of at least 2 HLDGC proteins claim 1 , at least 3 HLDGC proteins claim 1 , at least 4 HLDGC proteins claim 1 , at least 5 HLDGC proteins claim 1 , at least 6 HLDGC proteins claim 1 , at least 6 HLDGC proteins claim 1 , at least 7 HLDGC proteins claim 1 , or at least 8 HLDGC proteins is increased or decreased as compared to expression in a normal sample.5. The method of claim 1 , wherein the detecting comprises determining in the sample whether ...

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28-03-2013 дата публикации

ANTIBODIES TO THE C3d FRAGMENT OF COMPLEMENT COMPONENT 3

Номер: US20130078245A1

The present invention relates to methods and materials for modulating the complement alternative pathway (CAP), the complement classical pathway (CCP), the complement lectin/mannose pathway (CMP), or combinations thereof, as well as methods and materials for targeting prophylactic or therapeutic agents to localized areas of tissue within the body where they may more directly exert their effects upon the intended target cells or tissue, with reduced, associated systemic effects compared with administration of the same or similar agents in an untargeted, systemic manner. The methods and materials of the present invention may therefore allow for increased efficacy, lower threshold effective dosages and/or lower effective maintenance doses, and/or reduced associated undesired or adverse effects in terms of frequency or severity of occurrence, or both. The present invention also relates to methods and materials for modulating a host humoral immune response, especially reducing, inhibiting, or preventing a host humoral immune response. 1. An antibody or an antigen-binding fragment thereof comprisinglight chain complementarity determining regions (CDR) 1, 2 and 3, wherein light chain CDR 1 is SEQ ID NO:14 or SEQ ID NO:24, light chain CDR 2 is SEQ ID NO:15 or SEQ ID NO:25 and light chain CDR 3 is SEQ ID NO:16 or 26; orheavy chain complementarity determining regions (CDR) 1, 2 and 3, wherein heavy chain CDR 1 is SEQ ID NO:17 or SEQ ID NO:27, heavy chain CDR 2 is SEQ ID NO:18 or SEQ ID NO:28 and heavy chain CDR 3 is SEQ ID NO:19 or 29.2. The antibody of or an antigen-binding fragment thereof comprisinglight chain complementarity determining regions (CDR) 1, 2 and 3, wherein light chain CDR 1 is SEQ ID NO:14 or SEQ ID NO:24, light chain CDR 2 is SEQ ID NO:15 or SEQ ID NO:25 and light chain CDR 3 is SEQ ID NO:16 or 26; andheavy chain complementarity determining regions (CDR) 1, 2 and 3, wherein heavy chain CDR 1 is SEQ ID NO:17 or SEQ ID NO:27, heavy chain CDR 2 is SEQ ID NO:18 ...

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28-03-2013 дата публикации

Bispecific binding molecules binding to vegf and ang2

Номер: US20130078248A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

Bispecific binding molecules binding to both VEGF and Ang2, preferably in the form of immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing the same and their use in the treatment of diseases that are associated with VEGF- and/or Ang2-mediated effects on angiogenesis are disclosed. Further, nucleic acids encoding bispecific binding molecules, host cells and methods for preparing same are also described.

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28-03-2013 дата публикации

ANTI-MCSP ANTIBODIES

Номер: US20130078251A1
Принадлежит:

The invention provides anti-MCSP antibodies and methods of using the same. 1. An isolated antibody that binds to a membrane proximal epitope of human MCSP comprising a CSPG repeat-containing domain , wherein the antibody has been glycoengineered to modify the oligosaccharides in the Fc region and wherein the antibody has increased ADCC effector function as compared to an non-glycoengineered antibody.2. The antibody of claim 1 , wherein the CSPG repeat-containing domain comprises CSPG repeat 14 (SEQ ID NO: 3).3. The antibody of claim 1 , wherein the Fc region has a reduced number of fucose residues as compared to the nonglycoengineered antibody.4. The antibody of claim 1 , wherein the antibody has an increased ratio of GlcNAc residues to fucose residues in the Fc region compared to the non-glycoengineered antibody.5. The antibody of claim 1 , wherein the Fc region has an increased proportion of bisected oligosaccharides as compared to the non-glycoengineered antibody.6. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.7. The antibody of claim 1 , wherein the antibody is a human claim 1 , humanized claim 1 , or chimeric antibody.8. The antibody of claim 7 , wherein the antibody is a full-length IgG class antibody.9. The antibody of claim 1 , wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 14; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 15; and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 16.10. The antibody of claim 9 , further comprising (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11; and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 12.11. The antibody of claim 1 , wherein the antibody comprises (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 10; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 11; and (c) HVR-L3 comprising the amino acid sequence of SEQ ...

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28-03-2013 дата публикации

CANCER TARGETS AND USES THEREOF

Номер: US20130078253A1
Принадлежит: CELERA CORPORATION

Methods and compositions are provided for assessing, treating, and preventing diseases, especially cancer, using cancer-associated targets (“CAT”). Methods and compositions are also provided for determining or predicting the effectiveness of a treatment for these diseases or for selecting a treatment, using CAT. Methods and compositions are further provided for modulating cell function using CAT. Also provided are compositions that modulate CAT (e.g., antagonists or agonists), such as antibodies, proteins, small molecule compounds, and nucleic acid agents (e.g., RNAi and antisense agents), as well as pharmaceutical compositions thereof. Further provided are methods of screening for agents that modulate CAT, and agents identified by these screening methods. 1. An isolated protein comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-722 , 1975 , and 1977 and 1282-1974.2. A composition comprising the protein of and a pharmaceutically acceptable carrier.3. An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:a) SEQ ID NOS:723-1281, 1976, and 1978;b) nucleotide sequences that encode a protein comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-722, 1975, and 1977 and 1282-1974; andc) nucleotide sequences that are completely complementary to the nucleotide sequences of a) or b).4. An isolated RNAi or antisense nucleic acid molecule that selectively binds to the nucleic acid molecule of .5. An isolated antibody that selectively binds to the protein of .6. The antibody of claim 5 , wherein the antibody is at least one of a monoclonal claim 5 , polyclonal claim 5 , fully human claim 5 , humanized claim 5 , chimeric claim 5 , single-chain claim 5 , or anti-idiotypic antibody.7. A cell line claim 5 , hybridoma claim 5 , phage claim 5 , or transgenic organism that produces the antibody of .8. The antibody of claim 5 , wherein the antibody is coupled to a ...

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28-03-2013 дата публикации

AMYLOID BETA PEPTIDES, ASSEMBLIES THEREOF, AND RELATED METHODS

Номер: US20130078269A1
Принадлежит:

The present invention provides amyloid β peptide assemblies composed of at least three amyloid β peptide subunits, wherein at least one of the amyloid β peptide subunits is an amyloid β peptide analog. The invention further relates to metal complexes of amyloid β peptide assemblies and the use of amyloid β peptide assemblies as vaccines and in the identification of agents that modulate assembly of the amyloid β peptide subunits. 1. An amyloid beta peptide having the amino acid sequence Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr-Glu-Val-His-His-Gln-Lys-Leu-Val-Phe-Phe-Ala-Glu-Asp-Val-Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Nle-Val-(D)Pro-Gly-Val-Val-Ile-Ala (SEQ ID NO:41).2. A composition comprising the amyloid beta peptide of in admixture with an adjuvant.3. An isolated antibody that specifically binds to the amyloid beta peptide of . This application is a continuation of U.S. patent application Ser. No. 11/686,570, filed Mar. 16, 2007, which claims the benefit of priority from U.S. Provisional Patent Application Ser. No. 60/829,863, filed Oct. 17, 2006 and U.S. Provisional Patent Application Ser. No. 60/782,742, filed Mar. 15, 2006, and a continuation-in-part application of U.S. patent application Ser. No. 11/256,332, filed Oct. 31, 2005, now issued as U.S. Pat. No. 7,780,963, the contents of which are incorporated herein by reference in their entireties.This invention was made in the course of research sponsored by the National Institutes of Health. The U.S. government has certain rights in this invention.Alzheimer's disease (AD) is a progressive and degenerative dementia (Terry, et al. (1991) 30(4):572-80; Coyle (1987) in , Ed. G. Adelman, pp. 29-31, Birkhäuser: Boston-Basel-Stuttgart), which in its early stages manifests primarily as a profound inability to form new memories (Selkoe (2002) 298(5594):789-91). AD was first described nearly a century ago by German psychiatrist Alois Alzheimer, who identified prominent neuritic plaques and neurofibrillary tangles as ...

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28-03-2013 дата публикации

PYRENYLOXYSULFONIC ACID FLUORESCENT AGENTS

Номер: US20130079497A1
Принадлежит: LIFE TECHNOLOGIES CORPORATION

The invention provides a novel class of reactive fluorescent agents that are based on a pyrene sulfonic acid nucleus. The agents are readily incorporated into conjugates with other species by reacting the reactive group with a group of complementary reactivity on the other species of the conjugate. Also provided are methods of using the compounds of the invention to detect and/or quantify an analyte in a sample. In an exemplary embodiment, the invention provides multi-color assays incorporating the compounds of the invention. 125.-. (canceled)27. The compound of wherein s is 1 and t is 2.28. The compound of wherein the linker arm comprises a straight-chain claim 26 , saturated chain of atoms and includes unsubstituted polyalkylene.30. The compound of wherein s is 1 and t is 2.32. The conjugate of wherein s is 1 and t is 2.33. The conjugate of wherein the linker arm comprises a straight-chain claim 31 , saturated chain of atoms and includes unsubstituted polyalkylene.35. The conjugate of claim 34 , wherein the linker arm comprises a cleavable group.36. The conjugate of claim 34 , wherein the linker arm comprises —C(O)NH— claim 34 , —C(O)O— claim 34 , —NH— claim 34 , —S— claim 34 , or —O—.37. The conjugate of claim 34 , wherein s is 1 claim 34 , and t is 2.38. A kit for the detection of an analyte in a sample claim 26 , wherein said kit comprises a compound of .39. A kit for the detection of an analyte in a sample claim 29 , wherein said kit comprises a compound of .40. A kit for the detection of an analyte in a sample claim 31 , wherein said kit comprises a conjugate of .41. A kit for the detection of an analyte in a sample claim 34 , wherein said kit comprises a conjugate of . NOT APPLICABLENOT APPLICABLENOT APPLICABLEThe present invention relates to novel fluorescent compounds that have utility in detecting one or more selected analytes in a sample. The invention is of use in a variety of fields including immunology, diagnostics, molecular biology and fluorescence ...

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28-03-2013 дата публикации

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Номер: US20130079501A1
Принадлежит: Amgen Inc.

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described. 136-. (canceled)37. A antigen binding protein variant comprising:a heavy chain variable region that is at least 85% identical to the amino acid sequence of SEQ ID NO: 459; anda light chain variable region that is at least 85% identical to the amino acid sequence of SEQ ID NO: 461.38. The antigen binding protein variant of claim 37 , wherein the heavy chain variable region is at least 90% identical to the amino acid sequence of SEQ ID NO: 459 claim 37 , and wherein the light chain variable region is at least 90% identical to the amino acid sequence of SEQ ID NO: 461.39. The antigen binding protein variant of claim 37 , wherein the heavy chain variable region is at least 95% identical to the amino acid sequence of SEQ ID NO: 459 claim 37 , and wherein the light chain variable region is at least 95% identical to the amino acid sequence of SEQ ID NO: 461.40. The antigen binding protein variant of claim 37 , wherein the antigen binding protein specifically binds to PCSK9.41. The antigen binding protein variant of claim 37 , wherein the antigen binding protein is an antibody or a binding part thereof.42. A antigen binding protein variant comprising:a heavy chain variable region that is at least 85% identical to the amino acid sequence of SEQ ID NO: 463; anda light chain variable region that is at least 85% identical to the amino acid sequence of SEQ ID NO: 465.43. The antigen binding protein variant of claim 42 , wherein the heavy chain variable region is at least 90% identical to the amino acid sequence of SEQ ID NO: 463 claim 42 , and wherein the light chain variable region is at least ...

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28-03-2013 дата публикации

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Номер: US20130079502A1
Принадлежит: Amgen, Inc.

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described. 136-. (canceled)37. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake.38. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake and binds to human PCSK9 with an equilibrium dissociation constant (KD) of less than 1200 nM.39. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 500 nM.40. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 100 nM.41. The PCSK9-specific antagonist of that binds to human PCSK9 with a KD of less than 5 nM.42. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake at an ICof less than 500 nM.43. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an ICof less than 200 nM.44. The PCSK9-specific antagonist of that antagonizes PCSK9's inhibition of cellular LDL uptake at an ICof less than 100 nM.45. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 20%.46. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 50%.47. An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 60%.48. An isolated PCSK9-specific antibody molecule that antagonizes PCSK9's inhibition of cellular uptake by at least 20%.49. An isolated antigen binding molecule that binds to PCSK9 and reduces PCSK9's ability to inhibit cellular LDL uptake.50. The isolated antigen binding molecule of claim 49 ...

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04-04-2013 дата публикации

OLIGOMER-SPECIFIC AMYLOID BETA EPITOPE AND ANTIBODIES

Номер: US20130084283A1
Автор: Cashman Neil R.
Принадлежит:

A novel constrained peptide epitope derived from Aβ, wherein the eptitope comprises the amino acid sequence SNK, related antibody compositions and methods of use. An isolated antibody that specifically binds to a cyclic peptide comprising the conformational epitope which comprises the amino acid sequence SNK and corresponding to a solvent-exposed, antibody accessible knuckle region of oligomeric Aβ is described. An antigenic peptide comprising an epitope having a constrained cyclic configuration, which comprises the amino acid sequence SNK and corresponding to a solvent-exposed, antibody accessible knuckle region of oligomeric Aβ is also described. Methods of treating, preventing and diagnosing Alzheimer's disease are also described. 1. An isolated antibody that specifically binds to a cyclic peptide derived from Aβ , wherein the cyclic peptide comprises a conformational epitope having an amino acid sequence of at least SNK corresponding to a solvent-exposed , antibody accessible knuckle region of oligomeric Aβ.2. An isolated antibody that specifically binds to a cyclic peptide derived from Aβ , wherein the cyclic peptide comprises a conformational epitope having an amino acid sequence corresponding to SEQ ID NO: 1 corresponding to a solvent-exposed , antibody accessible knuckle region of oligomeric Aβ.3. The isolated antibody of or , wherein the antibody specifically binds with greater affinity to an oligomeric form of Aβ than to a non-oligomeric form of Aβ.4. The isolated antibody of any of to , wherein the antibody is monoclonal.5. The isolated antibody of any of to , wherein the antibody is humanized.6. An antigenic peptide comprising an epitope having a constrained cyclic configuration , wherein the epitope having an amino acid sequence of at least SNK corresponding to a solvent-exposed , antibody accessible knuckle region of oligomeric Aβ.7. An antigenic peptide comprising an epitope having a constrained cyclic configuration , wherein the epitope having an ...

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04-04-2013 дата публикации

HISTAMINE-RELEASING FACTOR (HRF), HRF-RECEPTOR AND METHODS OF MODULATING INFLAMMATION

Номер: US20130084293A1

Methods of treating a food allergy, allergic reactions, hypersensitivity, inflammatory responses, inflammation are provided. In one method, histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) is contacted with a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin in order to treat the food allergy, allergic reaction, hypersensitivity, inflammatory response, or inflammation. Methods of reducing or decreasing the probability, severity, frequency, duration or preventing a subject from having an acute or chronic food allergy, allergic reaction, hypersensitivity, an inflammatory response or inflammation, are also provided. In one method, histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) is contacted with a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin in order to reduce or decrease the probability, severity, frequency, duration or prevent a subject from having an acute or chronic food allergy, allergic reaction, hypersensitivity, an inflammatory response or inflammation. 1. (canceled)2. A method of treating an allergic reaction , hypersensitivity , an inflammatory response or inflammation , comprising contacting histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) with a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin thereby treating the allergic reaction , hypersensitivity , inflammatory response or inflammation.3. (canceled)4. The method of claim 2 , wherein the compound comprises a peptide or polypeptide.5. The method of claim 4 , wherein the peptide or polypeptide comprises an antibody or an antibody subsequence that binds to HRF/TCTP.6. The method of claim 5 , wherein the antibody or antibody subsequence is human or humanized.7. The method of claim 5 , wherein the antibody or antibody subsequence is monoclonal.8. The method of claim 5 , wherein the antibody or antibody subsequence competes for binding ...

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04-04-2013 дата публикации

Novel anti-clathrin heavy chain monoclonal antibody for inhibition of tumor angiogenesis and growth and application thereof

Номер: US20130084298A1
Автор: Han-Chung Wu, Kuo-Hua Tung
Принадлежит: Academia Sinica

A purified monoclonal antibody, or an. antigen-binding portion thereof, which specifically binds to human clathrin heavy chain (CHC) is disclosed. The antibody, or antigen-binding portion, thereof, exhibits at least one, two, three, four, five, six, seven, or all eight of the following properties: (a) specifically binds to pancreatic adenocarcinoma cells; (b) binding to the cell surface and cytosol of cancer cells and tumor blood vessels; (c) internalized by CHC-expressing cells; (d) inhibiting tumor growth, invasion ability, migration, and angiogenesis; (e) inducing apoptosis in cancer cells and human umbilical vein endothelial cells; (f) inhibiting tumor growth and tumor blood vessels in pancreatic cancer in vivo; (g) suppressing epidermal growth factor, transferrin, and VEGF internalizations by cancer cells; and (h) suppressing hypoxia-inducible factor-1α expression and vascular endothelial growth factor secretion. Methods for inhibiting tumor cell growth and/or angiogenesis, and detecting cancer in a subject is also disclosed.

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04-04-2013 дата публикации

Immunoassay for chromogranin a, antibodies and kit

Номер: US20130084585A1
Принадлежит: Euro-Diagnostic AB

The invention relates to monoclonal antibodies which are reactive with an epitope in the polypeptide represented by amino acid sequence 236 to 251 or 264 to 279 of the human CGA amino acid sequence. The invention further relates to the use of these monoclonal antibodies in an immunoassay for CGA, to immunoreagents comprising any of these two antibodies, and to test kits for the determination of CGA containing immunoreagents based on both of the monoclonal antibodies.

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04-04-2013 дата публикации

ANTIGEN BINDING PROTEINS TO PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 (PCSK9)

Номер: US20130085265A1
Принадлежит: Amgen Inc.

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described. 136-. (canceled)37. An antigen binding protein that competes for binding to PCSK9 with at least one of the following antigen binding proteins:a) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 79 and a light chain variable region of SEQ ID NO: 35;b) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 80 and a light chain variable region of SEQ ID NO: 36;c) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 76 and a light chain variable region of SEQ ID NO: 37;d) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 77 and a light chain variable region of SEQ ID NO: 38;e) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 78 and a light chain variable region of SEQ ID NO: 39;f) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 83 and a light chain variable region of SEQ ID NO: 40;g) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 67 and a light chain variable region of SEQ ID NO: 12;h) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 483 and a light chain variable region of SEQ ID NO: 485;i) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 459 and a light chain variable region of SEQ ID NO: 461; orj) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 463 and a light chain variable region of SEQ ID NO: 465.38. The antigen binding protein of claim 37 , wherein the antigen ...

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04-04-2013 дата публикации

ANTI-PCSK9 ANTIBODIES WITH pH-DEPENDENT BINDING CHARACTERISTICS

Номер: US20130085266A1
Принадлежит: Regeneron Pharmaceuticals, Inc.

The present invention provides antibodies and antigen-binding fragments thereof that specifically bind human proprotein convertase subtilisin/kexin type 9 (hPCSK9) which do not exhibit enhanced binding affinity for hPCSK9 at acidic pH relative to neutral pH. In certain embodiments, the antibodies and antigen-binding fragments of the invention bind hPCSK9 with a lower affinity at acidic pH than at neutral pH. 15-. (canceled)6. An isolated antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin/kexin type 9 (hPCSK9) , wherein the antibody or antigen-binding fragment thereof does not exhibit an enhanced binding affinity for hPCSK9 at an acidic pH relative to a neutral pH , as measured by surface plasmon resonance.7. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment thereof binds hPCSK9 with a lower affinity at acidic pH than at neutral pH.8. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment thereof binds hPCSK9 with a shorter t½ at acidic pH than at neutral pH claim 6 , as measured by surface plasmon resonance.9. The isolated antibody or antigen-binding fragment of claim 6 , wherein the antibody or antigen-binding fragment thereof: (a) binds hPCSK9 with a lower affinity at acidic pH than at neutral pH; and (b) binds hPCSK9 with a shorter t½ at acidic pH than at neutral pH claim 6 , as measured by surface plasmon resonance.10. An isolated antibody or antigen-binding fragment thereof that specifically binds human proprotein convertase subtilisin/kexin type 9 (hPCSK9) claim 6 , wherein the antibody or antigen-binding fragment thereof: (a) binds hPCSK9 with a lower affinity at acidic pH than at neutral pH; and (b) exhibits a serum half-life which is greater than the serum half-life of an anti-hPCSK9 antibody that does not exhibit lower affinity binding to hPCSK9 at acidic pH.11. An isolated antibody ...

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11-04-2013 дата публикации

TUMOR TARGETED ANTIBODIES AND METHOD FOR USING THE SAME

Номер: US20130089496A1
Автор: PANDEY Janardan P.

Isolated and recombinant antibodies, such as EGFR-binding antibodies. Antibodies can comprising the sequence of an immunoglobulin heavy constant gamma-1 region encoded by a human G1M3 allele. For example, antibodies of the embodiments can comprise an immunoglobulin heavy constant gamma-1 region wherein position 214 is arginine; position 356 is glutamic acid; position 358 is methionine and/or position 431 is alanine. Methods for treating diseases, such as cancer, in a human subject with such antibodies are also provided. 1. A pharmaceutical composition comprising a purified EGFR-binding antibody which has a human immunoglobulin heavy constant gamma-1 region with arginine at position 214 and a pharmaceutically acceptable carrier.2. The composition of claim 1 , wherein the human immunoglobulin heavy constant gamma-1 region has glutamic acid claim 1 , methionine claim 1 , and alanine at positions 356 claim 1 , 358 claim 1 , and 431 claim 1 , respectively.3. The composition of claim 1 , wherein the human immunoglobulin heavy constant gamma-1 region is encoded by a human G1M3 allele.4. The composition of claim 1 , wherein the antibody is a humanized antibody.5. The composition of claim 1 , wherein the antibody is a human antibody.6. The composition of claim 1 , wherein the antibody is a chimeric antibody.7. The composition of claim 1 , wherein the EGFR is HER2 (human epidermal growth factor receptor 2).8. The composition of claim 1 , wherein the EGFR is HER1 (human epidermal growth factor receptor 1).9. The composition of claim 1 , wherein the antibody is coupled to a therapeutic claim 1 , a reporter claim 1 , or a targeting moiety.10. The composition of claim 9 , wherein the therapeutic is a nucleotide claim 9 , a peptide claim 9 , a small molecule claim 9 , a therapeutic radionuclide claim 9 , a chemotherapeutic claim 9 , a tumor suppressor claim 9 , an apoptosis inducer claim 9 , an enzyme claim 9 , a second antibody claim 9 , an siRNA claim 9 , a hormone claim 9 , a ...

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11-04-2013 дата публикации

Antibodies Directed to ERBB2

Номер: US20130089544A1
Принадлежит: MedImmune Limited

The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that specifically bind to ErbB2, preferably human ErbB2. In another embodiment, the antibodies or antigen-binding portions thereof inhibit ErbB2. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins or portions thereof derived from human anti-ErbB2 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-ErbB2 antibodies. The invention also relates to transgenic animals or plants comprising nucleic acid molecules of the present invention 1. A targeted binding agent that specifically binds to ErbB2.2. The targeted binding agent according to claim 1 , wherein said targeted binding agent possesses at least one of the following properties:(a) binds to human cells;(b) binds to cells expressing cynomolgus ErbB2;(c) competes partially with Herceptin® but does not compete with 2C4;(d) inhibits ErbB2 phosphorylation in MCF7 cells with a EC50 of less than 50 ng/ml;(e) inhibits cell proliferation with an EC50 of less than 50 ng/ml in SKBR3 cells;(f) binds to ErbB2 with a KD of 13.5 nM or less; or(g) has an off rate (koff) for ErbB2 of 2.14×10-4 s-1 or smaller.3. The targeted binding agent to claim 2 , wherein said targeted binding agent binds ErbB2 with a KD of 13.5 nM or less and inhibits activation of ErbB2.4. The targeted binding agent of claim 1 , wherein said targeted binding agent is a monoclonal antibody selected from the group consisting of a chimeric antibody claim 1 , a human antibody and a humanized antibody.5. ...

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11-04-2013 дата публикации

METHOD AND COMPOSITIONS TO INDUCE APOPTOSIS OF TUMORAL CELLS EXPRESSING SHH

Номер: US20130089548A1
Принадлежит: NETRIS PHARMA

A method for inducing apoptosis of tumoral cells in a patient having cancer cells bearing Cell-adhesion molecule-related/Downregulated by Oncogenes (CDO) receptors and expressing Sonic Hedgehog (SHH), including administering to the patient an effective amount of an agonist of CDO's apoptotic function, wherein the agonist is selected from the group consisting of a CDO fragment, a fusion protein comprising a CDO fragment, an antibody against SHH, and an siRNA which is capable of inhibiting SHH expression, and related CDO fragments, fusion proteins comprising a CDO fragment, antibodies against SHH, and siRNAs which are capable of inhibiting SHH expression. 114.-. (canceled)15. A method for inducing apoptosis of tumoral cells in a patient having cancer cells bearing Cell-adhesion molecule-related/Downregulated by Oncogenes (CDO) receptors and expressing Sonic Hedgehog (SHH) , comprising administering to the patient an effective amount of an agonist of CDO's apoptotic function , wherein the agonist is selected from the group consisting of a CDO fragment , a fusion protein comprising a CDO fragment , an antibody against SHH , and an siRNA which is capable of inhibiting SHH expression.16. The method of claim 15 , wherein the patient has tumoral cells bearing CDO and Patched 1 (PTC1) receptors and expressing SHH claim 15 , comprising administering to the patient an effective amount of the agonist of the CDO's apoptotic function and an effective amount of an agonist of PTC1 apoptotic function.17. The method of claim 15 , wherein the agonist of the CDO's apoptotic function is a CDO fragment or a fusion protein containing a CDO fragment which specifically binds to Sonic Hedgehog (SHH).18. The method of claim 17 , wherein the CDO fragment is the extracellular domain of CDO.19. The method of claim 17 , wherein the CDO fragment is selected from the group consisting of CDO Fibronectin Type III domain 3 (CDO FnIII (3)) claim 17 , CDO Fibronectin Type III domains 1-3 (CDO FnIII (1-3 ...

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11-04-2013 дата публикации

ACYLGLYCEROL ACYLTRANSFERASE-LIKE PROTEIN MGAT-X1 AND USES THEREOF

Номер: US20130089552A1
Принадлежит:

The present invention is directed to a polynucleotide sequence of a novel acylglycerol acyltransferase-like protein MGAT-X1. The invention also provides the human MGAT-X1 associated with the dermatological diseases, urological diseases, muscle-skeleton disorders, hematological diseases, cancer, reproduction disorders, neurological diseases, metabolic diseases, cardiovascular diseases or gastroenterological diseases. The invention also provides assays for the identification of compounds useful for the modulation of dermatological diseases, urological diseases, muscle-skeleton disorders, hematological diseases, cancer, reproduction disorders, neurological diseases, metabolic diseases, cardiovascular diseases or gastroenterological diseases for treating of such diseases associated with expression of the MGAT-X1. The invention also features compounds which bind to and/or activate or inhibit the activity of MGAT-X1 as well as pharmaceutical compositions comprising such compounds. 1. A preparation of purified antibodies which specifically bind to a polypeptide comprising the amino acid sequence SEQ ID NO:2.2. The preparation of claim 1 , wherein the antibodies are selected from the group consisting of intact immunoglobulin molecules claim 1 , Fab fragments claim 1 , F(ab′)fragments claim 1 , Fv fragments claim 1 , monoclonal antibodies claim 1 , chimeric antibodies claim 1 , partially humanized antibodies claim 1 , fully humanized antibodies claim 1 , and single chain antibodies.3. A pharmaceutical composition comprising:purified antibodies which specifically bind to a polypeptide comprising the amino acid sequence SEQ ID NO:2; anda pharmaceutically acceptable carrier.4. The pharmaceutical composition of claim 3 , wherein the antibodies are selected from the group consisting of intact immunoglobulin molecules claim 3 , Fab fragments claim 3 , F(ab′)fragments claim 3 , Fv fragments claim 3 , monoclonal antibodies claim 3 , chimeric antibodies claim 3 , partially humanized ...

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11-04-2013 дата публикации

ANTIBODIES TO TUMOR ASSOCIATED PROTEINS

Номер: US20130090376A1
Принадлежит: Agensys, Inc.

A novel gene 024P4C12 (also designated 24P4C12) and its encoded protein, and variants thereof, are described wherein 24P4C12 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 24P4C12 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 24P4C12 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 24P4C12 can be used in active or passive immunization. 1. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes at least the variable regions of an antibody that binds specifically to a 24P4C12 protein.2. The nucleic acid molecule of wherein said 24P4C12 protein comprises SEQ ID NO:3 claim 1 , SEQ ID NO:7 claim 1 , SEQ ID NO:11 claim 1 , SEQ ID NO:13 claim 1 , SEQ ID NO:15 claim 1 , SEQ ID NO:17 or SEQ ID NO:19.3. The nucleic acid molecule of wherein said variable regions are humanized.4. The nucleic acid molecule of wherein said nucleotide sequence further encodes a toxic and/or therapeutic protein.5. The nucleic acid molecule of wherein said nucleotide sequence further encodes a nuclear targeting signal.6. The nucleic acid molecule of which further comprises a nucleotide sequence encoding a leader peptide coupled to the sequence at the N-terminus-encoding end and an endoplasmic reticulum retention signal encoding sequence at the C-terminal-encoding end.7. The nucleic acid molecule of wherein said encoding nucleotide sequence is operably linked to control sequences effective for its expression.8. Recombinant host cells modified to contain the nucleic acid molecule of .9. The recombinant host cells of that are mammalian cells.10. A method to produce a recombinant protein that immunospecifically binds 24P4C12 protein which comprises culturing the cells of and recovering said protein.11. A ...

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18-04-2013 дата публикации

FACTOR XII INHIBITORS FOR TREATING INTERSTITIAL LUNG DISEASE

Номер: US20130095108A1
Принадлежит: JUSTUS-LIEBIG-UNIVERSITAT GIESSEN

The present invention provides methods for treating interstitial lung diseases, comprising administering to an individual an effective amount of an inhibitor of coagulation factor XII. The invention further provides uses and pharmaceutical kits for that treatment. 1. Non-endogenous inhibitor of the cellular activity of factor XII and/or factor XIIa (FXII/FXIIa) for treating and/or preventing a fibroproliferative interstitial lung disease.2. The inhibitor of claim 1 , which is a compound capable of inhibiting the catalytic activity of factor XIIa.3. The inhibitor of claim 1 , which is a compound capable of reducing or abolishing expression of factor XII in a cell.4. The inhibitor of claim 1 , which is a compound capable of inhibiting the conversion of factor XII into factor XIIa.54. The inhibitor any one of to claim 1 , which is a serine protease inhibitor.6. The inhibitor of claims 1 , which is selected of the group consisting of (a) the N-terminal amino acids 2-13 of the wild type Infestin-4 sequence and at least one and up to five amino acid mutations outside said N-terminal amino acids that result in differences from the wild type Infestin-4 sequence; and/or', '(b) six conserved cysteine residues from the wild type Infestin-4 sequence and a homology of at least 70% to the wild type Infestin-4 sequence;, '(i) the wild type Infestin-4 polypeptide sequence (SEQ ID NO: 33), or a variant thereof, wherein a variant comprises'} a) the N-terminal amino acids 2-13 of the wild type Infestin-4 sequence; and at least one and up to five amino acid mutations outside said N-terminal amino acids that result in differences from the wild type SPINK-1 sequence and which increase the homology of the variant to the wild type Infestin-4 sequence; and/or', 'b) six conserved cysteine residues from the wild type SPINK-1 sequence and a homology of at least 70% to the wild type SPINK-1 sequence;, '(ii) SPINK-1 (SEQ ID NO:29), which is mutated to include the N-terminal amino acids 2-13 of ...

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18-04-2013 дата публикации

COMPOSITIONS AND METHODS FOR TREATING NEUROLOGICAL DISORDERS

Номер: US20130095113A1
Принадлежит: THE J. DAVID GLADSTONE INSTITUTES

The present disclosure provides methods for treating neurological disorders, generally involving modulating protein kinase D1 (PKD1) activity levels in a neuron or glial cell in an individual in need thereof. The present disclosure provides antibodies specific for PKD1. The present disclosure provides a genetically modified non-human mammal deficient in PKD1 activity. 1. A method for treating a neurological disorder or a neurodegenerative disease in an individual , the method comprising administering to the individual an effective amount of an agent that inhibits activity of protein kinase D1 (PKD1) in a neuronal cell and/or a glial cell in the individual.2. The method of claim 1 , wherein the agent is a small molecule inhibitor of PKD1.3. The method of claim 1 , wherein the agent is an inhibitory nucleic acid that reduces the level of active PKD1 in the neuronal cell.4. The method of claim 1 , wherein the agent is an antibody that specifically binds PKD1.5. The method of claim 1 , wherein the neurodegenerative disease is Parkinson's disease claim 1 , Huntington's disease claim 1 , amyotrophic lateral sclerosis claim 1 , multiple sclerosis claim 1 , or Alzheimer's disease.6. The method of claim 1 , wherein the neurological disorder is stroke claim 1 , spinal cord injury claim 1 , or head injury.7. An isolated interfering nucleic acid that specifically reduces the level of protein kinase D1 (PKD1) in a cell.8. The interfering nucleic acid of claim 7 , wherein the interfering nucleic acid is a short interfering RNA (siRNA).9. A recombinant construct comprising a nucleotide sequence encoding the interfering nucleic acid of .10. An isolated antibody that specifically binds protein kinase D1 (PKD1).11. The antibody of claim 10 , wherein the antibody is a polyclonal antibody.12. The antibody of claim 10 , wherein the antibody is a monoclonal antibody.13. The antibody of claim 10 , wherein the antibody binds a PKD1 polypeptide with an affinity of at least about 10M.14. A ...

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18-04-2013 дата публикации

RSPO Binding Agents and Uses Thereof

Номер: US20130095116A1
Принадлежит: OncoMed Pharmaceuticals, Inc.

The present invention relates to RSPO-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO proteins and modulate β-catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO proteins, such as antibodies that specifically bind RSPO1, RSPO2, and/or RSPO3 and inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer. 1173-. (canceled)174. An isolated antibody that specifically binds human R-spondin 1 (RSPO1) , which comprises:(a) a heavy chain CDR1 comprising TGYTMH (SEQ ID NO:12), a heavy chain CDR2 comprising GINPNNGGTTYNQNFKG (SEQ ID NO:13), and a heavy chain CDR3 comprising KEFSDGYYFFAY (SEQ ID NO:14); and(b) a light chain CDR1 comprising KASQDVIFAVA (SEQ IL NO:15), a light chain CDR2 comprising WASTRHT (SEQ ID NO:16), and a light chain CDR3 comprising QQHYSTPW (SEQ ID NO:17).175. The antibody of claim 174 , which comprises:(a) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO:10, and a light chain variable region having at least 90% sequence identity to SEQ ID NO:11; or(b) a heavy chain variable region having at least 90% sequence identity to SEQ ID NO:55, and a light chain variable region having at least 90% sequence identity to SEQ ID NO:59.176. The antibody of claim 174 , which is a recombinant antibody claim 174 , a monoclonal antibody claim 174 , a chimeric antibody claim 174 , a bispecific antibody claim 174 , a humanized antibody claim 174 , a human antibody claim 174 , an IgG1 antibody claim 174 , or an IgG2 antibody.177. The antibody of claim 174 , which inhibits binding of RSPO1 to at least one leucine-rich repeat containing G protein coupled receptor (LGR).178. The antibody of claim 177 , wherein the LGR is ...

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18-04-2013 дата публикации

ANTI-PLATELET MEMBRANE GLYCOPROTEIN VI MONOCLONAL ANTIBODY

Номер: US20130095120A1
Принадлежит: MOCHIDA PHARMACEUTICAL CO., LTD.

The present invention provides an antibody which has the following features, its active fragment, or a derivative thereof: a) It specifically binds to human platelet membrane glycoprotein VI (GPVI); b) The function to activate a platelet and/or the function to induce a thrombocytopenia in vivo are low; and c) It at least partially depletes GPVI on the platelet membrane by contacting with a platelet. 1. An isolated antibody or antigen-binding fragment thereof that specifically binds to loop 9 in domain 2 of human platelet glycoprotein VI (GPVI).2. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof comprises a variable heavy chain (VH) with 3 complementarity determining regions (CDR) and a variable light chain (VL) with 3 complementarity determining regions (CDR) claim 1 , comprising ther following VH CDR1 claim 1 , VH CDR2 claim 1 , VH CDR3 claim 1 , VL CDR1 claim 1 , VL CDR2 claim 1 , and VL CDR3 claim 1 , respectively of:(i) SEQ ID NOs: 335, 336, 337, 377, 378 and 379;(ii) SEQ ID NOs: 344, 345, 346, 386, 387 and 388;(iii) SEQ ID NOs: 347, 348, 349, 389, 390 and 391;(iv) SEQ ID NOs: 356, 357, 358, 398, 399, and 400; or(v) SEQ ID NOs: 371, 372, 373, 413, 414, 415.3. The antibody or antigen-binding fragment thereof of claim 1 , which is a chimeric antibody.4. The antibody or antigen-binding fragment thereof of claim 1 , which is a humanized antibody.5. The antibody or antigen-binding fragment thereof of claim 1 , wherein its antigen-binding valency is monovalent.6. The antibody or antigen-binding fragment thereof of claim 1 , which is polyethyleneglycolated (PEGylated).7. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 1 , and a pharmaceutically acceptable excipient.8. The antigen binding fragment according to claim 1 , which is an Fab claim 1 , Fab′ claim 1 , F(ab′)2 claim 1 , single-chain antibody (scFv) claim 1 , sc(Fv)2 claim 1 , disulfide- ...

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18-04-2013 дата публикации

ANTI-A(BETA) OLIGOMER HUMANIZED ANTIBODY

Номер: US20130095526A1
Принадлежит: KYOWA HAKKO KIRIN CO., LTD.

An anti-Aβ oligomer humanized antibody which does not bind to Aβ monomers and specifically binds only to Aβ oligomers; an anti-cognitive dysfunction agent, an agent for treating Alzheimer's disease, an agent for suppressing formation of neuritic plaque and an inhibitor of formation of Aβ amyloid fiber comprising the antibody as an active ingredient; a method for at least one of preventing and treating cognitive dysfunction or Alzheimer's disease, comprising the step of administering the antibody; and a method for suppressing progression of Alzheimer's disease, comprising the step of administering the antibody. 19-. (canceled)10. A DNA which encodes a variable region of an antibody or an antibody fragment thereof , wherein the antibody heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 12 or 15 or the antibody light chain variable region comprises the amino acid sequence of SEQ ID NO: 14 , 16 or 17.11. A recombinant vector which comprises the DNA according to .12. A transformant obtainable by introducing the recombinant vector according to into a host cell.13: A process for producing an antibody or antibody fragment thereof claim 12 , wherein the antibody heavy chain variable region comprises the amino acid sequence of SEQ NO: 12 or 15 and the antibody light chain variable region comprises the amino acid sequence of SEQ ID NO: 14 claim 12 , 16 or 17 claim 12 , comprising culturing the transformant described in in a medium to form and accumulate the antibody or the antibody fragment thereof claim 12 , wherein the antibody heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 12 or 15 and the antibody light chain variable region comprises the amino acid sequence represented by SEQ ID NO: 14 claim 12 , 16 or 17 in the culture and collecting the antibody or the antibody fragment thereof from the culture. 1. Field of the InventionThe present invention relates to an antibody which specifically binds to an amyloid-β ( ...

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25-04-2013 дата публикации

SPARC BINDING ANTIBODIES AND USES THEREOF

Номер: US20130101504A1
Принадлежит: ABRAXIS BIOSCIENCE, LLC

The invention provides SPARC binding antibodies that target disease sites, in particular, tumors and uses thereof to diagnose and treat diseases, in particular, cancerous tumors. 1. A composition comprising a SPARC binding antibody , wherein the SPARC binding antibody comprises Imm-2 , Imm-3 , or a combination thereof.2. The composition of wherein the SPARC binding antibody comprises Imm-2.3. The composition of wherein the SPARC binding antibody comprises Imm-3.4. The composition of wherein the SPARC binding antibody comprises both Imm-2 and Imm-3.5. The composition of claim 1 , further comprising an active agent claim 1 , wherein the active agent is conjugated to the SPARC binding antibody.6. The composition of claim 5 , wherein the active agent comprises a therapeutic agent or a diagnostic agent.7. The composition of claim 6 , wherein the therapeutic agent or diagnostic agent is a therapeutic agent selected from the group consisting of tyrosine kinase inhibitors claim 6 , kinase inhibitors claim 6 , biologically active agents claim 6 , biological molecules claim 6 , radionuclides claim 6 , adriamycin claim 6 , ansamycin antibiotics claim 6 , asparaginase claim 6 , bleomycin claim 6 , busulphan claim 6 , cisplatin claim 6 , carboplatin claim 6 , carmustine claim 6 , capecitabine claim 6 , chlorambucil claim 6 , cytarabine claim 6 , cyclophosphamide claim 6 , camptothecin claim 6 , dacarbazine claim 6 , dactinomycin claim 6 , daunorubicin claim 6 , dexrazoxane claim 6 , docetaxel claim 6 , doxorubicin claim 6 , etoposide claim 6 , epothilones claim 6 , floxuridine claim 6 , fludarabine claim 6 , fluorouracil claim 6 , gemcitabine claim 6 , hydroxyurea claim 6 , idarubicin claim 6 , ifosfamide claim 6 , irinotecan claim 6 , lomustine claim 6 , mechlorethamine claim 6 , mercaptopurine claim 6 , meplhalan claim 6 , methotrexate claim 6 , rapamycin (sirolimus) claim 6 , mitomycin claim 6 , mitotane claim 6 , mitoxantrone claim 6 , nitrosurea claim 6 , paclitaxel claim 6 ...

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25-04-2013 дата публикации

BTNL9 PROTEINS, NUCLEIC ACIDS, AND ANTIBODIES AND USES THEREOF

Номер: US20130101590A1
Принадлежит:

The invention provides novel BTNL9 proteins, including multimers, fragments, and variants of a human BTNL9 protein. In addition, antibodies that can bind to BTNL9 proteins and nucleic acids encoding BTNL9 proteins are provided. Uses for BTNL9 proteins, and agonists or antagonists thereof, are described. 167-. (canceled)68. An isolated soluble BTNL9 protein comprising(a) a polypeptide having an amino acid sequence at least 90% identical to amino acids 35-257 of SEQ ID NO:2, and(b) a second polypeptide having an amino acid sequence at least 90% identical to amino acids 35-257 of SEQ ID NO:2,wherein the alignment window of the amino acid sequences of the polypeptides of (a) and (b) with amino acids 35-257 of SEQ ID NO:2 is at least 80 amino acids long,wherein BTNL9 protein has a molecular weight greater than about three times as large as that of a polypeptide of (a), andwherein the BTNL9 protein can inhibit the proliferation of a T cell stimulated by an anti-CD3 antibody.69. The BTNL9 protein of claim 68 , wherein the polypeptides of (a) and (b) are at east 95% identical to amino acids 35-257 of SEQ ID NO:2.70. The BTNL9 protein of claim 69 , wherein the polypeptides of (a) and (h) comprise the amino acid sequence of amino acids 35-257 of SEQ ID NO:2.71. The BNTL9 protein of claim 68 , which does not comprise amino acids 258 to 277 of SEQ ID NO:2.72. The BTNL9 protein of claim 68 , wherein the polypeptides of (a) and (b) each comprise another polypeptide.73. The BTNL9 protein of claim 72 , wherein the other polypeptide comprises an Fc portion of an antibody claim 72 , wherein the Fc portion comprises an amino acid sequence that has not more than 15 insertions claim 72 , deletions claim 72 , or substitutions of a single amino acid relative to the amino acid sequence of a native claim 72 , human IgG Fc region claim 72 , wherein the BTNL9 protein can bind to FcRn.74. The BTNL9 protein of claim 73 , wherein the Fc portion has not more than 10 insertions claim 73 , ...

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25-04-2013 дата публикации

BMP-ALK3 ANTAGONISTS AND USES FOR PROMOTING BONE GROWTH

Номер: US20130101603A1
Автор: Seehra Jasbir
Принадлежит: Acceleron Pharma, Inc.

In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density and strength. In certain embodiments, the present invention provides ALK3 polypeptides, including ALK3-Fc fusion proteins. 1. An isolated polynucleotide comprising a coding sequence for a polypeptide comprising the amino acid sequence of SEQ ID NO:7.2. The isolated polynucleotide of claim 1 , wherein the isolated polynucleotide comprises a sequence of SEQ ID NO: 12.3. A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of .4. A cell transformed with a recombinant polynucleotide of .5. The cell of claim 4 , wherein the cell is a mammalian cell.6. The cell of claim 5 , wherein the cell is a CHO cell or a human cell.7. A method for promoting bone growth claim 5 , increasing bone density or increasing bone strength claim 5 , the method comprising administering to a subject an effective amount of a BMP or ALK3 antagonist selected from the group consisting of:a) a polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO: 3;b) a polypeptide comprising at least 50 consecutive amino acids selected from SEQ ID NO: 3;c) an antibody that binds to BMP2 and inhibits the interaction between BMP2 and ALK3;d) an antibody that binds to BMP4 and inhibits the interaction between BMP4 and ALK3; ande) an antibody that binds to ALK3 and inhibits the interaction between ALK3 and one or more ligands of ALK3. This application is a divisional of U.S. application Ser. No. 12/750,604, filed Mar. 30, 2010, which claims the benefit of U.S. Provisional Application No. 61/211,557, filed on Mar. 30, 2009, 61/306,331, filed on Feb. 19, 2010, and 61/314,556, filed on Mar. 16, 2010. The specifications of each of the foregoing applications are incorporated herein by reference in their entirety.The instant application contains a Sequence Listing which has been submitted via EFS-Web and is hereby incorporated ...

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25-04-2013 дата публикации

Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) Single Chain FV Antibody Fragment Conjugates and Methods of Use Thereof

Номер: US20130101607A1
Принадлежит:

Compositions including an antibody single-chain variable fragment (scFv) conjugate that specifically binds to ROR1 tumor-associated antigen are provided. The anti-ROR1 scFv antibody and conjugates may include a biologically-active molecule. Such conjugates may comprise a chimeric receptor to direct T cells to respond to ROR1 cancer cells, Methods to use the scFV conjugates to target cells expressing ROR1 for therapeutic and diagnostic purposes are also provided. 1. An antibody single-chain variable fragment (scFv) conjugate comprising ,an scFv having an amino acid sequence at least 90% identical to SEQ ID NO: 1 or SEQ ID NO: 2; anda biologically active molecule.2. The conjugate of claim 1 , wherein the amino acid sequence of the scFv is at least 95% identical to SEQ ID NO: 1 or SEQ ID NO: 2.3. The conjugate of claim 1 , wherein the amino acid sequence of the scFv is 100% identical to SEQ LD NO: 1 or SEQ LD NO: 2.4. The conjugate of claim 1 , wherein the scFv has a binding specificity of an antibody as produced by a hybridoma having Accession No. PTA 8634 by the American Type Culture Collection.5. The conjugate of claim 1 , wherein the biologically active molecule is selected from the group consisting of a polypeptide claim 1 , a peptidomimetic claim 1 , a nucleic acid molecule claim 1 , a lipid claim 1 , a drug compound claim 1 , chemotherapeutic agent claim 1 , an antagonist and an agonist.6. The conjugate of claim 5 , wherein the biologically active molecule is a polypeptide.7. The conjugate of claim 6 , wherein the polypeptide is an antibody or an antibody fragment.8. The conjugate of claim 7 , wherein the antibody fragment is selected from the group consisting of a Fab fragment claim 7 , a F(ab)2 fragment claim 7 , an FV fragment claim 7 , a single chain FV (scFV) fragment claim 7 , a dsFV fragment claim 7 , a CH fragment and a dimeric scFV.9. The conjugate of claim 8 , wherein the CH fragment is an IgG CH fragment.10. The conjugate of claim 9 , wherein the IgG ...

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25-04-2013 дата публикации

HUMAN ANTIBODY DRUG CONJUGATES AGAINST TISSUE FACTOR

Номер: US20130101608A1
Принадлежит: GENMAB A/S

Antibody drug conjugates against tissue factor. Also disclosed are pharmaceutical compositions comprising the antibodies and antibody drug conjugates, and therapeutic and diagnostic methods for using the antibodies and antibody drug conjugates. 1. An antibody drug conjugate comprising an antibody which binds to tissue factor and which comprises(i) a VH region comprising a CDR1 region comprising the amino acid sequence set forth in SEQ ID NO:6, a CDR2 region comprising the amino acid sequence set forth in SEQ ID NO: 7, and a CDR3 region comprising the amino acid sequence set forth in SEQ ID NO: 8, and a VL region comprising a CDR1 region comprising the amino acid sequence set forth in SEQ ID NO:46, a CDR2 region comprising the amino acid sequence set forth in SEQ ID NO: 47, and a CDR3 region comprising the amino acid sequence set forth in SEQ ID NO: 48, or(ii) a VH region comprising a CDR1 region comprising the amino acid sequence set forth in SEQ ID NO:34, a CDR2 region comprising the amino acid sequence set forth in SEQ ID NO: 35, and a CDR3 region comprising the amino acid sequence set forth in SEQ ID NO: 36, and a VL region comprising a CDR1 region comprising the amino acid sequence set forth in SEQ ID NO:74, a CDR2 region comprising the amino acid sequence set forth in SEQ ID NO: 75, and a CDR3 region comprising the amino acid sequence set forth in SEQ ID NO: 76, or(iii) a VH region comprising a CDR1 region comprising the amino acid sequence set forth in SEQ ID NO:38, a CDR2 region comprising the amino acid sequence set forth in SEQ ID NO: 39, and a CDR3 region comprising the amino acid sequence set forth in SEQ ID NO: 40, and a VL region comprising a CDR1 region comprising the amino acid sequence set forth in SEQ ID NO:78, a CDR2 region comprising the amino acid sequence set forth in SEQ ID NO: 79, and a CDR3 region comprising the amino acid sequence set forth in SEQ ID NO: 80, or(iv) a VH region comprising a CDR1 region comprising the amino acid sequence set ...

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25-04-2013 дата публикации

Immunoglobulin Preparations Having Increased Stability

Номер: US20130102760A1
Принадлежит:

The present invention relates to a protein preparation having increased stability, comprising a stabiliser selected from the group consisting of non-polar and basic amino acids and having a pH of 4.0 to 5.2. The invention further relates to a pharmaceutical composition and a method of stabilising protein preparations. 121.-. (canceled)22. A liquid IgG preparation , comprising a polyclonal IgG concentrate purified from pooled human blood plasma and a stabilizer consisting essentially of proline , wherein the preparation has a pH of about 4.2 to about 5.4 , and wherein the preparation is not lyophilized prior to administration.23. The preparation of claim 22 , wherein said preparation has a pH of about 4.6 to about 5.0.24. The preparation of claim 22 , wherein the praline is L-proline and the concentration of the L-proline in the preparation is from 0.2 to 0.4 M claim 22 , and wherein the concentration of IgG in the preparation is 6-15% w/v.25. The preparation of claim 22 , wherein the proline is L-proline and the concentration of the L-proline in the preparation is from 0.2 to 0.3 M claim 22 , and wherein the concentration of IgG in the preparation is 8-12% w/v.26. The preparation of claim 25 , wherein the concentration of IgG in the preparation is 10% w/v.27. The preparation of claim 22 , wherein the praline is L-proline and the concentration of the L-proline in the preparation is from 0.2 to 0.4 M claim 22 , and wherein the concentration of IgG in the preparation is 15-20% w/v. The present invention relates to a protein preparation having increased stability, comprising a stabiliser selected from the group consisting of non-polar and basic amino acids and having a pH of 4.2 to 5.4. The invention further relates to a pharmaceutical composition and a method of stabilising protein preparations.Protein preparations, in particular immunoglobulin preparations for intravenous injection, have been in use for quite some time. Proteins, and immunoglobulin in particular, tend ...

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02-05-2013 дата публикации

IMMUNOTHERAPY AND DIAGNOSIS OF MUCORMYCOSIS USING CotH

Номер: US20130108642A1
Принадлежит:

The invention provided Mucorales CotH polypeptides and encoding nucleic acid molecules. The Mucorales CotH polypeptides and encoding nucleic acids can be advantageously used to diagnose, treat or prevent fungal conditions, in particular mucormycosis. 1. An isolated nucleic acid encoding a Mucorales CotH polypeptide , an immunogenic fragment thereof , or a functional fragment thereof.2. The isolated nucleic acid of claim 1 , wherein said nucleic acid comprises a nucleic acid selected from:(a) nucleic acid encoding an amino acid sequence set forth in SEQ ID NOS: 1, 3, 5, 11, 15, 16, 18, 20, 22, 24, 26, 28, 30 or 32, or(b) nucleic acid that hybridizes to the nucleic acid of (a) under moderately stringent conditions, wherein said nucleic acid contiguously encodes biologically active Mucorales CotH polypeptide, or(c) nucleic acid degenerate with respect to either (a) or (b) above, wherein said nucleic acid encodes biologically active Mucorales CotH polypeptide.3. (canceled)4. The nucleic acid of claim 2 , wherein said amino acid sequence comprises least 65% claim 2 , 70% claim 2 , 75% claim 2 , 80% claim 2 , 85% claim 2 , 90% claim 2 , 95% claim 2 , 98% or 99% sequence identity to the amino acids sequence set forth in SEQ ID NOS: 1 claim 2 , 3 claim 2 , 5 claim 2 , 11 claim 2 , 15 claim 2 , 16 claim 2 , 18 claim 2 , 20 claim 2 , 22 claim 2 , 24 claim 2 , 26 claim 2 , 28 claim 2 , 30 or 32.56-. (canceled)7. A vector containing the nucleic acid of .8. A recombinant cell containing the nucleic acid of .9. A CotH oligonucleotide claim 2 , comprising between 15 and 300 contiguous nucleotides of SEQ ID NOS: 2 claim 2 , 4 claim 2 , 6 claim 2 , 9 claim 2 , 10 claim 2 , 12-14 claim 2 , 17 claim 2 , 19 claim 2 , 21 claim 2 , 23 claim 2 , 25 claim 2 , 27 claim 2 , 29 or 31 or the anti-sense strand thereof.10. (canceled)11. An antisense-nucleic acid capable of specifically binding to mRNA encoded by said nucleic acid according to .12. A kit for detecting the presence of a Mucorales ...

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02-05-2013 дата публикации

Inhibition of AXL Signaling in Anti-Metastatic Therapy

Номер: US20130108644A1
Принадлежит: Leland Stanford Junior University

Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL and its ligand GAS6.

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02-05-2013 дата публикации

ANTI-APOPTOTIC PROTEIN ANTIBODIES

Номер: US20130108690A1
Принадлежит:

Single-domain antibodies that bind pro-apoptotic proteins Bax and caspase-3 are identified and isolated. These single-domain antibodies may be used to modulate the activity of Bax and caspase-3, thereby modulating the symptoms and steps of oxidative stress and/or cell apoptosis, including Bax dimerization, mitochondrial permeabilization and the release of apoptotic proteins. 1. An isolated single-domain antibody having an amino acid sequence that comprises at least one of SEQ. ID NO: 7 or SEQ. ID NO: 8.2. An isolated single-domain antibody having a binding affinity for caspase-3 and having an amino acid sequence encoded by a nucleic acid sequence that comprises at least one of SEQ ID NO: 16 or SEQ ID NO:17.3. A single-domain antibody as claimed in that is fused to a polypeptide.4. A single-domain antibody as claimed in that is fused to an antibody domain.5. A single-domain antibody as claimed in wherein the antibody domain is an Immunoglobulin (Ig) light chain variable domain (VL) claim 4 , an Ig heavy chain variable domain (VH) claim 4 , a camelid (camels and llamas) heavy chain antibody variable domain (VHH) claim 4 , a nurse shark and wobbegong shark Ig new antigen receptor(IgNAR) variable domain (VH) claim 4 , or a T cell receptor variable domain.6. A single-domain antibody as claimed in wherein the polypeptide is a marker protein.7. A single-domain antibody as claimed in wherein the polypeptide is a signal protein or sequence determining cellular localization.8. A single-domain antibody as claimed in wherein the signal protein is a mitochondrial transport signal protein.9. A single-domain antibody as claimed in wherein the polypeptide has the ability to cross cell membranes.10. A single-domain antibody as claimed in wherein the polypeptide is a membrane translocating sequence or protein transduction domain.11. A single-domain antibody as claimed in wherein the polypeptide is an internalizing protein.12. An immunoliposome comprising a single-domain antibody as ...

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02-05-2013 дата публикации

Usp2a peptides and antibodies

Номер: US20130109587A1
Автор: Patrick J. Muraca
Принадлежит: Nuclea Biotechnologies Inc

The invention relates to novel USP2a peptides and antibodies, as well as nucleic acids related to them. The peptides, antibodies and the nucleic acids are useful for the detection, staging and monitoring of the progression of cancer, as well as for determining or monitoring the efficacy of treatment.

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02-05-2013 дата публикации

ANTI-cMET ANTIBODY

Номер: US20130109840A1
Принадлежит:

Antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region. A composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer. 1. A monoclonal antibody , or a divalent functional fragment or derivative thereof , capable of inhibiting c-Met dimerization , wherein the antibody comprises:a heavy chain comprising CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID Nos. 1, 2, and 3, respectively;a light chain comprising CDR-L1, CDR-L2, and CDR-L3 comprising amino acid sequences SEQ ID Nos. 5, 6, and 7; anda modified hinge region comprising the amino acid sequence SEQ ID No. 56.233.-. (canceled) The present invention relates to a novel divalent antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, as well as the amino acid and nucleic acid sequences coding for said antibody. More particularly, the antibody according to the invention is capable of inhibiting the c-Met dimerization. The invention likewise comprises the use of said antibody as a medicament for the prophylactic and/or therapeutic treatment of cancers or any pathology connected with the overexpression of said receptor as well as in processes or kits for diagnosis of illnesses connected with the over-expression of c-Met. The invention finally comprises products and/or compositions comprising such an antibody in combination with other antibodies and/or chemical compounds directed against other growth factors involved in tumor progression or metastasis and/or compounds and/or anti-cancer agents or agents conjugated with toxins and their use for the prevention and/or the treatment of certain cancers.Receptor tyrosine kinase (RTK) targeted agents such as trastuzumab, ...

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02-05-2013 дата публикации

ANTI-cMET ANTIBODY

Номер: US20130109841A1
Принадлежит:

Antibody capable of binding specifically to the luman c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region. A composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer. 1. A monoclonal antibody , or a divalent functional fragment or derivative thereof , capable of inhibiting c-Met dimerization , wherein the antibody comprises:a heavy chain comprising CDR-H1, CDR-H2, and CDR-H3 comprising amino acid sequences SEQ ID Nos. 1, 2, and 3, respectively;a light chain comprising CDR-L1, CDR-L2, and CDR-L3 comprising amino acid sequences SEQ ID Nos. 5, 6, and 7; anda modified hinge region comprising the amino acid sequence SEQ ID No. 56.233.-. (canceled) The present invention relates to a novel divalent antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, as well as the amino acid and nucleic acid sequences coding for said antibody. More particularly, the antibody according to the invention is capable of inhibiting the c-Met dimerization. The invention likewise comprises the use of said antibody as a medicament for the prophylactic and/or therapeutic treatment of cancers of any pathology connected with, the overexpression of said receptor as well as in processes or kits for diagnosis of illnesses connected with the over-expression of c-Met. The invention finally comprises products and/or compositions comprising such an antibody in combination with other antibodies and/or chemical, compounds directed against, other growth factors involved in tumor progression or metastasis and/or compounds and/or anti-cancer agents or agents conjugated with toxins and their use for the prevention and/or the treatment of certain cancers.Receptor tyrosine kinase (RTK) targeted, agents such, as trastuzumab, ...

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