Polypeptides that bind tissue inhibitor of metalloproteinase type three (timp-3), compositions and methods

The present invention relates to TIMP-3 binding compositions, methods of producing such compositions, and methods of using such compositions, including in the treatment of various conditions.

Mmp-8 activation product, its determination and use

MMP-8 activation products are disclosed that have a MMP-8 middle-part activation product having a size between 20-35 kDa. Methods of detecting the MMP-8 activation product or activated MMP-8 fragments in a biological sample derived from a subject are also disclosed. The MMP-8 activation product or activated MMP-8 fragments diagnose diseases based on abnormal or elevated levels of activated MMP-8.

BIFUNCTIONAL PEPTIDE

The bifunctional peptide is capable of activating collagen synthesis and inhibiting the production of matrix metallo-proteinases. The peptide has a sequence including three peptide parts A, B and C. The first peptide part A corresponds to a hexapeptide repeated at least three times, the part A being capable of bonding to a receptor elastin-binding protein in order to stimulate collagen synthesis. The second peptide part B corresponds to a tetrapeptide capable of acting as a competitive inhibitor of urokinase protease and of being cleaved by said protease. The third peptide part C corresponds to a tripeptide occupying at least one active site of the matrix metallo-proteinases in order to enable inhibition of the proteinases. The present invention further concerns a cosmetic and/or pharmaceutical composition incorporating the bifunctional peptide. 1. Bifunctional peptide activating synthesis of collagen and inhibiting production of matrix metallo-proteinases , said peptide comprising:a sequence comprising a first peptide portion A, a second peptide portion B, and a third peptide portion C,wherein the first peptide portion A corresponds to a hexapeptide repeated at least three times, said first peptide portion A bonding to an elastin-binding receptor protein in order to stimulate collagen synthesis,wherein the second peptide portion B corresponds to a tetrapeptide acting as a competitive inhibitor of urokinase protease and being cleaved by said urokinase protease, andwherein the third peptide portion C corresponds to a tripeptide occupying at least one active site of the matrix metallo-proteinases in order to permit an inhibition of said proteinases.2. Bifunctional peptide according to claim 1 , wherein the first peptide portion A comprises:X1-Gly-X2-X3-Pro-Gly sequence, being repeated at least three times, wherein saidX1 corresponds to any amino acid, whereinX2 corresponds to an amino acid selected from a group consisting of Val, Thr, Gln, Ala, and Leu, andX3 ...

VARIANTS OF TISSUE INHIBITOR OF METALLOPROTEINASE TYPE THREE (TIMP-3), COMPOSITIONS AND METHODS

There are disclosed TIMP-3 muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them. 1. An isolated TIMP-3 mutein having a mature region that is at least 95% identical in amino acid sequence to the mature region of TIMP-3 set forth in SEQ ID NO:2 , having at least one mutation , the mutation being selected from the group consisting of K45E; K45N; K45S; V47T; K49N; K49E; K49S; K50N; L51T; L51N; V52T; K53T; P56N; F57N; G58T; T63E; T63N; K65T; K65N; M67T; K68S; T74E; K75N; P77T; H78D; H78E; H78N; Q80E; Q80T; K94N; E96T; E96N; V97N; N98T; K99T; D110N; K112T; Q126N; K133S; R138T; R138N; H140T; T158N; K160T; T166N; M168T; G173T; H181N; A183T; R186N; R186Q , R186E , K188T; K188Q , K188E , P201N; K203T; I205F , I205Y , A208G , A208V , and A208Y.2. An isolated TIMP-3 mutein having a mature region that is at least 95% identical in amino acid sequence to the mature region of TIMP-3 set forth in SEQ ID NO:2 , having , having the mutation F57N and at least one further mutation , wherein the mutation is substitution at one or more of K residues of TIMP-3.3. The TIMP-3 mutein of wherein the further mutation introduces an N-linked glycosylation site into the amino acid sequence.4. An isolated TIMP-3 mutein having a mature region that is at least 90% identical in amino acid sequence to the mature region of TIMP-3 set forth in SEQ ID NO:2 claim 2 , wherein the mutein has at least one mutation that introduces at least one N-linked glycosylation site into the amino acid sequence.5. The TIMP-3 mutein of claim 4 , wherein two claim 4 , three claim 4 , four claim 4 , five claim 4 , or six N-linked glycosylation sites are introduced.6. The TIMP-3 mutein of claim 3 , wherein the N-linked glycosylation site is introduced at a region of the TIMP-3 amino acid sequence selected from the group consisting of: the region comprising amino acids 48-54; the region comprising amino acids 93-100; the region comprising amino acids 121-125; the region ...

VARIANTS OF TISSUE INHIBITOR OR METALLOPROTIENASE TYPE THREE (TIMP-3), COMPOSITIONS AND METHODS

The application concerns tissue inhibitor of metalloproteinase 3 (TIMP-3) muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them; in particular, muteins of TIMP-3 with specific amino acid substitutions in order to introduce N-linked glycosylation sites. 1. An isolated TIMP-3 mutein having a mature region that is at least 90% identical in amino acid sequence to the mature region of TIMP-3 set forth in SEQ ID NO:2 , selected from the group consisting of:a) a TIMP-3 mutein having two or more pairs of mutations selected from the group consisting of K45N/V47T; K50N/V52T; P56N/G58T; H78N/Q80T; K94N/E96T; and D110N/K112T;b) a TIMP-3 mutein having one or more pairs of mutations selected from the group consisting of K45N/V47T; K50N/V52T; P56N/G58T; H78N/Q80T; K94N/E96T; and D110N/K112T; and an additional mutation that is selected from the group consisting of R138T; G173T, and both R138T and G173T; andc) the TIMP-3 mutein according to a) or b) that further comprises the mutation F57N.2. A TIMP-3 mutein having a mature region that is at least 90% identical in amino acid sequence to amino acids 24-211 of SEQ ID NO:2 , selected from the group consisting of:a) a TIMP-3 mutein having two or more pairs of mutations selected from the group consisting of K45N/V47T; K50N/V52T; P56N/G58T; H78N/Q80T; K94N/E96T; and D110N/K112T;b) a TIMP-3 mutein having one or more pairs of mutations selected from the group consisting of K45N/V47T; K50N/V52T; P56N/G58T; H78N/Q80T; K94N/E96T; and D110N/K112T; and an additional mutation that is selected from the group consisting of R138T; G173T, and both R138T and G173T; andc) the TIMP-3 mutein according to a) or b) that further comprises the mutation F57N.3. The TIMP-3 mutein of or , wherein mutations are selected from the group consisting of K45N , V47T , P56N , G58T , Q126N , R138T; K45N , V47T , P56N , G58T , K94N , E96T , R138T; K45N , V47T , P56N , G58T , R138T , G173T; K45N , V47T , F57N , K94N , E96T , ...

MODIFIED ANTI-INFLAMMATORY PROTEINS AND METHOD OF USE

A modified Ac-TMP-2 protein lacks one or a plurality of acidic C-terminal amino acids normally present in a full-length or wild-type Ac-TMP-2 protein and may also lack one or a plurality of N-terminal amino acids while retaining the amino acid sequence C-S-C at or near the N-terminus. The modified Ac-TMP-2 protein may be useful in method and composition for reducing or alleviating inflammation in a subject. Inflammation may be associated with a disease is a disease of the digestive tract such as chronic gastritis or an inflammatory bowel disease such as Crohn's disease or ulcerative colitis, or a disease of the respiratory system, such as asthma, emphysema, chronic bronchitis, and chronic obstructive pulmonary disease. 1. A modified Ac-TMP-2 protein which lacks one or a plurality of N- and/or C-terminal amino acids normally present in a full-length or wild-type Ac-TMP-2 protein , or a fragment , variant or derivative thereof.2. The modified Ac-TMP-2 protein claim 1 , fragment claim 1 , variant or derivative thereof of claim 1 , which also lacks a plurality of C-terminal amino acids normally present in a full-length or wild-type Ac-TMP-2 protein claim 1 , wherein the plurality of C-terminal amino acids includes one or a plurality of acidic amino acids.3. The modified Ac-TMP-2 protein claim 1 , fragment claim 1 , variant or derivative thereof of or claim 1 , which comprises the amino acid sequence C-X-C at or near the N-terminus.4. The modified Ac-TMP-2 protein claim 1 , fragment claim 1 , variant or derivative thereof of claim 1 , or claim 1 , comprising an amino acid sequence set forth in SEQ ID NO:1 claim 1 , SEQ ID NO:2 claim 1 , SEQ ID NO:4 claim 1 , SEQ ID NO:5 or an amino acid sequence at least 70% identical thereto.5. The modified Ac-TMP-2 protein of any preceding claim claim 1 , which is capable of preventing claim 1 , reducing and/or alleviating inflammation upon administration to a subject.6. A pharmaceutical composition comprising a therapeutically ...

MMP-8 ACTIVATION PRODUCT, ITS DETERMINATION AND USE

The present invention relates to a novel MMP-8 activation product such as a MMP-8 middle-part activation product. The invention also relates to detecting such a MMP-8 activation product or activated MMP-8 fragments in a biological sample derived from a subject and to the use thereof for diagnosing diseases which relate to abnormal or elevated levels of activated MMP-8. 1. A method of treating a gynecological disease in a subject , the method comprising:obtaining a non-oral sample from the subject;determining matrix metalloproteinase-8 (MMP-8) activation in the non-oral sample by determining a level of a MMP-8 middle-part activation product from a middle region domain of the MMP-8 sequence, having a size between 10-35 kDa, and comprising SEQ ID NO: 1 and/or SEQ ID NO: 2, or a fragment of the MMP-8 middle-part activation product, in the non-oral sample, wherein the level of the MMP-8 middle-part activation product in the non-oral sample is an indicator of the level of active MMP-8 in the non-oral sample; the reference sample is derived from a subject or a patient group that does not have the gynecological disease, wherein the subject has the gynecological disease if the level of the MMP-8 middle-part activation product, or fragment thereof, is greater than the level of the MMP-8 middle-part activation product, or fragment thereof, in the reference sample; or', 'the reference sample is derived from a subject or a patient group that has the gynecological disease, wherein the subject has the gynecological disease if the level of the MMP-8 middle-part activation product, or fragment thereof, is about equal to or greater than the level of the MMP-8 middle-part activation product, or fragment thereof, detected in the reference sample; and, 'comparing the level of the MMP-8 middle-part activation product, or fragment thereof, to the MMP-8 middle-part activation product, or fragment thereof, in a reference sample wherein'}treating the subject in need for the gynecological ...

VARIANTS OF TISSUE INHIBITOR OF METALLOPROTEINASE TYPE THREE (TIMP-3), COMPOSITIONS AND METHODS

There are disclosed TIMP-3 muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them. 112.-. (canceled)13. A method of treating a condition in which matrix metalloproteases (MMPs) and/or other proteinases that are inhibited or inhibitable by Tissue Inhibitor of Metalloproteinase Type Three (TIMP-3) play a causative or exacerbating role , comprising administering to an individual afflicted with such a condition an amount of a composition comprising a TIMP-3 mutein sufficient to treat the condition , wherein the TIMP-3 mutein comprises a mature region that is at least 90% identical in amino acid sequence to the mature region of TIMP-3 set forth in SEQ ID NO:2 and:(a) two or more pairs of mutations selected from K45N/V47T; K50N/V52T; P56N/G58T; H78N/Q80T; K94N/E96T; or D110N/K112T;(b) one or more pairs of mutations selected from K45N/V47T; K50N/V52T; P56N/G58T; H78N/Q80T; K94N/E96T; or D110N/K112T; and an additional mutation selected from R138T; G173T, or both R138T and G173T; or(c) the mutations of (a) or (b) further comprising the mutation F57N.1413. The method of , wherein the condition is an inflammatory conditions , osteoarthritis , myocardial ischemia , reperfusion injury , or progression to congestive heart failure.15. The method of claim 13 , wherein the condition is asthma claim 13 , chronic obstructive pulmonary disease (COPD) claim 13 , idiopathic pulmonary fibrosis (IPF) claim 13 , inflammatory bowel disease claim 13 , psoriasis claim 13 , myocarditis claim 13 , inflammation related to atherosclerosis claim 13 , or an arthritic conditions.16. The method of claim 13 , wherein the condition is rheumatoid arthritis claim 13 , psoriatic arthritis claim 13 , viral myocarditis claim 13 , dystrophic epidermolysis bullosa claim 13 , osteoarthritis claim 13 , pseudogout claim 13 , rheumatoid arthritis claim 13 , juvenile rheumatoid arthritis claim 13 , ankylosing spondylitis claim 13 , periodontal disease claim 13 , ...

Variants of tissue inhibitor of metalloproteinase type three (timp-3), compositions and methods

There are disclosed TIMP-3 muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them.

USE OF METALLOPROTEINASE INHIBITORS AGAINST BACTERIAL INFECTIONS

A composition comprising as components a polypeptide IMPIα (including wild type) and/or a polypeptide IMPIα-fusion and at least one antibiotic compound, in particular an aminoglycoside antibiotic, and/or at least one bactericidal compound, wherein the polypeptides, the at least one antibiotic and the at least one bactericidal compound is present in the composition in concentrations which exhibit in combination a synergistic effect against resistant bacteria. 1. A composition comprising: (i) a polypeptide IMPIα , a polypeptide IMPIα-fusion , or both a polypeptide IMPIα and a polypeptide IMPIα-fusion; and (ii) at least one antibiotic compound , in particular an aminoglycoside antibiotic , at least one bactericidal compound , or both at least one antibiotic compound and at least one bactericidal compound , wherein the polypeptides , the at least one antibiotic and the at least one bactericidal compound , when present are in concentrations which exhibit in combination a synergistic effect against resistant bacteria.2. The composition of claim 1 , wherein the IMPIα is a polypeptide having at least 70% claim 1 , optionally at least 80% claim 1 , optionally at least 90% or optionally at least 95% homology to the polypeptide of SEQ ID NO:2 claim 1 , or is the polypeptide of SEQ ID NO:2.3. The composition of claim 1 , wherein the polypeptide is selected from the group of SEQ ID NOs: 10 claim 1 , 18 claim 1 , 20 claim 1 , 22 claim 1 , 24 claim 1 , 26 claim 1 , 28 claim 1 , 30 claim 1 , 32 claim 1 , 34 claim 1 , 36 claim 1 , 38 claim 1 , 40 claim 1 , 42 claim 1 , 44 claim 1 , 46 claim 1 , 48 claim 1 , 50 claim 1 , 52 claim 1 , 54 claim 1 , 56 claim 1 , 58 claim 1 , 60 claim 1 , 62 claim 1 , 64 claim 1 , 66 claim 1 , 68 claim 1 , 70 claim 1 , 72 claim 1 , 74 claim 1 , 76 claim 1 , 78 claim 1 , 80 claim 1 , 82 claim 1 , 84 claim 1 , and IMPIα-fusions claim 1 , having the amino acid sequences of SEQ ID NOs: 6 claim 1 , 8 claim 1 , 12 claim 1 , 86 claim 1 , 88 claim 1 , 90 claim 1 ...

TIMP3 AS VEGF INHIBITOR

Polypeptides or proteins comprising tissue inhibitor of mettaloproteinases-3 (TIMP3) or variants of TIMP3 can be used to substantially inhibit vascular endothelial growth factor (VEGF) binding to VEGF receptor-2 (VEGFR2/KDR/Flk-1)) without substantially inhibiting VEGF binding to VEGF receptor 1 (VEGFR1/Flt-1). 1. A purified polypeptide comprising SEQ ID NO: 9; wherein said polypeptide inhibits the binding of VEGF to VEGFR2 (KDR/Flk1) without substantially inhibiting the binding of VEGF to VEGFR1 (Flt1).23-. (canceled)4. The polypeptide of being free of mettaloproteinase inhibiting activity.5. The polypeptide of claim 1 , being linked to a therapeutic agent.6. The polypeptide of claim 5 , the therapeutic agent being at least one of a chemotherapeutic agent claim 5 , a radiotherapeutic agent claim 5 , cytotoxic agent claim 5 , anti-angiogenic agent claim 5 , coagulent claim 5 , or anti-tubulin drug.78-. (canceled)9. The polypeptide of claim 1 , being a fusion protein.10. The polypeptide of being capable of inhibiting the proliferation of vascular endothelial cells mediated by VEGF.11. The polypeptide of claim 1 , wherein said polypeptide is capable of inhibiting angiogensis mediated by VEGF.12. A pharmaceutical composition comprising the polypeptide of and a pharmaceutically acceptable carrier.13. A therapeutic kit comprising the pharmaceutical composition of .1421-. (canceled)22. A method of targeting or delivering at least one diagnostic agent or therapeutic agent to cells expressing VEGFR2 (KDR/Flk1) claim 12 , the method comprising linking the at least one diagnostic agent or therapeutic agent to a polypeptide comprising at least a portion of the C-terminal domain of TIMP3 claim 12 , the at least portion of the C-terminal domain of TIMP3 comprising SEQ ID NO: 9.23. (canceled)24. The method of claim 22 , the therapeutic agent comprising at least one of chemotherapeutic agent claim 22 , a radiotherapeutic agent claim 22 , cytotoxic agent claim 22 , anti-angiogenic ...

INSECT METALLOPROTEINASE INHIBITORS

A polypeptide having at least 70% homology, in particular 80%, 90% or 95% homology to the polypeptide of SEQ ID NO:2 representing the wild-type of the protein insect metalloproteinase inhibitor IMPIα and having at least one mutation at position 35, 36 and/or 39 of the amino acid sequence of IMPIα and the polypeptide having an ICvalue to thermolysine of less than the ICvalue of IMPIα wherein 1. A polypeptide having at least 70% homology , in particular 80% , 90% or 95% homology to the polypeptide of SEQ ID NO: 2 representing the wild-type of the protein insect metalloproteinase inhibitor IMPIα and having at least one mutation at position 35 , 36 and/or 39 of the amino acid sequence of IMPIα and the polypeptide having an ICvalue to thermolysine of less than the ICvalue of IMPIα whereinthe nonpolar amino acid isoleucine at position 35 of IMPIα is replaced either by a nonpolar amino acid selected from the group consisting of leucine, methionine and phenylalanine or by polar amino acid selected from the group consisting of cysteine, asparagine, glutamine, histidine, lysine and arginine; and/orthe nonpolar amino acid isoleucine at position 36 of IMPIα is replaced either by a nonpolar amino acid selected from the group consisting of valine, phenylalanine and tryptophan or by polar amino acid selected from the group consisting of tyrosine, serine, threonine, asparagine, glutamine, histidine, lysine and arginine; and/orthe polar amino acid position 39 of IMPIα is replaced either by the nonpolar amino acid valine or by the polar amino acids histidine or lysine.2. The polypeptide of having the amino acid sequences of SEQ ID NOs: 10 claim 1 , 18 claim 1 , 20 claim 1 , 22 claim 1 , 24 claim 1 , 26 claim 1 , 28 claim 1 , 30 claim 1 , 32 claim 1 , 34 claim 1 , 36 claim 1 , 38 claim 1 , 40 claim 1 , 42 claim 1 , 44 claim 1 , 46 claim 1 , 48 claim 1 , 50 claim 1 , 52 claim 1 , 54 claim 1 , 56 claim 1 , 58 claim 1 , 60 claim 1 , 62 claim 1 , 64 claim 1 , 66 claim 1 , 68 claim 1 , 70 ...

Modulation of timp1 and timp2 expression

Provided herein are compositions, methods and kits for modulating expression of target genes, particularly of tissue inhibitor of metalloproteinase 1 and of tissue inhibitor of metalloproteinase 2 (TIMP1 and TIMP2, respectively). The compositions, methods and kits may include nucleic acid molecules (for example, short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA) or short hairpin RNA (shRNA)) that modulate a gene encoding TIMP1 and TIMP2, for example, the gene encoding human TIMP1 and TIMP2. The composition and methods disclosed herein may also be used in treating conditions and disorders associated with TIMP1 and TIMP2 including fibrotic diseases and disorders including liver fibrosis, pulmonary fibrosis, peritoneal fibrosis and kidney fibrosis.

Amyloid beta-protein-specific production-inhibiting polypeptide

A primary object of the present invention is to develop a compound that specifically inhibits the production of Aβ protein and serves as an active ingredient of a drug to treat and/or prevent Alzheimer's disease. This object can be achieved by a polypeptide having the amino acid sequence represented by any one of SEQ ID NOs: 1, 13, 14, and 22, that binds to the N-terminal region of βCTF; a γ-secretase activity inhibitor containing the polypeptide; β-secretase activity inhibitor; Aβ protein production inhibitor; and an agent for treating and/or preventing Alzheimer's disease.

Compositions and methods for modifying activity of extracellular mmp-2

Provided are compositions and methods for inhibiting extracellular matrix metalloproteinase-2 (MMP-2) activity. Inhibition of extracellular MMP-2 activity can be useful for restricting extracellular matrix remodeling, tumor cell migration, cell invasion, and/or metastasis. The compositions comprise mutants of Tissue Inhibitor of Metalloproteinase-2 (TIMP-2), where the tyrosine at position 62, 90 and/or 165 has been substituted with a non-phosphorylatable amino acid or with a phosphomimetic of phosphorylated tyrosine, and/or anti-Src antibodies. The method comprises delivering to an extracellular region of a tissue, a composition comprising a TIMP-2 mutant and/or an anti-Src antibody.

Novel il-15 prodrugs and methods of use thereof

Provided herein are IL-15 cytokine prodrugs and methods of making and using thereof.

METHODS AND COMPOSITIONS FOR INHIBITING CANCER CELL GROWTH

Described are methods and compositions that provide for generating synthetic or recombinant proline rich peptides. In some aspects, p1978 compositions are used to inhibit breast cancer cell growth and thus provided is a method for treating and preventing breast cancer cell growth in a mammal. 1. A recombinant polypeptide comprising the p1978 amino acid coding sequence.2. The polypeptide of claim 1 , wherein the polypeptide is a fusion protein comprising the p1978 coding sequence and a heterologous polypeptide sequence.3. The polypeptide of claim 1 , wherein the polypeptide is no more than 50 amino acids in length.4. The polypeptide of claim 1 , wherein the polypeptide is no more than 20 amino acids in length.5. The polypeptide of claim 1 , wherein the N-terminus claim 1 , the C-terminus or both are blocked.6. A synthetic polypeptide comprising a p1978 amino acid coding sequence according to .7. A composition comprising the polypeptide of .8. The composition of claim 7 , wherein composition is frozen or lyophilized.9. An isolated polynucleotide molecule comprising a nucleic acid sequence encoding the polypeptide of p1978.10. The polynucleotide molecule of claim 9 , wherein the nucleic acid sequence encoding the polypeptide is operably linked to a promoter.11. A host cell comprising a polynucleotide molecule of .12. A method of manufacturing a recombinant polypeptide comprising:{'claim-ref': {'@idref': 'CLM-00010', 'claim 10'}, '(a) expressing a polynucleotide molecule according to ; and'}(b) purifying the polypeptide from the cell.13. A method of treating or preventing a cancer in a subject comprising administering an effective amount of a composition comprising the polypeptide of .14. The method of claim 13 , wherein the cancer is a breast cancer.15. The method of claim 14 , wherein the breast cancer is triple negative breast cancer.16. The method of claim 13 , wherein the composition is administered by intravenous injection or catheter delivery.17. The method of ...

Recombinant dna expression vectors

The invention provides expression vectors containing the promoter, enhancer and substantially complete 5'-untranslated region including the first intron of the major immediate early gene of human cytomegalovirus. Further vectors including the hCMV-MIE DNA linked directly to the coding sequence of a heterologous gene are described. Host cells transfected with the vectors and a process for producing heterologous polypeptides using the vectors and the use of the hCMV-MIE DNA for expression of a heterologous gene are also included within the invention.

Recombinant DNA expression vectors

The invention provides expression vectors containing the promoter, enhancer and substantially complete 5'-untranslated region including the first intron of the major immediate early gene of human cytomegalovirus. Further vectors including the hCMV-MIE DNA linked directly to the coding sequence of a heterologous gene are described, Host cells transfected with the vectors and a process for producing heterologous polypeptides using the vectors and the use of the hCMV-MIE DNA for expression of a heterologous gene are also included within the invention.

Recombinant DNA expression vectors

The invention provides expression vectors containing the promoter, enhancer and substantially complete 5'-untranslated region including the first intron of the major immediate early gene of human cytomegalovirus. Further vectors including the hCMV-MIE DNA linked directly to the coding sequence of a heterologous gene are described. Host cells transfected with the vectors and a process for producing heterologous polypeptides using the vectors and the use of the hCMV-MIE DNA for expression of a heterologous gene are also included within the invention.

Application of protein hydrolysates for stabilisation of detergent compositions of metalloprotease

FIELD: biotechnologies. SUBSTANCE: composition of neutral metalloprotease stabilised with an inhibitor is proposed to produce a liquid detergent solution. The composition contains from approximately 0.001% to approximately 10% wt of neutral metalloprotease and a competitive inhibitor. Besides, the competitive inhibitor represents a protein hydrolysate and is connected with at least approximately 90% of molecules of the specified neutral metalloprotease. Also the method is proposed to produce a composition of neutral metalloprotease stabilised with an inhibitor. The mixture is incubated, which contains at least one neutral metalloprotease and a protein substrate, in the water buffer at pH in the range from approximately 6.5 to approximately 11 and at the temperature from approximately 22°C to approximately 37°C. In process of incubation the substrate protein is split when exposed to metalloprotease, which results in formation of the hydrolysis product. The hydrolysis product is extracted with molecular weight of less than approximately 5000 Da and combined with neutral metalloprotease. EFFECT: higher stability of detergent compositions during storage without reduction of desired activity of neutral metalloprotease in process of application. 12 cl, 3 dwg, 5 tbl, 3 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 484 138 (13) C2 (51) МПК C12N C11D C11D 9/96 (2006.01) 3/38 (2006.01) 3/386 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2009144091/10, 23.04.2008 (24) Дата начала отсчета срока действия патента: 23.04.2008 (72) Автор(ы): ЛИ Санг-Киу (US), ВИНЕЦКИ Дебора С. (US) (43) Дата публикации заявки: 10.06.2011 Бюл. № 16 2 4 8 4 1 3 8 (45) Опубликовано: 10.06.2013 Бюл. № 16 2 4 8 4 1 3 8 R U (85) Дата начала рассмотрения заявки PCT на национальной фазе: 30.11.2009 C 2 C 2 (56) Список документов, цитированных в отчете о поиске: WO 2007044993 А2, 19.04.2007. KAMMOUN R. ET AL. Protein size distribution and ...

A novel expression vector which produces water soluble protein

본 발명은 라이실-tRNA 합성효소의 구조 및 발현 특성을 이용하여 이와 융합한 외래 단백질을 수용성 형태로 생산할 수 있는 새로운 발현 플라스미드 및 이를 이용하여 외래 단백질을 대장균에서 효과적으로 제조하는 방법에 관한 것으로서, 본 발명의 방법을 이용하면 활성이 있는 외래 단백질을 용이하게 대량 생산할 수 있어 산업적으로 널리 이용될 수 있다. The present invention relates to a novel expression plasmid capable of producing an exogenous protein fused with the lysyl-tRNA synthetase using the structure and expression characteristics of the lysyl-tRNA synthetase, and a method for efficiently producing an exogenous protein in E. coli using the expression plasmid. By using the method of the present invention, an active foreign protein can be mass-produced easily and can be widely used in industry.

Genetically modified umbilical mesenchymal stem cell, preparation method and application

本发明公开了一种基因修饰的脐间充质干细胞、制备方法及应用，包括以下步骤：步骤1：将hTIMP2基因连接到腺相关病毒载体AAV8上，得到AAV‑hTIMP2；步骤2：将脐带间充质干细胞(hUB‑MSCs)接种至培养皿中培养，hUB‑MSCs感染AAV‑hTIMP2，得到hTIMP2基因修饰的hUB‑MSCs；步骤3：将基因修饰的hUB‑MSCs进行传代扩增至P4，即得所需基因修饰的脐带间充质干细胞；本发明构建的基因修饰的脐带间充质干细胞仍保留了干细胞的特性，如表面标志物的表达情况、三分化能力等，而且同时分泌TIMP2蛋白；有望用于制备治疗AD药物。

The purposes of protein hydrolysates to stabilize metalloprotease detergent formulations

本发明提供了包含金属蛋白酶和蛋白质水解产物抑制剂的组合物和制剂，其展示出升高的储存稳定性。在一个实施方案中，本发明提供了包含至少一种金属蛋白酶(例如，芽孢杆菌属中性金属蛋白酶)的液体洗涤剂制剂，其中所述至少一种金属蛋白酶通过在该洗涤剂制剂中包含的蛋白质水解产物来稳定。本发明也提供了通过用金属蛋白酶消化蛋白质底物来制备用于稳定洗涤剂制剂的蛋白质水解产物的方法。

COMPOSITIONS FOR ANTIFIBRINOLYTIC TREATMENT

1. Применение нейтрализующего антитела к матриксной металлопротеиназе-10 (ММР-10) для приготовления лекарственного средства, которое можно применять для антифибринолитического лечения. ! 2. Применение по п.1 для приготовления лекарственного средства, которое можно применять для лечения кровотечений и геморрагических осложнений. ! 3. Применение по п.2 для приготовления лекарственного средства, предназначенного для лечения кровотечений и геморрагических осложнений у пациентов с гиперфибринолитическими состояниями, обусловленными врожденными патологиями. ! 4. Применение по п.2 для приготовления лекарственного средства, предназначенного для лечения кровотечений и геморрагических осложнений у пациентов, подвергающихся лечению с помощью антикоагулянтов. ! 5. Применение по п.2 для приготовления лекарственного средства, предназначенного для лечения кровотечений и геморрагических осложнений у пациентов с диссеминированным внутрисосудистым свертыванием крови. ! 6. Применение по п.2 для приготовления лекарственного средства, предназначенного для лечения кровотечений и геморрагических осложнений, обусловленных хирургическими процедурами. ! 7. Применение по п.2 для приготовления лекарственного средства, применяемого в качестве альтернативы трансфузии крови при остром кровотечении. РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2010 102 090 (13) A (51) МПК A61K 39/39 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2010102090/15, 26.06.2008 (71) Заявитель(и): ПРОЙЕКТО ДЕ БИОМЕДИСИНА СИМА, С.Л. (ES) Приоритет(ы): (30) Конвенционный приоритет: 26.06.2007 ES P200701786 A Адрес для переписки: 101000, Москва, М.Златоустинский пер., 10, кв.15, "ЕВРОМАРКПАТ", пат.пов. И.А.Веселицкой, рег.№ 0011 R U (57) Формула изобретения 1. Применение нейтрализующего антитела к матриксной металлопротеиназе-10 (ММР-10) для приготовления лекарственного средства, которое можно применять для антифибринолитического лечения. 2. ...

Use of protein hydrolysates to stabilize metalloprotease detergent formulations

The present invention provides compositions and formulations comprising metalloprotease enzymes and protein hydrolysate inhibitors that exhibit increased storage stability. In one embodiment, the present invention provides liquid detergent formulations comprising at least one metalloprotease (e.g., Bacillus sp. neutral metalloprotease) that is stabilized by the inclusion of a protein hydrolysate in the detergent formulation. The invention also provides a method for making a protein hydrolysate for stabilizing a detergent formulation by digesting a protein substrate with a metalloprotease enzyme.

Use of protein hydrolysates to stabilize metalloprotease detergent formulations

본 발명은 증가된 보관 안정성을 보여주는 메탈로프로테아제 효소 및 단백질 가수분해물 억제제를 포함하는 조성물 및 제제를 제공한다. 한 구현예에서, 본 발명은 세제 제제에 단백질 가수분해물을 포함하여 안정화된, 하나 이상의 메탈로프로테아제 (예를 들어, 바실러스 sp. 중성 메탈로프로테아제) 를 포함하는 액체 세제 제제를 제공한다. 본 발명은 또한, 메탈로프로테아제 효소를 사용해 단백질 기질을 분해함으로써 세제 제제를 안정화시키기 위한 단백질 가수분해물의 제조 방법을 제공한다. 메탈로프로테아제 The present invention provides compositions and formulations comprising a metalloprotease enzyme and a protein hydrolyzate inhibitor exhibiting increased storage stability. In one embodiment, the present invention provides a liquid detergent formulation comprising one or more metalloproteases (e.g., Bacillus sp. Neutral metalloprotease) stabilized with a protein hydrolyzate in a detergent formulation. The present invention also provides a method for producing a protein hydrolyzate for stabilizing a detergent formulation by decomposing a protein substrate using a metalloprotease enzyme. Metalloprotease

Compositions for antifibrinolytic treatment

FIELD: medicine. SUBSTANCE: invention refers to medicine, particularly to applying a neutralising antibody to matrix metalloproteinase-10 (MMP-10) for preparing a drug applicable for antifibrinolytic therapy and treating bleedings and hemorrhagic complications of various aetiology: hyperfibrinolytic conditions caused by congenital pathologies, anticoagulant therapy, surgical procedures. EFFECT: invention provides higher selectivity of inhibitors which block molecular mechanisms associated with specific matrix metalloproteinases that allows avoiding undesired events. 7 cl, 4 ex, 2 tbl РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) 2 453 337 (13) C2 (51) МПК A61K 39/395 (2006.01) A61P 7/04 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (21)(22) Заявка: 2010102090/15, 26.06.2008 (24) Дата начала отсчета срока действия патента: 26.06.2008 (56) Список документов, цитированных в отчете о поиске: US 5922322 А, 13.07.1999. ЕР 1060747 А2, 20.12.2000. RU 2250105 С2, 20.04.2005. RU 2293730 С2, 20.02.2007. 2 4 5 3 3 3 7 R U (86) Заявка PCT: ES 2008/000453 (26.06.2008) C 2 C 2 (85) Дата начала рассмотрения заявки PCT на национальной фазе: 26.01.2010 (87) Публикация заявки РСТ: WO 2009/000957 (31.12.2008) Адрес для переписки: 105082, Москва, Спартаковский пер., 2, стр.1, секция 1, этаж 3, "ЕВРОМАРКПАТ" (54) КОМПОЗИЦИИ ДЛЯ АНТИФИБРИНОЛИТИЧЕСКОГО ЛЕЧЕНИЯ (57) Реферат: Изобретение относится к медицине, в частности к применению нейтрализующего антитела, к матриксной металлопротеиназе-10 (ММР-10) для приготовления лекарственного средства, которое можно применять для антифибринолитического лечения и лечения кровотечений и геморрагических осложнений различной этиологии: гиперфибринолитические состояния, обусловленные врожденными патологиями; лечение с помощью антикоагулянтов; хирургические процедуры. Изобретение обеспечивает большую избирательность ингибиторов, которые блокируют молекулярные механизмы, ассоциированные с конкретными матриксными ...

Novel il-15 prodrugs and methods of use thereof

Provided herein are IL-15 cytokine prodrugs and methods of making and using thereof.

Modified peptides as therapeutic agents

The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.

Metalloproteinase inhibitor

DNA FRAGMENT, PLASMID VECTOR, METHOD FOR PREPARING POLYPEPTIDE AND POLYPEPTIDE ELICITING IL-1β PROTEASE ACTIVITY

FIELD: molecular biology, genetic engineering, biochemistry. SUBSTANCE: invention relates to preparing biologically active IL-1β protease by technology of recombinant DNAs and can be used in medicine. DNA sequence encoding the complete amino acid sequence (precursor) of IL-1β is isolated where region encoding "mature" form of enzyme is identified. As result of expression of indicated DNA sequences in cultured mammalian cells the biologically active IL-1β protease is synthesized that is able to cleave inactive precursor of IL-1β at position between 116 and 117 amino acid residues to form active cytokine. EFFECT: improved preparing method, valuable properties of polypeptide. 5 cl, 7 dwg, 2 tbl, 5 ex па (19) ВИ "” 2 206 611” С2 50 МК’ С 12 М 15/57, 9/64, С 12Р 21/02 РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 94028712/13, 12.09.1991 (71) Заявитель: ВЕРТЕКС ФАРМАСЬЮТИКАЛЗ (24) Дата начала действия патента: 12.09.1991 ИНКОРПОРЕЙТЕД (1$) (30) Приоритет: 30.08.1991 Ш$ 750,644 (72) Изобретатель: БЛЭК Рой А. (ЦЗ), СМИТ Паул Р. (4$), КРОНХЕЙМ Ширлей Р. (43) Дата публикации заявки: 10.03.1997 (0$) (46) Дата публикации: 20.06.2003 С 2 (73) Патентообладатель: ВЕРТЕКС ФАРМАСЬЮТИКАЛЗ (56) Ссылки: 1. К.А. ВЕАСК её| а!., РЕВЗ еНегс, ИНКОРПОРЕЙТЕД (ЦЗ) у. 247, №2, 386-390, 1989. 2. КА. ВШАСК Ее. а|., /. Во|1. Спет., м. 263, № 19, 9437-9442, 1988. 3. К.А. ВЕАСК в. а|., 4. Во. Спет., м. 264, № 10, 5323-5326, 1989. (74) Патентный поверенный: Лебедева Наталья Георгиевна (85) Дата перевода заявки РСТ на национальную фазу: 10.02.1994 (86) Заявка РСТ: 1$ 9106595 (12.09.1991) (87) Публикация РСТ: \М/О 93/05071 (18.03.1993) 2206611 (98) Адрес для переписки: 129010, Москва, ул. Б.Спасская, 25, стр.3, ООО "Юридическая фирма Городисский и Партнеры", пат.пов. Н.Г.Лебедевой, рег.№ 112 КО (54) ФРАГМЕНТ ДНК, ПЛАЗМИДНЫЙ ВЕКТОР, СПОСОБ ПОЛУЧЕНИЯ ПОЛИПЕПТИДА И ПОЛИПЕПТИД, ОБЛАДАЮЩИЙ 1-1Вв ПРОТЕАЗНОЙ АКТИВНОСТЬЮ ( ...

Unique T-lymphocyte line and products derived therefrom

Human T-lymphoblast cell line, Proteinaceous products produced therefrom, messenger RNA and DNA expressing the proteinaceous products. A human T-lymphoblast cell line (Mo) maintained as a continuous culture constitutively produces proteins, including immune interferon, neutrophil migration inhibition factor, granulocyte-macrophage colony-stimulating activity and erythroid-potentiating activity, as well as other proteins produced by T-cells.

Serum-free medium for tissue culture containing tissue inhibitor of metalloproteinases and method for growing cells using the medium

Provided are serum-free media for tissue culture containing tissue inhibitor of metalloproteinases and methods for culturing animal cells using these media.

Anti-adam-15 antibodies and utilization of the same

A remedy for cancer obtained from a different viewpoint from the viewpoints employed in developing the existing anticancer drugs, i.e., focusing on the intercellular adhesion of cancer cells. Namely, provided is a remedy for cancer with fewer side effects which inhibits the proliferation of cancer cells and the intercellular adhesion of cancer cells. Also provided is an antibody, which recognizes the disintegrin domain of ADAM-15 and is usable as an anticancer agent, and so on. An antibody, which recognizes the disintegrin domain of ADAM-15 but does not recognize the RGD sequence or loop region in the disintegrin domain of ADAM-15, and so on; an antibody, which inhibits ADAM-15 and integrin αvβ3-dependent cell adhesion, and so on; and an antibody, which inhibits ADAM-15 and integrin α9β1-dependent cell adhesion, and so on.

Polypeptides that bind tissue inhibitor of metalloproteinase type three (timp-3), compositions and methods

The present invention relates to TIMP-3 binding compositions, methods of producing such compositions, and methods of using such compositions, including in the treatment of various conditions.

Anti-adam-15 antibodies and utilization of the same

A remedy for cancer obtained from a different viewpoint from the viewpoints employed in developing the existing anticancer drugs, i.e., focusing on the intercellular adhesion of cancer cells. Namely, provided is a remedy for cancer with fewer side effects which inhibits the proliferation of cancer cells and the intercellular adhesion of cancer cells. Also provided is an antibody, which recognizes the disintegrin domain of ADAM-15 and is usable as an anticancer agent. An antibody, which recognizes the disintegrin domain of ADAM-15 but does not recognize the RGD sequence or loop region in the disintegrin domain of ADAM-15; an antibody, which inhibits ADAM-15 and integrin .alpha.v.beta.3-dependent cell adhesion; and an antibody, which inhibits ADAM-15 and integrin .alpha.9.beta.1-dependent cell adhesion.

Pepstatin

Inhibition of tumor growth and invasion by anti-matrix metalloproteinase dnazymes

The presently disclosed subject matter provides DNA molecules designed to down regulate the expression of MMP genes in a cell. Also provided are compositions comprising the DNA molecules. The presently disclosed subject matter further provides methods of using the DNA molecules to inhibit metastasis of a cancer cell. The presently disclosed subject matter also provides methods of using the DNA molecules to modulate tumor growth in a subject.

Modified peptides as therapeutic agents

The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.

Fusogenic polypeptide for inhibiting neovascularization and coding gene and application thereof

本发明公开了一种抑制新生血管生成的融合多肽及其编码基因与应用，该融合多肽是靶向性抑制金属基质蛋白酶的活性十肽、恩度的前25肽和人纤溶酶原的kringle 5结构域组成的三靶点多肽。细胞试验表明，该融合多肽可以有效的抑制内皮细胞的增殖、迁移，进而抑制新生血管的生成，从而可应用于制备治疗由新生血管增生异常产生的疾病的药物，并可用于肿瘤治疗。

Modified peptides as therapeutic agents

本发明涉及Fc区与生物活性肽的融合体和采用生物活性肽制备药物的方法。在本发明中，通过包括以下步骤的方法制备药理学活性化合物：a)选择至少一种调节目的蛋白活性的肽；和b)制备一种药理学因子，其包含共价连接于所述选定肽的至少一个氨基酸的至少一个Fc区。与载体的连接增加所述肽的半寿期，所述肽在其它情况下可能在体内快速降解。优选的载体是Fc区。所述肽最好通过噬菌体展示、大肠杆菌展示、核糖体展示、RNA－肽筛选或化学－肽筛选进行选择。

Therapeutic agents and methods of use thereof for the modulation of angiogenesis

The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.

Modified peptides, comprising an fc domain, as therapeutic agents

The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.

Inhibition of tumor growth and invasion by anti matrix metalloproteinase DNAzymes

The presently disclosed subject matter provides DNA molecules designed to down regulate the expression of MMP genes in a cell. Also provided are compositions comprising the DNA molecules. The presently disclosed subject matter further provides methods of using the DNA molecules to inhibit metastasis of a cancer cell. The presently disclosed subject matter also provides methods of using the DNA molecules to modulate tumor growth in a subject.

MMP-8 activating substance and determination and use of the substance

Modified peptides as therapeutic agents

The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.

Compositions for anti-fibrinolitic treatment

The present invention concerns the use of a neutralising antibody for matrix metalloproteinase-10 (MMP-10) in the preparation of a medicine useful for anti-fibrinolytic treatment, and for haemorrhages and haemorrhagic complications of various etiologies.

Interleukin-1 beta protease and interleukin-1 beta protease inhibitors

There is disclosed an isolated polypeptide and derivatives thereof having protease biological activity for human precursor IL=1.beta. and for a substrate comprising: R1-Asp-R2-R3 wherein R1 and R3 are independently any D or L isomer amino acid, R2 is Ala or Gly, and wherein the specific protease cleavage site is between Asp and R2. Inhibitor compounds; compositions and methods for inhibiting Interleukin 1.beta. protease activity are also disclosed. The inhibitor compounds comprise an amino acid sequence of from 1 to about 5 amino acids having an N-terminal blocking group and a C-terminal Asp residue connected to an electronegative leaving group, wherein the amino acid sequence corresponds to the sequence Ala-Tyr-Val-His-Asp.

Patent FR2052964B1

Patent FR2181710B1

Use of protein hydrolysates to stabilize metalloprotease detergent formulations

The present invention provides compositions and formulations comprising metalloprotease enzymes and protein hydrolysate inhibitors that exhibit increased storage stability. In one embodiment, the present invention provides liquid detergent formulations comprising at least one metalloprotease (e.g., Bacillus sp. neutral metalloprotease) that is stabilized by the inclusion of a protein hydrolysate in the detergent formulation. The invention also provides a method for making a protein hydrolysate for stabilizing a detergent formulation by digesting a protein substrate with a metalloprotease enzyme.

Process for the production of a protein

A process for producing a metalloproteinase inhibitor or a precursor thereof comprising culturing host cells trans­ formed with a vector including a gene coding for the metalloproteinase inhibitor or the precursor and, if appropri­ ate, cleaving the precursor to yield metalloproteinase inhibi­ tor. The precursor may be a premetalloproteinase inhibitor or a fusion protein comprising a heterologous protein and a metalloproteinase inhibitor. The metalloproteinase inhibitor has application as the effective component in a pharmaceu­ tical composition for the treatment of disease processes where accelerated breakdown of the extracellular organic matrix is observed.

Modulation of timp1 and timp2 expression

Provided herein are compositions, methods and kits for modulating expression of target genes, particularly of tissue inhibitor of metalloproteinase 1 and of tissue inhibitor of metalloproteinase 2 (TIMP1 and TIMP2, respectively). The compositions, methods and kits may include nucleic acid molecules (for example, short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA) or short hairpin RNA (shRNA)) that modulate a gene encoding TIMP1 and TIMP2, for example, the gene encoding human TIMP1 and TIMP2. The composition and methods disclosed herein may also be used in treating conditions and disorders associated with TIMP1 and TIMP2 including fibrotic diseases and disorders including liver fibrosis, pulmonary fibrosis, peritoneal fibrosis and kidney fibrosis.

Patent NO136204B

Fremgangsmåte for fremstilling av proteaseinhibitoren plasminostreptin.

Method for designing peptides

The present invention relates to genetic engineering and, in specific, to design, generation, and modification of recombinant peptides using a combination of phage display and intein-mediated protein cleavage reaction.

Mmp-8 activation product, its determination and use

The present invention relates to a novel MMP-8 activation product such as a MMP-8 middle-part activation product. The invention also relates to detecting such a MMP-8 activation product or activated MMP-8 fragments in a biological sample derived from a subject and to the use thereof for diagnosing diseases which relate to abnormal or elevated levels of activated MMP-8.

ANTI-AGING AND HEALING COMPOSITIONS

ÐÎÑÑÈÉÑÊÀß ÔÅÄÅÐÀÖÈß (19) RU (51) ÌÏÊ 7 (11) 2004 103 071 (13) A C 07 K 14/00, 14/50, C 12 N 9/99, A 61 K 38/55, A 61 P 17/00 ÔÅÄÅÐÀËÜÍÀß ÑËÓÆÁÀ ÏÎ ÈÍÒÅËËÅÊÒÓÀËÜÍÎÉ ÑÎÁÑÒÂÅÍÍÎÑÒÈ, ÏÀÒÅÍÒÀÌ È ÒÎÂÀÐÍÛÌ ÇÍÀÊÀÌ (12) ÇÀßÂÊÀ ÍÀ ÈÇÎÁÐÅÒÅÍÈÅ (21), (22) Çà âêà: 2004103071/13, 15.08.2002 (71) Çà âèòåëü(è): ÊÈÌÁÅÐËÈ-ÊËÀÐÊÂÎÐËÄÂÀÉÄ, ÈÍÊ. (US) (30) Ïðèîðèòåò: 16.08.2001 US 60/312,726 21.12.2001 US 10/032,376 21.05.2002 US 10/153,185 (85) Äàòà ïåðåâîäà çà âêè PCT íà íàöèîíàëüíóþ ôàçó: 16.03.2004 (74) Ïàòåíòíûé ïîâåðåííûé: Êâàøíèí Âàëåðèé Ïàâëîâè÷ (87) Ïóáëèêàöè PCT: WO 03/016520 (27.02.2003) Àäðåñ äë ïåðåïèñêè: 103064, Ìîñêâà, óë. Êàçàêîâà,16, ÍÈÈÐ Êàíöåë ðè "Ïàòåíòíûå ïîâåðåííûå Êâàøíèí, Ñà ïåëüíèêîâ è ïàðòíåðû", Â.Ï.Êâàøíèíó R U Ôîðìóëà èçîáðåòåíè 1. Ïåïòèä, ñîäåðæàùèé ïîñëåäîâàòåëüíîñòü íîìåð 1, ïîñëåäîâàòåëüíîñòü íîìåð 2, ïîñëåäîâàòåëüíîñòü íîìåð 3, ïîñëåäîâàòåëüíîñòü íîìåð 4, ïîñëåäîâàòåëüíîñòü íîìåð 5, ïîñëåäîâàòåëüíîñòü íîìåð 6, ïîñëåäîâàòåëüíîñòü íîìåð 7, ïîñëåäîâàòåëüíîñòü íîìåð 8, ïîñëåäîâàòåëüíîñòü íîìåð 9, ïîñëåäîâàòåëüíîñòü íîìåð 10, ïîñëåäîâàòåëüíîñòü íîìåð 11, ïîñëåäîâàòåëüíîñòü íîìåð 12, ïîñëåäîâàòåëüíîñòü íîìåð 13, ïîñëåäîâàòåëüíîñòü íîìåð 15, ïîñëåäîâàòåëüíîñòü íîìåð 16 èëè ïîñëåäîâàòåëüíîñòü íîìåð 17, ïðè÷åì ýòîò ïåïòèä ìîæåò èíãèáèðîâàòü ìàòðèêñíóþ ìåòàëëîïðîòåèíàçó-2 èëè ñòèìóëèðîâàòü êëåòî÷íóþ ïðîëèôåðàöèþ ôèáðîáëàñòîâ èëè êåðàòèíîöèòîâ. 2. Ïåïòèä ïî ï.1, ïðè÷åì óêàçàííûé ïåïòèä âë åòñ õåìîàòòðàêòàíòîì äë ôèáðîáëàñòîâ èëè êåðàòèíîöèòîâ. 3. Ïåïòèä ïî ï.1, ïðè÷åì óêàçàííûé ïåïòèä ìîæåò ñòèìóëèðîâàòü ïðîäóêöèþ êîëëàãåíà â ôèáðîáëàñòàõ. 4. Êîìïîçèöè , ñîäåðæàùà òåðàïåâòè÷åñêè ýôôåêòèâíîå êîëè÷åñòâî ïåïòèäà ôîðìóëû I è ôàðìàöåâòè÷åñêè ïðèåìëåìûé íîñèòåëü: ãäå Xaa1, Xaa4 è Xaa6 íåçàâèñèìî äðóã îò äðóãà îáîçíà÷àþò íåïîë ðíûå àìèíîêèñëîòû; Xaa2 âë åòñ îñíîâíîé àìèíîêèñëîòîé; Xaa3 âë åòñ öèñòåèíî-ïîäîáíîé àìèíîêèñëîòîé; Xaa5 âë åòñ ïîë ðíîé èëè àëèôàòè÷åñêîé àìèíîêèñëîòîé; Xaa7 âë åòñ êèñëîé àìèíîêèñëîòîé; Ñòðàíèöà: 1 RU A 2 0 0 4 1 0 3 0 7 1 A (54) ...

Multifunctional protease inhibitors and their use in treatment of disease

The present invention provides a fusion protein comprising a first protease inhibitor comprising alpha 1-antitrypsin or a functionally active portion thereof, and a second protease inhibitor or a functionally active portion thereof.

Compositions and methods for modifying activity of extracellular mmp-2

Provided are compositions and methods for inhibiting extracellular matrix metalloproteinase-2 (MMP-2) activity. Inhibition of extracellular MMP-2 activity can be useful for restricting extracellular matrix remodeling, tumor cell migration, cell invasion, and/or metastasis. The compositions comprise mutants of Tissue Inhibitor of Metalloproteinase-2 (TIMP-2), where the tyrosine at position 62, 90 and/or 165 has been substituted with a non-phosphorylatable amino acid or with a phosphomimetic of phosphorylated tyrosine, and/or anti-Src antibodies. The method comprises delivering to an extracellular region of a tissue, a composition comprising a TIMP-2 mutant and/or an anti-Src antibody.

Pepstatin

Variants of tissue inhibitor of metalloproteinase type three (TIMP-3), compositions and methods

Abstract There are disclosed TIMP-3 muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them.

Multifunctional protease inhibitors and their use in treatment of disease

Fusion proteins of protease inhibitors are provided, in particular fusion proteins of alpha 1-antitrypsin (AAT) and a second protease inhibitor, such as secretory leukocyte protease inhibitor (SLPI) or tissue inhibitor of metalloproteases (TIMP). Polynucleotides encoding the fusion proteins, vectors comprising such polynucleotides, and host cells containing such vectors are also provided. Methods of making the fusion proteins of the invention are also provide, as well as methods of using the fusion proteins, for example to inhibit protease activity in a biological sample or in the treatment of an individual suffering from, or at risk for, a disease or disorder involving unwanted protease activity.

Therapeutic agents and methods of use thereof for the modulation of angiogenesis

The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.

Interleukin-1b proteas and inhibitors of interleukin-1b proteas

Modified peptides as therapeutic agents

The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.

COMPOSITIONS AND METHODS OF TISSUE INHIBITOR VARIANTS OF METALOPROTEINASE TYPE THREE (TIMP 3)

Se describen muteinas TIMP-3, variantes y derivados, los acidos nucleicos que las codifican, y los metodos de fabricacion y uso de ellos

Patent FR2181710A1

MULTIFUNCTIONAL PROTEASE INHIBITORS AND THEIR USE FOR THE TREATMENT OF DISEASES

Use of metalloproteinase inhibitors against bacterial infections

A composition comprising as components a polypeptide IMPIa (including wild type) and/or a polypeptide IMPIa-fusion and at least one antibiotic compound, in particular an aminoglycoside antibiotic, and/or at least one bactericidal compound, wherein the polypeptides, the at least one antibiotic and the at least one bactericidal compound is present in the composition in concentrations which exhibit in combination a synergistic effect against resistant bacteria.

Methionine aminopeptidase-2 inhibitors and methods of use thereof

The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or mo re of the angiogenesis inhibitor compounds of the invention.

Interleukin-1 beta protease and interleukin-1 beta protease¹inhibitors

There is disclosed an isolated polypeptide and derivatives thereof having protease biological activity for human precursor IL-1 beta and for a substrate comprising : R1-Asp-R2-R3 wherein R1 and R3 are independently any D or L isomer amino acid, R2 is Ala or Gly, and wherein the specific protease cleavage site is between Asp and R2. Inhibitor compounds, compositions and methods for inhibiting Interleukin 1 beta protease activity are also disclosed. The inhibitor compounds comprise an amino acid sequence of from 1 to about 5 amino acids having an N-terminal blocking group and a C-terminal Asp residue connected to an electronegative leaving group, wherein the amino acid sequence corresponds to the sequence Ala-Tyr-Val-His-Asp.

Recombinant Vector Containing ptsL Promoter and Method for Producing Exogeneous Proteins Using the Same

본 발명은 대장균 유래 ptsL 프로모터를 함유하는 재조합벡터 및 이를 이용한 외래 단백질의 생산방법에 관한 것으로, 보다 구체적으로는 대장균 유래 ptsL 프로모터 및 외래 단백질을 코딩하는 유전자를 함유하는 재조합벡터가 도입된 형질전환체를 이용하여 외래 단백질을 세포 성장 정지기에 선택적으로 발현시키는 방법에 관한 것이다. The present invention relates to a recombinant vector containing an E. coli-derived ptsL promoter and a method for producing a foreign protein using the same, and more specifically, a transformant into which a recombinant vector containing a E. coli-derived ptsL promoter and a gene encoding a foreign protein is introduced. It relates to a method for selectively expressing foreign proteins in the cell growth arrester using. 본 발명에 따르면 성장 정지기에 자동 발현되는 ptsL 프로모터를 이용하여 외래 단백질이나 펩타이드를 성장 정지기에 효율적으로 발현시킬 수 있고, 특정 유도체 없이 성장기에 따라 자동으로 발현되므로 경제적이며, 고농도 배양에서의 낮은 발현 효율 문제를 해결하는데 유용하다. According to the present invention, the foreign protein or peptide can be efficiently expressed at the growth stop phase by using the ptsL promoter, which is automatically expressed at the growth stop phase, and it is economical because it is automatically expressed according to the growth phase without a specific derivative, and the expression efficiency in high concentration culture is low. This is useful for solving problems. ptsL 프로모터, 성장 정지기 발현, 발현 억제 단백질, 유해 단백질, 항미생물 펩타이드 ptsL promoter, growth arrestor expression, expression inhibitory proteins, harmful proteins, antimicrobial peptides

A composition of compound comprising modified peptides as therapeutic agents and process for preparing this compound

본 발명은 생물학적으로 활성인 펩티드와 Fc 도메인과의 융합 및 생물학적으로 활성인 펩티드를 사용하여 제약학적 제제를 제조하는 방법에 관한 것이다. 본 발명에 있어서, 약리학적으로 활성인 화합물은 다음 단계를 포함하는 방법에 의하여 제조된다 : a) 목적 단백질의 활성을 조절하는 적어도 하나의 펩티드를 선택하는 단계 ; 및 b) 적어도 하나의 선택된 펩티드의 아미노산에 Fc 도메인을 공유 결합함을 포함하는 약리학적 제제를 제조하는 단계. 본 발명의 화합물은 매개체와 결합하여 생체내에서 빠르게 분해되지 않도록 펩티드의 반감기를 증가시킨다. 바람직한 매개체는 Fc 도메인이다. 펩티드는 바람직하게, 파지 디스플레이, E. coli 디스플레이, 리보솜 디스플레이, RNA-펩티드 스크리닝 또는 화학적-펩티드 스크리닝에 의해 선택된다. Fc 도메인 융합, 파지 디스플레이, 유사 펩티드, 길항 펩티드, TPO, EPO

POLYEPEPTIDE, PROTEASE, DNA, VECTOR, METHOD FOR PRODUCING PROTEASE, COMPOUNDS, COMPOSITIONS, METHOD FOR INHIBITING ACTIVITY, METHOD OF TREATMENT

РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) 77 (11) | ‚ к щх(13) САМ МА ЗУ А АТА ЗА 6 МК’ С 07К 7/06, С 12 М 15/25, 9/50, А 61 К 38/04, А 61Р 37/00 2 2 # ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ, ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (12 ИЗВЕЩЕНИЯ К ЗАЯВКЕ НА ИЗОБРЕТЕНИЕ (21), (22) Заявка: 2002128757/13, 25.10.2002 (71) Заявитель(и): ВЕРТЕКС ФАРМАСЬЮТИКАЛЗ (30) Приоритет: 30.08.1991 ЦЗ 750,644 ИНКОРПОРЕЙТЕД (45$) (43) Дата публикации заявки: 27.07.2004 (72) Автор(ы): БЛЭК Рой А. (15), СМИТ Паул Р. (1$), КРОНХЕЙМ Ширлей Р. (ЦЗ) Адрес для переписки: 129010, Москва, ул. Б.Спасская, 25, стр.3, ООО "Юридическая фирма Городисский и Партнеры", пат.пов. Г.Б. Егоровой (74) Патентный поверенный: Егорова Галина Борисовна па (54) ПОЛИПЕПТИД, ПРОТЕАЗА, ДНК, ВЕКТОР, СПОСОБ ПОЛУЧЕНИЯ ПРОТЕАЗЫ, СОЕДИНЕНИЯ, КОМПОЗИЦИИ, СПОСОБ ИНГИБИРОВАНИЯ АКТИВНОСТИ, СПОСОБ ЛЕЧЕНИЯ ГАЗА - Признание заявок на изобретение отозванными в связи с непредставлением в установленный срок ходатайства о проведении экспертизы заявки по существу А 2002128757 ко (51) С07К Дата отзыва заявки: 15.11.2005 Извещение опубликовано: 27.12.2005 БИ: 36/2005 Страница: 1 4918 с1С00Сс А"

Metalloproteinase inhibitor sequence recombinant vector system for using same and recombinant-dna method for the manufacture of same.

Séquence d'ADN portable pouvant réguler la production intracellulaire d'inhibiteurs de métalloprotéinase. Sont également décrits des vecteurs contenant cette séquence d'ADN portable, comprenant le vecteur pUC9-F5/237P10. Procédé de production microbienne d'un inhibiteur de métalloprotéinase grâce à l'ADN recombinant, ce procédé utilisant au moins l'une des séquences d'ADN et les vecteurs ci-décrits. Portable DNA sequence capable of regulating intracellular production of metalloproteinase inhibitors. Also described are vectors containing this portable DNA sequence, comprising the vector pUC9-F5 / 237P10. Process for the microbial production of a metalloproteinase inhibitor using recombinant DNA, this process using at least one of the DNA sequences and the vectors described above.

Recombinant DNA processes for the production of tissue inhibitor of metalloproteinase

Modified peptides as therapeutic agents

The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by selecting a peptide that modulates the activity of a protein of interest and preparing a pharmacologic agent having an Fc domain covalently linked to the peptide. Linkage to the Fc domain increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The peptide can be selected, for example, by phage display, E. coli display, ribosome display, RNA-peptide screening, yeast-based screening, chemical-peptide screening, rational design, or protein structural analysis.

Anti-ADAM-15 antibody and use thereof

【課題】これまでの抗癌剤開発の観点と異なる観点、即ち、癌細胞の細胞−細胞間接着に焦点を当てた癌の治療薬を提供することを目的とする。即ち、本発明は、癌細胞の増殖、及び、癌細胞の細胞−細胞間接着を抑制する、副作用が低減された癌の治療薬を提供することを目的とする。また、本発明は、ＡＤＡＭ−１５のディスインテグリンドメインを認識し、抗癌剤として利用可能な抗体等を提供することを目的とする。【解決手段】ＡＤＡＭ−１５のディスインテグリンドメインを認識し、かつ、ＡＤＡＭ−１５のディスインテグリンドメイン内のＲＧＤ配列又はループ領域を認識しない抗体等ＡＤＡＭ−１５及びインテグリンαｖβ３依存性細胞接着を阻害する抗体等、ＡＤＡＭ−１５及びインテグリンα９β１依存性細胞接着を阻害する抗体等。【選択図】なし An object of the present invention is to provide a therapeutic drug for cancer that focuses on a different aspect from the conventional development of anticancer drugs, that is, cell-cell adhesion of cancer cells. That is, an object of the present invention is to provide a therapeutic agent for cancer with reduced side effects, which suppresses proliferation of cancer cells and cell-cell adhesion of cancer cells. Another object of the present invention is to provide an antibody that recognizes the disintegrin domain of ADAM-15 and can be used as an anticancer agent. An antibody that recognizes the disintegrin domain of ADAM-15 and that does not recognize an RGD sequence or loop region in the disintegrin domain of ADAM-15, such as an antibody that inhibits ADAM-15 and integrin αvβ3-dependent cell adhesion Antibodies that inhibit ADAM-15 and integrin α9β1-dependent cell adhesion, and the like. [Selection figure] None

Anti-angiogenic peptides

Variants, compositions and methods of tissue inhibitors of type three metalloprotease (TIMP-3)

本发明公开TIMP‑3突变蛋白、变体和衍生物，编码它们的核酸以及制造和使用它们的方法。

Buforin 1 as a specific inhibitor and therapeutic agent for botulinum toxin b and tetanus neurotoxins

The compounds of the invention are generally described by the formula (I): X1X2B3X4B5X*6X7X8B9X10B11X12B13X14B15X16B17X*18X*19B20X21X22X23Q24F25Z*26X27X28 B29X30B31B32X33X34B35B36X37Z38Z39, and the salts, esters, amides, and acyl forms thereof. Up to 15 amino acids may be truncated from the N-terminus and up to 6 amino acids may be truncated from the C-terminus. Each position represented by a letter indicates a single amino acid residue wherein B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. These compounds may be used to inhibit the protease activity of Botulinum B and tetanus toxins.

Metalloproteinase inhibitor sequence recombinant vector system for using the same and recombinant-dna method for the manufacture of same

A portable DNA sequence is disclosed which is capable of directing intracellular production of metalloproteinase inhibitors. Vectors containing this portable DNA sequence are also set forth, including the vector pUC9-FS/237P10 (ATCC Accession No. 53003). A recombinant-DNA method for the microbial production of a metalloproteinase inhibitor, which method incorporates at least one of the portable DNA sequences and the vectors disclosed herein.

Modified peptides as therapeutic agents

The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologicall y active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least on e amino acid of the selected peptide. Linkage to the vehicle increases the hal f- life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by pha ge display, E. coli display, ribosome display, RNA-peptide screening, or chemic al- peptide screening.

Novel expression vectors for production of foreign proteins as soluble forms

The present invention relates to novel expression vectors which can produce foreign proteins as soluble forms by using lysyl-tRNA synthetase and a process for preparing foreign proteins by using the expression vectors. Particularly, the present invention relates to the expression vectors which can provide foreign proteins as fused and soluble forms by exploiting the structure and expression pattern of lysyl-tRNA synthetase and the processes for preparing foreign proteins in E. coli effectively, which can be utilized industrially to produce active proteins in mass.

Prevention of protein degradation in mammalian cell cultures

A method for the production of a Factor VIII polypeptide, the method comprising a) culturing a mammalian cell transfected with an expression vector comprising a nucleic acid molecule encoding said Factor VIII polypeptide and expression. control regions operatively linked to thereto, in a cell culture medium under conditions.suitable for expression of said polypeptide; and b) isolating the expressed Factor VIII polypeptide; wherein the cell culture medium in step a) comprises a tissue inhibitor of metalloproteinase (TIMP).

TIMP3 as VEGF inhibitor

Polypeptides or proteins comprising tissue inhibitor of mettaloproteinases-3 (TIMP3) or variants of TIMP3 can be used to substantially inhibit vascular endothelial growth factor (VEGF) binding to VEGF recptor-2 (VEGFR2/KDR/Flk-1)) without substantially inhibiting VEGF binding to VEGF receptor 1 (VEGFR1/Flt-1).

Modified peptides as therapeutic agents

MODIFIKOVANI PEPTIDI KAO TERAPEUTSKI AGENSI. Kompozicija supstance formule (X1)a-F1-(X2)bi njegovih multimera, naznačena time, što:F1 je Fc domen; svaki od X1 i X2 je nezavisno odabran od-(L1)C -P1,-(L1)c -P1(L2)d -P2,-(L1)c -P1- (L2)d- P2- (L3)e -P3, i-(L1)c -P1 -(L2)d-P2 -(L3)e -P3 -(L4)f -P4svaki od P1, P2, P3 i P4 je nezavisno nasumična (randomizovana) sekvenca farmakološki aktivnih peptida odabranih odIL-1 antagonist peptidnih sekvenci odabrane od SEQ ID NO: 212, 907, 908, 909, 910, 917 i 979 i IL-1 -antagonist peptidnih sekvenci odabrane od SEQ ID NO: 213 do 271, 671 do 906, 911 do 916 i 918 do 1023;EPO-mimetičkih peptidnih sekvenci odabrane iz tabele 5; TPO-mimetičkih peptidnih sekvenci odabrane iz tabele 6; TNF-antagnostičkih peptidnih sekvenci odabrane iz tabele 8; GCSF-mimetičkih peptidnih sekvenci odabrane iza tabele 7; svaki od L1, L2, L3, i L4 je nezavisno linker; ia, b, c, d, e, i f su svaki za sebe 0 ili 1, pod uslovom da je bar najmanje jedan a ili b jednak 1, igde se „peptid" odnosi na molekule sa 2 do 40 amino kiselina. Prijava sadrži još 24 patentna zahteva.

Inhibitor of interleukin-1-beta protease

(57)【要約】 【課題】 新規インターロイキン−１βプロテアーゼ阻 害剤の提供。 【解決手段】 Ｎ末端保護基および電気的陰性脱離基に 連結されたＣ末端Asp 残基を有する１〜約５個のアミノ 酸残基のアミノ酸配列を有し、そのアミノ酸配列が、配 列Ala-Tyr-Val-His-Asp 、すなわち配列番号３の残基１ １２〜１１６の少なくとも一部分に実質的に相当する化 合物。

Wound care compositions

The invention provides polypeptides that can inhibit the activity of matrix metalloproteinases. Such polypeptides are useful for treating wounds, for example, chronic wounds.

METHOD OF MANUFACTURING NEW PEPSIN INHIBITORS.

Method for extracting compound cell factor from umbilical cord tissue

本发明提供一种从脐带组织中提取复合细胞因子的方法，所述方法包括以下步骤：1)脐带组织的处理、2)复合细胞因子的富集、3)复合蛋白因子的分离、4)将步骤3)得到的上清液加压过滤，并进一步使用3KD浓缩脱盐，既得。本发明还提供了一种从脐带组织中提取的复合细胞因子。本发明直接从脐带组织中获得复合细胞因子，这些复合细胞因子均为人体成分，可以直接被皮肤吸收，避免过敏反应，无副作用。本发明的方法不涉及高温及化学灭菌的方式，仅仅利用过滤法去除微生物污染，既避免了产品出现污染变质问题，又保证生物活性成分不被高温、辐射或化学杀菌剂改变结果，保证了产品中细胞因子的活性，使产品效果稳定。

Anti-aging and wound healing compounds

The invention provides inhibitors of matrix metalloproteinases that are useful for encouraging the development of healthy skin and for treating wounds. The inhibitors are peptides having sequences related to cleavage regions of the proenzyme forms of matrix metalloproteinases. The peptide inhibitors of the invention can be formulated into therapeutic compositions, lotions, creams, skin covering and wound dressings that facilitate healing and healthy skin development, discourage scarring and wrinkling and ameliorate the effects of healing.

Modified anti-inflammatory proteins and method of use

Expression of potato proteinase inhibitor II in microbial hosts

Multiple microbial host genetic systems with various molecular constructs enabling subcellular targeting, fusion protein generation and co-expression of ancillary enzymatic activities are used in the expression of potato proteinase inhibitor II. The expression levels achieved exceed previous reports by up to 10 to 1000 fold.

Modified peptides as therapeutic agents

본 발명은 생물학적으로 활성인 펩티드와 Fc 도메인과의 융합 및 생물학적으로 활성인 펩티드를 사용하여 제약학적 제제를 제조하는 방법에 관한 것이다. 본 발명에 있어서, 약리학적으로 활성인 화합물은 다음 단계를 포함하는 방법에 의하여 제조된다 : a) 목적 단백질의 활성을 조절하는 적어도 하나의 펩티드를 선택하는 단계 ; 및 b) 적어도 하나의 선택된 펩티드의 아미노산에 Fc 도메인을 공유 결합함을 포함하는 약리학적 제제를 제조하는 단계. 본 발명의 화합물은 매개체와 결합하여 생체내에서 빠르게 분해되지 않도록 펩티드의 반감기를 증가시킨다. 바람직한 매개체는 Fc 도메인이다. 펩티드는 바람직하게, 파지 디스플레이, E. coli 디스플레이, 리보솜 디스플레이, RNA-펩티드 스크리닝 또는 화학적-펩티드 스크리닝에 의해 선택된다.

Protease inhibitor from streptomyces

Anti-aging and wound healing compounds

The invention provides inhibitors of matrix metalloproteinases that are useful for encouraging the development of healthy skin and for treating wounds. The inhibitors are peptides having sequences related to cleavage regions of the proenzyme forms of matrix metalloproteinases. The peptide inhibitors of the invention can be formulated into therapeutic compositions, lotions, creams, skin covering and wound dressings that facilitate healing and healthy skin development, discourage scarring and wrinkling and ameliorate the effects of healing.

Novel biomarkers of aggrecanase activity

Biomarkers for detecting aggrecanas-1 and/or aggrecanase-2 activity are disclosed. The biomarkers are specific peptide fragments of α2 macroglobulin.

Anti-angiogenic peptides

A purified polypeptide includes about 10 to about 40 amino acids and has an amino acid sequence corresponding to a portion of SEQ ID NO: 2. The polypeptide can inhibit binding of VEGF to VEGFR2 of cells that express VEGFR2.