US5491129A
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Synthetic peptides derived from vitronectin and pharmaceutical compositions comprising them
Assignee: Yeda Research and Development Co Ltd
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Filing: 1993-07-29
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Granted: 1996-02-13
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Expires: 2013-07-29
Abstract
Abstract The invention relates to synthetic peptides derived from the K 348 -A 380 (8-40 of SEQ ID NO:1) sequence of the vitronectin molecule. The peptides modulate the biological activities of plasminogen activator inhibitor-1 (PAI-1) and are useful as active ingredients of pharmaceutical compositions for the treatment of disorders such as bleeding disorders, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, disseminated intravascular coagulation, tumor cell invasion and metastasis, inflammation, liver diseases, bacterial blood infections, pregnancy toxicosis, and pathological conditions associated with the control of angiogenesis, or with nerve regeneration, or with excessive tPA-mediated proteolysis.
Inventors
- 👤 Shmuel Shaltiel
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 19:26
CPC Classifications
C; C12; C12N; C12N9/00; C12N9/14; C12N9/24; C12N9/2402; C12N9/2474; C07; C07K; C07K14/00; C07K14/435; C07K14/78; A; A61; A61P; A61P7/00; A61P7/02; A61K; A61K38/00; C12Y; C12Y302/00; C12Y302/01; C12Y302/01035
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
101 words
A molecule capable of inhibiting a biological activity of plasminogen activator inhibitor-1 (PAI-1) consisting of a peptide having 8 to 23 consecutive amino acids of the sequence Lys-Lys-Glu-Arg-Phe-Arg-His-Arg-Asn-Arg-Lys-Gly-Tyr-Arg-Ser-Gln-Arg-Gly-His-Ser-Arg-Gly-Arg (8-30 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide, wherein said molecule does not include the peptides of residues 8-21 of SEQ ID NO:1 or 17-30 of SEQ ID NO:1.
Claim 2
Dependent Claim
101 words
A molecule capable of inhibiting a biological activity of plasminogen activator inhibitor-1 (PAI-1) consisting of a peptide having 8 to 23 consecutive amino acids of the sequence Lys-Lys-Glu-Arg-Phe-Arg-His-Arg-Asn-Arg-Lys-Gly-Tyr-Arg-Ser-Gln-Arg-Gly-His-Ser-Arg-Gly-Arg (8-30 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide, wherein said molecule does not include the peptides of residues 8-21 of SEQ ID NO:1 or 17-30 of SEQ ID NO:1.
Claim 3
Dependent Claim
15 words
A molecule according to claim 1 wherein all amino acid residues have the L configuration.
Claim 4
Dependent Claim
19 words
A molecule according to claim 1, wherein said amino acid sequence consists of residues 18-30 of SEQ ID NO:1.
Claim 5
Dependent Claim
19 words
A molecule according to claim 1, wherein said amino acid sequence consists of residues 8-23 of SEQ ID NO:1.
Claim 6
Dependent Claim
19 words
A molecule according to claim 1, wherein at least one of the amino acid residues has the D configuration.
Claim 7
Dependent Claim
30 words
A peptide according to claim 5, wherein said amino acid sequence consists of the sequence: Lys-Lys-Gln-Arg-Phe-Arg-His-Arg-Asn-Arg-Lys-Gly-Tyr-Arg-Ser-Gln (8-23 of SEQ ID NO:1), wherein the underlined amino acids have the D configuration.
Claim 8
Dependent Claim
16 words
A molecule according to claim 1 wherein all optically active amino acids have the D configuration.
Claim 9
Dependent Claim
19 words
A molecule according to claim 7, wherein said amino acid sequence consists of residues 8-23 of SEQ ID NO:1.
Claim 10
Dependent Claim
19 words
A molecule according to claim 7, wherein said amino acid sequence consists of residues 16-23 of SEQ ID NO:1.
Claim 11
Dependent Claim
20 words
A pharmaceutical composition comprising an effective amount of a molecule in accordance with claim 1 and a pharmaceutically acceptable carrier.
Claim 12
Independent Claim
97 words
A method of treating an animal in need of increased fibrinolysis, comprising administering an effective amount of a molecule capable of inhibiting a biological activity of plasminogen activator inhibitor-1 (PAI-1) consisting of a peptide having 8 to 23 consecutive amino acids of the sequence Lys-Lys-Gln-Arg-Phe-Arg-His-Arg-Asn-Arg-Lys-Gly-Tyr-Arg-Ser-Gln-Arg-Gly-His-Ser-Arg-Gly-Arg (8-30 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide.
Claim 13
Independent Claim
97 words
A method of treating an animal in need of increased fibrinolysis, comprising administering an effective amount of a molecule capable of inhibiting a biological activity of plasminogen activator inhibitor-1 (PAI-1) consisting of a peptide having 8 to 23 consecutive amino acids of the sequence Lys-Lys-Gln-Arg-Phe-Arg-His-Arg-Asn-Arg-Lys-Gly-Tyr-Arg-Ser-Gln-Arg-Gly-His-Ser-Arg-Gly-Arg (8-30 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide.
Claim 14
Dependent Claim
31 words
A method in accordance with claim 11, wherein said animal in need of increased fibrinolysis is a human having acute myocardial infarction, deep vein thrombosis, pulmonary embolism or disseminated intravascular coagulation.
Claim 15
Dependent Claim
17 words
A method in accordance with claim 11, wherein said molecule is BP5, BP6, BP7, BP8 or BP14.
Claim 16
Dependent Claim
98 words
A molecule capable of enhancing a biological activity of plasminogen activator inhibitor-1 (PAI-1), consisting of a peptide having 7 to 19 consecutive amino acids of the sequence: Ser-Gln-Arg-Gly-His-Ser-Arg-Gly-Arg-Asn-Gln-Asn-Ser-Arg-Arg-Pro-Ser-Arg-Ala (22-40 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide, wherein said molecule of the peptide does not include the peptide of residues 26-39 of SEQ ID NO:1.
Claim 17
Dependent Claim
98 words
A molecule capable of enhancing a biological activity of plasminogen activator inhibitor-1 (PAI-1), consisting of a peptide having 7 to 19 consecutive amino acids of the sequence: Ser-Gln-Arg-Gly-His-Ser-Arg-Gly-Arg-Asn-Gln-Asn-Ser-Arg-Arg-Pro-Ser-Arg-Ala (22-40 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide, wherein said molecule of the peptide does not include the peptide of residues 26-39 of SEQ ID NO:1.
Claim 18
Dependent Claim
19 words
A molecule according to claim 14, wherein said amino acid sequence consists of residues 22-40 of SEQ ID NO:1.
Claim 19
Dependent Claim
19 words
A molecule according to claim 14, wherein said amino acid sequence consists of residues 22-30 of SEQ ID NO:1.
Claim 20
Dependent Claim
15 words
A peptide according to claim 14, wherein all amino acid residues have the L configuration.
Claim 21
Dependent Claim
21 words
An antifibrinolytic pharmaceutical composition comprising an effective amount of a molecule in accordance with claim 14 and a pharmaceutically acceptable carrier.
Claim 22
Independent Claim
97 words
A method for the treatment of disorders associated with excessive fibrinolysis, comprising administering an effective amount of a molecule capable of enhancing a biological activity of plasminogen activator inhibitor-1 (PAI-1), consisting of a peptide having 7 to 19 consecutive amino acids of the sequence: Ser-Gln-Arg-Gly-His-Ser-Arg-Gly-Arg-Asn-Gln-Asn-Ser-Arg-Arg-Pro-Ser-Arg-Ala (22-40 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide.
Claim 23
Independent Claim
97 words
A method for the treatment of disorders associated with excessive fibrinolysis, comprising administering an effective amount of a molecule capable of enhancing a biological activity of plasminogen activator inhibitor-1 (PAI-1), consisting of a peptide having 7 to 19 consecutive amino acids of the sequence: Ser-Gln-Arg-Gly-His-Ser-Arg-Gly-Arg-Asn-Gln-Asn-Ser-Arg-Arg-Pro-Ser-Arg-Ala (22-40 of SEQ ID NO:1), or a salt, functional derivative or analog thereof, said analog being obtained by one or more amino acid substitutions, additions or deletions such that the overall properties of the analog are conserved with regard to the overall positive charge density and overall hydrophilic character of the peptide.
References Cited (Backward Citations)
JPH0454199A
Cited
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