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US4661471A
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Method of inhibiting and inducing human platelet aggregation
Assignee: Beth Israel Deaconess Medical Center
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Filing: 1984-04-10
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Granted: 1987-04-28
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Expires: 2004-04-10
Abstract
Abstract A method of inhibiting thrombin or ADP-induced human platelet aggregation by fibrinogen has been developed. The administration of the small molecular weight peptide or the synthetic inhibitory molecule of the invention significantly inhibits thrombin or ADP-modified human platelets binding of fibrinogen, a plasma protein necessary for platelet aggregation. The method of the invention is useful for inhibiting of the formation of hemostatic platelet plugs and of the initiation of thrombotic lesions. The blockage caused by hemostatic platelet plugs and the damage caused by thrombotic lesions are major factors in heart disease and stroke. The invention also includes a method of inducing the formation of thrombin or ADP-modified platelet aggregates by administration of a synthetic aggregating molecule which represents a functional substitute for fibrinogen.
Inventors
- 👤 Jack J. Hawiger
- 👤 Sheila Timmons
- 👤 Thomas J. Lukas
- 👤 Marek Kloczewiak
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 21:41
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/745; C07K14/75; C07K19/00; A; A61; A61K; A61K38/00
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
55 words
A method for inhibiting thrombin or ADP-induced fibrinogen aggregation of human platelets comprising the step of incubating human platelets with a synthetic peptide analog of the platelet receptor recognition site of fibrinogen which contains 6-14 residues having a carboxyl terminal sequence Lys-X-X-X-Asp-Val-COOH where each X is individually selected from a group consisting of amino acids.
Claim 2
Independent Claim
55 words
A method for inhibiting thrombin or ADP-induced fibrinogen aggregation of human platelets comprising the step of incubating human platelets with a synthetic peptide analog of the platelet receptor recognition site of fibrinogen which contains 6-14 residues having a carboxyl terminal sequence Lys-X-X-X-Asp-Val-COOH where each X is individually selected from a group consisting of amino acids.
Claim 3
Dependent Claim
16 words
The method of claim 1 wherein said synthetic peptide analog has the carboxyl terminal sequence Lys-Gln-Ala-Gly-Asp-Val-COOH.
Claim 4
Dependent Claim
31 words
The method of claim 1 wherein said synthetic peptide analog is a dodecapeptide having the sequence H.sub.2 N-His-His-X-X-X-X-Lys-X-X-X-Asp-Val-COOH where each X is individually selected from a group consisting of amino acids.
Claim 5
Dependent Claim
18 words
The method of claim 3 wherein said synthetic peptide analog has the carboxyl terminal sequence H.sub.2 N-His-His Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val-COOH.
Claim 6
Independent Claim
61 words
A method of inhibiting thrombin or ADP-induced fibrinogen aggregation of human platelets comprising the step of incubating human platelets with a molecule having a carboxyl terminal sequence consisting of Cys-X-X-X-X-His-His-X-X-X-X-Lys-X-X-X-Asp-Val-COOH where each X is individually selected from a group consisting of amino acids, where said carboxyl terminal sequence is a synthetic peptide analog of the platelet receptor recognition site of fibrinogen.
Claim 7
Independent Claim
61 words
A method of inhibiting thrombin or ADP-induced fibrinogen aggregation of human platelets comprising the step of incubating human platelets with a molecule having a carboxyl terminal sequence consisting of Cys-X-X-X-X-His-His-X-X-X-X-Lys-X-X-X-Asp-Val-COOH where each X is individually selected from a group consisting of amino acids, where said carboxyl terminal sequence is a synthetic peptide analog of the platelet receptor recognition site of fibrinogen.
Claim 8
Dependent Claim
14 words
The method of claim 5 wherein said molecule has the carboxyl terminal sequence Cys-Tyr-Gly-Gln-Gln-His-His-Leu-Gly-Gly-Ala-Lys-Gln-AlaGly-Asp-Val-COOH.
Claim 9
Dependent Claim
17 words
The method of claim 5 wherein said molecule comprises a cystinyl-linked dimer of said carboxyl terminal sequence.
Claim 10
Dependent Claim
17 words
The method of claim 6 wherein said molecule comprises a cystinyl-linked dimer of said carboxyl terminal sequence.
Claim 11
Dependent Claim
43 words
The method of claim 5 wherein said molecule comprises said carboxyl terminal sequence grafted to a carrier molecule backbone in a proportion such that each carrier molecule backbone contains no more than one of said synthetic peptide analogs having this carboxyl terminal sequence.
Claim 12
Dependent Claim
13 words
The method of claim 9 wherein said carrier molecule backbone comprises a protein.
Claim 13
Dependent Claim
14 words
The method of claim 9 wherein said carrier molecule backbone comprises human serum albumin.
Claim 14
Independent Claim
75 words
A method of aggregating thrombin or ADP-modified human platelets in the absence of fibrinogen comprising the step of forming an artificial aggregation molecule by grafting to a carrier molecule backbone a plurality of synthetic peptide analogs of the platelet receptor recognition site of fibrinogen each having the carboxyl terminal sequence, Cys-X-X-X-X-His-His-X-X-X-X-Lys-X-X-X-Asp-Val-COOH where each X is individually selected from a group consisting of amino acids, and treating said modified human platelets with said artificial aggregation molecule.
Claim 15
Independent Claim
75 words
A method of aggregating thrombin or ADP-modified human platelets in the absence of fibrinogen comprising the step of forming an artificial aggregation molecule by grafting to a carrier molecule backbone a plurality of synthetic peptide analogs of the platelet receptor recognition site of fibrinogen each having the carboxyl terminal sequence, Cys-X-X-X-X-His-His-X-X-X-X-Lys-X-X-X-Asp-Val-COOH where each X is individually selected from a group consisting of amino acids, and treating said modified human platelets with said artificial aggregation molecule.
Claim 16
Dependent Claim
16 words
The method of claim 12 wherein said synthetic peptide analog has the carboxyl terminal sequence Cys-Tyr-Gly-Gln-Gln-His-His-Leu-Gly-Gly-Ala-Lys-Gln-AlaGly-Asp-Val-COOH.
Claim 17
Dependent Claim
13 words
The method of claim 12 wherein said carrier molecule backbone comprises a protein.
Claim 18
Dependent Claim
14 words
The method of claim 12 wherein said carrier molecule backbone comprises human serum albumin.
Claim 19
Dependent Claim
49 words
A synthetic molecule capable of replacing fibrinogen in the thrombin or ADP-induced aggregation of human platelets comprising a plurality of synthetic peptide analogs of the platelet receptor recognition site of fibrinogen sulfhydrally grafted to a carrier molecule backbone, each of said peptides having the carboxyl terminal sequence Cys-Tyr-Gly-Gln-Gln His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val-COOH.
Claim 20
Dependent Claim
49 words
A synthetic molecule capable of replacing fibrinogen in the thrombin or ADP-induced aggregation of human platelets comprising a plurality of synthetic peptide analogs of the platelet receptor recognition site of fibrinogen sulfhydrally grafted to a carrier molecule backbone, each of said peptides having the carboxyl terminal sequence Cys-Tyr-Gly-Gln-Gln His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val-COOH.
Claim 21
Dependent Claim
15 words
The synthetic molecule of claim 16 wherein said carrier molecule backbone comprises human serum albumin.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1990-04-27 | 1990-10-27 | 1991-04-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-04-27 | 1994-10-27 | 1995-04-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-04-27 | 1998-10-27 | 1999-04-28 | $7700.00 | Window Closed / Lapsed |