US5021404A
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Angiostatic collagen modulators
Assignee: Boston Children's Hospital
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Filing: 1988-04-20
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Granted: 1991-06-04
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Expires: 2008-04-20
Abstract
Abstract Angiostatic compounds are potentiated by collagen matrix metabolism modulators including: a) proline analogs which inhibit proline hydroxylation when substituted for proline in collagen; b) inhibitors of proline hydroxylase; c) inhibitors of collagen cross-linking; and d) all trans-retinoic acid. In methods and therapeutic compositions for inhibiting angiogenesis in a mammal, the collagen matrix modulator is administered with an angiostatic steroid or with heparin (including angiostatic heparin fragments of six or more sugar units, and synthetic fragments).
Inventors
- 👤 Judah Folkman
- 👤 Donald Ingber
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 03:51
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K31/715; A61K31/56; A61K31/57; A61P; A61P27/00; A61P27/02; A61P43/00; A61P9/00
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
67 words
A method of inhibiting angiogenesis in a mammal by administering to said mammal an angiogenesis-inhibiting dose of a collagen matrix metabolism modulator in combination with an angiostatic compound, said collagen matrix modulator being selected from the group consisting of: (a) proline analogs which inhibit proline hydroxylation when substituted for proline in collagen; (b) inhibitors of proline hydroxylase; (c) inhibitors of collagen cross-linking; and (d) all trans-retinoic acid;
Claim 2
Independent Claim
67 words
A method of inhibiting angiogenesis in a mammal by administering to said mammal an angiogenesis-inhibiting dose of a collagen matrix metabolism modulator in combination with an angiostatic compound, said collagen matrix modulator being selected from the group consisting of: (a) proline analogs which inhibit proline hydroxylation when substituted for proline in collagen; (b) inhibitors of proline hydroxylase; (c) inhibitors of collagen cross-linking; and (d) all trans-retinoic acid;
Claim 3
Dependent Claim
26 words
The method of claim 1 wherein said proline analog is selected from the group consisting of: a) L-azetidine-2-carboxylic acid; b) cis-hydroxyproline; c) D,L-3,4-dehydroproline; and d) thioproline.
Claim 4
Dependent Claim
13 words
The method of claim 1 wherein said inhibitor of proline hydroxylase is α,α-dipyridyl.
Claim 5
Dependent Claim
13 words
The method of claim 1 wherein said inhibitor of collagen cross-linking is β-aminoproprionitrile.
Claim 6
Independent Claim
22 words
The method of any one of claims 1-4 wherein said collagen matrix metabolism modulator is administered in combination with an angiostatic steroid.
Claim 7
Dependent Claim
35 words
The method of claim 5 wherein said angiostatic steroid is selected from the group consisting of: cortisone, epicortisol, hydrocortisone, tetrahydrocortisone S, 17α-hydroxyprogesterone, cortexolone, corticosterone, desoxycorticosterone, hydrocortisol, 6α-fluororo-7,21-dihydroxy-16β-methyl pregna4,9-(11)-dione-3,20-dione; 11α-hydrocortisone, 11-desoxycortisol, and 4,9(11) pregnadien-17α,21 diol-3,20 dione.
Claim 8
Independent Claim
42 words
The method of any one of claims 1-4 wherein said angiostatic compound is selected from the group consisting of: heparin; an angiostatic heparin fragment which is a hexasaccharide or larger; or an angiostatic synthetic analog of heparin or of a heparin fragment.
Claim 9
Dependent Claim
22 words
The method of claim 1 wherein said collagen matrix metabolism modulator and said angiostatic compound are administered from a sustained release body.
Claim 10
Dependent Claim
56 words
A therapeutic composition comprising a mixture of a pharmaceutically acceptable vehicle, a collagen matrix metabolism modulator, and an angiostatic compound, said collagen matrix metabolism modulator being selected from the group consisting of: a) proline analogs which inhibit proline hydroxylation when substituted for proline in collagen; (b) inhibitors of proline hydroxylase; and (c) inhibitors of collagen cross-linking
Claim 11
Dependent Claim
56 words
A therapeutic composition comprising a mixture of a pharmaceutically acceptable vehicle, a collagen matrix metabolism modulator, and an angiostatic compound, said collagen matrix metabolism modulator being selected from the group consisting of: a) proline analogs which inhibit proline hydroxylation when substituted for proline in collagen; (b) inhibitors of proline hydroxylase; and (c) inhibitors of collagen cross-linking
Claim 12
Dependent Claim
27 words
The therapeutic composition of claim 9 wherein said proline analog is selected from the group consisting of: a) L-azetidine-2-carboxylic acid; b) cis-hydroxyproline; c) D,L-3,4-dehydroproline; and d) thioproline.
Claim 13
Dependent Claim
14 words
The therapeutic composition of claim 9 wherein said inhibitor of proline hydroxylase is α,α-dipyridyl.
Claim 14
Dependent Claim
14 words
The therapeutic composition of claim 9 wherein said inhibitor of collagen cross-linking is β-aminoproprionitrile.
Claim 15
Dependent Claim
16 words
The therapeutic composition of any one of claims 9-12 wherein said composition comprises an angiostatic steroid.
Claim 16
Dependent Claim
38 words
The therapeutic composition of claim 13 wherein said angiostatic steroid is selected from the group consisting of: cortisone, epicortisol, hydrocortisone, tetrahydrocortisone S, 17 α-hydroxyprogesterone, cortexolone, corticosterone, desoxycorticosterone, hydrocortisol, 6 α-fluororo-7,21-dihydroxy-16β-methyl-pregna-4,9-(11)-dione-3,20-dione; 11 α-hydrocortisone, 11-desoxycortisol, and 4,9(11) pregnadien-17α,21 diol-3,20 dione.
Claim 17
Dependent Claim
43 words
The therapeutic composition of any one of claims 9-12 wherein said angiostatic compound is selected from the group consisting of: heparin; an angiostatic heparin fragment which is a hexasaccharide or larger; or an angiostatic synthetic analog of heparin or of a heparin fragment.
Claim 18
Dependent Claim
11 words
A sustained release body comprising the therapeutic composition of claim 9.
Claim 19
Dependent Claim
10 words
The composition of claim 9 further comprising all trans-retinoic acid.
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) | 1994-06-03 | 1994-12-03 | 1995-06-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-06-03 | 1998-12-03 | 1999-06-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-06-03 | 2002-12-03 | 2003-06-04 | $7700.00 | Window Closed / Lapsed |