WO1997030085B1 - Troponin subunits and fragments useful as angiogenesis inhibitors - Google Patents
Troponin subunits and fragments useful as angiogenesis inhibitorsInfo
- Publication number
- WO1997030085B1 WO1997030085B1 PCT/US1997/002439 US9702439W WO9730085B1 WO 1997030085 B1 WO1997030085 B1 WO 1997030085B1 US 9702439 W US9702439 W US 9702439W WO 9730085 B1 WO9730085 B1 WO 9730085B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- fact
- troponin subunit
- peptide
- subunit
- human
- Prior art date
Links
- 239000012634 fragment Substances 0.000 title claims abstract 7
- 229940121369 angiogenesis inhibitor Drugs 0.000 title claims 2
- 239000004037 angiogenesis inhibitor Substances 0.000 title claims 2
- 230000033115 angiogenesis Effects 0.000 claims abstract 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 5
- 206010028980 Neoplasm Diseases 0.000 claims abstract 3
- 230000002401 inhibitory effect Effects 0.000 claims abstract 2
- 241000282414 Homo sapiens Species 0.000 claims 19
- 108090000765 processed proteins & peptides Proteins 0.000 claims 14
- 239000000203 mixture Substances 0.000 claims 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 241000283690 Bos taurus Species 0.000 claims 5
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 claims 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims 3
- 150000001413 amino acids Chemical class 0.000 claims 3
- 230000004663 cell proliferation Effects 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000035475 disorder Diseases 0.000 claims 3
- 210000002889 endothelial cell Anatomy 0.000 claims 3
- 239000003112 inhibitor Substances 0.000 claims 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 2
- 241000699666 Mus <mouse, genus> Species 0.000 claims 2
- 241000283973 Oryctolagus cuniculus Species 0.000 claims 2
- 241000700159 Rattus Species 0.000 claims 2
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims 1
- 208000025997 central nervous system neoplasm Diseases 0.000 claims 1
- 230000036461 convulsion Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- LQRJAEQXMSMEDP-XCHBZYMASA-N peptide a Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)NCCCC[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)C(\NC(=O)[C@@H](CCCCN)NC(=O)CNC(C)=O)=C/C=1C=CC=CC=1)C(N)=O)C(=O)C(\NC(=O)[C@@H](CCCCN)NC(=O)CNC(C)=O)=C\C1=CC=CC=C1 LQRJAEQXMSMEDP-XCHBZYMASA-N 0.000 claims 1
- 230000000699 topical effect Effects 0.000 claims 1
- 206010003645 Atopy Diseases 0.000 abstract 1
- 108010033276 Peptide Fragments Proteins 0.000 abstract 1
- 102000007079 Peptide Fragments Human genes 0.000 abstract 1
- 210000003169 central nervous system Anatomy 0.000 abstract 1
Abstract
The invention concerns methods of inhibiting atopic angiogenesis using troponin subunits and peptide fragments thereof. The invention further concerns pharmaceutical compositions comprising a troponin subunit or a fragment thereof. The pharmaceutical compositions and the methods of the invention are useful in the treatment of solid tumors, particularly tumors of the central nervous system and of the eye.
Claims
1. A pharmaceutical composition comprising an amount of at least one peptide that is effective to inhibit angiogenesis and a pharmaceutically acceptable carrier therefor, characterized by the fact that the peptide is a troponin subunit selected from the group consisting of subunits C, I and T, or an analog or fragment thereof.
2. A pharmaceutical composition according to claim 1, characterized by the fact that the composition comprises additionally an effective amount of a molecule, other than said troponin subunit, which negatively regulates angiogenesis.
3. A pharmaceutical composition according to claim 1 or 2, characterized by the fact that the peptide is: a. an inhibitor of bFGF-stimulated bovine endothelial cell proliferation having an IC50 of at least 10 μM; b. greater than 75 amino acids in length; and c. greater than 80% homologous with a subunit selected from the group consisting of human fast-twitch troponin subunit C (SEQ ID No:l), human fast-twitch troponin subunit I (SEQ ID NO: 2), and human fast- twitch troponin subunit T (SEQ ID NO:3).
4. A composition according to claim 3, characterized by the fact that the peptide is a mammalian troponin subunit selected from the group consisting of human, bovine, rabbit, mouse and rat troponin subunits.
5. A composition according to claim 3 or 4, characterized by the fact that the peptide is greater than 80% homologous with human fast-twitch troponin subunit C or human fast-twitch troponin subunit I.
6. A composition according to claim 3, characterized by the fact that the peptide is greater than 95% homologous with a human troponin subunit.
- 44 -
7. A composition according to claim 6, characterized by the fact that the human troponin subunit is human fast-twitch troponin subunit C, or human fast-twitch troponin subunit I.
8. A composition according to claim 3, characterized by the fact that the peptide is a fragment of a mammalian troponin subunit.
9. A composition according to claim 8, characterized by the fact that the peptide is a fragment of a troponin subunit C or troponin subunit I selected from the group consisting of human, bovine, rabbit, mouse and rat troponin subunit C and subunit I.
10. A composition according to any one of claims 1 to 9, characterized by the fact that the carrier is acceptable for topical application to the eye or to the skin.
11. A composition according to any one of claims 3 to 9, characterized by the fact that the angiogenesis inhibitor is in a biodegradable, biocompatible polymeric delivery device.
12. The use of a peptide in an amount effective to inhibit angiogenesis, characterized by the fact that the peptide is a troponin subunit selected from the group consisting of subunits C, I, and T, or an analog or fragment thereof.
13. The use according to claim 12, characterized by the fact that the peptide is: a. an inhibitor of bFGF-stimulated bovine endothelial cell proliferation having an IC50 of at least 10 μM; b. greater than 75 amino acids in length; and c. greater than 80% homologous with a subunit selected from the group consisting of human fast-twitch troponin subunit C (SEQ ID NO: l), human fast-twitch troponin subunit I (SEQ ID NO:2), and human fast-twitch troponin subunit T (SEQ ID NO: 3).
- 45 -
14. A method of inhibiting angiogenesis in a subject having a disease or disorder associated with angiogenesis which comprises administering to said subject an effective amount of a peptide, characterized by the fact that the peptide is a troponin subunit selected from the group consisting of subunits C, I and T, or an analog or fragment thereof.
15. A method according to claim 14, characterized by the fact that the peptide
a. an inhibitor of bFGF-stimulated bovine endothelial cell proliferation having an IC50 of at least 10 μM; b. greater than 75 amino acids in length; and c. greater than 80% homologous with a subunit selected from the group consisting of human fast-twitch troponin subunit C (SEQ ID NO:l), human fast-twitch troponin subunit I (SEQ ID NO: 2), and human fast-twitch troponin subunit T (SEQ ID NO: 3).
16. A method according to claim 15, characterized by the fact that the peptide is greater than 80% homologous with human fast-twitch troponin subunit C or human fast-twitch troponin subunit I.
17. A method according to claim 15 or 16, characterized by the fact that the disease or disorder is a solid tumor, or a tumor of the central nervous system, or an ophthalmologic disease or disorder.
- 46 -
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP52953997A JP3990456B2 (en) | 1996-02-16 | 1997-02-14 | Troponin subunits and fragments useful as inhibitors of angiogenesis |
| DE69729125T DE69729125T2 (en) | 1996-02-16 | 1997-02-14 | TROPONIN SUB-UNITS AND FRAGMENTS FOR USE AS INHIBITORS OF ANGIOGENESIS |
| AT97905992T ATE266675T1 (en) | 1996-02-16 | 1997-02-14 | TROPONIN SUBUNITS AND FRAGMENTS FOR USE AS INHIBITORS OF ANGIOGENESIS |
| CA2247247A CA2247247C (en) | 1996-02-16 | 1997-02-14 | Troponin subunits and fragments useful as angiogenesis inhibitors |
| EP97905992A EP1007556B1 (en) | 1996-02-16 | 1997-02-14 | Troponin subunits and fragments useful as angiogenesis inhibitors |
| AU22753/97A AU707262B2 (en) | 1996-02-16 | 1997-02-14 | Troponin subunits and fragments useful as angiogenesis inhibitors |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/602,941 US5837680A (en) | 1996-02-16 | 1996-02-16 | Pharmaceutical compositions comprising troponin subunits, fragments and analogs thereof and methods of their use to inhibit angiogenesis |
| US08/602,941 | 1996-02-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1997030085A1 WO1997030085A1 (en) | 1997-08-21 |
| WO1997030085B1 true WO1997030085B1 (en) | 1997-09-25 |
Family
ID=24413387
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1997/002439 WO1997030085A1 (en) | 1996-02-16 | 1997-02-14 | Troponin subunits and fragments useful as angiogenesis inhibitors |
Country Status (8)
| Country | Link |
|---|---|
| US (4) | US5837680A (en) |
| EP (1) | EP1007556B1 (en) |
| JP (1) | JP3990456B2 (en) |
| AT (1) | ATE266675T1 (en) |
| AU (1) | AU707262B2 (en) |
| CA (1) | CA2247247C (en) |
| DE (1) | DE69729125T2 (en) |
| WO (1) | WO1997030085A1 (en) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6586401B1 (en) | 1996-02-16 | 2003-07-01 | Children's Medical Center Corporation | Troponin subunit I fragment and homologs thereof |
| US5837680A (en) | 1996-02-16 | 1998-11-17 | Children's Medical Center Corporation | Pharmaceutical compositions comprising troponin subunits, fragments and analogs thereof and methods of their use to inhibit angiogenesis |
| US6589936B1 (en) | 1996-02-16 | 2003-07-08 | Children's Medical Center Corporation | Pharmaceutical compositions comprising recombinant troponin subunits |
| US6465431B1 (en) * | 1999-11-17 | 2002-10-15 | Boston Life Sciences, Inc. | Pharmaceutical compositions comprising troponin subunits, fragments and homologs thereof and methods of their use to inhibit angiogenesis |
| US7220557B2 (en) | 1997-04-24 | 2007-05-22 | Human Genome Sciences, Inc. | METH1 polynucleotides |
| US20030166065A1 (en) * | 1997-04-24 | 2003-09-04 | Human Genome Sciences, Inc. | Novel integrin ligand ITGL-TSP |
| US6248869B1 (en) * | 1997-05-29 | 2001-06-19 | Medical Analysis Systems, Inc. | Troponin I forms and use of the same |
| US6468519B1 (en) * | 1997-09-10 | 2002-10-22 | Rutgers, The State University Of New Jersey | Polyanhydrides with biologically active degradation products |
| AU9673998A (en) * | 1997-10-01 | 1999-04-23 | G.D. Searle & Co. | Fusion proteins comprising an angiostatin moiety and their use in anti-tumor treatment |
| KR100335397B1 (en) * | 1998-05-25 | 2002-09-05 | 주식회사 하이닉스반도체 | Sense Amplifier Sequential Drive |
| EP1098971B1 (en) | 1998-07-17 | 2006-08-30 | Licentia Ltd. | Myotilin, an actin-organizing protein |
| US6378526B1 (en) * | 1998-08-03 | 2002-04-30 | Insite Vision, Incorporated | Methods of ophthalmic administration |
| WO2000023585A1 (en) * | 1998-10-21 | 2000-04-27 | Spectral Diagnostics, Inc. | Cardiac troponin i polypeptide fragments and uses in diagnostics |
| WO2000054770A1 (en) * | 1999-03-15 | 2000-09-21 | Boston Life Sciences, Inc. | Pharmaceutical compositions comprising troponin subunits, fragments and homologs thereof and methods of their use to inhibit angiogenesis |
| CA2382774A1 (en) * | 1999-05-25 | 2000-11-30 | Human Genome Sciences, Inc. | Meth1 and meth2 polynucleotides and polypeptides |
| US20020142982A1 (en) * | 1999-09-02 | 2002-10-03 | Timothy Hla | Method for regulating angiogenesis |
| PT1299727E (en) | 2000-07-12 | 2009-07-09 | Agensys Inc | Novel tumor antigen useful in diagnosis and therapy of bladder, ovary, lung and kidney cancers |
| US20030236188A1 (en) * | 2001-05-03 | 2003-12-25 | Spytek Kimberly A. | Novel human proteins, polynucleotides encoding them and methods of using the same |
| ATE471371T1 (en) * | 2002-02-04 | 2010-07-15 | Yoshida Hideo | ANTICANCER AGENT WITH VEROTOXINVARIANTS |
| US7261876B2 (en) | 2002-03-01 | 2007-08-28 | Bracco International Bv | Multivalent constructs for therapeutic and diagnostic applications |
| EP2014310B8 (en) | 2002-03-01 | 2012-12-26 | Dyax Corp. | KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy |
| US7794693B2 (en) | 2002-03-01 | 2010-09-14 | Bracco International B.V. | Targeting vector-phospholipid conjugates |
| US7211240B2 (en) * | 2002-03-01 | 2007-05-01 | Bracco International B.V. | Multivalent constructs for therapeutic and diagnostic applications |
| US8623822B2 (en) * | 2002-03-01 | 2014-01-07 | Bracco Suisse Sa | KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy |
| CA2513044A1 (en) | 2002-03-01 | 2004-08-05 | Dyax Corp. | Kdr and vegf/kdr binding peptides and their use in diagnosis and therapy |
| WO2003080116A1 (en) * | 2002-03-21 | 2003-10-02 | University Of Florida | Modulating angiogenesis |
| US20060189519A1 (en) * | 2002-09-26 | 2006-08-24 | Karl Volz | Anti-angiogenic fragments fo pigment epithelium-derived factor (pedf) |
| WO2004078778A2 (en) | 2003-03-03 | 2004-09-16 | Dyax Corp. | PEPTIDES THAT SPECIFICALLY BIND HGF RECEPTOR (cMet) AND USES THEREOF |
| CN1294987C (en) * | 2003-04-15 | 2007-01-17 | 刘凤鸣 | Protein having antitumor function, and high performance expression in vitro |
| ES2737835T3 (en) | 2003-04-23 | 2020-01-16 | Valeritas Inc | Hydraulically driven pump for long-term medication administration |
| WO2006014425A1 (en) | 2004-07-02 | 2006-02-09 | Biovalve Technologies, Inc. | Methods and devices for delivering glp-1 and uses thereof |
| US8697139B2 (en) | 2004-09-21 | 2014-04-15 | Frank M. Phillips | Method of intervertebral disc treatment using articular chondrocyte cells |
| US7265248B1 (en) | 2005-04-29 | 2007-09-04 | Technology Innovations, Llc | Compositions and methods for the treatment of malaria |
| US20070130009A1 (en) * | 2005-06-01 | 2007-06-07 | Chad Steelberg | System and method for media play pricing |
| WO2007067611A2 (en) * | 2005-12-07 | 2007-06-14 | The Brigham And Women's Hospital, Inc. | Methods of treating cardiac reperfusion disease |
| EP2005309B1 (en) | 2006-03-30 | 2016-02-17 | Valeritas, Inc. | Multi-cartridge fluid delivery device |
| US8468561B2 (en) | 2006-08-09 | 2013-06-18 | Google Inc. | Preemptible station inventory |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991011193A1 (en) * | 1990-01-25 | 1991-08-08 | Children's Hospital | Method and compositions for inhibiting angiogenesis |
| FR2701954B1 (en) * | 1993-02-23 | 1995-07-07 | Pasteur Sanofi Diagnostics | Stabilized troponin composition for immunoassays and method for stabilizing troponin for immunoassays. |
| US5837680A (en) * | 1996-02-16 | 1998-11-17 | Children's Medical Center Corporation | Pharmaceutical compositions comprising troponin subunits, fragments and analogs thereof and methods of their use to inhibit angiogenesis |
-
1996
- 1996-02-16 US US08/602,941 patent/US5837680A/en not_active Expired - Lifetime
-
1997
- 1997-02-14 AT AT97905992T patent/ATE266675T1/en not_active IP Right Cessation
- 1997-02-14 JP JP52953997A patent/JP3990456B2/en not_active Expired - Fee Related
- 1997-02-14 AU AU22753/97A patent/AU707262B2/en not_active Ceased
- 1997-02-14 WO PCT/US1997/002439 patent/WO1997030085A1/en active IP Right Grant
- 1997-02-14 EP EP97905992A patent/EP1007556B1/en not_active Expired - Lifetime
- 1997-02-14 CA CA2247247A patent/CA2247247C/en not_active Expired - Fee Related
- 1997-02-14 DE DE69729125T patent/DE69729125T2/en not_active Expired - Lifetime
- 1997-10-30 US US08/961,264 patent/US6025331A/en not_active Expired - Lifetime
-
1999
- 1999-08-04 US US09/368,214 patent/US6403558B1/en not_active Expired - Fee Related
-
2000
- 2000-11-28 US US09/724,401 patent/US6653283B1/en not_active Expired - Fee Related
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