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WO1997030085B1 - Troponin subunits and fragments useful as angiogenesis inhibitors - Google Patents

Troponin subunits and fragments useful as angiogenesis inhibitors

Info

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
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1997/002439
Other languages
French (fr)
Other versions
WO1997030085A1 (en
Filing date
Publication date
Priority claimed from US08/602,941 external-priority patent/US5837680A/en
Application filed filed Critical
Priority to AU22753/97A priority Critical patent/AU707262B2/en
Priority to DE69729125T priority patent/DE69729125T2/en
Priority to AT97905992T priority patent/ATE266675T1/en
Priority to EP97905992A priority patent/EP1007556B1/en
Priority to JP52953997A priority patent/JP3990456B2/en
Priority to CA2247247A priority patent/CA2247247C/en
Publication of WO1997030085A1 publication Critical patent/WO1997030085A1/en
Publication of WO1997030085B1 publication Critical patent/WO1997030085B1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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

[received by the International Bureau on 5 August 1997 (05.08.97); original claims 1-23 replaced by new claims 1-17 (3 pages)]
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 -
PCT/US1997/002439 1996-02-16 1997-02-14 Troponin subunits and fragments useful as angiogenesis inhibitors Ceased WO1997030085A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
AU22753/97A AU707262B2 (en) 1996-02-16 1997-02-14 Troponin subunits and fragments useful as angiogenesis inhibitors
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
EP97905992A EP1007556B1 (en) 1996-02-16 1997-02-14 Troponin subunits and fragments useful as angiogenesis inhibitors
JP52953997A JP3990456B2 (en) 1996-02-16 1997-02-14 Troponin subunits and fragments useful as inhibitors of angiogenesis
CA2247247A CA2247247C (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 Ceased 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)

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US6589936B1 (en) * 1996-02-16 2003-07-08 Children's Medical Center Corporation Pharmaceutical compositions comprising recombinant troponin subunits
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
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
US20030166065A1 (en) * 1997-04-24 2003-09-04 Human Genome Sciences, Inc. Novel integrin ligand ITGL-TSP
US7220557B2 (en) 1997-04-24 2007-05-22 Human Genome Sciences, Inc. METH1 polynucleotides
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
AU756370B2 (en) * 1998-07-17 2003-01-09 Licentia Ltd Myotilin, an actin-organizing protein
US6378526B1 (en) * 1998-08-03 2002-04-30 Insite Vision, Incorporated Methods of ophthalmic administration
AU6117099A (en) * 1998-10-21 2000-05-08 Spectral Diagnostics Inc. Cardiac troponin i polypeptide fragments and uses in diagnostics
JP2002539161A (en) * 1999-03-15 2002-11-19 ボストン ライフ サイエンシズ，インコーポレーテッド． Pharmaceutical compositions comprising troponin subunits, fragments and homologs thereof and methods of using them for inhibiting 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
JP2004511219A (en) 2000-07-12 2004-04-15 アジェンシス，インコーポレイテッド Tumor antigens useful for diagnosis and treatment of bladder, ovarian, lung, and kidney cancer
US20030236188A1 (en) * 2001-05-03 2003-12-25 Spytek Kimberly A. Novel human proteins, polynucleotides encoding them and methods of using the same
JP4214397B2 (en) * 2002-02-04 2009-01-28 秀男 吉田 Anticancer drugs using mutant verotoxins
US8623822B2 (en) * 2002-03-01 2014-01-07 Bracco Suisse Sa KDR and VEGF/KDR binding peptides and their use in diagnosis and therapy
US7211240B2 (en) * 2002-03-01 2007-05-01 Bracco International B.V. Multivalent constructs for therapeutic and diagnostic applications
WO2004065621A1 (en) 2002-03-01 2004-08-05 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
US7261876B2 (en) 2002-03-01 2007-08-28 Bracco International Bv Multivalent constructs for therapeutic and diagnostic applications
JP2006514915A (en) 2002-03-01 2006-05-18 ダイアックス、コープ KDR and VEGF / KDR binding peptides and their use in diagnosis and therapy
EP1490107A4 (en) 2002-03-21 2005-11-09 Univ Florida MODULATION OF ANGIOGENESIS
AU2003275259A1 (en) * 2002-09-26 2004-04-19 Northwestern University Anti-angiogenic fragments of pigment epithelium-derived factor (pedf)
DK2284180T3 (en) 2003-03-03 2015-12-21 Dyax Corp Uses of peptides that specifically bind to the HGF receptor (cMET)
CN1294987C (en) * 2003-04-15 2007-01-17 刘凤鸣 Protein having antitumor function, and high performance expression in vitro
CA2820537C (en) 2003-04-23 2015-10-20 Valeritas, Inc. Hydraulically actuated pump for fluid administration
US9089636B2 (en) 2004-07-02 2015-07-28 Valeritas, 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
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* Cited by examiner, † Cited by third party
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AU652744B2 (en) * 1990-01-25 1994-09-08 Children's Medical Center Corporation 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

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