Pharmaceutical compositions comprising troponin subunits, fragments and analogs thereof and methods of their use to inhibit angiogenesis

• US 5,837,680 A
• Filed: 02/16/1996
• Issued: 11/17/1998
• Est. Priority Date: 02/16/1996
• Status: Expired due to Term

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Langer, Robert S., Moses, Marsha A., Wu, Inmin, Sytkowski, Arthur, Wiederschain, Dimitri G.
• Primary Examiner(s): Tsang, Cecilia J.
• Assistant Examiner(s): BORIN, MICHAEL L
• Application Number:
  US08/602,941
• Time in Patent Office: 1,005 Days
• Field of Search: 514/12, 530/324, 530/350
• US Class Current: 514/9.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/4716 Muscle proteins, e.g. myosin, actin

Abstract

The present invention relates to pharmaceutical compositions containing troponin subunits C, I, or T, or fragments thereof, in therapeutically effective amounts that are capable of inhibiting endothelial cell proliferation. The invention also relates to pharmaceutical compositions containing analogs of troponin subunits C, I, or T and analogs of their fragments, in therapeutically effective amounts that are capable of inhibiting endothelial cell proliferation. The invention further relates to treatment of neovascular disorders by administration of a therapeutic compound of the invention.

Claims

1. A method of inhibiting atopic angiogenesis in a subject, having a disease or disorder causing atopic angiogenesis comprising applying to a site of atopic angiogenesis an amount of a peptide that is effective to inhibit angiogenesis, in which the peptide is:

a. an inhibitor of bFGF-stimulated bovine endothelial cell proliferation having an IC₅₀ of at least 10 μ

M;

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 I subunit (SEQ. ID. NO;

2), human fast-twitch troponin C subunit (SEQ. ID. NO;

1) and human fast-twitch troponin T subunit (SEQ. ID. NO;

3).

2. The method of claim 1, in which the subunit is human fast-twitch troponin C (SEQ. ID. NO:

1) or human fast-twitch troponin I.

3. The method of claim 2, in which the disease disorder is a solid tumor.

4. The method of claim 2, in which the tumor is a tumor of the central nervous system.

5. The method according to claim 2, in which the disease or disorder is an ophthalmologic disease or disorder.