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

• US 6,653,283 B1
• Filed: 11/28/2000
• Issued: 11/25/2003
• Est. Priority Date: 02/16/1996
• Status: Expired due to Fees

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Wu, Inmin, Sytkowski, Arthur, Wiederschain, Dimitri G., Langer, Robert S., Moses, Marsha A.
• Primary Examiner(s): BORIN, MICHAEL L
• Application Number:
  US09/724,401
• Time in Patent Office: 1,092 Days
• Field of Search: 514/12, 514/21, 530/324
• 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

Pharmaceutical compositions and methods of treatment of diseases or disorders involving angiogenesis with therapeutically effective amounts of troponin C, I, or T, subunits, fragments, or analogs thereof.

Claims

1. A method of inhibiting angiogenesis in a subject, having a disease or disorder causing angiogenesis comprising administering to the subject 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 10 μ

M or less;

(b) selected from the group consisting of fast-twitch troponin subunit C (SEQ ID NO;

1), fast-twitch troponin subunit I (SEQ ID NO;

2), and fast-twitch troponin subunit T (SEQ ID NO;

3), and cartilage troponin I (SEQ ID NO;

17).

2. The method of claim 1 in which the disease or disorder is a solid tumor.

3. The method of claim 2 in which the solid tumor is selected from the group consisting of sarcomas and carcinomas including fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesotheliorna, Ewing'"'"'s tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms'"'"' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, Kaposi'"'"'s sarcoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma, and retinoblastoma.

4. The method of claim 1 in which the disease or disorder is an ophthalmic disease or disorder.