CA2184493A1 - Methods and compositions useful for inhibition of angiogenesis - Google Patents

Methods and compositions useful for inhibition of angiogenesis

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Publication number
CA2184493A1
CA2184493A1 CA002184493A CA2184493A CA2184493A1 CA 2184493 A1 CA2184493 A1 CA 2184493A1 CA 002184493 A CA002184493 A CA 002184493A CA 2184493 A CA2184493 A CA 2184493A CA 2184493 A1 CA2184493 A1 CA 2184493A1
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tissue
angiogenesis
beta
alpha
antagonist
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CA002184493A
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French (fr)
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CA2184493C (en
Inventor
Peter Brooks
David A. Cheresh
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Scripps Research Institute
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70546—Integrin superfamily
    • C07K14/70557—Integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2839—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily
    • C07K16/2848—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Abstract

The present invention describes methods for inhibiting angiogenesis in tissues using vitronectin .alpha.v.beta.3 antagonists, and particularly for inhibiting angiogenesis in inflamed tissues and in tumor tissues and metastases using therapeutic compositions containing .alpha.v.beta.3 antagonists.

Claims (54)

  1. What Is Claimed Is:
    l. A method for inhibiting angiogenesis in a tissue comprising administering to said tissue a composition comprising an angiogenesis-inhibiting amount of an .alpha.v.beta.3 antagonist.
  2. 2. The method of claim 1 wherein said .alpha.v.beta.3 antagonist inhibits binding of fibrinogen to .alpha.v.beta.3 but does not substantially inhibit binding of fibrinogen to .alpha.IIb.beta.3 or .alpha.v.beta.1.
  3. 3. The method of claim 1 wherein said .alpha.v.beta.3 antagonist is a monoclonal antibody immunospecific for .alpha.v.beta.3.
  4. 4. The method of claim 3 wherein said monoclonal antibody has the immunoreaction characteristics of the monoclonal antibody LM609 (ATCC HB 9537).
  5. 5. The method of claim 1 wherein said .alpha.v.beta.3 antagonist is an RGD-containing polypeptide.
  6. 6. The method of claim 5 wherein said polypeptide is selected from the group consisting of c-(GrGDFV) (SEQ ID NO 4), c-(RGDfV) (SEQ ID NO
    5), c-(RGDEv) (SEQ ID NO 7), and YTAECKPQVTRGDVF
    (SEQ ID NO 8), and a salt thereof.
  7. 7. The method of claim 6 wherein said salt is hydrochloride or trifluoroacetate.
  8. 3. The method of claim 1 wherein said tissue is inflamed and said angiogenesis is inflamed tissue angiogenesis.
  9. 9. The method of claim 8 wherein said tissue is arthritic.
  10. 10. The method of claim 9 wherein said arthritic tissue is present in a mammal with rheumatoid arthritis.
  11. 11. The method of claim 1 wherein said tissue is the retinal tissue of a patient with diabetic retinopathy and said angiogenesis is retinal angiogenesis .
  12. 12. The method of claim 1 wherein said tissue is a hemangioma.
  13. 13. The method of claim 1 wherein said tissue is a solid tumor or a solid tumor metastasis and said angiogenesis is tumor angiogenesis.
  14. 14. The method of claim 1 wherein said angiogenesis-inhibiting amount is from about 2 uM
    to 5 mM.
  15. 15. The method of claim 1 wherein said administering comprises intravenous, transdermal, intrasynovial, intramuscular, or oral administration .
  16. 16. The method of claim 1 wherein said administering is conducted in conjunction with chemotherapy .
  17. 17. The method of claim 1 wherein said administering comprises a single dose intravenously .
  18. 18. A method for regression of established tumor in a tissue comprising administering to said tissue a composition comprising an angiogenesis-inhibiting amount of an .alpha.v.beta.3 antagonist.
  19. 19. The method of claim 18 wherein said .alpha.v.beta.3 antagonist inhibits binding of fibrinogen to .alpha.v.beta.3 but does not substantially inhibit binding of fibrinogen to .alpha.IIb.beta.3 or .alpha.v.beta.1.
  20. 20. The method of claim 18 wherein said .alpha.v.beta.3 antagonist is a monoclonal antibody immunospecific for .alpha.v.beta.3.
  21. 21. The method of claim 20 wherein said monoclonal antibody has the immunoreaction characteristics of the monoclonal antibody LM609 (ATCC HB 9537).
  22. 22. The method of claim 18 wherein said .alpha.v.beta.3 antagonist is an RGD-containing polypeptide.
  23. 23. The method of claim 22 wherein said polypeptide is selected from the group consisting of c-(GrGDFV) (SEQ ID NO 4), c-(RGDfV) (SEQ ID NO

    5), c-(RGDFv) (SEQ ID NO 7), and YTAECKPQVTRGDVF
    (SED ID NO 8), and a salt thereof.
  24. 24. The method of claim 23 wherein said salt is hydrochloride or trifluoroacetate.
  25. 25. The method of claim 18 wherein said tissue is inflamed and said angiogenesis is inflamed tissue angiogenesis
  26. 26. The method of claim 25 wherein said tissue is arthritic.
  27. 27. The method of claim 26 wherein said arthritic tissue is present in a mammal with rheumatoid arthritis.
  28. 28. The method of claim 18 wherein said tissue is the retinal tissue of a patient with diabetic retinopathy and said angiogenesis is retinal angiogenesis.
  29. 29. The method of claim 18 wherein said tissue is a hemangioma.
  30. 30, The method of claim 18 wherein said tissue is a solid tumor or a solid tumor metastasis and said angiogenesis is tumor angiogenesis.
  31. 31. The method of claim 18 wherein said angiogenesis-inhibiting amount is from about 2 uM
    to 5 mM.
  32. 32. The method of claim 18 wherein said administering comprises intravenous, transdermal, intrasynovial, intramuscular, or oral administration.
  33. 33. The method of claim 18 wherein said administering is conducted in conjunction with chemotherapy.
  34. 34. The method of claim 18 wherein said administering comprises a single dose intravenously.
  35. 35. The method of claim 18 wherein said regression occurs 7 days following administration of said angiogenesis-inhibiting antagonist.
  36. 36. A method of inducing apoptosis in neo-vasculature in a tissue comprising administering to said tissue a composition comprising an angiogenesis-inhibiting amount of an .alpha.v.beta.3 antagonist.
  37. 37. The method of claim 36 wherein said .alpha.v.beta.3 antagonist inhibits binding of fibrinogen to .alpha.v.beta.3 but does not substantially inhibit binding of fibrinogen to .alpha.IIb.beta.3 or .alpha.v.beta.1.
  38. 38. The method of claim 36 wherein said .alpha.v.beta.3 antagonist is a monoclonal antibody immunospecific for .alpha.v.beta.3.
  39. 39. The method of claim 38 wherein said monoclonal antibody has the immunoreaction characteristics of the monoclonal antibody LM609 (ATCC HB 9537).
  40. 40. The method of claim 36 wherein said .alpha.v.beta.3 antagonist is an RGD-containing polypeptide.
  41. 41. The method of claim 40 wherein said polypeptide is selected from the group consisting of c-(GrGDFV) (SEQ ID NO 4), c-(RGDfV) (SEQ ID NO 5), c-(RGDFv) (SEQ ID NO 7), and YTAECKPQVTRGDVF (SEQ
    ID NO 8), and a salt thereof .
  42. 42. The method of claim 41 wherein said salt is hydrochloride or trifluoroacetate.
  43. 43. The method of claim 36 wherein said tissue is inflamed and said angiogenesis is inflamed tissue angiogenesis.
  44. 44. The method of claim 43 wherein said tissue is arthritic.
  45. 45. The method of claim 44 wherein said arthritic tissue is present in a mammal with rheumatoid arthritis.
  46. 46. The method of claim 36 wherein said tissue is the retinal tissue of a patient with diabetic retillopathy and said angiogenesis is retinal angiogenesis.
  47. 47. The method of claim 36 wherein said tissue is a hemangioma.
  48. 48. The method of claim 36 wherein said tissue is a solid tumor or a solid tumor metastasis and said angiogenesis is tumor angiogenesis.
  49. 49. The method of claim 36 wherein said angiogenesis-inhibiting amount is from about 2 uM
    to 5 mM.
  50. 50. The method of claim 36 wherein said administering comprises intravenous, transdermal, intrasynovial, intramuscular, or oral administration.
  51. 51. The method of claim 36 wherein said administering is conducted in conjunction with chemotherapy.
  52. 52. The method of claim 36 wherein said administering comprises a single dose intravenously.
  53. 53. The method of claim 36 wherein said apoptosis occurs at least 48 hours following administration of said angiogenesis-inhibiting antagonist.
  54. 54. The method of claim 1 wherein said tissue is a coronary artery at risk of restenosis following coronary angioplasty.
CA2184493A 1994-03-18 1995-03-09 Methods and compositions useful for inhibition of angiogenesis Expired - Fee Related CA2184493C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US08/210,715 1994-03-18
US08/210,715 US5753230A (en) 1994-03-18 1994-03-18 Methods and compositions useful for inhibition of angiogenesis
US08/366,665 US5766591A (en) 1994-03-18 1994-12-30 Methods and compositions useful for inhibition of angiogenesis
US08/366,665 1994-12-30
PCT/US1995/003035 WO1995025543A1 (en) 1994-03-18 1995-03-09 Methods and compositions useful for inhibition of angiogenesis

Publications (2)

Publication Number Publication Date
CA2184493A1 true CA2184493A1 (en) 1995-09-28
CA2184493C CA2184493C (en) 2010-05-11

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CA2184493A Expired - Fee Related CA2184493C (en) 1994-03-18 1995-03-09 Methods and compositions useful for inhibition of angiogenesis

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US (7) US5753230A (en)
EP (3) EP1410807B1 (en)
JP (2) JP4268222B2 (en)
KR (1) KR100327081B1 (en)
CN (1) CN1161152C (en)
AT (3) ATE255907T1 (en)
AU (1) AU709645B2 (en)
CA (1) CA2184493C (en)
CZ (1) CZ294650B6 (en)
DE (2) DE69532279T3 (en)
DK (3) DK1410807T3 (en)
ES (3) ES2355074T3 (en)
FI (1) FI121916B (en)
HK (1) HK1013960A1 (en)
HU (1) HU221988B1 (en)
MX (1) MX9604145A (en)
NO (1) NO322441B1 (en)
NZ (3) NZ511293A (en)
PT (2) PT754059E (en)
RU (1) RU2162712C2 (en)
SI (1) SI0754059T2 (en)
SK (1) SK284586B6 (en)
UA (1) UA44729C2 (en)
WO (1) WO1995025543A1 (en)
ZA (1) ZA952214B (en)

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