CA2443840A1 - Cripto blocking antibodies and uses thereof - Google Patents

Cripto blocking antibodies and uses thereof Download PDF

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Publication number
CA2443840A1
CA2443840A1 CA002443840A CA2443840A CA2443840A1 CA 2443840 A1 CA2443840 A1 CA 2443840A1 CA 002443840 A CA002443840 A CA 002443840A CA 2443840 A CA2443840 A CA 2443840A CA 2443840 A1 CA2443840 A1 CA 2443840A1
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CA
Canada
Prior art keywords
antibody
cripto
group
epitope
tumor
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Granted
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CA002443840A
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French (fr)
Other versions
CA2443840C (en
Inventor
Michele Sanicola-Nadel
Kevin Williams
Susan Schiffer
Paul Rayhorn
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Biogen MA Inc
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Individual
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Application filed by Individual filed Critical Individual
Priority to CA2715570A priority Critical patent/CA2715570A1/en
Publication of CA2443840A1 publication Critical patent/CA2443840A1/en
Application granted granted Critical
Publication of CA2443840C publication Critical patent/CA2443840C/en
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Expired - Fee Related legal-status Critical Current

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Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07K16/30—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The invention provides Cripto blocking antibodies, or biologically functiona l fragments thereof, and uses thereof. Antibodies which bind Cripto and modula te Cripto signaling are provided. Antibodies which bind Cripto and block the interaction between Cripto and ALK4 are provided. Antibodies which bind Crip to and modulate tumor growth are also provided. Antibodies which bind Cripto, modulate signaling, and modulate tumor growth are also provided. Antibodies which bind Cripto, block the interaction between Cripto and ALK4 and modulat e tumor growth are provided. The invention also provides methods of using thes e antibodies in therapeutic, diagnostic, and research applications.

Claims (61)

1. An antibody that specifically binds to an epitope in the ligand/receptor binding domain of Cripto.
2. The antibody of claim 1 wherein the Cripto is selected from the group consisting of SEQ ID NO: 1 or 2.
3. The antibody of claim 2 wherein the epitope is in an EGF-like domain.
4. The antibody of claim 2 wherein the epitope is in a cys-rich domain.
5. The antibody of claim 2 which is selected from the group consisting of A6C12.11, A6F8.6, A7H1.19, A8F1.30, A8G3.5, A8H3.1, A8H3.2, A19A10.30, A10B2.18, A27F6.1, A40G12.8, A2D3.23, A7A10.29, A9G9.9, A15C12.10, A15E4.14, A17A2.16, A17C12.28, A17G12.1, A17H6.1, A18B3.11, A19E2.7, B3F6.17, and B6G7.10.
6. The antibody of claim 3 which is selected from the group consisting of A40G12.8, A8H3.1, A27F6.1, B6G7.10, A17G12.1 and A18B3.11.
7. The antibody of claim 4 which is selected from the group consisting of A19A10.30, A8G3.5, A6F8.6 and A6C12.11.
8. An antibody that specifically binds to an epitope comprised in the domain spanning amino acid residues 46-62 of Cripto.
9. The antibody of claim 8 which is A10B2.l8 and B3F6.17.
10. An antibody which binds specifically to an epitope selected from the group of epitopes to which antibodies A6C12.11, A6F8.6, A7H1.19, A8F1.30, A8G3.5, A8H3.1, A8H3.2, A19A10.30, AlOB2.18, A27F6.1, A40G12.8, A2D3.23, A7A10.29, A9G9.9, A15C12.10, A15E4.14, A17A2.16, A17C12.28, A17G12.1, A17H6.1, A18B3.11, A19E2.7, B3F6.17, and B6G7.10 bind.
11. An antibody which binds specifically to Cripto and is capable of modulating Cripto signaling.
12. The antibody of claim 11 which specifically binds to an epitope in an EGF-like domain of Cripto.
13. The antibody of claim 12 which is selected from A40G12.8, A8H3.1 and A27F6.1.
14. The antibody of claim 11 which specifically binds to an epitope in a cys-rich domain of Cripto.
15. The antibody of claim 14 which is A6C12.11.
16. The antibody of claim 11 which is selected from the group consisting of A40G12.8, A8H3.1, A27F6.1, and A6C12.11.
17. An antibody which binds specifically to Cripto and is capable of modulating tumor growth.
18. The antibody of claim 17 which specifically binds to an epitope in an EGF-like domain of Cripto.
19. The antibody of claim 17 which specifically binds to an epitope in a cys-rich domain of Cripto.
20. The antibody of claim 17 which is selected from the group consisting of A27F6.1, A8G3.5 and B6G7.10.
21. An antibody which binds specifically to Cripto, which is capable of modulating Cripto signaling, and which is capable of modulating tumor growth.
22. The antibody of claim 21 which specifically binds to an epitope in an EGF-like domain of Cripto.
23. The antibody of claim 21 which specifically binds to an epitope in a cys-rich domain of Cripto.
24. The antibody of claim 21 which is A27F6.1.
25. An antibody produced by a hybridoma selected from the group consisting of A6F8.6 (ATCC Accession No. PTA-3318), A8G3.5 (ATCC Accession No. PTA-3317), A8H3.1 (ATCC Accession No. PTA-3315), A10B2.18 (ATCC Accession No.
PTA-3311), A27F6.1 (ATCC Accession No. PTA-3310), A40G12.8 (ATCC Accession No. PTA-3316), A17G12.1 (ATCC Accession No. PTA-3314), A18B3.11 (ATCC
Accession No. PTA-3312), B3F6.17 (ATCC Accession No. PTA-3319), and B6G7.10 (ATCC Accession No. PTA-3313).
26. An antibody which binds specifically to Cripto and is capable of blocking the interaction between Cripto and ALK4.
27. The antibody of claim 26 which specifically binds to an epitope in an EGF-like domain of Cripto.
28. The antibody of claim 26 which specifically binds to an epitope in a cys-rich domain of Cripto.
29. The antibody of claim 26 which is selected from the group consisting of A8G3.5, A6F8.6 and A6C12.11.
30. An antibody which binds specifically to Cripto, which is capable of blocking the interaction between Cripto and ALK4, and which is capable of modulating tumor growth.
31. The antibody of claim 30 which specifically binds to an epitope in an EGF-like domain of Cripto.
32. The antibody of claim 30 which specifically binds to an epitope in a cys-rich domain of Cripto.
33. The antibody of claim 30 which is A8G3.5.
34. A Cripto antibody capable of internalizing Cripto.
35. The antibody of claim 34 wherein the antibody is conjugated to a chemotherapeutic.
36. The antibody of claim 34 which is selected from A27F6.1 and B3F6.17.
37. A composition for administration to a subject having a tumor that expresses Cripto comprising at least one of the antibodies of any of claims 1-35.
38. The composition according to claim 37, wherein the subject is human.
39. The composition according to claim 37, further comprising a pharmaceutically acceptable excipient.
40. The composition according to claim 37, wherein the antibody is conjugated to a chemotherapeutic.
41. The composition according to claim 37, further comprising a nonconjugated chemotherapeutic.
42. A method of modulating growth of tumor cells in vitro in a sample comprising the step of adding to the sample the composition of claim 37.
43. A method of modulating growth of tumor cells in vivo in a subject comprising the step of administering to the subject an effective amount of the composition of claim 37.
44. The method according to claim 43, wherein the subject is human.
45. A method of treating a subject having a tumor that over-expresses Cripto comprising administering to said subject the composition of claim 37 in an effective amount.
46. A method of treating a patient having a tumor that over-expresses Cripto comprising administering to said patient the composition of claim 39 in an effective amount.
47. A method of treating a patient having a tumor that over-expresses Cripto comprising administering to said patient the composition of claim 40 in an effective amount.
48. A method of treating a patient having a tumor that over-expresses Cripto comprising administering to said patient the composition of claim 41 in an effective amount.
49. The method according to claim 42, wherein the tumor cell is selected from the group consisting of breast, testicular, colon, lung, ovary, bladder, uterine, cervical, pancreatic, and stomach tumor cells.
50. The method according to claim 43, wherein the tumor cell is selected from the group consisting of breast, testicular, colon, lung, ovary, bladder, uterine, cervical, pancreatic, and stomach tumor cells.
51. The method according to claim 44, wherein the tumor cell is selected from the group consisting of breast, testicular, colon, lung, ovary, bladder, uterine, cervical, pancreatic, and stomach tumor cells.
52. The method according to claim 45, wherein the tumor is selected from the group consisting of breast, testicular, colon, lung, ovary, bladder, uterine, cervical, pancreatic, and stomach tumors.
53. The method according to claim 46, wherein the tumor is selected from the group consisting of breast, testicular, colon, lung, ovary, bladder, uterine, cervical, pancreatic, and stomach tumors.
54. The method according to claim 47, wherein the tumor is selected from the group consisting of breast, testicular, colon, lung, ovary, bladder, uterine, cervical, pancreatic, and stomach tumors.
55. The method according to claim 48, wherein the tumor is selected from the group consisting of breast, testicular, colon, lung, ovary, bladder, uterine, cervical, pancreatic, and stomach tumors.
56. A method of determining whether a tissue expresses Cripto, comprising the step of analyzing tissue from the subject in an immunoassay using an antibody of any of claims 1-37.
57. A method of determining whether a cell line overexpresses Cripto, comprising the step of analyzing the cell line in an immunoassay using an antibody of any of claims 1-37.
58. The antibody of claim 1 wherein the antibody is monoclonal antibodies.
59. The antibody of claim 1 wherein the antibody is humanized antibodies.
60. The antibody of claim 1 wherein the antibody is human antibodies.
61. A method of treating a subject for a condition associated with undesired cell proliferation, said method comprising administering to said subject the composition of claim 37.
CA2443840A 2001-04-26 2002-04-17 Cripto blocking antibodies and uses thereof Expired - Fee Related CA2443840C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA2715570A CA2715570A1 (en) 2001-04-26 2002-04-17 Cripto blocking antibodies and uses thereof

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US28678201P 2001-04-26 2001-04-26
US60/286,782 2001-04-26
US29302001P 2001-05-17 2001-05-17
US60/293,020 2001-05-17
US30109101P 2001-06-26 2001-06-26
US60/301,091 2001-06-26
US36700202P 2002-03-22 2002-03-22
US60/367,002 2002-03-22
PCT/US2002/011950 WO2002088170A2 (en) 2001-04-26 2002-04-17 Cripto blocking antibodies and uses thereof

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CA2715570A Division CA2715570A1 (en) 2001-04-26 2002-04-17 Cripto blocking antibodies and uses thereof

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CA2443840A1 true CA2443840A1 (en) 2002-11-07
CA2443840C CA2443840C (en) 2010-10-26

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CA2715570A Abandoned CA2715570A1 (en) 2001-04-26 2002-04-17 Cripto blocking antibodies and uses thereof
CA2443840A Expired - Fee Related CA2443840C (en) 2001-04-26 2002-04-17 Cripto blocking antibodies and uses thereof

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