Claims for Patent: 7,815,907

Summary for Patent: 7,815,907

Title:	Antibodies to insulin-like growth factor I receptor
Abstract:	The present invention relates to antibodies and antigen-binding portions thereof that specifically bind to insulin-like growth factor I receptor (IGF-IR), which is preferably human IGF-IR. The invention also relates to human anti-IGF-IR antibodies, including chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulin molecules derived from anti-IGF-IR antibodies and nucleic acid molecules encoding such molecules. The present invention also relates to methods of making anti-IGF-IR antibodies, pharmaceutical compositions comprising these antibodies and methods of using the antibodies and compositions thereof for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-IGF-IR antibodies. The invention also relates to gene therapy methods and transgenic animals comprising nucleic acid molecules of the present invention.
Inventor(s):	Cohen; Bruce D (East Lyme, CT), Beebe; Jean (Salem, CT), Miller; Penelope E (Mystic, CT), Moyer; James D (East Lyme, CT), Corvalan; Jose R (Foster City, CA), Gallo; Michael (North Vancouver, CA)
Assignee:	Amgen Fremont Inc. (Fremont, CA) Pfizer Inc. (New York, NY)
Application Number:	11/144,248
Patent Claims:	1. A human monoclonal antibody or an antigen-binding portion thereof that specifically binds insulin-like growth factor I receptor (IGF-IR), wherein the antibody comprises: (a) the variable domain of the light chain of antibody 2.12.1; or (b) the variable domain of a light chain comprising the amino acid sequence in SEQ ID NO: 2. 2. The monoclonal antibody or antigen-binding portion according to claim 1, further comprising the amino acid sequences of the heavy chain CDRs of antibody 2.12.1. 3. A human monoclonal antibody or an antigen binding portion thereof that specifically binds IGF-IR, wherein said antibody comprises the amino acid sequence in SEQ ID NO: 2. 4. A human monoclonal antibody or an antigen-binding portion thereof that specifically binds IGF-IR, wherein said antibody comprises the variable domain of a heavy chain that comprises the amino acid sequence in SEQ ID NO: 49 without the signal sequence. 5. The monoclonal antibody or antigen-binding portion according to claim 4, wherein said antibody further comprises the amino acid sequence in SEQ ID NO: 2. 6. A monoclonal antibody that specifically binds IGF-IR, or an antigen-binding portion of said antibody, wherein said antibody comprises the amino acid sequence of the heavy chain sequence within SEQ ID NO: 49 without the signal sequence, and the amino acid sequence of the light chain sequence within SEQ ID NO: 51 without the signal sequence. 7. A monoclonal antibody that specifically binds IGF-IR, or an antigen-binding portion of said antibody, wherein said antibody comprises the CDR1, CDR2 and CDR3 amino acid sequences, respectively, in SEQ ID NO: 49 and the CDR1, CDR2 and CDR3 amino acid sequences, respectively, in SEQ ID NO: 51, wherein said antibody further comprises the framework amino acid sequences in SEQ ID NO: 49. 8. A human monoclonal antibody that specifically binds IGF-IR, or an antigen-binding portion of said antibody, wherein said antibody comprises the amino acid sequence of SEQ ID NO: 49 without the signal sequence. 9. A human monoclonal antibody that specifically binds IGF-IR, or an antigen-binding portion of said antibody, wherein said antibody comprises the amino acid sequence in SEQ ID NO: 51 without the signal sequence. 10. A monoclonal antibody that specifically binds IGF-IR, or an antigen-binding portion of said antibody, wherein the heavy chain amino acid sequence of said antibody is SEQ ID NO: 49 without the signal sequence, and the light chain amino acid sequence of said antibody is SEQ ID NO: 51 without the signal sequence. 11. A hybridoma cell line having American Type Culture Collection (ATCC) accession number PTA-2792. 12. A monoclonal antibody that specifically binds IGF-IR, or an antigen-binding portion of said antibody, wherein said antibody comprises the heavy chain variable domain and the light chain variable domain of the antibody produced by the hybridoma cell line having the American Type Culture Collection (ATCC) accession number PTA-2792. 13. The monoclonal antibody produced by the hybridoma cell line of claim 11. 14. A monoclonal antibody that specifically binds IGF-IR, or an antigen-binding portion of said antibody, wherein said antibody comprises the heavy chain amino acid sequence and the light chain amino acid sequence of the monoclonal antibody of claim 13. 15. A monoclonal antibody that specifically binds IGF-IR, or an antigen-binding portion of said antibody, wherein said antibody comprises the amino acid sequence of the heavy chain and the amino acid sequence of the light chain of antibody 2.12.1. 16. The monoclonal antibody according to claim 15, wherein the antibody is monoclonal antibody 2.12.1. 17. The monoclonal antibody or antigen-binding portion according to claim 1, wherein said antibody is selected from the group consisting of: an immunoglobulin G (IgG), an IgM, an IgE, an IgA and an IgD, a single chain antibody, and a bispecific antibody. 18. The antigen-binding portion according to claim 1, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 19. The antigen-binding portion according to claim 2, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 20. The antigen-binding portion according to claim 3, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 21. The antigen-binding portion according to claim 4, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 22. The antigen-binding portion according to claim 5, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 23. The antigen-binding portion according to claim 6, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 24. The antigen-binding portion according to claim 7, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 25. The antigen-binding portion according to claim 8, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 26. The antigen-binding portion according to claim 9, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 27. The antigen-binding portion according to claim 10, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 28. The antigen-binding portion according to claim 12, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 29. The antigen-binding portion according to claim 14, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 30. The antigen-binding portion according to claim 15, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 31. The antigen-binding portion according to claim 17, wherein said portion is selected from the group consisting of: an Fab fragment, an F(ab').sub.2 fragment and an Fv fragment. 32. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 1 and a pharmaceutically acceptable carrier. 33. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 2 and a pharmaceutically acceptable carrier. 34. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 3 and a pharmaceutically acceptable carrier. 35. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 4 and a pharmaceutically acceptable carrier. 36. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 5 and a pharmaceutically acceptable carrier. 37. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 6 and a pharmaceutically acceptable carrier. 38. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 7 and a pharmaceutically acceptable carrier. 39. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 8 and a pharmaceutically acceptable carrier. 40. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 9 and a pharmaceutically acceptable carrier. 41. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 10 and a pharmaceutically acceptable carrier. 42. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 12 and a pharmaceutically acceptable carrier. 43. A pharmaceutical composition comprising the monoclonal antibody according to claim 13 and a pharmaceutically acceptable carrier. 44. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 14 and a pharmaceutically acceptable carrier. 45. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 15 and a pharmaceutically acceptable carrier. 46. A pharmaceutical composition comprising the monoclonal antibody according to claim 16 and a pharmaceutically acceptable carrier. 47. A pharmaceutical composition comprising the monoclonal antibody or antigen-binding portion according to claim 17 and a pharmaceutically acceptable carrier. 48. The pharmaceutical composition according to claim 32, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 49. The pharmaceutical composition according to claim 33, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 50. The pharmaceutical composition according to claim 34, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 51. The pharmaceutical composition according to claim 35, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 52. The pharmaceutical composition according to claim 36, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 53. The pharmaceutical composition according to claim 37, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 54. The pharmaceutical composition according to claim 38, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 55. The pharmaceutical composition according to claim 39, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 56. The pharmaceutical composition according to claim 40, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 57. The pharmaceutical composition according to claim 41, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 58. The pharmaceutical composition according to claim 42, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 59. The pharmaceutical composition according to claim 43, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 60. The pharmaceutical composition according to claim 44, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 61. The pharmaceutical composition according to claim 45, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 62. The pharmaceutical composition according to claim 46, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 63. The pharmaceutical composition according to claim 47, further comprising an anti-neoplastic, chemotherapeutic, anti-angiogenic, or anti-tumor agent. 64. An isolated cell line that produces the antibody according to claim 1. 65. The cell line according to claim 64 that produces antibody 2.12.1 or an antibody comprising the amino acid sequences of antibody 2.12.1. 66. A method of detecting the presence or location of an IGF-IR-expressing tumor in a subject in need thereof comprising the steps of: a) administering the antibody or antigen-binding portion according to claim 1 to the subject; and b) detecting binding of said antibody or antigen-binding portion to cells in the subject, wherein said binding indicates the presence or location of the tumor. 67. A method of treating cancer in a patient that overexpresses IGF-I or IGF-IR, comprising the step of administering to the patient an amount of the antibody or antigen-binding portion according to claim 1 effective to treat said cancer. 68. A method of treating a patient in need thereof wherein said patient overexpresses IGF-I or IGF-IR, comprising the step of administering to the patient an effective amount of the antibody or antigen-binding portion according to claim 1. 69. The method according to claim 67, further comprising the step of administering an anti-neoplastic, anti-tumor, anti-angiogenic, or chemotherapeutic agent. 70. A method for decreasing IGF-IR activation in a subject in need thereof comprising the step of administering to the subject the monoclonal antibody or antigen-binding portion according to claim 6. 71. A method for inhibiting IGF-IR associated tyrosine phosphorylation in a subject in need thereof comprising the step of administering to the subject the monoclonal antibody or antigen-binding portion according to claim 6. 72. A method for decreasing IGF-IR signaling in a subject in need thereof comprising the step of administering to the subject the monoclonal antibody or antigen-binding portion according to claim 6. 73. A method for decreasing IGF-IR binding to IGF-I in a subject in need thereof comprising the step of administering to the subject the monoclonal antibody or antigen-binding portion according to claim 6. 74. A method for decreasing the level of IGF-IR in a subject in need thereof comprising the step of administering to the subject the monoclonal antibody or antigen-binding portion according to claim 6. 75. A method for inhibiting tumor growth in a subject in need thereof wherein said subject overexpresses IGF-I or IGF-IR, comprising the step of administering to the subject the monoclonal antibody or antigen-binding portion according to claim 6. 76. The method according to claim 75, wherein the tumor is a colorectal tumor. 77. The method according to claim 75, wherein the tumor is a breast tumor. 78. The method according to claim 75, wherein the tumor is an epidermoid carcinoma cell tumor. 79. The method according to claim 69, wherein the anti-neoplastic agent is adriamycin. 80. A method of detecting the presence or location of an IGF-IR-expressing tumor in a subject in need thereof comprising the steps of: (a) administering the antibody or portion according to any one of claims 6, 10, and 15; and (b) detecting binding of said antibody or antigen-binding portion to cells in the subject, wherein said binding indicates the presence or location of the tumor. 81. A method of treating cancer in a patient that overexpresses IGF-I or IGF-IR, comprising the step of administering to the patient an amount of the antibody or portion according to claim 6, 10, or 15 effective to treat said cancer. 82. A method of treating a patient in need thereof, wherein said patient overexpresses IGF-I or IGF-IR, comprising the step of administering to the patient an effective amount of the antibody or portion according to claim 6, 10, or 15. 83. The method according to claim 81, further comprising the step of administering an anti-neoplastic, anti-tumor, anti-angiogenic, or chemotherapeutic agent. 84. A method for decreasing IGF-IR activation in a subject in need thereof comprising the step of administering to the subject the antibody or portion according to claim 10. 85. A method for inhibiting IGF-IR associated tyrosine phosphorylation in a subject in need thereof, comprising the step of administering to the subject the antibody or portion according to claim 10. 86. A method for decreasing IGF-IR signaling in a subject in need thereof, comprising the step of administering to the subject the antibody or portion according to claim 10. 87. A method for decreasing IGF-IR binding to IGF-I in a subject in need thereof, comprising the step of administering to the subject the antibody or portion according to claim 10. 88. A method for decreasing the level of IGF-IR in a subject in need thereof, comprising the step of administering to the subject the antibody or portion according to claim 10. 89. A method for inhibiting tumor growth in a subject in need thereof wherein said subject overexpresses IGF-I or IGF-IR, comprising the step of administering to the subject the antibody or portion according to claim 10. 90. The method according to claim 89, wherein the tumor is a colorectal tumor. 91. The method according to claim 89, wherein the tumor is a breast cancer tumor. 92. The method according to claim 89, wherein the tumor is an epidermoid carcinoma cell tumor. 93. The method according to claim 83, wherein the anti-neoplastic agent is adriamycin. 94. The method according to claim 67, further comprising the step of administering at least one additional chemotherapeutic agent. 95. The method according to claim 67, wherein said method further comprises radiotherapy. 96. The method according to claim 81, further comprising the step of administering at least one additional chemotherapeutic agent. 97. The method according to claim 81, wherein said method further comprises radiotherapy.

Details for Patent 7,815,907

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Octapharma Pharmazeutika Produktionsges.m.b.h.	CUTAQUIG	immune globulin subcutaneous (human)-hipp	Solution	125668	12/12/2018		2021-01-05