NOVEL RAAG10 CELL SURFACE TARGET AND A FAMILY OF ANTIBODIES RECOGNIZING THAT TARGET

• US 20090202561A1
• Filed: 03/27/2009
• Published: 08/13/2009
• Est. Priority Date: 06/19/2002
• Status: Active Grant

• Current Assignee: MacroGenics, Inc.
• Original Assignee: MacroGenics, Inc.
• Inventors: Roberts, Penelope E., Pan, Zhuangyu, Li, Ronghao, MATHER, Jennie P.
• Granted Patent: US 8,779,098 B2
• Time in Patent Office: Days
• US Class Current: 424/156.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• 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: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/70532 : B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/2827 : against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/30 : from tumour cells
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: G01N 2333/70503 : Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
• CPC Class Codes: G01N 33/57492 : involving compounds localized on the membrane of tumor or cancer cells

Abstract

The invention provides the identification and characterization of disease and cancer-associated antigen, RAAG10. The invention also provides a family of monoclonal antibodies that bind to antigen RAAG10, methods of diagnosing and treating various human cancers and diseases that express RAAG10.

Claims

1. A substantially purified immunoglobulin polypeptide or an antigen binding fragment thereof, that specifically binds to RAAG10, and has at least one or more of the following characteristics:

a. the ability to bind to RAAG10 on a cancer cell;

b. ability to bind to a portion of RAAG10 that is exposed on the surface of a living cell in vitro or in vivo;

c. ability to deliver a therapeutic agent or detectable marker to a cancer cell expressing RAAG10; and

d. ability to deliver a therapeutic agent or detectable marker into a cancer cell expressing RAAG10.

2. The purified immunoglobulin polypeptide or antigen binding fragment of claim 1, wherein said cancer cell is selected from the group consisting of cancer cells from adrenal gland tumors, AIDS-associated cancers, alveolar soft part sarcoma, astrocytic tumors, bladder cancer (squamous cell carcinoma and transitional cell carcinoma), bone cancer (adamantinoma, aneurismal bone cysts, osteochondroma, osteosarcoma), brain and spinal cord cancers, metastatic brain tumors, breast cancer, carotid body tumors, cervical cancer, chondrosarcoma, dhordoma, chromophobe renal cell carcinoma, clear cell carcinoma, colon cancer, colorectal cancer, cutaneous benign fibrous histiocytomas, desmoplastic small round cell tumors, ependymomas, Ewing'"'"'s tumors, extraskeletal myxoid chondrosarcoma, fibrogenesis imperfecta ossium, fibrous dysplasia of the bone, gallbladder and bile duct cancers, gestational trophoblastic disease, germ cell tumors, head and neck cancers, islet cell tumors, Kaposi'"'"'s Sarcoma, kidney cancer (nephroblastoma, papillary renal cell carcinoma), leukemias, lipomalbenign lipomatous tumors, liposarcoma/malignant lipomatous tumors, liver cancer (hepatoblastoma, hepatocellular carcinoma), lymphomas, lung cancer, medulloblastoma, melanoma, meningiomas, multiple endocrine neoplasia, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumors, ovarian cancer, pancreatic cancers, papillary thyroid carcinomas, parathyroid tumors, pediatric cancers, peripheral nerve sheath tumors, phaeochromocytoma, pituitary tumors, prostate cancer, posterious unveal melanoma, rare hematologic disorders, renal metastatic cancer, rhabdoid tumor, rhabdomysarcoma, sarcomas, skin cancer, soft-tissue sarcomas, squamous cell cancer, stomach cancer, synovial sarcoma, testicular cancer, thymic carcinoma, thymoma, thyroid metastatic cancer, and uterine cancers (carcinoma of the cervix, endometrial carcinoma, and leiomyoma).

3. An isolated nucleic acid sequence coding for the immunoglobulin polypeptide or antigen binding fragment thereof of claim 1.

4. The nucleic acid of claim 3, wherein the nucleic acid is operably linked to a promoter.

5. The nucleic acid of claim 4, wherein the promoter and the nucleic acid are contained in an expression vector.

6. The nucleic acid of claim 3, wherein the polypeptide is a monoclonal antibody.

7. A cell line transfected, transformed, or infected with a vector containing a nucleic acid of claim 3.

8. A method of producing a substantially purified immunoglobulin polypeptide, or an antigen binding fragment thereof, comprising the steps of:

a. Growing a cell line transformed with the nucleic acid of claim 3 under conditions in which the immunoglobulin polypeptide or antigen binding fragment is expressed; and

b. Harvesting the expressed immunoglobulin polypeptide or fragment.

9. The method of claim 8, wherein the cell line is a hybridoma.

10. The method of claim 9, wherein the hybridoma is selected from the group consisting of ATCC No. PTA-4217, ATCC No. PTA-4218, ATCC No. PTA-4244, and ATCC No. PTA-4245.

11. The method of claim 8, wherein the immunoglobulin polypeptide is a monoclonal antibody.

12. A pharmaceutical composition comprising a therapeutically effective dose of the purified immunoglobulin or antigen binding fragment of claim 1, together with a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising a therapeutically effective dose of a monoclonal antibody or an antigen binding fragment thereof that specifically binds to RAAG10, and has at least one or more of the following characteristics:

a. the ability to bind to RAAG10 on a cancer cell;

b. ability to bind to a portion of RAAG10 that is exposed on the surface of a living cell in vitro or in vivo;

c. ability to deliver a therapeutic agent or detectable marker to a cancer cell expressing RAAG10; and

d. ability to deliver a therapeutic agent or detectable marker into a cancer cell expressing RAAG10;

together with a pharmaceutically acceptable carrier.

14. The pharmaceutical composition of claim 13, wherein the composition comprises an additional therapeutic moiety.

15. An isolated cell line selected from the group consisting of ATCC No. PTA-4217, ATCC No. PTA-4218, ATCC No. PTA-4244, and ATCC No. PTA-4245, or progeny thereof.

16. A method for delivering a chemotherapeutic agent to a cancer cell comprising administering a composition comprising an anti-RAAG10 antibody associated with the chemotherapeutic agent, wherein the cancer cell is selected from the group consisting of cancer cells from adrenal gland tumors, AIDS-associated cancers, alveolar soft part sarcoma, astrocytic tumors, bladder cancer (squamous cell carcinoma and transitional cell carcinoma), bone cancer (adamantinoma, aneurismal bone cysts, osteochondroma, osteosarcoma), brain and spinal cord cancers, metastatic brain tumors, breast cancer, carotid body tumors, cervical cancer, chondrosarcoma, dhordoma, chromophobe renal cell carcinoma, clear cell carcinoma, colon cancer, colorectal cancer, cutaneous benign fibrous histiocytomas, desmoplastic small round cell tumors, ependymomas, Ewing'"'"'s tumors, extraskeletal myxoid chondrosarcoma, fibrogenesis imperfecta ossium, fibrous dysplasia of the bone, gallbladder and bile duct cancers, gestational trophoblastic disease, germ cell tumors, head and neck cancers, islet cell tumors, Kaposi'"'"'s Sarcoma, kidney cancer (nephroblastoma, papillary renal cell carcinoma), leukemias, lipomalbenign lipomatous tumors, liposarcoma/malignant lipomatous tumors, liver cancer (hepatoblastoma, hepatocellular carcinoma), lymphomas, lung cancer, medulloblastoma, melanoma, meningiomas, multiple endocrine neoplasia, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumors, ovarian cancer, pancreatic cancers, papillary thyroid carcinomas, parathyroid tumors, pediatric cancers, peripheral nerve sheath tumors, phaeochromocytoma, pituitary tumors, prostate cancer, posterious unveal melanoma, rare hematologic disorders, renal metastatic cancer, rhabdoid tumor, rhabdomysarcoma, sarcomas, skin cancer, soft-tissue sarcomas, squamous cell cancer, stomach cancer, synovial sarcoma, testicular cancer, thymic carcinoma, thymoma, thyroid metastatic cancer, and uterine cancers (carcinoma of the cervix, endometrial carcinoma, and leiomyoma).

17. The method of claim 16, wherein the chemotherapeutic agent is administered to an individual.

18. The method of claim 16, wherein the hybridoma is selected from the group consisting of ATCC No. PTA-4217, ATCC No. PTA-4218, ATCC No. PTA-4244, and ATCC No. PTA-4245 or progeny thereof.

19. A method of inhibiting growth of cancer cells in an individual comprising administering to the individual an effective amount of a composition comprising an anti-RAAG10 antibody associated with a chemotherapeutic agent to the individual, wherein the cancer cells are selected from the group consisting of cancer cells from adrenal gland tumors, AIDS-associated cancers, alveolar soft part sarcoma, astrocytic tumors, bladder cancer (squamous cell carcinoma and transitional cell carcinoma), bone cancer (adamantinoma, aneurismal bone cysts, osteochondroma, osteosarcoma), brain and spinal cord cancers, metastatic brain tumors, breast cancer, carotid body tumors, cervical cancer, chondrosarcoma, dhordoma, chromophobe renal cell carcinoma, clear cell carcinoma, colon cancer, colorectal cancer, cutaneous benign fibrous histiocytomas, desmoplastic small round cell tumors, ependymomas, Ewing'"'"'s tumors, extraskeletal myxoid chondrosarcoma, fibrogenesis imperfecta ossium, fibrous dysplasia of the bone, gallbladder and bile duct cancers, gestational trophoblastic disease, germ cell tumors, head and neck cancers, islet cell tumors, Kaposi'"'"'s Sarcoma, kidney cancer (nephroblastoma, papillary renal cell carcinoma), leukemias, lipomalbenign lipomatous tumors, liposarcoma/malignant lipomatous tumors, liver cancer (hepatoblastoma, hepatocellular carcinoma), lymphomas, lung cancer, medulloblastoma, melanoma, meningiomas, multiple endocrine neoplasia, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumors, ovarian cancer, pancreatic cancers, papillary thyroid carcinomas, parathyroid tumors, pediatric cancers, peripheral nerve sheath tumors, phaeochromocytoma, pituitary tumors, prostate cancer, posterious unveal melanoma, rare hematologic disorders, renal metastatic cancer, rhabdoid tumor, rhabdomysarcoma, sarcomas, skin cancer, soft-tissue sarcomas, squamous cell cancer, stomach cancer, synovial sarcoma, testicular cancer, thymic carcinoma, thymoma, thyroid metastatic cancer, and uterine cancers (carcinoma of the cervix, endometrial carcinoma, and leiomyoma).

20. The method of claim 19, wherein the chemotherapeutic agent is delivered into the cancer cells.

21. The method of claim 19, wherein the anti-RAAG10 antibody is a monoclonal antibody expressed by cell line wherein the hybridoma is selected from the group consisting of ATCC No. PTA-4217, ATCC No. PTA-4218, ATCC No. PTA-4244, and ATCC No. PTA-4245 or progeny thereof.

22. A method for detecting the presence or absence of a cancer cell in an individual comprising contacting cells from the individual with an anti-RAAG10 antibody, and detecting a complex of RAAG10 from the cells and the antibody, if any, wherein the cancer cell is selected from the group consisting of cancer cells from adrenal gland tumors, AIDS-associated cancers, alveolar soft part sarcoma, astrocytic tumors, bladder cancer (squamous cell carcinoma and transitional cell carcinoma), bone cancer (adamantinoma, aneurismal bone cysts, osteochondroma, osteosarcoma), brain and spinal cord cancers, metastatic brain tumors, breast cancer, carotid body tumors, cervical cancer, chondrosarcoma, dhordoma, chromophobe renal cell carcinoma, clear cell carcinoma, colon cancer, colorectal cancer, cutaneous benign fibrous histiocytomas, desmoplastic small round cell tumors, ependymomas, Ewing'"'"'s tumors, extraskeletal myxoid chondrosarcoma, fibrogenesis imperfecta ossium, fibrous dysplasia of the bone, gallbladder and bile duct cancers, gestational trophoblastic disease, germ cell tumors, head and neck cancers, islet cell tumors, Kaposi'"'"'s Sarcoma, kidney cancer (nephroblastoma, papillary renal cell carcinoma), leukemias, lipomalbenign lipomatous tumors, liposarcoma/malignant lipomatous tumors, liver cancer (hepatoblastoma, hepatocellular carcinoma), lymphomas, lung cancer, medulloblastoma, melanoma, meningiomas, multiple endocrine neoplasia, multiple myeloma, myelodysplastic syndrome, neuroblastoma, neuroendocrine tumors, ovarian cancer, pancreatic cancers, papillary thyroid carcinomas, parathyroid tumors, pediatric cancers, peripheral nerve sheath tumors, phaeochromocytoma, pituitary tumors, prostate cancer, posterious unveal melanoma, rare hematologic disorders, renal metastatic cancer, rhabdoid tumor, rhabdomysarcoma, sarcomas, skin cancer, soft-tissue sarcomas, squamous cell cancer, stomach cancer, synovial sarcoma, testicular cancer, thymic carcinoma, thymoma, thyroid metastatic cancer, and uterine cancers (carcinoma of the cervix, endometrial carcinoma, and leiomyoma).

23. An agent that blocks at least one of the following interactions between RAAG10 and an RAAG10 binding partner:

a. the ability to bind to RAAG10 on a cancer cell;

b. ability to bind to a portion of RAAG10 that is exposed on the surface of a living cell in vitro or in vivo;

c. ability to deliver a therapeutic agent or detectable marker to a cancer cell expressing RAAG10; and

d. ability to deliver a therapeutic agent or detectable marker into a cancer cell expressing A RAAG10;

24. A pharmaceutical composition comprising a therapeutically effective dose of an agent according to claim 23, together with a pharmaceutically acceptable carrier.