Antigen PIPA and antibodies that bind thereto

• US 7,405,061 B2
• Filed: 11/13/2003
• Issued: 07/29/2008
• Est. Priority Date: 11/13/2002
• Status: Expired due to Fees

• Current Assignee: MacroGenics, Inc.
• Original Assignee: Raven Technology (Beijing) Co., Ltd.
• Inventors: Mather, Jennie P., Liang, Tony W., Li, Ronghao
• Primary Examiner(s): Harris; Alana M.
• Assistant Examiner(s): Holleran; Anne L
• Application Number:
  US10/713,248
• Publication Number:
  US 20040171814A1
• Time in Patent Office: 1,720 Days
• Field of Search: 530/387.1, 530/388.1, 530/388.22, 424/130.1, 424/141.1, 424/143.1, 536/23.53, 435/70.21, 435/320.1, 435/330
• US Class Current: 435/70.21
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/77 Internalization into the cell

Abstract

Provided herein is disclosure about the identification and characterization of disease and cancer associated antigen PIPA. The invention also provides a family of monoclonal antibodies that bind to antigen PIPA, and methods of diagnosing and treating various human cancers and diseases that express PIPA.

Claims

1. An isolated antibody PIP produced by a host cell with a deposit number of ATCC No. PTA-4220.

2. A single-chain Fv comprising the variable regions of the light and heavy chains of the antibody PIP of claim 1, wherein said single-chain Fv has the binding specificity of said antibody PIP.

3. A chimeric antibody comprising the variable regions of the light chain and the heavy chain of the antibody PIP of claim 1 and constant regions of the light chain and the heavy chain of a human antibody, wherein said chimeric antibody has the binding specificity of said antibody PIP.

4. A composition comprising the antibody of claim 3, wherein the antibody is linked to a therapeutic agent.

5. A pharmaceutical composition comprising the antibody of claim 3 and a pharmaceutically acceptable excipient, wherein the antibody is linked to a therapeutic agent.

6. A fragment of the chimeric antibody according to claim 3, wherein said fragment has the binding specificity of said antibody PIP.

7. A pharmaceutical composition comprising a therapeutically effective dose of the antibody of claim 3, linked or bound to a therapeutic moiety, and a pharmaceutically acceptable carrier.

8. A humanized antibody comprising each of three CDRs from the light chain of the antibody PIP of claim 1 and each of three CDRs from the heavy chain of the antibody of PIP of claim 1, wherein said humanized antibody has the binding specificity of said antibody PIP.

9. A composition comprising the antibody of claim 8, wherein the antibody is linked to a therapeutic agent.

10. A pharmaceutical composition comprising the antibody of claim 8 and a pharmaceutically acceptable excipient, wherein the antibody is linked to a therapeutic agent.

11. A fragment of the humanized antibody according to claim 8, wherein said fragment has the binding specificity of said antibody PIP.

12. A pharmaceutical composition comprising a therapeutically effective dose of the antibody of claim 8, linked or bound to a therapeutic moiety, and a pharmaceutically acceptable carrier.

13. A method of generating an antibody, comprising expressing one or more polynucleotides encoding the antibody of claim 3 or claim 8 respectively, and purifying the antibody, thereby generating the antibody.

14. A kit comprising an antibody according to any one of claims 1, 3, and 8.

15. An isolated nucleic acid comprising a polynucleotide sequence coding for the antibody of any one of claims 1, 3, 8, or an antigen-binding fragment thereof.

16. The nucleic acid of claim 15, wherein the nucleic acid is operably linked to a promoter.

17. The nucleic acid of claim 16, wherein the promoter and the nucleic acid are contained in an expression vector.

18. A cultured cell line transfected, transformed or infected with a vector containing the nucleic acid of claim 15.

19. 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 15 under conditions in which an immunoglobulin polypeptide or antigen binding fragment is expressed; and

b. harvesting the expressed immunoglobulin polypeptide or fragment.

20. A fragment of the PIP antibody of claim 1, wherein the fragment comprises the variable region of the heavy chain and the variable region of the light chain of said antibody PIP, and wherein said fragment has the binding specificity of said antibody PIP.

21. A pharmaceutical composition comprising a therapeutically effective dose of the fragment of the antibody of claim 20, linked or bound to a therapeutic moiety, and a pharmaceutically acceptable carrier.

22. A method of generating an antibody fragment comprising expressing one or more polynucleotides encoding the fragment of claim 20, and purifying the fragment, thereby generating the fragment.

23. The fragment of claim 20, wherein the fragment is a Fab.

24. The fragment of claim 20, wherein the fragment is a Fab′

.

25. The fragment of claim 20, wherein the fragment is a F(ab′

)₂.

26. The fragment of claim 20, wherein the fragment is a Fv.

27. A composition comprising the fragment of any one of claims 20, 6, and 11, 23-26 wherein the fragment is linked to a therapeutic agent.

28. A kit comprising the fragment according to any one of claims 20, 6, and 11, 23-26.

29. The antibody of claim 1, wherein said antibody has the ability to bind to an antigen target that is exposed on the surface of a living cell in vitro or in vivo.

30. A pharmaceutical composition comprising a therapeutically effective dose of the purified antibody of claim 1 or an antigen-binding fragment thereof, linked or bound to a therapeutic moiety, together with a pharmaceutically acceptable carrier.

31. A pharmaceutical composition comprising a therapeutically effective dose of the antibody PIP of claim 1, linked or bound to a therapeutic moiety, and a pharmaceutically acceptable carrier.

32. An isolated nucleic acid comprising a polynucleotide sequence coding for the monoclonal antibody of claim 1 or an antigen binding fragment thereof.

33. 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 32 under conditions in which an immunoglobulin polypeptide or antigen binding fragment is expressed; and

b. harvesting the expressed immunoglobulin polypeptide or fragment.

34. The antibody of claim 1, wherein said antibody has the ability to bind to an antigen target on a cancer cell.

35. The antibody of claim 34, 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, bone cancer, brain and spinal cord cancers, metastatic brain tumors, breast cancer, carotid body tumors, cervical cancer, chondrosarcoma, chordoma, 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, leukemias, lipoma/benign lipomatous tumors, liposarcoma/malignant lipomatous tumors, liver cancer, 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, pheochromocytoma, pituitary tumors, prostate cancer, posterior uveal 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.

36. The antibody of claim 35, wherein the bladder cancer is selected from the group consisting of squamous cell carcinoma and transitional cell carcinoma.

37. The antibody of claim 35, wherein the bone cancer is selected from the group consisting of admantinoma, aneurismal bone cysts, osteochondroma and osteosarcoma.

38. The antibody of claim 35, wherein the kidney cancer is selected from the group consisting of nephroblastoma and papillary renal cell carcinoma.

39. The antibody of claim 35, wherein the liver cancer is selected from the group consisting of hepatoblastoma and hepatocellular carcinoma.

40. The antibody of claim 35, wherein the uterine caner is selected from the group consisting of carcinoma of the cervix, endometrial carcinoma and leiomyoma.

41. An isolated cell line having a deposit number of ATCC No. PTA-4220.

42. A method of generating antibody PIP comprising culturing the isolated cell line according to claim 41 under conditions that allow production of antibody PIP, and purifying the antibody, thereby generating antibody PIP.