Claims for Patent: 8,029,783

Summary for Patent: 8,029,783

Title:	DR5 antibodies and articles of manufacture containing same
Abstract:	The invention concerns anti-DR5 antibodies with improved properties, compositions comprising such antibodies, methods and means for making such antibodies, and their therapeutic use, in particular in the treatment of cancer.
Inventor(s):	Adams; Camellia W. (San Jose, CA), Ashkenazi; Avi J. (San Mateo, CA)
Assignee:	Genentech, Inc. (South San Francisco, CA)
Application Number:	11/344,564
Patent Claims:	1. An anti-DR5 antibody comprising amino acid substitutions in the heavy and light chains of full-length antibody 16E2 (SEQ ID NOS: 11 and 13, respectively), or a functional fragment thereof, wherein said antibody or antibody fragment has a greater affinity for DR5 than said full-length antibody 16E2, and/or exhibits a greater biological activity and/or potency than said full-length antibody 16E2, and wherein the amino acid substitutions comprise: (a) a set of heavy chain substitutions selected from the group consisting of (i) M34L, N53Q, L102Y; (ii) M34L, N53Y, L102Y; (iii) G33A, N53Q, L102Y; (iv) G33A, N53Y, L102Y; (v) T28A, N53Q, L102Y in the amino acid sequence of SEQ ID NO: 11; and (b) a set of light chain substitutions selected from the group consisting of (i) Q24S, G50K, K51D, H95bY, N25S, N53E; (ii) Q24S, K51A, D92S, S93Y; and (iii) Q24S, K51A, R91A in the amino acid sequence of SEQ ID NO: 13. 2. The anti-DR5 antibody of claim 1, or a functional fragment thereof, further comprising one or more substitutions in the framework of the full length 16E2 antibody heavy chain (SEQ ID NO: 11) variable domain. 3. The anti-DR5 antibody of claim 2, or a functional fragment thereof, comprising the framework substitutions Q6E, V11L, E12V, R13Q, and K105Q. 4. The anti-DR5 antibody of claim 1 or claim 3 comprising the substitutions G33A, N53Q, L102Y in the amino acid sequence of SEQ ID NO: 11, and the substitutions Q24S, K51A, R91A in the amino acid sequence of SEQ ID NO: 13. 5. The anti-DR5 antibody of claim 1, or a functional fragment thereof, selected from the group consisting of antibodies 1.1, 2.1, 3.1, 4.1, 5.1, 6.1, 7.1, 8.1, 9.1, 1.2, 2.2, 3.2, 4.2, 5.2, 6.2, 7.2, 8.2, 9.2, 1.3, 2.2, 3.3, 4.3, 5.3, 6.3, 7.3, 8.3, and 9.3. 6. The anti-DR5 antibody of claim 5 which is antibody 7.3 or 8.3, or a functional fragment thereof. 7. The anti-DR5 antibody of claim 6 which is antibody 7.3, or a functional fragment thereof. 8. The anti-DR5 antibody of claim 1 or claim 7, wherein said fragment is selected from the group consisting of Fab, Fab', F(ab')2, and Fv fragments, diabodies, single chain antibody molecules, and multispecific antibodies formed from antibody fragments. 9. The anti-DR5 antibody of claim 8 wherein said antibody is a single-chain antibody. 10. The anti-DR5 antibody of claim 8 wherein said fragment is an Fv fragment. 11. The anti-DR5 antibody or antibody fragment of claim 1 wherein said biological activity is activation or stimulation of apoptosis in cancer cells. 12. The anti-DR5 antibody or antibody fragment of claim 1 wherein said biological activity is anti-cancer activity. 13. The anti-DR5 antibody or antibody fragment of claim 12 wherein cancer is selected from the group consisting of carcinoma, lymphoma, blastoma, sarcoma and leukemia. 14. The anti-DR5 antibody or antibody fragment of claim 13 wherein said cancer is selected from the group consisting of squamous cell cancer, small-cell lung cancer, non-small cell lung cancer (NSCLC), non-Hodgkin's lymphoma, blastoma, gastrointestinal cancer, renal cancer, ovarian cancer, liver cancer, stomach cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, pancreatic cancer, endometrial carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, and head and neck cancer. 15. The anti-DR5 antibody or antibody fragment of claim 14 wherein said cancer is NSCLC, non-Hodgkin's lymphoma, colorectal cancer, or pancreatic cancer. 16. The anti-DR5 antibody or antibody fragment of claim 13 wherein said cancer is an adenocarcinoma. 17. The anti-DR5 antibody or antibody fragment of claim 16 wherein said adenocarcinoma is colorectal, pancreatic, or metastatic adenocarcinoma. 18. The anti-DR5 antibody or antibody fragment of claim 1 wherein said potency is determined in an in vitro tumor killing assay. 19. The anti-DR5 antibody or antibody fragment of claim 1 which is a chimeric, humanized, or human antibody. 20. The anti-DR5 antibody or antibody fragment of claim 1 which mediates antibody-dependent cellular cytotoxicity (ADCC). 21. The anti-DR5 antibody of claim 1, or a functional fragment thereof, in a dimeric form. 22. The anti-DR5 antibody of claim 1, or a functional fragment thereof, cross-linked with an anti-human IgG Fc region. 23. The anti-DR5 antibody of claim 1, or a functional fragment thereof, fused to an epitope tag sequence. 24. The anti-DR5 antibody of claim 1 which comprises antibody 7.3, or antibody 8.3, or a functional fragment thereof. 25. A chimeric molecule comprising the antibody of claim 24 fused to a heterologous amino acid sequence. 26. The chimeric molecule of claim 25 wherein said heterologous amino acid sequence comprises an immunoglobulin sequence. 27. The chimeric molecule of claim 26 wherein said immunoglobulin sequence is an anti-human IgG Fc region. 28. A composition comprising an anti-DR5 antibody of claim 1, 6 or 7, or a fragment thereof, and a carrier. 29. The composition of claim 28 wherein said carrier is a pharmaceutically-acceptable carrier. 30. The composition of claim 29 further comprising an additional anti-cancer agent. 31. The composition of claim 30 wherein said additional anti-cancer agent is an antibody. 32. The composition of claim 31 wherein said antibody is selected from the group consisting of an additional anti-DR5 antibody, Rituxan (rituximab), and an anti-VEGF antibody. 33. The composition of claim 30 wherein said additional anti-cancer agent is a chemotherapeutic agent. 34. The composition of claim 33 wherein said chemotherapeutic agent is selected from the group consisting of CPT-11 (irinotecan), gemcitabine, carboplatin, taxol, and paclitaxel. 35. The composition of claim 30 wherein said additional anti-cancer agent is an Apo2L ligand comprising amino acids 114-281 of FIG. 1 (SEQ ID NO: 1). 36. An article of manufacture comprising a container and compositions contained within said container, wherein the composition includes an anti-DR5 antibody of claim 1, 6, or 7, or a fragment thereof. 37. The article of manufacture of claim 36 further comprising instructions for using the anti-DR5 antibody in vitro or in vivo. 38. The article of manufacture of claim 37 wherein said instructions concern the treatment of cancer. 39. An anti-DR5 antibody which is antibody 7.3, or a functional fragment thereof. 40. The anti-DR5 antibody of claim 39, wherein said antibody is a single-chain antibody. 41. The anti-DR5 antibody of claim 39, wherein said functional fragment is selected from the group consisting of Fab, Fab', F(ab')2, and Fv fragments. 42. The anti-DR5 antibody of claim 41 wherein said functional fragment is an Fv fragment.

Details for Patent 8,029,783

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2025-02-02
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2025-02-02
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2025-02-02