METHODS OF USING ANTI-PD-L1 ANTIBODIES AND THEIR USE TO ENHANCE T-CELL FUNCTION TO TREAT TUMOR IMMUNITY

• US 20130045201A1
• Filed: 05/23/2012
• Published: 02/21/2013
• Est. Priority Date: 12/09/2008
• Status: Abandoned Application

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: MARIATHASAN, SANJEEV, WU, YAN, IRVING, BRYAN, CHIU, HENRY, MAECKER, HEATHER, LEHAR, SOPHIE M., CHEUNG, JEANNE
• Application Number:
  US13/478,511
• Publication Number:
  US 20130045201A1
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• 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: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/1063 env, e.g. gp41, gp110/120, gp160, V3, PND, CD4 binding site
• CPC Class Codes: C07K 16/22 : against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/28 : against receptors, cell surface antigens or cell surface determinants
• 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 16/3046 : Stomach, Intestines
• CPC Class Codes: C07K 2317/14 : Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/52 : Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 : Framework region [FR]
• CPC Class Codes: C07K 2317/71 : Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/74 : Inducing cell proliferation
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present application relates to methods of using anti-PD-L1 antibodies to enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, including infection (e.g., acute and chronic) and tumor immunity.

Claims

1. A method of treating a T-cell dysfunctional disorder resulting from tumor immunity comprising administering an effective amount of an anti-PD-L1 antibody or antigen binding fragment thereof, wherein the antibody or antibody fragment comprises a heavy chain and a light chain variable region sequence, wherein:

(a) the heavy chain comprises an HVR-H1, HVR-H2 and HVR-H3, wherein further;

2. The method of claim 1 wherein X₁ is D;

X₂ is S and X₃ is T.

3. The method of claim 1, wherein X₄=D, X₅=V, X₆=5, X₇=A and X₈=V, X₉=F, and X₁₀=Y, X₁₁=Y, X₁₂=L, X₁₃=Y, X₁₄=H and X₁₅=A.

4. The method of claim 1, wherein X₁=D, X₂=S and X₃=T, X₄=D, X₅=V, X₆=S, X₇=A and X₈=V, X₉=F, and X₁₀=Y, X₁₁=Y, X₁₂=L, X₁₃=Y, X₁₄=H and X₁₅=A.

5. The method of claim 4, wherein the encoded variable region heavy chain framework sequences are juxtaposed between the HVRs according to the formula:

(HC-FR1)-(HVR-H1)-(HC-FR2)-(HVR-H2)-(HC-FR3)-(HVR-H3)-(HC-FR4) and/or the encoded variable region light chain framework sequences juxtaposed between the HVRs according to the formula;

(LC-FR1)-(HVR-L1)-(LC-FR2)-(HVR-L2)-(LC-FR3)-(HVR-L3)-(LC-FR4).

6. The method of claim 5, wherein the framework sequences are human.

7. The method of claim 6 wherein the variable heavy chain framework sequences are VH subgroup III consensus framework.

8. The method of claim 6 wherein the variable region light chain framework sequences are VL kappa I consensus framework.

9. The method of claim 7 wherein one or more of the heavy chain framework sequences is the following:

10. The method of claim 8 wherein one or more of the light chain framework sequences is the following:

11. The method of claim 6 wherein:

(a) one or more of the heavy chain framework sequences is the following;

12. The method of claim 11 further comprising a human constant region.

13. The method of claim 12, wherein the constant region is selected from the group consisting of IgG1, IgG2, IgG3 and IgG4.

14. The method of claim 13, wherein the constant region is IgG1.

15. The method of claim 14 having reduced or minimal effector function.

16. The method of claim 15, wherein the minimal effector function results from an effector-less Fc mutation.

17. The method of claim 16, wherein the effector-less Fc mutation is N297A.

18. The method of claim 16, wherein the effector-less Fc mutation is D265A/N297A.

19. The method of claim 15, wherein the minimal effector function results from aglycosylation.

20. A method of treating tumor immunity comprising administering to a patient a composition comprising a pharmaceutically-acceptable carrier and therapeutically effective amount of an anti-PD-L1 antibody or antigen binding fragment thereof, wherein the antibody or antibody fragment comprises a heavy chain and light chain variable region sequence, wherein:

(a) the heavy chain comprises the sequence;

EVQLVESGGGLVQPGGSLRLS CAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTI SADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVS A (SEQ ID NO;

20), and

(b) the light chain comprises the sequence;

DIQMTQSPSSLSASVGDRVTITC RASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTL TISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKR (SEQ ID NO;

21).

21. The method of claim 20 wherein the antibody further comprises a human constant region.

22. The method of claim 21, wherein the constant region is selected from the group consisting of IgG1, IgG2, IgG3 and IgG4.

23. The method of claim 22, wherein the constant region is IgG1.

24. The method of claim 23 having reduced or minimal effector function.

25. The nucleic acid of claim 24, wherein the minimal effector function results from an effector-less Fc mutation.

26. The method of claim 25, wherein the effector-less Fc mutation is N297A.

27. The method of claim 25, wherein the effector-less Fc mutation is D265A/N297A.

28. The method of claim 24, wherein the minimal effector function results from aglycosylation.

29. The method of claims 20-28, further comprising the administration of a vaccine.

30. The method of claims 20-28, further comprising the administration of a chemotherapeutic agent.

31. The method of claims 20-28, wherein the tumor immunity results from a cancer selected from the group consisting of breast, lung, colon, ovarian, melanoma, bladder, kidney, liver, saliary, stomach, gliomas, thyroid, thymic, epithelial, head and neck, gastric and pancreatic.

32. The method of claim 30, wherein the tumor immunity results from a cancer selected from the group consisting of breast, lung, colon, ovarian, melanoma, bladder, kidney, liver, saliary, stomach, gliomas, thyroid, thymic, epithelial, head and neck, gastric and pancreatic.

33. The method of claim 30, wherein the chemotherapeutic agent is an anti-VEGF antibody.

34. The method of claim 30, wherein the chemotherapeutic agent is FOLFOX.

35. The method of claim 34, wherein FOLFOX is a combination of oxaliplatin, 5-fluorouracil and leucovovin.

36. The method of claim 30, wherein the chemotherapeutic agent is oxaliplatin.

37. The method of claim 30, wherein the chemotherapeutic agent is a RAF inhibitor.