Anti-CD79B antibodies and immunoconjugates and methods of use

Patent metadata

Field	Value
Publication number	US-10494432-B2
Application number	US-201313973669-A
Country	US
Kind code	B2
Filing date	Aug 22, 2013
Priority date	Jul 16, 2007
Publication date	Dec 3, 2019
Grant date	Dec 3, 2019

Abstract

The present invention is directed to compositions of matter useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.

First claim

What is claimed is:

1. A method of treating a cancerous B cell proliferative disorder comprising administering to a human an effective amount of an immunoconjugate comprising an anti-CD79b antibody, wherein the antibody comprises (a) an HVR-L1 sequence of SEQ ID NO: 194; (b) an HVR-L2 sequence of SEQ ID NO: 195; (c) an HVR-L3 sequence of SEQ ID NO: 196; (d) an HVR-H1 sequence of SEQ ID NO: 202; (e) an HVR-H2 sequence of SEQ ID NO: 203; and (f) an HVR-H3 sequence of SEQ ID NO: 204; and, wherein said antibody is covalently attached to a cytotoxic agent.

2. The method of claim 1 , wherein the cancerous B cell proliferative disorder is selected from the group consisting of lymphoma, myeloma, non-Hodgkins lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), aggressive NHL, indolent lymphoma, follicular lymphoma (FL), relapsed aggressive NHL, relapsed indolent NHL, relapsed NHL, refractory NHL, refractory indolent NHL, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, leukemia, hairy cell leukemia (HCL), acute lymphocytic leukemia (ALL), and mantle cell lymphoma.

3. The method of claim 1 , wherein the cytotoxic agent is selected from the group consisting of a toxin, a chemotherapeutic agent, a drug moiety, an antibiotic, a radioactive isotope, and a nucleolytic enzyme.

4. The method of claim 1 , wherein the immunoconjugate comprises the formula Ab-(L-D) p , wherein Ab is the anti-CD79b antibody, D is a drug moiety, L is a linker moiety, and p ranges from 1 to 20.

5. The method of claim 4 , wherein L comprises the formula:
-A a -W w -Y y -
wherein:
A is a Stretcher unit covalently attached to Ab;
a is 0 or 1;
each W is independently an Amino Acid unit;
w is an integer ranging from 0 to 12;
Y is a Spacer unit covalently attached to the drug moiety; and
y is 0, 1 or 2.

6. The method of claim 5 wherein the immunoconjugate comprises the formula:

wherein PAB is para-aminobenzylcarbamoyl, and R 17 is a divalent radical selected from the group consisting of (CH 2 ) r , C 3 -C 8 carbocyclyl, O—(CH 2 ) r , arylene, (CH 2 ) r arylene, -arylene-(CH 2 ) r —, (CH 2 ) r —(C 3 C 8 carbocyclyl), (C 3 C 8 carbocyclyl)-(CH 2 ) r , C 3 -C 8 heterocyclyl, (CH 2 ) r —(C 3 -C 8 heterocyclyl), —C 3 -C 8 heterocyclyl)-(CH 2 ) r , —(CH 2 ) r C(O)NR b (CH 2 ) r —, —(CH 2 CH 2 O) r —, —(CH 2 CH 2 O) r —CH 2 , —(CH 2 ) r C(O)NR b (CH 2 CH 2 O) r —, —(CH 2 ) r C(O)NR b (CH 2 CH 2 O) r —CH 2 —, —CH 2 CH 2 O) r C(O)NR b (CH 2 CH 2 O) r —, —(CH 2 CH 2 O) r C(O)NR b (CH 2 CH 2 O) r —CH 2 —, and —(CH 2 CH 2 O) r C(O)NR b (CH 2 ) r —; wherein R b is H, C 1 -C 6 alkyl, phenyl, or benzyl; and r is independently an integer ranging from 1 to 10.

7. The method of claim 6 wherein W w , is valine-citrulline.

8. The method of claim 7 , wherein R 17 is (CH 2 ) 5 or (CH 2 ) 2 .

9. The method of claim 4 , wherein the immunoconjugate comprises the formula:

10. The method of claim 4 , wherein L comprises 4-((2,5-dioxopyrrolidin-1-yl)methyl)cyclohexanecarboxylic acid (SMCC), 4-mercaptopentanoic acid (SPP), 4-mercaptobutanoic acid (SPDB), 6-maleimidocaproyl (MC), valine-citrulline (val-cit), p aminobenzyloxycarbonyl (PAB), 6-maleimidocaproyl-valine-citrulline-p aminobenzyloxycarbonyl (MC-val-cit-PAB) and/or Bis-Maleimido polyethylene glycol (BMPEO).

11. The method of claim 4 , wherein D is auristatin.

12. The method of claim 11 , wherein the auristatin is monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF).

13. The method of claim 12 , wherein D is MMAE, having the structure:

wherein the wavy line indicates the attachment site to the linker L.

14. The method of claim 4 , wherein D is maytansinoid.

15. The method of claim 14 , wherein the maytansinoid is DM1 or DM4, having the structures:

wherein the wavy line indicates the attachment site to the linker L.

16. The method of claim 1 , wherein the anti-CD79b antibody comprises the heavy chain variable domain sequence of SEQ ID NO: 208 and the light chain variable domain sequence of SEQ ID NO: 207.

17. The method of claim 1 , wherein the anti-CD79b antibody comprises the heavy chain sequence of SEQ ID NO: 308 and the light chain sequence of SEQ ID NO: 307.

18. The method of claim 4 , wherein the anti-CD79b antibody comprises the heavy chain variable domain sequence of SEQ ID NO: 208 and the light chain variable domain sequence of SEQ ID NO: 207.

19. The method of claim 4 , wherein the anti-CD79b antibody comprises the heavy chain sequence of SEQ ID NO: 308 and the light chain sequence of SEQ ID NO: 307.

20. The method of claim 1 , wherein the cancerous B cell proliferative disorder is non-Hodgkins lymphoma (NHL).

21. The method of claim 1 , wherein the cancerous B cell proliferative disorder is diffuse large B-cell lymphoma (DLBCL).

22. The method of claim 1 , wherein the cancerous B cell proliferative disorder is relapsed NHL or refractory NHL.

23. The method of claim 1 , wherein the cancerous B cell proliferative disorder is follicular lymphoma (FL).

24. The method of claim 1 , further comprising administering to the human an effective amount of another therapeutic agent.

25. The method of claim 24 , wherein the therapeutic agent is selected from the group consisting of an antibody, a chemotherapeutic agent, a cytotoxic agent, an anti-angiogenic agent, an immunosuppressive agent, a prodrug, a cytokine, a cytokine antagonist, cytotoxic radiotherapy, a corticosteroid, a cancer vaccine, and a growth-inhibitory agent.

26. The method of claim 24 , wherein the therapeutic agent is selected from one or more of tamoxifen, letrozole, exemestane, anastrozole, irinotecan, cetuximab, fulvestrant, vinorelbine, erlotinib, bevacizumab, vincristine, imatinib mesylate, sorafenib, lapatinib, trastuzumab, cisplatin, gemcitabine, methotrexate, vinblastine, carboplatin, paclitaxel, 5-fluorouracil, doxorubicin, bortezomib, melphalan, prednisone, and docetaxel.

27. The method of claim 24 , wherein the therapeutic agent is an anti-CD20 antibody.

28. The method of claim 24 , wherein the therapeutic agent is an anti-CD20 antibody and wherein the cancerous B cell proliferative disorder is diffuse large B-cell lymphoma (DLBCL).

29. The method of claim 24 , wherein the therapeutic agent is an anti-CD20 antibody and wherein the cancerous B cell proliferative disorder is follicular lymphoma (FL).

30. The method of claim 27 , wherein the anti-CD20 antibody is rituximab.

31. The method of claim 24 , wherein the therapeutic agent is a chemotherapeutic agent.

32. The method of claim 31 , wherein the chemotherapeutic agent comprises one or more of cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone.

33. The method of claim 31 , wherein the chemotherapeutic agent comprises cyclophosphamide, doxorubicin, and prednisone.

34. The method of claim 27 , further comprising administering to

Assignees

• Genentech Inc

Inventors

• Chen Yvonne
• Dennis Mark
• Dornan David
• Elkins Kristi
• Junutula Jagath Reddy
• Polson Andrew
• Zheng Bing

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title