Anti-CD79B antibodies and immunoconjugates and methods of use

• US 8,722,857 B2
• Filed: 01/14/2009
• Issued: 05/13/2014
• Est. Priority Date: 01/31/2008
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Chen, Yvonne, Dennis, Mark, Dornan, David, Elkins, Kristi, Junutula, Jagath Reddy, Polson, Andrew
• Primary Examiner(s): SCHWADRON, RONALD B
• Application Number:
  US12/353,917
• Publication Number:
  US 20100215669A1
• Time in Patent Office: 1,945 Days
• Field of Search: None
• US Class Current: 530/387.3
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/537 spiro-condensed or forming part of bridged ring systems
• CPC Class Codes: A61K 38/05 Dipeptides
• 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 47/6803 Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 47/6867 the tumour determinant being from a cell of a blood cancer
• CPC Class Codes: A61K 51/1027 against receptors, cell-surface antigens or cell-surface determinants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/2803 : against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/3061 : Blood cells
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/40 : characterized by post-translational modification
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• 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 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: G01N 33/57492 : involving compounds localized on the membrane of tumor or cancer cells
• 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 invention is directed to cysteine-engineered anti-CD79b antibody, huMA79b.v28, and compositions of matter thereof useful for the treatment of hematopoietic tumor in mammals and to methods of using those compositions of matter for the same.

Claims

1. An anti-CD79b cysteine engineered antibody comprising a heavy and a light chain, a single free cysteine amino acid at position 118 of the heavy chain according to EU numbering convention, and

(i) an HVR-L1 sequence of KASQSVDYEGDSFLN (SEQ ID NO:

194);

(ii) an HVR-L2 sequence of AASNLES (SEQ ID NO;

     195);

(iii) an HVR-L3 sequence of QQSNEDPLT (SEQ ID NO;

     196);

(iv) an HVR-H1 sequence of GYTFSSYWIE (SEQ ID NO;

     202);

(v) an HVR-H2 sequence of GEILPGGGDTNYNEIFKG (SEQ ID NO;

     203); and

(vi) an HVR-H3 sequence of TRRVPIRLDY (SEQ ID NO;

     204).

4. The cysteine engineered antibody of any one of claims 1, 2, and 3, wherein the free cysteine amino acid has a thio reactivity value in the range of 0.6 to 1.0.

5. The cysteine engineered antibody of any one of claims 1, 2, and 3 prepared by a process comprising replacing an amino acid residue, of a parent antibody with the free cysteine amino acid, wherein the parent antibody binds CD79b.

6. The antibody of claim 5, wherein the cysteine engineered antibody is more reactive than the parent antibody with a thio-reactive reagent.

7. The cysteine engineered antibody of claim 5, wherein the process further comprises determining the thiol reactivity of the cysteine engineered antibody by reacting the cysteine engineered antibody with a thiol-reactive reagent;

wherein the cysteine engineered antibody is more reactive than the parent antibody with the thiol-reactive reagent.

12. The antibody of any one of claims 1, 2, 3, 8, and 9, wherein the antibody is selected from a monoclonal antibody, a bispecific antibody, a chimeric antibody, a human antibody, and a humanized antibody.

13. The antibody of any one of claims 1, 2, 3, 8, and 9, which is an antibody fragment.

14. The antibody of claim 13 wherein the antibody fragment is a Fab fragment.

15. The antibody of any one of claims 1, 2, 3, 8, and 9, which is produced in bacteria.

16. The antibody of any one of claims 1, 2, 3, 8, and 9, which is produced in CHO cells.

17. The cysteine engineered anti-CD79b antibody of any one of claims 1, 2, 3, 8, and 9 comprising a sequence selected from SEQ ID NOS:

251-258 and 278-284.

18. The cysteine-engineered anti-CD79b antibody of claim 17 wherein the free cysteine amino acid residue is located in a heavy chain.

19. The cysteine-engineered anti-CD79b antibody of claim 18 comprising one or more sequences selected from the group consisting of SEQ ID NO:

251, SEQ ID NO;

252, SEQ ID NO;

253, SEQ ID NO;

254, SEQ ID NO;

255, SEQ ID NO;

256, SEQ ID NO;

257, and SEQ ID NO;

258.

20. The cysteine-engineered anti-CD79b antibody of claim 17 wherein the free cysteine amino acid residue is located in a light chain.

21. The cysteine-engineered anti-CD79b antibody of claim 20 comprising one or more sequences selected from the group consisting of SEQ ID NO:

278, SEQ ID NO;

279, SEQ ID NO;

280, SEQ ID NO;

281, SEQ ID NO;

282, SEQ ID NO;

283, and SEQ ID NO;

284.

35. The cysteine-engineered anti-CD79b antibody of claim 18, comprising SEQ ID NO:

251.

36. The cysteine-engineered anti-CD79b antibody of claim 18, comprising SEQ ID NO:

252.

37. The cysteine-engineered anti-CD79b antibody of claim 18, comprising SEQ ID NO:

253.

38. The cysteine-engineered anti-CD79b antibody of claim 18, comprising SEQ ID NO:

254.

39. The cysteine-engineered anti-CD79b antibody of claim 18, comprising SEQ ID NO:

255.

40. The cysteine-engineered anti-CD79b antibody of claim 18, comprising SEQ ID NO:

256.

41. The cysteine-engineered anti-CD79b antibody of claim 18, comprising SEQ ID NO:

257.

42. The cysteine-engineered anti-CD79b antibody of claim 18, comprising SEQ ID NO:

258.

43. The cysteine-engineered anti-CD79b antibody of claim 20, comprising SEQ ID NO:

278.

44. The cysteine-engineered anti-CD79b antibody of claim 20, comprising SEQ ID NO:

279.

45. The cysteine-engineered anti-CD79b antibody of claim 20, comprising SEQ ID NO:

280.

46. The cysteine-engineered anti-CD79b antibody of claim 20, comprising SEQ ID NO:

281.

47. The cysteine-engineered anti-CD79b antibody of claim 20, comprising SEQ ID NO:

282.

48. The cysteine-engineered anti-CD79b antibody of claim 20, comprising SEQ ID NO:

283.

49. The cysteine-engineered anti-CD79b antibody of claim 20, comprising SEQ ID NO:

284.

2. An anti-CD79b cysteine engineered antibody comprising a heavy and a light chain, a single free cysteine amino acid at position 118 of the heavy chain according to EU numbering convention, and

(a) a heavy chain variable domain comprising an HVR1-HC, HVR2-HC and HVR3-HC sequence depicted in FIG. 17 (SEQ ID NO:

202-204), an FR1-HC, FR2-HC, FR3-HC and/or FR4-HC sequence depicted in FIG. 17 (SEQ ID NO;

198-201), and a CH1 and/or Fc sequence depicted in FIG. 17 (SEQ ID NO;

205 and/or

     206); and

(b) a light chain variable domain comprising an HVR1-LC, HVR2-LC and HVR3-LC sequence depicted in FIG. 17 (SEQ ID NO;

194-196), an FR1-LC, FR2-LC, FR3-LC and/or FR4-LC sequence depicted in FIG. 17 (SEQ ID NO;

190-193), and a CL1 sequence depicted in FIG. 17 (SEQ ID NO;

     197).

3. An anti-CD79b cysteine engineered antibody comprising a heavy and a light chain, a single free cysteine amino acid at position 118 of the heavy chain according to EU numbering convention, a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:

208, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO;

207.

8. An anti-CD79b cysteine engineered antibody comprising a heavy and a light chain, a single free cysteine amino acid at position 205 of the light chain according to Kabat numbering convention, and

(i) an HVR-L1 sequence of KASQSVDYEGDSFLN (SEQ ID NO:

194);

(ii) an HVR-L2 sequence of AASNLES (SEQ ID NO;

     195);

(iii) an HVR-L3 sequence of QQSNEDPLT (SEQ ID NO;

     196);

(iv) an HVR-H1 sequence of GYTFSSYWIE (SEQ ID NO;

     202);

(v) an HVR-H2 sequence of GEILPGGGDTNYNEIFKG (SEQ ID NO;

     203); and

(vi) an HVR-H3 sequence of TRRVPIRLDY (SEQ ID NO;

     204).

50. The cysteine engineered antibody of claim 8, wherein the free cysteine amino acid has a thio reactivity value in the range of 0.6 to 1.0.

51. The cysteine engineered antibody of claim 8 prepared by a process comprising replacing an amino acid residue, of a parent antibody with the free cysteine amino acid, wherein the parent antibody binds CD79b.

52. The antibody of claim 51, wherein the cysteine engineered antibody is more reactive than the parent antibody with a thio-reactive reagent.

53. The cysteine engineered antibody of claim 51, wherein the process further comprises determining the thiol reactivity of the cysteine engineered antibody by reacting the cysteine engineered antibody with a thiol-reactive reagent;

wherein the cysteine engineered antibody is more reactive than the parent antibody with the thiol-reactive reagent.

9. A cysteine engineered antibody comprising a heavy and a light chain, a single free cysteine amino acid at a position selected from 15, 110, 114, 121, 127, 168, and 205 of the light chain according to Kabat numbering convention and 5, 23, 84, 112 of the heavy chain according to Kabat numbering convention and 118, 120, 282, 375 and 400 of the heavy chain according to EU numbering convention, and

(i) an HVR-L1 sequence of KASQSVDYEGDSFLN (SEQ ID NO:

194);

(ii) an HVR-L2 sequence of AASNLES (SEQ ID NO;

     195);

(iii) an HVR-L3 sequence of QQSNEDPLT (SEQ ID NO;

     196);

(iv) an HVR-H1 sequence of GYTFSSYWIE (SEQ ID NO;

     202);

(v) an HVR-H2 sequence of GEILPGGGDTNYNEIFKG (SEQ ID NO;

     203); and

(vi) an HVR-H3 sequence of TRRVPIRLDY (SEQ ID NO;

     204).

10. The antibody of claim 9, wherein the free cysteine amino acid is at position 205 of the light chain.

11. The antibody of claim 9, wherein the free cysteine amino acid is at position 400 of the heavy chain.

22. The antibody of claim 9, wherein a cysteine is at position 15 of the light chain.

23. The antibody of claim 9, wherein a cysteine is at position 110 of the light chain.

24. The antibody of claim 9, wherein a cysteine is at position 114 of the light chain.

25. The antibody of claim 9, wherein a cysteine is at position 121 of the light chain.

26. The antibody of claim 9, wherein a cysteine is at position 127 of the light chain.

27. The antibody of claim 9, wherein a cysteine is at position 168 of the light chain.

28. The antibody of claim 9, wherein a cysteine is at position 5 of the heavy chain.

29. The antibody of claim 9, wherein a cysteine is at position 23 of the heavy chain.

30. The antibody of claim 9, wherein a cysteine is at position 84 of the heavy chain.

31. The antibody of claim 9, wherein a cysteine is at position 112 of the heavy chain.

32. The antibody of claim 9, wherein a cysteine is at position 120 of the heavy chain.

33. The antibody of claim 9, wherein a cysteine is at position 282 of the heavy chain.

34. The antibody of claim 9, wherein a cysteine is at position 375 of the heavy chain.