Anti-CD79B antibodies and immunoconjugates and methods of use

Patent metadata

Field	Value
Publication number	US-RE48558-E
Application number	US-201815908703-A
Country	US
Kind code	E1
Filing date	Feb 28, 2018
Priority date	Jul 16, 2007
Publication date	May 18, 2021
Grant date	May 18, 2021

Abstract

The present invention is directed to compositions of matter comprising immunoconjugates comprising an anti-CD79b antibody comprising: (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) and to methods of using those compositions of matter for the treatment of hematopoietic tumor in mammals.

First claim

What is claimed is:

1. An immunoconjugate comprising an anti-CD79b antibody comprising:
(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),
wherein said anti-CD79b antibody is covalently attached to a cytotoxic agent.

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

3. The immunoconjugate of claim 2 , wherein the immunoconjugate having comprises the formula Ab-(L-D)p, wherein:
(a) Ab is an anti-CD79b antibody comprising:
(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);

(b) L is a linker;
(c) D is a drug moiety; and
(d) p ranges from about 1 to 8.

4. The immunoconjugate of claim 3 , wherein L is selected from 6-maleimidocaproyl (MC), maleimidopropanoyl (MP), valine-citrulline (val-cit), alanine-phenylalanine (ala-phe), p-aminobenzyloxycarbonyl (PAB), N-Succinimidyl 4-(2-pyridylthio) pentanoate (SPP), N-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1 carboxylate N-succinimidyl 4-(N-maleimidomethyl) cyclohexane-1 carboxylate (SMCC), and N-Succinimidyl (4-iodo-acetyl)aminobenzoate N-Succinimidyl (4-iodoacetyl) aminobenzoate (SIAB).

5. The immunoconjugate of claim 3 , wherein D is selected from an auristatin and dolostatin a dolastatin.

6. The immunoconjugate of claim 3 , wherein L has comprises Formula II:
-A a -W w —Y y —  Formula II

wherein:
A is a Stretcher unit,
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, and
y is 0, 1 or 2,;
wherein p ranges from 1 to 20 8, and
wherein D is a drug moiety of Formula D E :

wherein the wavy line of D E indicates the covalent attachment site to A, W, or Y, and independently at each location:
R 2 is selected from H and C 1 -C 8 alkyl;
R 3 is selected from H, C 1 -C 8 alkyl, C 3 -C 8 carbocycle, aryl, C 1 -C 8 alkyl-aryl, C 1 -C 8 alkyl-(C 3 -C 8 carbocycle), C 3 -C 8 heterocycle and C 1 -C 8 alkyl-(C 3 -C 8 heterocycle);
R 4 is selected from H, C 1 -C 8 alkyl, C 3 -C 8 carbocycle, aryl, C 1 -C 8 alkyl-aryl, C 1 -C 8 alkyl-(C 3 -C 8 carbocycle), C 3 -C 8 heterocycle and C 1 -C 8 alkyl-(C 3 -C 8 heterocycle);
R 5 is selected from H and methyl;
or R 4 and R 5 jointly form a carbocyclic ring and have the formula —(CR a R b ) n — wherein R a and R b are independently selected from H, C 1 -C 8 alkyl and C 3 -C 8 carbocycle and n is selected from 2, 3, 4, 5 and 6;
R 6 is selected from H and C 1 -C 8 alkyl;
R 7 is selected from H, C 1 -C 8 alkyl, C 3 -C 8 carbocycle, aryl, C 1 -C 8 alkyl-aryl, C 1 -C 8 alkyl-(C 3 -C 8 carbocycle), C 3 -C 8 heterocycle and C 1 -C 8 alkyl-(C 3 -C 8 heterocycle);
each R 8 is independently selected from H, OH, C 1 -C 8 alkyl, C 3 -C 8 carbocycle and O—(C 1 -C 8 alkyl);
R 9 is selected from H and C 1 -C 8 alkyl; and
R 18 is selected from —C(R 8 ) 2 —C(R 8 ) 2 -aryl, —C(R 8 ) 2 —C(R 8 ) 2 —(C 3 -C 8 heterocycle), and —C(R 8 ) 2 —C(R 8 ) 2 —(C 3 -C 8 carbocycle).

7. The immunoconjugate of claim 6 , having An immunoconjugate comprising an anti-CD79b antibody (Ab), wherein the anti-CD79b antibody (Ab) comprises:
(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), and wherein said immunoconjugate comprises the formula:

Ab-6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (Ab-MC-vc-PAB-MMAE),
wherein Val is valine, and Cit is citrulline, and p ranges from 1 to about 8.

8. A pharmaceutical composition comprising the immunoconjugate of claim 3 or 6 and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8, wherein the pharmaceutical composition is lyophilized.

10. The pharmaceutical composition of claim 8, wherein the pharmaceutical composition is aqueous.

11. An immunoconjugate comprising an anti-CD79b antibody (Ab), wherein the anti-CD79b antibody (Ab) comprises the heavy chain variable domain sequence of SEQ ID NO:208 and the light chain variable domain sequence of SEQ ID NO:207, and wherein said immunoconjugate comprises the formula:

Ab-6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (Ab-MC-vc-PAB-MMAE),
wherein Val is valine, Cit is citrulline, and p ranges from 1 to about 8.

12. The immunoconjugate of claim 11, wherein the anti-CD79b antibody is a full-length antibody.

13. The immunoconjugate of claim 1, wherein the cytotoxic agent is the drug moiety monomethyl auristatin E (MMAE).

14. The immunoconjugate of claim 13, wherein the anti-CD79b antibody is covalently attached to MMAE via a linker, and the average number of MMAE drug moieties per anti-CD79b antibody is about 2 to about 5.

15. The immunoconjugate of claim 14, wherein the linker is connected to a sulfur atom of the anti-CD79b antibody.

16. The immunoconjugate of claim 15, wherein the linker comprises 6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (MC-val-cit-PAB).

17. The immunoconjugate of claim 3, wherein the linker is connected to a sulfur atom of the anti-CD79b antibody.

18. The immunoconjugate of claim 3, wherein the drug moiety is monomethyl auristatin E (MMAE).

19. The immunoconjugate of claim 18, wherein the anti-CD79b antibody is covalently attached to MMAE via a linker comprising valine-citrulline (val-cit).

20. The immunoconjugate of claim 6, wherein:
the Stretcher unit is 6-maleimidocaproyl (MC); the Amino Acid unit is valine-citrulline (val-cit); the drug moiety is monomethyl auristatin E (MMAE); and the Spacer unit is p-aminobenzyloxycarbonyl (PAB); wherein the Stretcher unit is covalently attached to a cysteine thiol of the anti-CD79b antibody; and the Spacer unit is linked to MMAE via a carbamate group.

21. The immunoconjugate of claim 3, 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.

22. The immunoconjugate of claim 3, wherein the anti-CD79b antibody is a full-length antibody.

23. The immunoconjugate of claim 7, wherein the anti-CD79b antibody is a full

Assignees

• Genentech Inc

Inventors

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

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N33/575

  for cancer · CPC title

• A61K47/68033

  the drug being a maytansine · CPC title

• A61K47/68031

  the drug being an auristatin · CPC title

• A61K47/6803

  Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates · CPC title