Anti-CD79B antibodies and immunoconjugates and methods of use

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 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 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 (SMCC), and N-Succinimidyl (4-iodo-acetyl)aminobenzoate (SIAB).

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

6. The immunoconjugate of claim 3 , wherein L has Formula II:

-A a -W w —Y y —

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,

p ranges from 1 to 20, and

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 the formula:

wherein Val is valine, and Cit is citrulline.

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