ANTI-CD79B ANTIBODIES AND IMMUNOCONJUGATES AND METHODS OF USE

• US 20100215669A1
• Filed: 01/14/2009
• Published: 08/26/2010
• 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, Dornan, David, Polson, Andrew, Dennis, Mark, Junutula, Jagath Reddy, Elkins, Kristi
• Granted Patent: US 8,722,857 B2
• Time in Patent Office: Days
• US Class Current: 424/173.100
• 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 compositions of matter 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 antibody comprising:

(a) at least one HVR sequence selected from the group consisting of;

(i) HVR-L1 comprising sequence A1-A15, wherein A1-A15 is KASQSVDYDGDSFLN (SEQ ID NO;

     131)

(ii) HVR-L2 comprising sequence B1-B7, wherein B1-B7 is AASNLES (SEQ ID NO;

     132)

(iii) HVR-L3 comprising sequence C1-C9, wherein C1-C9 is QQSNEDPLT (SEQ ID NO;

     133)

(iv) HVR-H1 comprising sequence D1-D10, wherein D1-D10 is GYTFSSYWIE (SEQ ID NO;

     134)

(v) HVR-H2 comprising sequence E1-E18, wherein E1-E18 is GEILPGGGDTNYNEIFKG (SEQ ID NO;

     135)

(vi) HVR-H3 comprising sequence F1-F10, wherein F1-F10 is TRRVPVYFDY (SEQ ID NO;

     136); and

(b) at least one variant HVR, wherein the variant HVR comprises modification of at least one residue of the sequence depicted in SEQ ID NO;

131, 132, 133, 134, 135 or 136.

2. The antibody of claim 1, wherein F6 in a variant HVR-H3 is I, F7 is R and F8 is L.

3. The antibody of claim 1 or 2, wherein A9 in a variant HVR-L1 is E or S.

4. The antibody of claim 1, wherein at least a portion of the framework sequence is a human consensus framework sequence.

5. The antibody of claim 1, wherein said modification is substitution, insertion or deletion.

6. The antibody of claim 1, wherein a HVR-L1 variant comprises one substitution in any of the following positions:

A4(K), A9 (E or S) and A10 (A or S).

7. The antibody of claim 1, wherein a HVR-L2 variant comprises 1-5 (1, 2, 3, 4 or 5) substitutions in any one or combination of the following positions:

B2 (S or G), B3 (R or G), B4 (K, R, Y, I, H or Q), B5 (R), B6 (G, K, A, R, S or L) and B7 (R, N, T or G).

8. The antibody of claim 1, wherein a HVR-L3 variant comprises 1-4 (1, 2, 3 or 4) substitutions in any one or combination of the following positions:

C1 (N or D), C2 (N or P), C3 (D or R), C5 (S, K, A, Q, D, L or G), C6 (A, E or N), C7 (A), C8 (R) and C9 (N).

9. The antibody of claim 1, wherein a HVR-H1 variant comprises 1-7 (1, 2, 3, 4, 5, 6, or 7) substitutions in any one or combination of the following positions:

D1 (P), D2 (F), D3 (P, S, Y, G or N), D4 (L or V), D5 (T, R, N, K, C, G or P), D6 (R, T, K or G), D8 (F), D9 (V or L) and D10 (S, Q, N or D).

10. The antibody of claim 1, wherein a HVR-H3 variant comprises 1-3 (1, 2, or 3) substitutions in any one or combination of the following positions:

F4 (R or I), F6 (I or F), F7 (K, C, R, V or F), F8 (L), and F9 (S).

11. The antibody of claim 1 comprising a HVR-H2 having the sequence of SEQ ID NO:

135.

12. The antibody of claim 1, wherein F6 in a variant HVR-H3 is I.

13. The antibody of claim 1, wherein F7 in a variant HVR-H3 is R.

14. The antibody of claim 1, wherein F8 in a variant HVR-H3 is L.

15. The antibody of claim 1, wherein A9 in a variant HVR-L1 is E.

16. The antibody of claim 1, wherein A9 in a variant HVR-L1 is S.

32. The antibody of claims 1-3 comprising human κ

subgroup 1 consensus framework sequence.

33. The antibody of claims 1-3 comprising heavy chain human subgroup III consensus framework sequence.

34. The antibody of claim 33 wherein the framework sequence comprises a substitution at position 71, 73 and/or 78.

35. The antibody of claim 34 wherein said substitution is R71A, N73T and/or L78A.

36. The antibody of claim 35 wherein the framework sequence comprises a substitution at position 48, 67, 69, 71, 73 and/or 78.

37. The antibody of claim 36 wherein said substitution is V48I, F67A, I69F, R71A, N73T and/or L78A.

38. The antibody of claim 33 wherein the framework sequence comprises a substitution at position 48, 67, 69, 71, 73, 75, 78 and/or 80.

39. The antibody of claim 38 wherein said substitution is V48I, F67A, I69F, R71A, N73T, K75S, L78A, and/or L80M.

40. The antibody of claim 32 wherein the framework sequence comprises a substitution at position 4.

41. The antibody of claim 40 wherein said substitution is M4L.

42. The antibody of claim 32 wherein the framework sequence comprises a substitution at position 47.

43. The antibody of claim 42 wherein said substitution is L47F.

44. The antibody of claim 32 wherein the framework sequence comprises a substitution at position 4 and/or position 47.

45. The antibody of claim 44 wherein said substitution is M4L and/or L47F.

47. The antibody of the preceding claims, wherein both the humanized antibody and chimeric antibody are monovalent or bivalent.

48. The antibody of the preceding claims, wherein both the humanized antibody and chimeric antibody comprise a single Fab region linked to an Fc region.

93. The antibody of claim 1, wherein the antibody comprises a light chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

169.

94. The antibody of claim 1, wherein the antibody comprises a heavy chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

170.

95. The antibody of claim 1, wherein the antibody comprises a light chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

188.

96. The antibody of claim 1, wherein the antibody comprises a heavy chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

189.

97. The antibody of claim 1, wherein the antibody comprises a light chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

207.

98. The antibody of claim 1, wherein the antibody comprises a heavy chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

208.

99. The antibody of claim 1, wherein the antibody comprises a light chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

226.

100. The antibody of claim 1, wherein the antibody comprises a heavy chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

227.

101. The antibody of claim 1, wherein the antibody comprises a heavy chain variable domain comprising one, two, three or four framework amino acid sequences selected from SEQ ID NOs:

143, 144, 145 and 146.

102. The antibody of claim 1, wherein the antibody comprises a light chain variable domain comprising one, two, three or four framework amino acid sequences selected from SEQ ID NOs:

139, 140, 141 and 142.

103. The antibody of claim 1, wherein the antibody comprises a heavy chain variable domain comprising one, two, three or four framework amino acid sequences having at least 90% amino acid sequence identity to an amino acid selected from SEQ ID NOs:

143, 144, 145 and 146.

104. The antibody of claim 1, wherein the antibody comprises a light chain variable domain comprising one, two, three or four framework amino acid sequences having at least 90% amino acid sequence identity to an amino acid selected from selected from SEQ ID NOs:

139, 140, 141 and 142.

105. The antibody of claim 93, wherein the antibody comprises a heavy chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

170.

106. The antibody of claim 94, wherein the antibody comprises a light chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

169.

107. The antibody of claim 95, wherein the antibody comprises a heavy chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

189.

108. The antibody of claim 96, wherein the antibody comprises a light chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

188.

109. The antibody of claim 97, wherein the antibody comprises a heavy chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

208.

110. The antibody of claim 98, wherein the antibody comprises a light chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

207.

111. The antibody of claim 99, wherein the antibody comprises a heavy chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

227.

112. The antibody of claim 100, wherein the antibody comprises a light chain variable domain having at least 90% amino acid sequence identity to an amino acid sequence selected from SEQ ID NO:

226.

125. A polynucleotide encoding an antibody of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258.

126. A vector comprising the polynucleotide of claim 125.

127. A host cell comprising the vector of claim 126.

129. The antibody of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258, wherein the antibody binds to an epitope within a region of CD79b from amino acid 29-39 of SEQ ID NO:

2 or amino acid 1-11 of SEQ ID NO;

16.

130. The antibody of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258, wherein the CD79b is expressed on the surface of a cell.

131. The antibody of claim 130, wherein the cell is a B cell.

132. The antibody of claim 131, wherein the B cell is associated with a B cell proliferative disorder.

133. The antibody of claim 132, wherein the B cell proliferative disorder is a cancer.

134. The antibody of claim 133, wherein the B cell proliferative disorder is selected from selected from lymphoma, non-Hodgkins lymphoma (NHL), aggressive NHL, relapsed aggressive NHL, relapsed indolent 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.

135. The antibody of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258, wherein the antibody is a monoclonal antibody.

136. The antibody of claim 135, wherein the antibody is an antibody fragment selected from a Fab, Fab′

-SH, Fv, scFv or (Fab′

)₂ fragment.

137. The antibody of claim 135, wherein the antibody is humanized.

138. The antibody of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258, wherein the antibody binds to the same epitope as an antibody selected from ATCC as HB11413, deposited on Jul. 20, 1993;

an antibody comprising a heavy chain variable domain of SEQ ID NO;

170 and a light chain variable domain of SEQ ID NO;

169;

an antibody comprising a heavy chain variable domain of SEQ ID NO;

189 and a light chain variable domain of SEQ ID NO;

188;

an antibody comprising a heavy chain variable domain of SEQ ID NO;

208 and a light chain variable domain of SEQ ID NO;

207; and

an antibody comprising a heavy chain variable domain of SEQ ID NO;

227 and a light chain variable domain of SEQ ID NO;

226.

139. An immunoconjugate comprising an antibody of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258 covalently attached to a cytotoxic agent.

140. The immunoconjugate of claim 139, wherein the cytotoxic agent is selected from a toxin, a chemotherapeutic agent, a drug moiety, an antibiotic, a radioactive isotope and a nucleolytic enzyme.

141. The immunoconjugate of claim 140, wherein the immunoconjugate having the formula Ab-(L-D)p, wherein:

(a) Ab is the antibody of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258;

(b) L is a linker;

(c) D is a drug moiety.

142. The immunoconjugate of claim 141, 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).

143. The immunoconjugate of claim 141, wherein D is selected from an auristatin and dolostatin.

144. A pharmaceutical composition comprising the immunoconjugate of claim 141 and a pharmaceutically acceptable carrier.

145. A method of inhibiting the growth of a cell that expresses CD79b, said method comprising contacting said cell with an antibody of any of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258, thereby causing an inhibition of growth of said cell.

146. The method of claim 145 wherein said antibody is conjugated to a cytotoxic agent.

147. The method of claim 145 wherein said antibody is conjugated to a growth inhibitory agent.

148. A method of treating a subject having cancer, said method comprising administering to the subject an effective amount of a an antibody of any of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258.

149. The method of claim 148 wherein the cancer is selected from lymphoma, non-Hodgkins lymphoma (NHL), aggressive NHL, relapsed aggressive NHL, relapsed indolent 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.

150. The method of claim 148 wherein said antibody is conjugated to a cytotoxic agent.

151. The method of claim 148 wherein said antibody is conjugated to a growth inhibitory agent.

152. A method of treating a proliferative disorder in a subject, said method comprising administering to the subject an effective amount of an antibody of any of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258.

153. The method of claim 152 wherein said proliferative disorder is cancer.

154. The method of claim 153 wherein said cancer is selected from lymphoma, non-Hodgkins lymphoma (NHL), aggressive NHL, relapsed aggressive NHL, relapsed indolent 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.

155. The method of claim 152 wherein said antibody is conjugated to a cytotoxic agent.

156. The method of claim 152 wherein said antibody is conjugated to a growth inhibitory agent.

157. The method of inhibiting the growth of a cell, wherein growth of said cell is at least in part dependent upon a growth potentiating effect of CD79b, said method comprising contacting said cell with an effective amount of an antibody of any of the claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258, thereby inhibiting the growth of said cell.

158. The method of claim 157 wherein said antibody is conjugated to a cytotoxic agent.

159. The method of claim 157 wherein said antibody is conjugated to a growth inhibitory agent.

160. A method of therapeutically treating a tumor in a mammal, wherein the growth of said tumor is at least in part dependent upon a growth potentiating effect of CD79b, said method comprising contacting said cell with an effective amount of an antibody of any of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258.

161. The method of claim 160 wherein said tumor is associated with lymphoma, non-Hodgkins lymphoma (NHL), aggressive NHL, relapsed aggressive NHL, relapsed indolent 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.

162. The method of claim 160 wherein said antibody is conjugated to a cytotoxic agent.

163. The method of claim 160 wherein said antibody is conjugated to a growth-inhibitory agent.

164. A method of inhibiting B cell proliferation comprising exposing a cell to an immunoconjugate of claim 142 under conditions permissive for binding of the immunoconjugate to CD79b.

165. The method of claim 164, wherein the B cell proliferation is selected from lymphoma, non-Hodgkins lymphoma (NHL), aggressive NHL, relapsed aggressive NHL, relapsed indolent 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.

166. The method of claim 164, wherein the B cell is a xenograft.

167. The method of claim 164, wherein the exposing takes place in vitro.

168. The method of claim 164, wherein the exposing takes place in vivo.

169. A method of determining the presence of CD79b in a biological sample suspected of containing CD79b, said method comprising exposing said sample to an antibody of any of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258, and determining binding of said antibody to CD79b in said sample wherein binding of said antibody to CD79b in said sample is indicative of the presence of said protein in said sample.

170. The method of claim 169 wherein the biological sample is from a patient suspected of having a B cell proliferative disorder.

171. The method of claim 170 wherein the B cell proliferative disorder is selected from lymphoma, non-Hodgkins lymphoma (NHL), aggressive NHL, relapsed aggressive NHL, relapsed indolent 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.

172. A method of binding an antibody of any of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258 to a cell that expresses CD79b, said method comprising contacting said cell with an antibody of any of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258.

173. The method of claim 172 wherein said antibody is conjugated to a cytotoxic agent.

174. The method of claim 172 wherein said antibody is conjugated to a growth-inhibitory agent.

175. A cysteine engineered antibody comprising one or more free cysteine amino acids, wherein the cysteine engineered antibody is prepared by a process comprising replacing one or more amino acid residues of a parent antibody by a free cysteine amino acid, wherein the parent antibody is an antibody of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258.

176. The antibody of claim 175 wherein the one or more free cystein amino acids have a thio reactivity value in the range of 0.6 to 1.0.

177. The cysteine engineered antibody of claim 175, wherein the cysteine engineered antibody is more reactive than the parent antibody with a thio-reactive reagent.

178. The cysteine engineered antibody of claim 175 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.

179. The cysteine engineered antibody of claim 175 wherein the one or more free cysteine amino acid residues are located in a light chain.

180. The cysteine engineered antibody of claim 175, wherein the antibody is an immunoconjugate comprising the cysteine engineered antibody covalently attached to a cytotoxic agent.

181. The cysteine engineered antibody of claim 180, wherein the cytotoxic agent is selected from a toxin, a chemotherapeutic agent, a drug moiety, an antibiotic, a radioactive isotope, and a nucleolytic enzyme.

182. The cysteine engineered antibody of claim 175, wherein the antibody is covalently attached to a capture label, a detection label, or a solid support.

183. The cysteine engineered antibody of claim 182 wherein the antibody is covalently attached to a biotin capture label.

184. The cysteine engineered antibody of claim 182 wherein the antibody is covalently attached to a fluorescent dye detection label.

185. The cysteine engineered antibody of claim 184 wherein the fluorescent dye is selected from a fluorescein type, a rhodamine type, dansyl, Lissamine, a cyanine, a phycoerythrin, Texas Red, and an analog thereof.

186. The cysteine engineered antibody of claim 182 wherein the antibody is covalently attached to a radionuclide detection label selected from ³H, ¹¹C, ¹⁴C, ¹⁸F, ³²P, ³⁵S, ⁶⁴Cu, ⁶⁸Ga, ⁸⁶Y, ⁹⁹Tc, ¹¹¹In, ¹²³I, ¹²⁴I, ¹²⁵I, ¹³¹I, ¹³³Xe, ¹⁷⁷Lu, ²¹¹At, and ²¹³Bi.

187. The cysteine engineered antibody of claim 182 wherein the antibody is covalently attached to a detection label by a chelating ligand.

188. The cysteine engineered antibody of claim 187 wherein the chelating ligand is selected from DOTA, DOTP, DOTMA, DTPA and TETA.

189. The antibody of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258 comprising an albumin binding peptide.

190. The antibody of claim 188, wherein the albumin binding peptide is selected from SEQ ID NOs:

246-250.

191. A cysteine engineered antibody comprising one or more free cysteine amino acids at one or more positions 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 in a parent antibody, wherein the parent antibody is an antibody of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258.

192. The antibody of claim 191, wherein a cysteine is at position 205 of the light chain.

193. The antibody of claim 191, wherein a cysteine is at position 118 of the heavy chain.

194. The antibody of claim 191, wherein a cysteine is at position 400 of the heavy chain.

195. The antibody of claim 191 wherein the antibody is selected from a monoclonal antibody, a bispecific antibody, a chimeric antibody, a human antibody, and a humanized antibody.

196. The antibody of claim 191 which is an antibody fragment.

197. The antibody of claim 196 wherein the antibody fragment is a Fab fragment.

198. The antibody of claim 191 which is selected from a chimeric antibody, a human antibody, or a humanized antibody.

199. The antibody of claim 191 which is produced in bacteria.

200. The antibody of claim 191 which is produced in CHO cells.

201. A method of determining the presence of a CD79b protein in a sample suspected of containing said protein, said method comprising exposing said sample to an antibody of claim 187 and determining binding of said antibody to said CD79b protein in said sample, wherein binding of the antibody to said protein is indicative of the presence of said protein in said sample.

202. The method of claim 201 wherein said sample comprises a cell suspected of expressing said CD79b protein.

203. The method of claim 201 wherein said cell is B cell.

204. The method of claim 201 wherein the antibody is covalently attached to a label selected from a fluorescent dye, a radioisotope, biotin, or a metal-complexing ligand.

205. A pharmaceutical formulation comprising the anti-CD79b antibody of claim 191, and a pharmaceutically acceptable diluent, carrier or excipient.

206. The antibody of claim 191 wherein the antibody is covalently attached to an auristatin or a maytansinoid drug moiety whereby an antibody drug conjugate is formed.

207. The antibody-drug conjugate of claim 206 comprising an antibody (Ab), and an auristatin or maytansinoid drug moiety (D) wherein the cysteine engineered antibody is attached through one or more free cysteine amino acids by a linker moiety (L) to D;

the compound having Formula I;

AB-(L-D)_p  

 

I

where p is 1, 2, 3, or 4.

208. The antibody-drug conjugate compound of claim 207 wherein p is 2.

209. The antibody-drug conjugate compound of claim 207 wherein L has the formula:

-A_a-W_w—

Y_y—

where;

A is a Stretcher unit covalently attached to a cysteine thiol of the cysteine engineered antibody (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.

210. The antibody-drug conjugate compound of claim 209 having the formula:

211. The antibody-drug conjugate compound of claim 209 wherein W_w is valine-citrulline.

212. The antibody-drug conjugate compound of claim 209 wherein R¹⁷ is (CH₂)₅ or (CH₂)₂.

213. The antibody-drug conjugate compound of claim 209 having the formula:

214. The antibody-drug conjugate compound of claim 213 wherein R¹⁷ is (CH₂)₅ or (CH₂)₂.

215. The antibody-drug conjugate compound of claim 209 having the formula:

216. The antibody-drug conjugate compound of claim 207 wherein L is SMCC, SPP, SPDB or BMPEO.

217. The antibody-drug conjugate compound of claim 207 wherein D is MMAE, having the structure:

218. The antibody-drug conjugate compound of claim 207 wherein D is MMAF, having the structure:

219. The antibody-drug conjugate compound of claim 207 wherein D is DM1 or DM4, having the structures:

220. The antibody-drug conjugate compound of claim 206 wherein the antibody is selected from a monoclonal antibody, a bispecific antibody, a chimeric antibody, a human antibody, a humanized antibody, and an antibody fragment.

221. The antibody-drug conjugate compound of claim 206 wherein the antibody fragment is a Fab fragment.

222. An antibody-drug conjugate compound selected from the structures:

223. The antibody drug conjugate of claim 206 wherein the auristatin is MMAE or MMAF.

224. The antibody drug conjugate of claim 207 wherein L is MC-val-cit-PAB or MC.

225. An assay for detecting B cells comprising:

(a) exposing cells to an antibody-drug conjugate compound of claim 206; and

(b) determining the extent of binding of the antibody-drug conjugate compound to the cells.

226. A method of inhibiting cellular proliferation comprising treating mammalian cancerous B cells in a cell culture medium with an antibody-drug conjugate compound of claim 206, whereby proliferation of the cancerous B cells is inhibited.

227. A pharmaceutical formulation comprising the antibody drug conjugate of claim 206, and a pharmaceutically acceptable diluent, carrier or excipient.

228. A method of treating cancer comprising administering to a patient the pharmaceutical formulation of claim 227.

229. The method of claim 228 wherein the cancer is selected from the group consisting of lymphoma, non-Hodgkins lymphoma (NHL), aggressive NHL, relapsed aggressive NHL, relapsed indolent 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.

230. The method of claim 228 wherein the patient is administered a cytotoxic agent in combination with the antibody-drug conjugate compound.

231. An article of manufacture comprising

the pharmaceutical formulation of claim 227;

a container; and

a package insert or label indicating that the compound can be used to treat cancer characterized by the overexpression of a CD79b polypeptide.

232. The article of manufacture of claim 231 wherein the cancer is selected from the group consisting of lymphoma, non-Hodgkins lymphoma (NHL), aggressive NHL, relapsed aggressive NHL, relapsed indolent 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.

233. A method for making an antibody drug conjugate compound comprising an anti-CD79b antibody (Ab) of claim 191, and an auristatin or maytansinoid drug moiety (D) wherein the antibody is attached through the one or more engineered cysteine amino acids by a linker moiety (L) to D;

the compound having Formula I;

Ab-(L-D)_p  

 

I

where p is 1, 2, 3, or 4;

the method comprising the steps of;

(a) reacting an engineered cysteine group of the antibody with a linker reagent to form antibody-linker intermediate Ab-L; and

(b) reacting Ab-L with an activated drug moiety D;

whereby the antibody-drug conjugate is formed;

or comprising the steps of;

(c) reacting a nucleophilic group of a drug moiety with a linker reagent to form drug-linker intermediate D-L; and

(d) reacting D-L with an engineered cysteine group of the antibody;

whereby the antibody-drug conjugate is formed.

234. The method of claim 233 further comprising the step of expressing the antibody in chinese hamster ovary (CHO) cells.

235. The method of claim 233 further comprising the step of treating the expressed antibody with a reducing agent.

236. The method of claim 235 wherein the reducing agent is selected from TCEP and DTT.

237. The method of claim 235 further comprising the step of treating the expressed antibody with an oxidizing agent, after treating with the reducing agent.

238. The method of claim 237 wherein the oxidizing agent is selected from copper sulfate, dehydroascorbic acid, and air.

239. The antibody of claim 191 wherein the antibody comprises a heavy chain sequence having at least 90% sequence identity to an amino acid sequence selected from any one of SEQ ID NOs:

304 or 228.

240. The antibody of claim 191 wherein the antibody comprises a light chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO:

303 and a heavy chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO;

228.

241. The antibody of claim 191 wherein the antibody comprises a heavy chain sequence having at least 90% sequence identity to an amino acid sequence selected from any one of SEQ ID NOs:

306 or 230.

242. The antibody of claim 191 wherein the antibody comprises a light chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO:

305 and a heavy chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO;

230.

243. The antibody of claim 191 wherein the antibody comprises a heavy chain sequence having at least 90% sequence identity to an amino acid sequence selected from any one of SEQ ID NOs:

308 or 232.

244. The antibody of claim 191 wherein the antibody comprises a light chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO:

307 and a heavy chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO;

232.

245. The antibody of claim 191 wherein the antibody comprises a heavy chain sequence having at least 90% sequence identity to an amino acid sequence selected from any one of SEQ ID NOs:

6 or 236.

246. The antibody of claim 191 wherein the antibody comprises a light chain sequence having at least 90% sequence identity to an amino acid sequence selected from any one of SEQ ID NOs:

4 or 235.

247. The antibody of claim 191 wherein the antibody comprises a light chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO:

4 and a heavy chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO;

236.

248. The antibody of claim 191 wherein the antibody comprises a light chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO:

235 and a heavy chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO;

6.

252. The antibody of claim 191 wherein the antibody comprises a heavy chain sequence having at least 90% sequence identity to an amino acid sequence selected from any one of SEQ ID NOs:

243 or 244.

253. The antibody of claim 191 wherein the antibody comprises a light chain sequence having at least 90% sequence identity to an amino acid sequence selected from any one of SEQ ID NOs:

241 or 300.

254. The antibody of claim 191 wherein the antibody comprises a light chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO:

241 and a heavy chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO;

244.

255. The antibody of claim 191 wherein the antibody comprises a light chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO:

300 and a heavy chain sequence having at least 90% sequence identity to an amino acid sequence of SEQ ID NO;

243.

256. A composition comprising the antibody of any of claim 1, 6-10, 58, 69, 80, 91, 115, 118, 121, 124, 251 or 258.

257. The composition of claim 256, wherein the composition comprises a carrier.

17. A humanized anti-CD79b antibody wherein monovalent affinity of the antibody to human CD79b is substantially the same as monovalent affinity of a murine antibody comprising a light chain and heavy chain variable sequence as depicted in FIGS. 7A-B (SEQ ID NO:

10) and FIGS. 8A-B (SEQ ID NO;

     14).

20. The humanized antibody of claim 17-19 wherein the murine antibody is produced by the hybridoma cell line deposited with the ATCC as HB11413 on Jul. 20, 1993.

30. The antibody of any of claims 17-29 wherein the binding affinity is expressed as a Kd value.

31. The antibody of any of claims 17-29 wherein the binding affinity is measured by Biacore or radioimmunoassay.

18. A humanized anti-CD79b antibody wherein monovalent affinity of the antibody to human CD79b is at least 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10-fold greater than monovalent affinity of a murine or chimeric antibody comprising a light chain and heavy chain variable sequence as depicted in FIGS. 7A-B (SEQ ID NO:

10) and FIGS. 8A-B (SEQ ID NO;

     14).

19. A humanized anti-CD79b antibody wherein monovalent affinity of the antibody to human CD79b is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55 or 60-fold lower than monovalent affinity of a murine or chimeric antibody comprising a light chain and heavy chain variable sequence as depicted in FIGS. 7A-B (SEQ ID NO:

10) and FIGS. 8A-B (SEQ ID NO;

     14).

21. A humanized anti-CD79b antibody wherein the affinity of the antibody in its bivalent form to human CD79b is substantially the same as the affinity of a murine antibody in its bivalent form and comprising a light chain and heavy chain variable sequence as depicted in FIGS. 7A-B (SEQ ID NO:

10) and FIGS. 8A-B (SEQ ID NO;

     14).

22. A humanized anti-CD79b antibody the affinity of the antibody in its bivalent form to human CD79b is at least 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10-fold greater than the affinity of a murine or chimeric antibody in its bivalent form and comprising a light chain and heavy chain variable sequence as depicted in FIGS. 7A-B (SEQ ID NO:

10) and FIGS. 8A-B (SEQ ID NO;

     14).

23. A humanized anti-CD79b antibody wherein the affinity of the antibody in its bivalent form to human CD79b is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55 or 60-fold lower than the affinity of a murine or chimeric antibody in its bivalent form comprising a light chain and heavy chain variable sequence as depicted in FIGS. 7A-B (SEQ ID NO:

10) and FIGS. 8A-B (SEQ ID NO;

     14).

24. A humanized anti-CD79b antibody wherein the affinity of the antibody in its bivalent form to human CD79b is 0.4 nM.

25. The humanized anti-CD79 antibody of claim 24 wherein the affinity of the antibody in its bivalent form to human CD79b is 0.4 nM +/−

0.04.

26. A humanized anti-CD79b antibody wherein the affinity of the antibody in its bivalent form to human CD79b is 0.2 nM.

27. The humanized anti-CD79 antibody of claim 26 wherein the affinity of the antibody in its bivalent form to human CD79b is 0.2 nM +/−

0.02.

28. A humanized anti-CD79b antibody wherein the affinity of the antibody in its bivalent form to human CD79b is 0.5 nM.

29. The humanized anti-CD79 antibody of claim 28 wherein the affinity of the antibody in its bivalent form to human CD79b is 0.5 nM +/−

0.1.

46. A humanized anti-CD79b antibody wherein the humanized antibody when conjugated to a cytotoxic agent inhibits tumor cell growth.

49. An antibody comprising a heavy chain variable domain comprising HVR1-HC, HVR2-HC and/or HVR3-HC sequence depicted in FIG. 15 (SEQ ID NO:

164-166).

50. The antibody of claim 49, wherein the variable domain comprises FR1-HC, FR2-HC, FR3-HC and/or FR4-HC sequence depicted in FIG. 15 (SEQ ID NO:

160-163).

51. The antibody of claim 49 or 50, wherein the antibody comprises CH1 and/or Fc sequence depicted in FIG. 15 (SEQ ID NO:

167 and/or

     168).

57. The antibody made by the process of:

(a) culturing a cell expressing an antibody comprising a heavy chain variable domain of any of claims 49-51 and a light chain variable domain of any of claims 52-54; and

(b) isolating the antibody from said cultured cell.

58. An antibody comprising a heavy chain variable domain of any of claims 49-51 and a light chain variable domain of any of claims 52-54.

59. The antibody of claim 58, wherein the antibody is monovalent and comprises an Fc region.

52. An antibody comprising a light chain variable domain comprising HVR1-LC, HVR2-LC and/or HVR3-LC sequence depicted in FIG. 15 (SEQ ID NO:

156-158).

53. The antibody of claim 52, wherein the variable domain comprises FR1-LC, FR2-LC, FR3-LC and/or FR4-LC sequence depicted in FIG. 15 (SEQ ID NO:

152-155).

54. The antibody of claim 52 or 53, wherein the antibody comprises CL1 sequence depicted in FIG. 15 (SEQ ID NO:

159).

55. The polypeptide comprising the sequence depicted in FIG. 15 (SEQ ID NO:

170).

56. The polypeptide comprising the sequence depicted in FIG. 15 (SEQ ID NO:

169).

60. An antibody comprising a heavy chain variable domain comprising HVR1-HC, HVR2-HC and/or HVR3-HC sequence depicted in FIG. 16 (SEQ ID NO:

183-185).

61. The antibody of claim 60, wherein the variable domain comprises FR1-HC, FR2-HC, FR3-HC and/or FR4-HC sequence depicted in FIG. 16 (SEQ ID NO:

179-182).

62. The antibody of claim 60 or 61, wherein the antibody comprises CH1 and/or Fc sequence depicted in FIG. 16 (SEQ ID NO:

186 and/or

     187).

68. The antibody made by the process of:

(a) culturing a cell expressing an antibody comprising a heavy chain variable domain of any of claims 60-62 and a light chain variable domain of any of claims 63-65; and

(b) isolating the antibody from said cultured cell.

69. An antibody comprising a heavy chain variable domain of any of claims 60-62 and a light chain variable domain of any of claims 63-65.

70. The antibody of claim 69, wherein the antibody is monovalent and comprises an Fc region.

63. An antibody comprising a light chain variable domain comprising HVR1-LC, HVR2-LC and/or HVR3-LC sequence depicted in FIG. 16 (SEQ ID NO:

175-177).

64. The antibody of claim 63, wherein the variable domain comprises FR1-LC, FR2-LC, FR3-LC and/or FR4-LC sequence depicted in FIG. 16 (SEQ ID NO:

171-174).

65. The antibody of claim 63 or 64, wherein the antibody comprises CL1 sequence depicted in FIG. 16 (SEQ ID NO:

178).

66. The polypeptide comprising the sequence depicted in FIG. 16 (SEQ ID NO:

189).

67. The polypeptide comprising the sequence depicted in FIG. 16 (SEQ ID NO:

188).

71. An antibody comprising a heavy chain variable domain comprising HVR1-HC, HVR2-HC and/or HVR3-HC sequence depicted in FIG. 17 (SEQ ID NO:

202-204).

72. The antibody of claim 71, wherein the variable domain comprises FR1-HC, FR2-HC, FR3-HC and/or FR4-HC sequence depicted in FIG. 17 (SEQ ID NO:

198-201).

73. The antibody of claim 71 or 72, wherein the antibody comprises CH1 and/or Fc sequence depicted in FIG. 17 (SEQ ID NO:

205 and/or

     206).

79. The antibody made by the process of:

(a) culturing a cell expressing an antibody comprising a heavy chain variable domain of any of claims 71-73 and a light chain variable domain of any of claims 74-76; and

(b) isolating the antibody from said cultured cell.

80. An antibody comprising a heavy chain variable domain of any of claims 71-73 and a light chain variable domain of any of claims 74-76.

81. The antibody of claim 80, wherein the antibody is monovalent and comprises an Fc region.

74. An antibody comprising a light chain variable domain comprising HVR1-LC, HVR2-LC and/or HVR3-LC sequence depicted in FIG. 17 (SEQ ID NO:

194-196).

75. The antibody of claim 74, wherein the variable domain comprises FR1-LC, FR2-LC, FR3-LC and/or FR4-LC sequence depicted in FIG. 17 (SEQ ID NO:

190-193).

76. The antibody of claim 74 or 75, wherein the antibody comprises CL1 sequence depicted in FIG. 17 (SEQ ID NO:

197).

77. The polypeptide comprising the sequence depicted in FIGS. 8A-B (SEQ ID NO:

208).

78. The polypeptide comprising the sequence depicted in FIGS. 7A-B (SEQ ID NO:

207).

82. An antibody comprising a heavy chain variable domain comprising HVR1-HC, HVR2-HC and/or HVR3-HC sequence depicted in FIG. 18 (SEQ ID NO:

221-223).

83. The antibody of claim 82, wherein the variable domain comprises FR1-HC, FR2-HC, FR3-HC and/or FR4-HC sequence depicted in FIG. 18 (SEQ ID NO:

217-220).

84. The antibody of claim 82 or 83, wherein the antibody comprises CH1 and/or Fc sequence depicted in FIG. 18 (SEQ ID NO:

224 and/or

     225).

90. The antibody made by the process of:

(a) culturing a cell expressing an antibody comprising a heavy chain variable domain of any of claims 82-84 and a light chain variable domain of any of claims 85-87; and

(b) isolating the antibody from said cultured cell.

91. An antibody comprising a heavy chain variable domain of any of claims 82-84 and a light chain variable domain of any of claims 85-87.

92. The antibody of claim 91, wherein the antibody is monovalent and comprises an Fc region.

85. An antibody comprising a light chain variable domain comprising HVR1-LC, HVR2-LC and/or HVR3-LC sequence depicted in FIG. 18 (SEQ ID NO:

213-215).

86. The antibody of claim 85, wherein the variable domain comprises FR1-LC, FR2-LC, FR3-LC and/or FR4-LC sequence depicted in FIG. 18 (SEQ ID NO:

209-212).

87. The antibody of claim 85 or 86, wherein the antibody comprises CL1 sequence depicted in FIG. 18 (SEQ ID NO:

216).

88. The polypeptide comprising the sequence depicted in FIG. 18 (SEQ ID NO:

227).

89. The polypeptide comprising the sequence depicted in FIG. 18 (SEQ ID NO:

226).

113. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

170.

114. An antibody that binds to CD79b, wherein the antibody comprises a light chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

169.

115. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

170 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

169.

116. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

189.

117. An antibody that binds to CD79b, wherein the antibody comprises a light chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

188.

118. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

189 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

188.

119. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

208.

120. An antibody that binds to CD79b, wherein the antibody comprises a light chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

207.

121. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

208 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

207.

122. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

227.

123. An antibody that binds to CD79b, wherein the antibody comprises a light chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

226.

124. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having a least 90% sequence identity to the amino acid sequence of SEQ ID NO:

227 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO;

226.

128. A method of making an anti-CD79b antibody, wherein the method comprises (a) culturing a host cell selected from the group comprising a eukaryotic cell and a CHO cell under conditions suitable for expression of the polynucleotide encoding the antibody, and (b) isolating the antibody.

249. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO:

301.

250. An antibody that binds to CD79b, wherein the antibody comprises a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO:

302.

251. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO:

301 and a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO;

302.

258. An antibody that binds to CD79b, wherein the antibody comprises a heavy chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO:

14 and a light chain variable domain having at least 90% sequence identity to an amino acid sequence selected from SEQ ID NO;

10.