Humanized anti-cd79b antibodies and immunoconjugates and methods of use

Patent metadata

Field	Value
Publication number	US-2018201679-A1
Application number	US-201715803495-A
Country	US
Kind code	A1
Filing date	Nov 3, 2017
Priority date	Jul 16, 2007
Publication date	Jul 19, 2018
Grant date	—

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

1 .- 179 . (canceled)

180 . A method of treating a subject having cancer, said method comprising administering to the subject an effective amount of an anti-CD79b antibody comprising the following hypervariable region (HVR) sequences:
(i) HVR-L1 comprising sequence KSSQSLLDSDGKTYLN (SEQ ID NO: 59); (ii) HVR-L2 comprising sequence LVSKLDS (SEQ ID NO: 60); (iii) HVR-L3 comprising sequence FQGTHFPFT (SEQ ID NO: 79); (iv) HVR-H1 comprising sequence GYTFTSYWMN (SEQ ID NO: 62); (v) HVR-H2 comprising sequence GMIDPSDSETHYNHIFKD (SEQ ID NO: 63); and (vi) HVR-H3 comprising sequence ARNLYL (SEQ ID NO: 64).

181 . The method of claim 180 , wherein the anti-CD79b antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 12.

182 . The method of claim 180 , wherein the anti-CD79b antibody is an immunoconjugate covalently attached to a cytotoxic agent.

183 . The method of claim 182 , wherein the cytotoxic agent covalently attached to the immunoconjugate is selected from a toxin, a chemotherapeutic agent, a drug moiety, an antibiotic, a radioactive isotope and a nucleolytic enzyme.

184 . The method of claim 182 , wherein the immunoconjugate comprises the formula Ab-(L-D)p, wherein:
(a) Ab is the antibody of claim 180 or 181 ; (b) L is a linker; (c) D is a drug moiety.

185 . The method of claim 184 , wherein the 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), MC-val-cit-PAB, and N-Succinimidyl (4-iodo-acetyl) aminobenzoate (SIAB).

186 . The method of claim 184 , wherein D is selected from an auristatin and a dolastatin.

187 . The method of claim 186 , wherein D is MMAE, comprising the structure:

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

188 . The method of claim 186 , wherein D is MMAF, comprising the structure:

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

189 . The method of claim 186 , wherein D is DM1 or DM4, comprising the structures:

190 . The method of claim 184 , wherein the immunoconjugate comprises the structure of:

wherein Val is valine; Cit is citrulline; p is 1, 2, 3, 4, 5, 6, 7 or 8.

191 . The method of claim 184 , wherein the immunoconjugate comprises the structure of:

wherein Val is valine; Cit is citrulline; p is 1, 2, 3, 4, 5, 6, 7 or 8.

192 . The method of claim 184 , wherein the immunoconjugate comprises the structure of:

wherein p is 1, 2, 3, 4, 5, 6, 7 or 8.

193 . The method of claim 182 , wherein the immunoconjugate comprises a cysteine engineered anti-CD79b antibody comprising one or more free cysteine amino acid residues located in the light chain.

194 . The method of claim 193 , wherein the cysteine engineered antibody further comprises a free cysteine amino acid at one or more positions selected from 15, 43, 110, 144, 168 and 205 of the light chain according to Kabat numbering convention and 41, 88, 115, 118, 120, 171, 172, 282, 375, and 400 of the heavy chain according to EU numbering convention.

195 . The method of claim 194 , wherein the cysteine is at position 205 of the light chain.

196 . The method of claim 194 , wherein the cysteine is at position 118 of the heavy chain.

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

198 . The method of claim 180 , wherein the cancer is selected from lymphoma, myeloma, 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), follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), and mantle cell lymphoma (MCL).

Assignees

• Genentech Inc

Inventors

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

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title