ANTI-CD79B ANTIBODIES AND IMMUNOCONJUGATES AND METHODS OF USE

• US 20110135667A1
• Filed: 11/05/2010
• Published: 06/09/2011
• Est. Priority Date: 07/16/2007
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: CHEN, YVONNE, DORNAN, DAVID, DENNIS, MARK, ELKINS, KRISTI, JUNUTULA, JAGATH REDDY, ZHENG, BING, POLSON, ANDREW
• Granted Patent: US 8,545,850 B2
• Time in Patent Office: Days
• US Class Current: 424/178.1
• 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 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• 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. (canceled)

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.

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;

(b) L is a linker;

(c) D is a drug moiety; and

(d) p ranges from about 1 to 8.

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.

259. The immunoconjugate of claim 143, wherein D is a drug moiety of formula D_E or D_F:

261. The immunoconjugate of claim 141, wherein the linker is attached to the antibody through a thiol group on the antibody.

262. The immunoconjugate of claim 141, wherein the linker is cleavable by a protease.

263. The immunoconjugate of claim 142, wherein the linker comprises a val-cit dipeptide.

264. The immunoconjugate of claim 141, wherein the linker comprises a p-aminobenzyl unit.

265. The immunoconjugate of claim 142, wherein the linker comprises 6-maleimidocaproyl.

266. The immunoconjugate of claim 259, wherein the drug is selected from MMAE and MMAF.

267. The immunoconjugate of claim 266, wherein the drug is MMAE.

268. The immunoconjugate of claim 266, wherein the drug is MMAF.

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139. An immunoconjugate comprising an anti-CD79b antibody comprising:

(i) an HVR-L1 sequence of KASOSVDYEGDSFLN (SEQ ID NO;

     194)

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

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

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(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.

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.

260. The immunoconjugate of claim 139, having in vitro or in vivo cell killing activity.

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