Antibodies against cd38 for treatment of multiple myeloma

Patent metadata

Field	Value
Publication number	US-2016130362-A1
Application number	US-201514878797-A
Country	US
Kind code	A1
Filing date	Oct 8, 2015
Priority date	Mar 23, 2005
Publication date	May 12, 2016
Grant date	—

Abstract

Isolated human monoclonal antibodies which bind to human CD38, and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

First claim

1 - 87 . (canceled)

88 . An in vitro method for detecting the presence of CD38 antigen, or a cell expressing CD38, in a sample comprising:
(a) contacting the sample with an antibody that binds to human CD38 encoded by: (i) human light chain and human heavy chain nucleic acids comprising nucleotide sequences in their variable regions as set forth in SEQ ID NO: 1 and SEQ ID NO: 6, respectively; (ii) human light chain and human heavy chain nucleic acids comprising nucleotide sequences in their variable regions as set forth in SEQ ID NO: 11 and SEQ ID NO: 16, respectively; (iii) human light chain and human heavy chain nucleic acids comprising nucleotide sequences in their variable regions as set forth in SEQ ID NO: 21 and SEQ ID NO: 26, respectively; or (iv) human light chain and human heavy chain nucleic acids comprising nucleotide sequences in their variable regions, which are conservative sequence modifications of the sequences as set forth in (i), (ii) or (iii), under conditions that allow formation of a complex between the antibody and CD38; and (b) detecting the formation of the complex.

89 . An in vivo method for detecting the presence of CD38 antigen, or a cell expressing CD38, in a subject comprising:
(a) administering to the subject an antibody that binds to human CD38 encoded by: (i) human light chain and human heavy chain nucleic acids comprising nucleotide sequences in their variable regions as set forth in SEQ ID NO: 1 and SEQ ID NO: 6, respectively; (ii) human light chain and human heavy chain nucleic acids comprising nucleotide sequences in their variable regions as set forth in SEQ ID NO: 11 and SEQ ID NO: 16, respectively; (iii) human light chain and human heavy chain nucleic acids comprising nucleotide sequences in their variable regions as set forth in SEQ ID NO: 21 and SEQ ID NO: 26, respectively; or (iv) human light chain and human heavy chain nucleic acids comprising nucleotide sequences in their variable regions, which are conservative sequence modifications of the sequences as set forth in (i), (ii) or (iii), under conditions that allow formation of a complex between the peptide and CD38; and (b) detecting the formation of the complex.

90 . An isolated nucleic acid encoding an antibody which binds to human CD38 (SEQ ID NO: 31), wherein:
(a) the antibody does not bind to a mutant human CD38, wherein in the mutant human CD38, the serine residue in position 274 has been substituted with a phenylalanine residue (SEQ ID NO: 34), and wherein the antibody inhibits the synthesis of cGDPR by at least 25% after 90 minutes at a concentration of 3 μg/ml; (b) the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 7 or encoded by the nucleotide sequence set forth in SEQ ID NO: 6; (c) the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 17 or encoded by the nucleotide sequence set forth in SEQ ID NO: 16; (d) the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 27 or encoded by the nucleotide sequence set forth in SEQ ID NO: 26; (e) the antibody comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 2 or encoded by the nucleotide sequence set forth in SEQ ID NO: 1; (f) the antibody comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 12 or encoded by the nucleotide sequence set forth in SEQ ID NO: 11 (g) the antibody comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22 or encoded by the nucleotide sequence set forth in SEQ ID NO: 21; (h) the antibody comprises heavy and light chain variable region amino acid sequences as set forth in (i) SEQ ID NOs: 7 and 2, respectively; (ii) SEQ ID NOs: 17 and 12, respectively; or (iii) SEQ ID NOs: 27 and 22, respectively; (i) the antibody comprises heavy and light chain variable regions encoded by the nucleotide sequence as set forth in (i) SEQ ID NOs: 6 and 1, respectively; (ii) SEQ ID NOs: 16 and 11, respectively; or (iii) SEQ ID NOs: 26 and 21, respectively; (j) the antibody comprises a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs: 8, 9, and 10, respectively, and a light chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively; (k) the antibody comprises a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs: 18, 19, and 20, respectively, and a light chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 13, 14, and 15, respectively; or (l) the antibody comprises a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs: 28, 29, and 30, respectively, and a light chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 23, 24, and 25, respectively.

91 . A vector encoding the nucleic acid of claim 90 .

92 . A method of treating a disease or disorder involving cells expressing CD38 comprising administering to a subject in need thereof an antibody which binds to human CD38 (SEQ ID NO: 31), wherein:
(a) the antibody does not bind to a mutant human CD38, wherein in the mutant human CD38, the serine residue in position 274 has been substituted with a phenylalanine residue (SEQ ID NO: 34), and wherein the antibody inhibits the synthesis of cGDPR by at least 25% after 90 minutes at a concentration of 3 μg/ml; (b) the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 7 or encoded by the nucleotide sequence set forth in SEQ ID NO: 6; (c) the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 17 or encoded by the nucleotide sequence set forth in SEQ ID NO: 16; (d) the antibody comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 27 or encoded by the nucleotide sequence set forth in SEQ ID NO: 26; (e) the antibody comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 2 or encoded by the nucleotide sequence set forth in SEQ ID NO: 1; (f) the antibody comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 12 or encoded by the nucleotide sequence set forth in SEQ ID NO: 11 (g) the antibody comprises a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 22 or encoded by the nucleotide sequence set forth in SEQ ID NO: 21; (h) the antibody comprises heavy and light chain variable region amino acid sequences as set forth in (i) SEQ ID NOs: 7 and 2, respectively; (ii) SEQ ID NOs: 17 and 12, respectively; or (iii) SEQ ID NOs: 27 and 22, respectively; (i) the antibody comprises heavy and light chain variable regions encoded by the nucleotide sequence as set forth in (i) SEQ ID NOs: 6 and 1, respectively; (ii) SEQ ID NOs: 16 and 11, respectively; or (iii) SEQ ID NOs: 26 and 21, respectively; (j) the antibody comprises a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs: 8, 9, and 10, respectively, and a light chain variable region comprising CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 3, 4, and 5, respectively; (k) the antibody comprises a heavy chain variable region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs: 18, 19, and 20, respectively, and a light chain variable region co

Assignees

• Genmab As

Inventors

• De Weers Michel
• Graus Yvo
• Oprins Judith
• Parren Paul
• Van De Winkel Jan
• Van Vugt Martine

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title