Anti-LAMP5 antibody and utilization thereof

Patent metadata

Field	Value
Publication number	US-9751942-B2
Application number	US-201314388649-A
Country	US
Kind code	B2
Filing date	Mar 29, 2013
Priority date	Mar 29, 2012
Publication date	Sep 5, 2017
Grant date	Sep 5, 2017

Abstract

A monoclonal antibody recognizing the extracellular region of LAMP5 was produced. The produced antibody demonstrated antibody-dependent cell-mediated cytotoxic activity, and/or cell growth inhibitory activity in the presence of a toxin-labeled secondary antibody, against a multiple myeloma cell line.

First claim

The invention claimed is:

1. A monoclonal antibody according to any of the following (1) to (9):
(1) an antibody comprising a heavy chain variable region comprising the CDR1 defined by SEQ ID NO: 35, the CDR2 defined by SEQ ID NO: 36 and the CDR3 defined by SEQ ID NO: 37, and a light chain variable region comprising the CDR1 defined by SEQ ID NO: 38, the CDR2 defined by SEQ ID NO: 39 and the CDR3 defined by SEQ ID NO: 40;
(2) an antibody comprising a heavy chain variable region comprising the CDR1 defined by SEQ ID NO: 41, the CDR2 defined by SEQ ID NO: 42 and the CDR3 defined by SEQ ID NO: 43, and a light chain variable region comprising the CDR1 defined by SEQ ID NO: 44, the CDR2 defined by SEQ ID NO: 45 and the CDR3 defined by SEQ ID NO: 46;
(3) an antibody comprising a heavy chain variable region comprising the CDR1 defined by SEQ ID NO: 47, the CDR2 defined by SEQ ID NO: 48 and the CDR3 defined by SEQ ID NO: 49, and a light chain variable region comprising the CDR1 defined by SEQ ID NO: 50, the CDR2 defined by SEQ ID NO: 51 and the CDR3 defined by SEQ ID NO: 52;
(4) an antibody comprising a heavy chain variable region comprising the CDR1 defined by SEQ ID NO: 53, the CDR2 defined by SEQ ID NO: 54 and the CDR3 defined by SEQ ID NO: 55, and a light chain variable region comprising the CDR1 defined by SEQ ID NO: 56, the CDR2 defined by SEQ ID NO: 57 and the CDR3 defined by SEQ ID NO: 58;
(5) the monoclonal antibody according to any of (1) to (4), comprising a heavy chain comprising a heavy chain constant region of human IgG and/or a light chain comprising a light chain constant region of human antibody;
(6) the monoclonal antibody according to (5), wherein the heavy chain comprising a heavy chain constant region of human IgG is a heavy chain comprising the heavy chain constant region defined by SEQ ID NO: 68;
(7) the monoclonal antibody according to (5) or (6), wherein the light chain comprising a light chain constant region of human antibody is a light chain comprising the light chain constant region defined by SEQ ID NO: 73;
(8) a monoclonal antibody in which one amino acid is substituted, deleted, added or inserted in the antibody according to any of (1) to (7) and which has binding activity equivalent to that of the monoclonal antibody according to any of (1) to (7) with respect to an epitope present at position 39 to position 289 of the polypeptide defined in SEQ ID NO: 8 expressed on a cell surface; or
(9) the monoclonal antibody according to (5) or (7), wherein the heavy chain comprising a heavy chain constant region of human IgG is a heavy chain that comprises one substitution of an amino acid selected from the group of amino acids at position 221, position 222, position 223, position 224, position 225, position 227, position 228, position 230, position 231, position 232, position 233, position 234, position 235, position 236, position 237, position 238, position 239, position 240, position 241, position 243, position 244, position 245, position 246, position 247, position 249, position 250, position 251, position 254, position 255, position 256, position 258, position 260, position 262, position 263, position 264, position 265, position 266, position 267, position 268, position 269, position 270, position 271, position 272, position 273, position 274, position 275, position 276, position 278, position 279, position 280, position 281, position 282, position 283, position 284, position 285, position 286, position 288, position 290, position 291, position 292, position 293, position 294, position 295, position 296, position 297, position 298, position 299, position 300, position 301, position 302, position 303, position 304, position 305, position 311, position 313, position 315, position 317, position 318, position 320, position 322, position 323, position 324, position 325, position 326, position 327, position 328, position 329, position 330, position 331, position 332, position 333, position 334, position 335, position 336, position 337, position 339, position 376, position 377, position 378, position 379, position 380, position 382, position 385, position 392, position 396, position 421, position 427, position 428, position 429, position 434, position 436 and position 440, as defined by the EU numbering system, in the heavy chain constant region of SEQ ID NO: 68.

2. A pharmaceutical composition comprising:
the monoclonal antibody according to claim 1 as an active ingredient thereof;
a pharmacologically acceptable carrier or additive; and
IL-6 or a salt thereof.

3. An anticancer drug comprising:
the monoclonal antibody according to claim 1 as an active ingredient thereof;
a pharmacologically acceptable carrier or additive; and IL-6 or a salt thereof, that allows for treating cancer.

4. A pharmaceutical composition comprising the monoclonal antibody according to claim 1 and IL-6 or a salt thereof as an active ingredient.

5. An anticancer drug comprising the monoclonal antibody according to claim 1 and IL-6 or a salt thereof as an active ingredient, that allows for treating cancer.

6. A monoclonal antibody, which binds to an epitope present from position 30 to position 235 of a polypeptide defined in SEQ ID NO: 65 expressed on a cell surface, wherein the monoclonal antibody has internalization activity, and is produced according to a method comprising recovering the monoclonal antibody from a culture fluid of a host cell comprising a vector selected from the group consisting of the following (A) to (D):
(A) the vector according to (1) below and the vector according to (4) below;
(B) the vector according to (2) below and the vector according to (5) below;
(C) the vector according to (3) below and the vector according to (5) below; and
(D) the vector according to any of (6) to (8) below:
(1) a vector comprising a polynucleotide encoding a heavy chain variable region selected from a group consisting of the following (a) to (d):
(a) a heavy chain variable region comprising the CDR1 defined by SEQ ID NO: 35, the CDR2 defined by SEQ ID NO: 36 and the CDR3 defined by SEQ ID NO: 37;
(b) a heavy chain variable region comprising the CDR1 defined by SEQ ID NO: 41, the CDR2 defined by SEQ ID NO: 42 and the CDR3 defined by SEQ ID NO: 43;
(c) a heavy chain variable region comprising the CDR1 defined by SEQ ID NO: 47, the CDR2 defined by SEQ ID NO: 48 and the CDR3 defined by SEQ ID NO: 49; or,
(d) a heavy chain variable region comprising the CDR1 defined by SEQ ID NO: 53, the CDR2 defined by SEQ ID NO: 54 and the CDR3 defined by SEQ ID NO: 55;
(2) a vector comprising a polynucleotide encoding the heavy chain variable region according to any of (a) to (d) of (1) above and the heavy chain constant region of SEQ ID NO: 68;
(3) a vector comprising a variant nucleotide encoding one substitution of an amino acid selected from the group of amino acids at position 221, position 222, position 223, position 224, position 225, position 227, position 228, position 230, position 231, position 232, position 233, position 234, position 235, position 236, position 237, position 238, position 239, position 240, position 241, position 243, position 244, position 245, position 246, position 247, position 249, position 250, position 251, position 254, position 255, position 256, position 258, position 260, position 262, position 263, position 264, position 265, position 266, position 267, position 268, position 269, position 270, position 271, position 272, position 273, position 274, position 275, position 276, position 278, position 279, position 280, position 281, position 282, position 283, position 284, position 285, position 286, position 288, position 290, position 291, position 292, position 293, position 294, position 295, position 296, position 297, position 298, position 299, position 300, po

Assignees

• Chugai Pharmaceutical Co Ltd

Inventors

• Kawai Shigeto

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2319/42

  containing a HA(hemagglutinin)-tag · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title