Cross reactive siglec antibodies

Patent metadata

Field	Value
Publication number	US-2017306014-A1
Application number	US-201515509859-A
Country	US
Kind code	A1
Filing date	Sep 9, 2015
Priority date	Sep 10, 2014
Publication date	Oct 26, 2017
Grant date	—

Abstract

This invention relates to agents that bind multiple Siglecs, including antibodies that neutralize the inhibitory activity of multiple Siglec-7 and Siglec-9 in lymphocytes. Such agents can be used for the treatment of cancers or infectious disease.

First claim

1 - 38 . (canceled)

39 . An isolated antibody that specifically binds to a human Siglec-7 polypeptide and to a human Siglec-9 polypeptide, wherein the antibody causes an increase in a marker associated with cytotoxicity in a Siglec-expressing lymphocyte, when the lymphocyte is brought into contact with a target human cell bearing a ligand of the Siglec on the target cell surface.

40 . The antibody of claim 39 , wherein the antibody lacks an Fc domain, is a human IgG4 isotype antibody, or is an antibody having an Fc domain that is modified to reduce binding between the Fc domain and a human Fcγ receptor.

41 . The antibody of claim 39 , which does not substantially bind to a third human CD33-related Siglec polypeptide, optionally wherein the antibody binds to the Siglec-7 and Siglec-9 with a KD at least a 100-fold lower than to a third human CD33-related Siglec polypeptide, optionally wherein the third human CD33-related Siglec is selected from the group consisting of Siglec-3, -5, -6, -8, -10, -11 and -12.

42 . The isolated antibody of claim 41 , wherein the third human CD33-related Siglec polypeptide is Siglec-12.

43 . The antibody of claim 39 , which inhibits activation of the Siglec by a natural a ligand the Siglec present on a cell.

44 . An isolated monoclonal antibody characterized by:
a) specifically binding to Siglec-7, and when bound to Siglec-7 on a human immune cell, increasing activation and/or cytotoxicity of said immune cell toward a target human cell bearing a ligand of Siglec-7 on the target cell surface, when said target cell comes into con-tact with said immune cell; b) specifically binding to Siglec-9, and when bound to Siglec-9 on a human lymphocyte, increasing activation and/or cytotoxicity of said immune cell toward a target human cell bearing a ligand of Siglec-9 on the target cell surface, when said target cell comes into con-tact with said immune cell; and c) not substantially binding to the CD16 human Fcγ receptor.

45 . The antibody of claim 44 , wherein said ligand of Siglec-7 and/or Siglec-9 comprises a sialic acid.

46 . The antibody of claim 39 , wherein the antibody is selected from the group consisting of:
(a) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 3 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 4; (b) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 21 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 22; and (c) a monoclonal antibody comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 39 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 40.

47 . The antibody of claim 39 , wherein said antibody is a chimeric, human or humanized antibody.

48 . The antibody of claim 39 , wherein the antibody comprises an antigen binding domain capable of binding to Siglec-7 and to Siglec-9.

49 . The antibody of claim 39 , wherein the antibody is a non-depleting antibody.

50 . The antibody of claim 39 , wherein said antibody is an antibody fragment selected from Fab, Fab′, Fab′-SH, F(ab′) 2, Fv, a diabody, a single-chain antibody fragment, or a multispecific antibody comprising multiple different antibody fragments.

51 . A pharmaceutical composition comprising an antibody according to claim 39 , and a pharmaceutically acceptable carrier.

52 . A nucleic acid encoding a heavy and/or light chain of an antibody of claim 39 .

53 . A hybridoma or recombinant host cell producing the antibody of claim 39 .

54 . A method for the treatment or prevention of cancer in a patient in need thereof, the method comprising administering to said patient an effective amount of an antibody of claim 39 .

55 . A method for modulating CD56 dim NK cells and/or CD56 bright NK cells and/or CD8+ T cells in a subject the method comprising administering to said subject an effective amount of an antibody of claim 39 .

56 . A method for modulating CD56 dim NK cells and/or CD56 bright NK cells and/or CD8+ T cells in a subject the method comprising administering to said subject an effective amount of a composition of claim 51 .

57 . A method of producing an antibody which cross-reacts with multiple Siglec gene products and which neutralizes the inhibitory activity of such Siglecs, said method comprising the steps of:
(a) providing a plurality of antibodies that bind Siglec-7 and Siglec-9 polypeptides, (b) selecting antibodies that cross-react with Siglec-7 and Siglec-9 polypeptides, and (c) selecting antibodies that neutralize the inhibitory activity of Siglec-7 and Siglec-9 polypeptides.

58 . The method of claim 57 , wherein step (c) comprises selecting an antibody capable of causing an increase in a marker associated with cytotoxicity in a Siglec-expressing lymphocyte, when the lymphocyte is brought into contact with a target human cell bearing a ligand of the Siglec on the target cell surface.

Assignees

• Innate Pharma

Inventors

• Cornen Stéphanie
• Rossi Benjamin
• Wagtmann Nicolai

Classifications

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07K16/30

  from tumour cells · CPC title