IP Library › Patent Application 17107334

Patent Application

App. No. 17/107,334

ANTI-SIRP ALPHA ANTIBODIES

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Patent No.: US None
App. No.: 17/107,334

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Abstract

The present invention relates to anti-SIRPα antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease.

Claims (116)

1 - 30 . (canceled)

31 . An antibody antibody having the following characteristics:

binds human SIRPαV1 protein having the sequence of SEQ ID NO: 34 with an EC 50 <1 nM;

does not cross-react with SIRPβ1 protein having the sequence of SEQ ID NO: 38; and

exhibits a T20 “humanness” score of at least 79.

32 . An antibody according to claim 31 , wherein the antibody binds to a cell expressing human SIRPαV1 protein with an EC 50 <10 nM;

binds to a cell expressing human SIRPαV2 protein with an EC 50 <10 nM;

exhibits at least a 100-fold higher EC 50 for SIRPαV1(P74A) having the sequence of SEQ ID NO: 62 as compared to the EC 50 for human SIRPαV1 protein; and

exhibits at least a 100-fold higher EC 50 for human SIRPβ1 protein as compared to the EC 50 for human SIRPαV1 protein.

33 . An antibody according to claim 31 , wherein the antibody inhibits binding between human SIRPα and CD47 with an IC 50 <2.5 nM.

34 . An antibody according to claim 32 , wherein the antibody inhibits binding between human SIRPα and CD47 with an IC 50 <2.5 nM.

35 . A composition comprising:

an antibody or antigen binding fragment of claim 31 ; and

a pharmaceutically acceptable carrier or diluent,

wherein the composition optionally comprises a second antibody or antigen binding fragment thereof that induces ADCC and/or ADCP, wherein said antibody or antigen binding fragment of claim 31 enhances the antibody-mediated destruction of cells by the second antibody.

36 . A composition comprising:

an antibody or antigen binding fragment of claim 31 ; and

a pharmaceutically acceptable carrier or diluent,

37 . A composition according to claim 36 , further comprising a second antibody or antigen binding fragment thereof that induces ADCC and/or ADCP.

38 . An antibody or antigen binding fragment thereof that binds to the same epitope of human SIRPα as an antibody comprising one of the following combinations of heavy chain sequence/light chain sequence:

SEQ ID NO: 78/SEQ ID NO: 90,

SEQ ID NO: 78/SEQ ID NO: 92,

SEQ ID NO: 78/SEQ ID NO: 94,

SEQ ID NO: 78/SEQ ID NO: 96,

SEQ ID NO: 78/SEQ ID NO: 98,

SEQ ID NO: 78/SEQ ID NO: 100,

SEQ ID NO: 80/SEQ ID NO: 90,

SEQ ID NO: 80/SEQ ID NO: 92,

SEQ ID NO: 80/SEQ ID NO: 94,

SEQ ID NO: 80/SEQ ID NO: 96,

SEQ ID NO: 80/SEQ ID NO: 98,

SEQ ID NO: 80/SEQ ID NO: 100,

SEQ ID NO: 82/SEQ ID NO: 90,

SEQ ID NO: 82/SEQ ID NO: 92,

SEQ ID NO: 82/SEQ ID NO: 94,

SEQ ID NO: 82/SEQ ID NO: 96,

SEQ ID NO: 82/SEQ ID NO: 98,

SEQ ID NO: 82/SEQ ID NO: 100,

SEQ ID NO: 84/SEQ ID NO: 90,

SEQ ID NO: 84/SEQ ID NO: 92,

SEQ ID NO: 84/SEQ ID NO: 94,

SEQ ID NO: 84/SEQ ID NO: 96,

SEQ ID NO: 84/SEQ ID NO: 98,

SEQ ID NO: 84/SEQ ID NO: 100,

SEQ ID NO: 86/SEQ ID NO: 90,

SEQ ID NO: 86/SEQ ID NO: 92,

SEQ ID NO: 86/SEQ ID NO: 94,

SEQ ID NO: 86/SEQ ID NO: 96,

SEQ ID NO: 86/SEQ ID NO: 98,

SEQ ID NO: 86/SEQ ID NO: 100,

SEQ ID NO: 88/SEQ ID NO: 90,

SEQ ID NO: 88/SEQ ID NO: 92,

SEQ ID NO: 88/SEQ ID NO: 94,

SEQ ID NO: 88/SEQ ID NO: 96,

SEQ ID NO: 88/SEQ ID NO: 98,

SEQ ID NO: 88/SEQ ID NO: 100,

SEQ ID NO: 10/SEQ ID NO: 20,

SEQ ID NO: 10/SEQ ID NO: 22,

SEQ ID NO: 10/SEQ ID NO: 24,

SEQ ID NO: 10/SEQ ID NO: 26,

SEQ ID NO: 10/SEQ ID NO: 28,

SEQ ID NO: 12/SEQ ID NO: 20,

SEQ ID NO: 12/SEQ ID NO: 22,

SEQ ID NO: 12/SEQ ID NO: 24,

SEQ ID NO: 12/SEQ ID NO: 26,

SEQ ID NO: 12/SEQ ID NO: 28,

SEQ ID NO: 14/SEQ ID NO: 20,

SEQ ID NO: 14/SEQ ID NO: 22,

SEQ ID NO: 14/SEQ ID NO: 24,

SEQ ID NO: 14/SEQ ID NO: 26,

SEQ ID NO: 14/SEQ ID NO: 28,

SEQ ID NO: 16/SEQ ID NO: 20,

SEQ ID NO: 16/SEQ ID NO: 22,

SEQ ID NO: 16/SEQ ID NO: 24,

SEQ ID NO: 16/SEQ ID NO: 26,

SEQ ID NO: 16/SEQ ID NO: 28,

SEQ ID NO: 18/SEQ ID NO: 20,

SEQ ID NO: 18/SEQ ID NO: 22,

SEQ ID NO: 18/SEQ ID NO: 24,

SEQ ID NO: 18/SEQ ID NO: 26,

SEQ ID NO: 18/SEQ ID NO: 28.

39 . An isolated nucleic acid encoding an antibody or antigen binding fragment thereof that binds to human SIRPα, wherein the antibody or antigen binding fragment comprises:

a. a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:69 or an amino acid sequence differing from SEQ ID NO: 1 by 1, 2, or 3 conservative substitutions,

b. a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:70 or an amino acid sequence differing from SEQ ID NO: 2 by 1, 2, or 3 conservative substitutions,

c. a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:71 or an amino acid sequence differing from SEQ ID NO: 3 by 1, 2, or 3 conservative substitutions,

d. a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:72 or an amino acid sequence differing from SEQ ID NO: 4 by 1, 2, or 3 conservative substitutions,

e. a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:73 or an amino acid sequence differing from SEQ ID NO: 5 by 1, 2, or 3 conservative substitutions, and

f. a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:74 or an amino acid sequence differing from SEQ ID NO: 6 by 1, 2, or 3 conservative substitutions.

or wherein the antibody or antigen binding fragment comprises:

g. a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:1 or an amino acid sequence differing from SEQ ID NO: 1 by 1, 2, or 3 conservative substitutions,

h. a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:2 or an amino acid sequence differing from SEQ ID NO: 2 by 1, 2, or 3 conservative substitutions,

i. a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:3 or an amino acid sequence differing from SEQ ID NO: 3 by 1, 2, or 3 conservative substitutions,

j. a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:4 or an amino acid sequence differing from SEQ ID NO: 4 by 1, 2, or 3 conservative substitutions,

k. a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:5 or an amino acid sequence differing from SEQ ID NO: 5 by 1, 2, or 3 conservative substitutions, and

l. a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:6 or an amino acid sequence differing from SEQ ID NO: 6 by 1, 2, or 3 conservative substitutions.

40 . An expression vector comprising the isolated nucleic acid of claim 39 .

41 . A host cell comprising expression vector of claim 40 .

42 . A method of producing an antibody or antigen binding fragment comprising:

culturing a host cell comprising a polynucleotide of claim 39 under conditions favorable to expression of the polynucleotide; and optionally, recovering the antibody or antigen binding fragment from the host cell and/or culture medium.

43 . A method for detecting the presence of a SIRPα peptide or a fragment thereof in a sample comprising contacting the sample with an antibody or fragment an antibody or antigen binding fragment thereof that binds to human SIRPα, wherein the antibody or antigen binding fragment comprises: