Bispecific anti-cd37 antibodies, monoclonal anti-cd37 antibodies and methods of use thereof

A method of treating cancer comprising administering to an individual in need thereof a therapeutically effective amount of an antibody which binds to human CD37, wherein the antibody comprises:

• (i) a VH region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:
• 16, 17, and 18, respectively, and a VL region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NO:
• 20, KAS, and SEQ ID NO:
• 21, respectively;
• (ii) a VH region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:
• 9, 10, and 11, respectively, and a variable light chain (VL) region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NO:
• 113, AAS, and SEQ ID NO:
• 14, respectively;
• (iii) a VH region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:
• 23, 24, and 25, respectively, and a VL region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NO:
• 27, YAS, and SEQ ID NO:
• 28, respectively;
• (iv) a VH region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:
• 23, 24, and 25, respectively, and a VL region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NO:
• 27, YAS, and SEQ ID NO:
• 31, respectively;
• (v) a VH region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:
• 2, 3, and 4, respectively, and a VL region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NO:
• 6, EAS, and SEQ ID NO:
• 7, respectively;
• (vi) a VH region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:
• 40, 41, and 42, respectively, and a VL region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NO:
• 44, FAK, and SEQ ID NO:
• 45, respectively, or
• (vii) a VH region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:
• 47, 48, and 49, respectively, and a VL region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NO:
• 51, VAT, and SEQ ID NO:
• 52, respectively,
• wherein the antibody of any one of (i)-(vii) optionally comprises an Fc region comprising at least one amino acid substitution selected from the group consisting of:
• E430G, E345K, E430S, E430F, E430T, E345Q, E345R, E345Y, S440Y and S440W;
• and
• wherein optionally the Fc region further comprises a K409R or F405L mutation.

A method of treating cancer comprising administering to an individual in need thereof a therapeutically effective amount of a bispecific antibody which binds to human CD37, wherein the bispecific antibody comprises a first binding arm and a second binding arm, wherein the first binding arm comprises a first antigen-binding region and the second binding arm comprises a second antigen-binding region, wherein both the first antigen-binding region and second antigen-binding region bind to human CD37, wherein the first antigen-binding region comprises:

• (a) a variable heavy chain (VH) region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:
• 16, 17, and 18, respectively, and a variable light chain (VL) region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NO:
• 20, KAS, and SEQ ID NO:
• 21, respectively, or
• (b) a variable heavy chain (VH) region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NOs:
• 9, 10, and 11, respectively, and a variable light chain (VL) region comprising CDR1, CDR2, and CDR3 sequences comprising the amino acid sequences set forth in SEQ ID NO:
• 13, AAS, and SEQ ID NO:
• 14, respectively.

A method of treating cancer comprising administering to an individual in need thereof a therapeutically effective amount of a bispecific antibody which binds to human CD37, wherein the bispecific antibody comprises a first binding arm comprising a first heavy chain and a first light chain and a second binding arm comprising a second heavy chain and a second light chain, wherein both the first binding arm and second binding arm bind to human CD37, and wherein:

• (i) the first heavy chain comprises a variable heavy chain (VH) region comprising the amino acid sequence set forth in SEQ ID NO:
• 22, and the first light chain comprises a variable light chain (VL) region comprising the amino acid sequence set forth in SEQ ID NO:
• 29, and
• (ii) the second heavy chain comprises a VH region comprising the amino acid sequence set forth in SEQ ID NO:
• 15, and the second light chain comprises a VL region comprising the amino acid sequence set forth in SEQ ID NO:
• 19,
• wherein the first heavy chain and second heavy chain comprise heavy chain constant regions comprising the amino acid sequences set forth in SEQ ID NOs:
• 59 and 60, respectively, or wherein the first heavy chain and second heavy chain comprise heavy chain constant regions comprising the amino acid sequences set forth in SEQ ID NOs:
• 60 and 59, respectively, and
• wherein both the first light chain and second light chain comprise a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO:
• 61.