Methods of use of anti-CD37 antibodies, monoclonal anti-CD37 antibodies
CD37-specific bispecific antibody molecules binding to different epitopes of the human CD37 antigen which bispecific antibody molecules have enhanced Fc-Fc interactions upon binding to CD37 on the cell surface. The invention also relates to the monoclonal parental antibodies from which the first or the second binding region of the bispecific antibody molecules is obtained. The invention also relates to pharmaceutical compositions containing these molecules and the treatment of cancer and other diseases using these compositions.
1 . A method of treating an autoimmune disease or inflammatory disease characterized by CD37 expression, the method 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: 13, 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; or
(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;
wherein the antibody of any one of (i)-(v) 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.
2 . The method of claim 1 , wherein the antibody comprises:
(i) a VH region comprising the amino acid sequence set forth in SEQ ID NO: 15 and a VL region comprising the amino acid sequence set forth in SEQ ID NO: 19,
(ii) a VH region comprising the amino acid sequence set forth in SEQ ID NO: 8 and a VL region comprising the amino acid sequence set forth in SEQ ID NO: 12,
(iii) a VH region comprising the amino acid sequence set forth in SEQ ID NO: 22 and a VL region comprising the amino acid sequence set forth in SEQ ID NO: 26,
(iv) a VH region comprising the amino acid sequence set forth in SEQ ID NO: 22 and a VL region comprising the amino acid sequence set forth in SEQ ID NO: 29,
(v) a VH region comprising the amino acid sequence set forth in SEQ ID NO: 1 and a VL region comprising the amino acid sequence set forth in SEQ ID NO: 5, or
(vi) a VH region comprising an amino acid sequence having at least 90% identity to a VH region comprising the amino acid sequence set forth in any one of (i) to (v), and a VL region comprising an amino acid sequence having at least 90% identity to a VL region comprising the amino acid sequence set forth in any one of (i) to (v).
3 . The method of claim 1 , wherein the antibody is an IgG1, IgG2, IgG3 or IgG4 isotype.
4 . The method of claim 1 , wherein the antibody is human, humanized or chimeric.
5 . The method of claim 1 , wherein the antibody comprises a human IgG1 constant region.
6 . The method of claim 1 , wherein the antibody comprises a kappa light chain constant region.
7 . The method of claim 1 , wherein the autoimmune disease or inflammatory disorder is allergy, transplantation rejection, arthritis, ankylosing spondylitis, systemic lupus erythematosus (SLE), neonatal lupus syndrome (NLE), lupus erythematosis disseminates, multiple sclerosis, inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), psoriasis, IgA nephropathy, IgM polyneuropathies, myasthenia gravis, diabetes mellitus, Reynaud's syndrome, glomerulonephritis, pustulosis palmoplantaris (PPP), erosive lichen planus, pemphigus bullosa, epidermolysis bullosa, contact dermatitis, atopic dermatitis, or polyradiculitis.
8 . The method of claim 7 , wherein the arthritis is rheumatoid arthritis, acute arthritis, gout or gouty arthritis, acute gouty arthritis, acute immunological arthritis, chronic inflammatory arthritis, degenerative arthritis, type II collagen-induced arthritis, infectious arthritis, Lyme arthritis, proliferative arthritis, psoriatic arthritis, Still's disease, vertebral arthritis, osteoarthritis, arthritis chronica progrediente, arthritis deformans, polyarthritis chronica primaria, reactive arthritis, or ankylosing spondylitis.
9 . The method of claim 7 , wherein the arthritis is chronic rheumatoid arthritis or juvenile-onset rheumatoid arthritis.
10 . The method of claim 7 , wherein the SLE is cutaneous SLE or subacute cutaneous SLE.
11 . The method of claim 7 , wherein the IBD is ulcerative colitis and Crohn's disease.
12 . The method of claim 7 , wherein the polyradiculitis is Guillain-Barre syndrome.