CD37-binding molecules and immunoconjugates thereof
Methods of using CD37 agents, including, but not limited to, antibodies and immunoconjugates, that bind to CD37 to deplete B-cells (e.g., non-cancerous B-cells) and methods of treating autoimmune and inflammatory diseases are further provided.
1. An antibody or antigen binding fragment thereof that specifically binds to CD37, wherein said antibody or fragment comprises a variable heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:171, a variable heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:172 or SEQ ID NO:181, and a variable heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:173, a variable light chain CDR1 comprising the amino acid sequence of SEQ ID NO:174, a variable light chain CDR2 comprising the amino acid sequence of SEQ ID NO:175, and a variable light chain CDR3 comprising the amino acid sequence of SEQ ID NO:176.
2. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof is murine, non-human, humanized, chimeric, resurfaced, or human.
3. The antibody or antigen-binding fragment thereof of claim 1 , which is a full length antibody.
4. The antibody or antigen-binding fragment thereof of claim 1 , which is an antigen-binding fragment.
5. The antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody or antigen-binding fragment thereof comprises a Fab, Fab′, F(ab′)2, single chain Fv or scFv, disulfide linked Fv, intrabody, IgGΔCH2, minibody, F(ab′)3, tetrabody, triabody, diabody, DVD-Ig, mAb2, (scFv)2, or scFv-Fc.
6. An immunoconjugate comprising the antibody or antigen binding fragment of claim 1 , a linker, and a cytotoxic agent.
7. The immunoconjugate of claim 6 , wherein said linker is selected from the group consisting of a cleavable linker, a non-cleavable linker, a hydrophilic linker, and a dicarboxylic acid based linker.
8. The immunoconjugate of claim 6 , wherein said linker is selected from the group consisting of: N-succinimidyl 4-(2-pyridyldithio)pentanoate (SPP); N-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB) or N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB); N-succinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (SMCC); N-sulfosuccinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (sulfoSMCC); N-succinimidyl-4-(iodoacetyl)-aminobenzoate (SIAB); and N-succinimidyl-[(N-maleimidopropionamido)-tetraethyleneglycol] ester (NHS-PEG4-maleimide).
9. The immunoconjugate of claim 6 , wherein said cytotoxic agent is selected from the group consisting of a maytansinoid, maytansinoid analog, doxorubicin, a modified doxorubicin, benzodiazepine, taxoid, CC-1065, CC-1065 analog, duocarmycin, duocarmycin analog, calicheamicin, dolastatin, dolastatin analog, auristatin, tomaymycin derivative, and leptomycin derivative or a prodrug of the agent.
10. The immunoconjugate of claim 9 , wherein said cytotoxic agent is a maytansinoid.
11. The immunoconjugate of claim 9 , wherein said cytotoxic agent is N(2′)-deacetyl-N(2′)-(3-mercapto-1-oxopropyl)-maytansine (DM1) or N(2′)-deacetyl-N(2′)-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4).
12. The immunoconjugate of claim 6 , wherein the immunoconjugate comprises 3-4 cytotoxic agents.
13. The antibody or antigen-binding fragment of claim 1 , wherein said antibody or fragment comprises the polypeptide sequences of SEQ ID NO:177 and SEQ ID NO:178.
14. An immunoconjugate comprising the antibody or antigen binding fragment of claim 13 , a linker, and a cytotoxic agent.
15. The immunoconjugate of claim 14 , wherein the cytotoxic agent is a maytansinoid.
16. The immunoconjugate of claim 15 , wherein the maytansinoid is N(2′)-deacetyl-N(2′)-(3-mercapto-1-oxopropyl)-maytansine (DM1) or N(2′)-deacetyl-N(2′)-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4).
17. The immunoconjugate of claim 14 , wherein the immunoconjugate comprises 3-4 cytotoxic agents.
18. The antibody or antigen-binding fragment of claim 1 , wherein said antibody or fragment comprises the polypeptide sequences of SEQ ID NO:179 and SEQ ID NO:180.
19. A method for depleting a B-cell comprising contacting a population of cells comprising a B-cell with the antibody or antigen-binding fragment of claim 1 , wherein the contacting results in depletion of the B-cell.
20. A method for depleting a B-cell comprising contacting a population of cells comprising a B-cell with the immunoconjugate of claim 6 , wherein the contacting results in depletion of the B-cell.