Parptinte, European Patent Office ~~PatentatI Postbus 5818 European 2280 HV Rijswijk Patent Office NETHERLANDS ~~Offe ourpefl Tel: +31 70 340 2040 J de brevets Fax: +31 70 340 3016 Application No.: U4 6U0 993.8 IV.2. Patent classification The classification has been changed. It now is as follows: INV. A61 K39/395 C07K1 628 A61 P35D0O A61 P37D0O C1 2N5/20 ADD. A61 K47/48 IV.3. Title of the invention The title indicated on the published patent application remains unchanged. It reads as follows: MEDIZINISCHE VERWENDUNG VON ANTI-CS1 ANTIKORPER THERAPEUTIC USE OF ANTI-CS1 ANTIBODIES UTILISATION THERAPEUTIQUE D'ANTICORPS ANTI-CS1 IV.4. Documentation Date Co one-van -ees, M iatei, ara Hix, Rebecca Chairman 1st examiner 2nd examiner Enclosure(s): QForm 2035.4 (Sheet1) 12.07TRI 1. A monoclonal anti-CS1 antibody or an anti-CS1 antigen binding fragment that binds a protein encoded by SEQ ID NO:1, inhibits 5 immunoglobulin secretion and competes for binding to said protein with a control antibody, wherein the control antibody: a) comprises a VH region comprising SEQ ID NO:5 and a VL region comprising SEQ ID NO:6; or b) is obtainable from a hybridoma bearing ATCC designation No. 10 PTA-5091. 2. The antibody or antigen binding fragment of claim 1 wherein the control antibody comprises a VH region comprising SEQ ID NO:5 and a VL region comprising SEQ ID NO:6. 3. The antibody or antigen binding fragment of claim 2 which decreases by at least 50% in a competitive binding assay the binding of the control antibody to the protein. 20 4. The antibody or antigen binding fragment of claim 2 or claim 3 which comprises amino acid sequences sharing at least 85% identity with SEQ ID NO:15, SEQ ID NO:16 and SEQ ID NO:17. 5. The antibody or antigen binding fragment of any one of claims 2 to 25 4 which comprises amino acid sequences sharing at least 85% identity with SEQ NO:18, SEQ NO:19 and SEQ ID NO:20. 6. The antibody or antigen binding fragment of claim 2 or claim 3 which comprises amino acid sequences corresponding to SEQ ID NO:15, 30 SEQ ID NO:16, SEQ ID NO:17, SEQ NO:18, SEQ NO:19 and SEQ ID NO:20. 7. The antibody or antigen binding fragment of any one of claims 2 to 5 which comprises amino acid sequences corresponding to SEQ ID NO:15, SEQ ID NO:95, SEQ ID NO:17, SEQ NO:18, SEQ NO:19 and SEQ ID NO:20. 8. The antibody or antigen binding fragment of claim 6 which 5 comprises a VH region comprising an amino acid sequence corresponding to SEQ ID NO:5, and a VL region comprising an amino acid sequence corresponding to SEQ ID NO:6. 9. The antibody or antigen binding fragment of claim 7 in which the 10 VH region comprises an amino acid sequence corresponding to SEQ ID NO:47 and the VL region comprises an amino acid sequence corresponding to SEQ ID NO:50. 10. The antibody or antigen binding fragment of claim 1 wherein the 15 control antibody is obtainable from a hybridoma bearing ATCC designation No. PTA-5091. 11. The antibody or antigen binding fragment of claim 10 which decreases by at least 50% in a competitive binding assay the binding of 20 the control antibody to the protein. 12. The antibody or antigen binding fragment of claim 10 or claim 11 which comprises an amino acid sequence sharing at least 85 % identity with a sequence selected from SEQ ID NO:9, SEQ ID NO:10 and SEQ ID 25 NO:11. 13. The antibody or antigen binding fragment of any one of claims 10 to 12 which comprises an amino acid sequence sharing at least 85% identity with a sequence selected from SEQ NO:12, SEQ NO:13 and SEQ ID 30 NO:14. 14. The antibody or antigen binding fragment of claim 10 or claim 11 which comprises amino acid sequences corresponding to SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11, SEQ NO:12, SEQ NO:13 and SEQ ID 35 NO:14. 15. The antibody or antigen binding fragment of claim 13 or claim 14 which comprises a VH region comprising an amino acid sequence corresponding to SEQ ID NO:3, and a VL region comprising an amino acid 5 sequence corresponding to SEQ ID NO:4. 16. The antibody or antigen binding fragment of claim 15 which is obtainable from a hybridoma bearing ATCC designation No. PTA-5091. 10 17. The antibody or antigen binding fragment of claim 10 or claim 11 which comprises an amino acid sequence sharing at least 85% identity with a sequence selected from SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23. 15 18. The antibody or antigen binding fragment of claim 10, claim 11 or claim 17 which comprises an amino acid sequence sharing at least 85% identity with a sequence selected from SEQ NO:24, SEQ NO:25 and SEQ ID NO:26. 20 19. The antibody or antigen binding fragment of claim 10 or claim 11 which comprises amino acid sequences corresponding to SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ NO:24, SEQ NO:25 and SEQ ID NO:26. 25 20. The antibody or antigen binding fragment of claim 18 or claim 19 which comprises a VH region comprising an amino acid sequence corresponding to SEQ ID NO:7, and a VL region comprising an amino acid sequence corresponding to SEQ ID NO:8. 30 21. The antibody or antigen binding fragment of any one of claims 1-7, 9-14 and 17-19 which is humanized. 22. The antibody or antigen binding fragment of any preceding claim which inhibits immunoglobulin secretion by at least 40%. 23. The antibody or antigen binding fragment of claim 1 which is an IgG1. 24. A conjugate compound comprising an antibody or antigen binding 5 fragment according to any one of claims 1-22 linked to an effector moiety and/or a detectable label. 25. A conjugate compound according to claim 24 wherein the antibody or antigen binding fragment is conjugated to a detectable label. 26. A conjugate compound according to claim 25 wherein the detectable label is a radioactive compound, a fluorescent compound, an enzyme, a substrate, an epitope tag or a toxin. 15 27. A conjugate compound according to claim 25 wherein the detectable label is a cytotoxic agent. 28. A conjugate compound according to claim 24, wherein the effector moiety is a detection moiety, an activatable moiety, a chemotherapeutic 20 agent, a lipase, an antibiotic, a chemoattracting moiety, an immune modulator, or a radioisotope. 29. A pharmaceutical composition comprising an antibody or antigen binding fragment according to any one of claims 1-23 or a conjugate 25 compound according to any one of claims 24-28. 30. An antibody or antigen binding fragment according to any one of claims 1-23 or a conjugate compound according to any one of claims 24 28 for use in therapy. 31. An antibody or antigen binding fragment according to any one of claims 1-23 or a conjugate compound according to any one of claims 24 28 for treatment of cancer. 32. The antibody, antigen binding fragment or conjugate compound of claim 31, wherein the cancer is a plasma cell neoplasm. 33. The antibody, antigen binding fragment or conjugate compound of 5 claim 32 in which the plasma cell neoplasm is multiple myeloma, myeloma of bone, extramedullary plasmacytoma, macroglobulinemia (including Waldenstrom's macroglobulinemia), heavy-chain disease, primary amyloidosis and monoclonal gammopathy of unknown significance. 10 34. The antibody, antigen binding fragment or conjugate compound of claim 31, wherein the cancer is a non-plasma cell cancer. 35. The antibody, antigen binding fragment or conjugate compound of claim 34, wherein the non-plasma cell cancer is chronic lymphocytic 15 leukemia 36. An antibody or antigen binding fragment according to any one of claims 1-23 or a conjugate compound according to any one of claims 24 28 for treatment of hyperviscocity syndrome. 37. An antibody or antigen binding fragment according to any one of claims 1-23 or a conjugate compound according to any one of claims 24 28 for treatment of autoimmune disease. 25 38. The antibody, antigen binding fragment or conjugate compound of claim 37 in which the autoimmune disease is systemic lupus erythrematosus (SLE), inflammatory bowel disease (IBD), thrombocytopenia, rheumatoid arthritis (RA), autoimmune hemolytic anemia, or myasthenia gravis. 39. The antibody or antigen binding fragment of claim 31 for administration after or in combination with one or more immunosuppressive drugs and immunomodulators and wherein the cancer is myeloma. 40. The antibody or antigen binding fragment of claim 31 for administration after or in combination with an immunomodulator and wherein the cancer is myeloma. 5 41. The antibody or antigen binding fragment according to any one of claims 1-23 in combination with one or more immunosuppressive drugs and immunomodulators for treatment of myeloma. 42. The antibody or antigen binding fragment according to any one of 10 claims 1-23 in combination with an immunomodulator for treatment of myeloma.