Therapeutic use of anti-CS1 antibodies
View Patent ↗The present invention is directed to antagonists of CS1 that bind to and neutralize at least one biological activity of CS1. The invention also includes a pharmaceutical composition comprising such antibodies or antigen-binding fragments thereof. The present invention also provides for a method of preventing or treating disease states, including autoimmune disorders and cancer, in a subject in need thereof, comprising administering into said subject an effective amount of such antagonists.
1. A method of treating multiple myeloma, comprising the step of administering to a patient in need thereof a therapeutically effective amount of a combination of:
(a) a monoclonal anti-CS1 antibody or an anti-CS1 antigen binding fragment, wherein said monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment binds to a protein encoded by SEQ ID NO:1 and comprises
(i) a heavy chain variable region with complementarity determining region (CDR) sequences having amino acid sequences of SEQ ID NO:15, SEQ ID NO:16 or SEQ ID NO:87, and SEQ ID NO:17; and
(ii) a light chain variable region with CDR sequences having amino acid sequences of SEQ ID NO:18, SEQ ID NO:19, and SEQ ID NO:20; and
(b) velcade.
2. The method of claim 1 , wherein the heavy chain variable region has CDR sequences having the amino acid sequences of SEQ ID NO:15, SEQ ID NO:16, and SEQ ID NO:17.
3. The method of claim 1 , wherein the heavy chain variable region has CDR sequences having the amino acid sequences of SEQ ID NO:15, SEQ ID NO:87, and SEQ ID NO:17.
4. The method of claim 3 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment is humanized.
5. The method of any one of claims 1 - 4 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment is an IgG 1 .
6. The method of claim 3 , wherein the heavy chain variable region of the monoclonal antibody or antigen binding fragment comprises the amino acid sequence of SEQ ID NO:41.
7. The method of claim 3 or claim 6 , wherein the light chain variable region of the monoclonal antibody or antigen binding fragment comprises the amino acid sequence of SEQ ID NO:44.
8. A method of treating multiple myeloma, comprising the step of administering to a patient in need thereof a therapeutically effective amount of a combination of:
(a) a conjugate compound comprising a monoclonal anti-CS1 antibody or an anti-CS1 antigen binding fragment linked to an effector moiety, wherein said monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment binds to a protein encoded by SEQ ID NO:1 and comprises
(i) a heavy chain variable region with complementarity determining region (CDR) sequences having amino acid sequences of SEQ ID NO:15, SEQ ID NO:16 or SEQ ID NO:87, and SEQ ID NO:17; and
(ii) a light chain variable region with CDR sequences having amino acid sequences of SEQ ID NO:18, SEQ ID NO:19, and SEQ ID NO:20; and
(b) velcade.
9. The method of claim 8 , wherein the effector moiety is a cytotoxic agent.
10. The method of claim 8 , wherein the effector moiety is a detection moiety, an activatable moiety, a chemotherapeutic agent, a lipase, an antibiotic, a chemoattracting agent, an immune modulator or a radioisotope.
11. The method of any one of claims 8 - 10 , wherein the heavy chain variable region has CDR sequences having the amino acid sequences of SEQ ID NO:15, SEQ ID NO:16, and SEQ ID NO:17.
12. The method of claim 11 , wherein the heavy chain variable region has CDR sequences having the amino acid sequences of SEQ ID NO:15, SEQ ID NO:87, and SEQ ID NO:17.
13. The method of claim 12 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment is humanized.
14. The method of claim 13 , wherein the monoclonal anti-CS1 antibody or anti-CS1 antigen binding fragment is an IgG 1 .
15. The method of claim 12 , wherein the heavy chain variable region of the monoclonal antibody or antigen binding fragment comprises the amino acid sequence of SEQ ID NO:41.
16. The method of claim 15 , wherein the light chain variable region of the monoclonal antibody or antigen binding fragment comprises the amino acid sequence of SEQ ID NO:44.