Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide and Methods Using Same

Abstract

The invention features methods for preventing or treating CGRP associated disorders such as vasomotor symptoms and/or headaches (e.g., migraine, cluster headache, and tension headache) by administering an anti-CGRP antagonist antibody. Compositions for use in the disclosed methods are also provided. Antagonist antibody G1 and antibodies derived from G1 directed to CGRP are also described.

1 .- 26 . (canceled) 
     
     
         27 . A method of decreasing a number of monthly headache hours experienced by a subject, comprising administering to the subject an amount of a monoclonal antibody that modulates the CGRP pathway, wherein the monoclonal antibody is in an amount effective to decrease the number of monthly headache hours by at least 20 after a single dose. 
     
     
         28 . A method of decreasing a number of monthly headache hours experienced by a subject, comprising administering to the subject an amount of a monoclonal antibody that modulates the CGRP pathway, wherein the monoclonal antibody is in an amount effective to decrease the number of monthly headache hours by at least 15% after a single dose. 
     
     
         29 . A method of decreasing a number of monthly headache days experienced by a subject, comprising administering to the subject an amount of a monoclonal antibody that modulates the CGRP pathway, wherein the monoclonal antibody is in an amount effective to decrease the number of monthly headache days by at least 3 after a single dose. 
     
     
         30 .- 33 . (canceled) 
     
     
         34 . The method of  claim 27 , wherein the monoclonal antibody is an anti-CGRP antagonist antibody. 
     
     
         35 . The method of  claim 27 , wherein the amount of the monoclonal antibody is less than 1000 mg. 
     
     
         36 . The method of  claim 27 , wherein the subject is administered less than 3 doses per month. 
     
     
         37 . The method of  claim 27 , wherein the administering is subcutaneous or intravenous administration. 
     
     
         38 . The method of  claim 27 , wherein the monoclonal antibody is formulated at a concentration of at least 150 mg/mL. 
     
     
         39 . The method of  claim 27 , wherein the monoclonal antibody is administered in a volume of less than 2 mL. 
     
     
         40 . The method of  claim 27 , wherein the subject is human. 
     
     
         41 . The method of  claim 27 , wherein the monoclonal antibody is human or humanized. 
     
     
         42 . The method of  claim 27 , wherein the monoclonal antibody comprises (a) an antibody having a CDR H1 as set forth in SEQ ID NO: 3; a CDR H2 as set forth in SEQ ID NO: 4; a CDR H3 as set forth in SEQ ID NO: 5; a CDR L1 as set forth in SEQ ID NO: 6; a CDR L2 as set forth in SEQ ID NO: 7; and a CDR L3 as set forth in SEQ ID NO: 8; or (b) a variant of an antibody according to (a) as shown in Table 6. 
     
     
         43 .- 44 . (canceled) 
     
     
         45 . The method of  claim 28 , wherein the monoclonal antibody is an anti-CGRP antagonist antibody. 
     
     
         46 . The method of  claim 28 , wherein the amount of the monoclonal antibody is less than 1000 mg. 
     
     
         47 . The method of  claim 28 , wherein the subject is administered less than 3 doses per month. 
     
     
         48 . The method of  claim 28 , wherein the administering is subcutaneous or intravenous administration. 
     
     
         49 . The method of  claim 28 , wherein the monoclonal antibody is formulated at a concentration of at least 150 mg/mL. 
     
     
         50 . The method of  claim 28 , wherein the monoclonal antibody is administered in a volume of less than 2 mL. 
     
     
         51 . The method of  claim 28 , wherein the monoclonal antibody is human or humanized. 
     
     
         52 . The method of  claim 28 , wherein the monoclonal antibody comprises (a) an antibody having a CDR H1 as set forth in SEQ ID NO: 3; a CDR H2 as set forth in SEQ ID NO: 4; a CDR H3 as set forth in SEQ ID NO: 5; a CDR L1 as set forth in SEQ ID NO: 6; a CDR L2 as set forth in SEQ ID NO: 7; and a CDR L3 as set forth in SEQ ID NO: 8; or (b) a variant of an antibody according to (a) as shown in Table 6.