Methods for reducing migraine frequency in a subject in need thereof
The present invention relates to methods for selecting a headache patient responsive to treatment with an anti-CGRP antibody and to methods for reducing headache frequency in the selected patient comprising administering an anti-CGRP antibody.
1. A method for reducing migraine frequency in a subject suffering from chronic or episodic migraine comprising administering to the subject an antibody or antigen-binding fragment thereof that blocks, inhibits, suppresses, or reduces the calcitonin gene related peptide (CGRP) pathway, wherein the antibody or antigen-binding fragment thereof is an anti-CGRP antagonist antibody or an anti-CGRP receptor antibody, thereby reducing migraine frequency in the subject, wherein, prior to administration of the antibody or antigen-binding fragment thereof, the subject is known to exhibit allodynia and/or hyperalgesia during an acute phase of a migraine but not during an interictal phase of the migraine.
2. The method of claim 1 , wherein the subject suffers from episodic migraine.
3. The method of claim 1 , wherein the subject suffers from chronic migraine.
4. The method of claim 1 , wherein the subject is known to exhibit allodynia and or hyperalgesia during an acute phase of a migraine but not during an interictal phase of the migraine.
5. The method of claim 1 , wherein the absence of allodynia and/or hyperalgesia during the interictal phase of migraine was determined by quantitative sensory testing (QST).
6. The method of claim 1 , further comprising determining whether the subject exhibits allodynia and/or hyperalgesia during an acute phase of a migraine but not during an interictal phase of the migraine prior to administration of the antibody or antigen-binding fragment thereof.
7. The method of claim 6 , wherein absence of allodynia and/or hyperalgesia during the interictal phase of migraine is determined by quantitative sensory testing (QST).
8. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody, a humanized antibody, or an antigen-binding fragment selected from a Fab, a Fab′, a F(ab′)2, an Fv, or an ScFv.
9. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO: 3; a CDR H2 amino acid sequence as set forth in SEQ ID NO: 4; a CDR H3 amino acid sequence as set forth in SEQ ID NO: 5; a CDR L1 amino acid sequence as set forth in SEQ ID NO: 6; a CDR L2 amino acid sequence as set forth in SEQ ID NO: 7; and a CDR L3 amino acid sequence as set forth in SEQ ID NO: 8.
10. The method of claim 9 , wherein:
the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 1, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO:2; or
the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO: 11, and a light chain comprising the amino acid sequence as set forth in SEQ ID NO: 12.
11. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO: 87; a CDR H2 amino acid sequence as set forth in SEQ ID NO: 88; a CDR H3 amino acid sequence as set forth in SEQ ID NO:89; a CDR L1 amino acid sequence as set forth in SEQ ID NO:84; a CDR L2 amino acid sequence as set forth in SEQ ID NO:85; and a CDR L3 amino acid sequence as set forth in SEQ ID NO:86.
12. The method of claim 11 , wherein:
the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 82, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 80; or
the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO: 83, and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:81.
13. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO:93; a CDR H2 amino acid sequence as set forth in SEQ ID NO:94; a CDR H3 amino acid sequence as set forth in SEQ ID NO:95; a CDR L1 amino acid sequence as set forth in SEQ ID NO:91; a CDR L2 amino acid sequence as set forth in SEQ ID NO:92; and a CDR L3 amino acid sequence as set forth in SEQ ID NO:90.
14. The method of claim 13 , wherein:
the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 97, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 96; or
the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO:99, and a light chain comprising the amino acid sequence as set forth in SEQ ID NO:98.
15. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a CDR H1 amino acid sequence as set forth in SEQ ID NO: 103; a CDR H2 amino acid sequence as set forth in SEQ ID NO: 104; a CDR H3 amino acid sequence as set forth in SEQ ID NO: 105; a CDR L1 amino acid sequence as set forth in SEQ ID NO: 100; a CDR L2 amino acid sequence as set forth in SEQ ID NO: 101; and a CDR L3 amino acid sequence as set forth in SEQ ID NO: 102.
16. The method of claim 15 , wherein:
the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 107, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 106; or
the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO: 109, and a light chain comprising the amino acid sequence as set forth in SEQ ID NO: 108.
17. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof is administered while the patient is migraine-free.
18. A method for reducing migraine frequency in a subject suffering from chronic or episodic migraine comprising:
a) determining whether the subject exhibits allodynia and/or hyperalgesia during the interictal phase of a migraine, and
b) administering an antibody or antigen-binding fragment thereof that blocks, inhibits, suppresses, or reduces the calcitonin gene related peptide (CGRP) pathway to the subject that does not exhibit signs of allodynia and/or hyperalgesia during the interictal phase of the migraine; wherein the antibody or antigen-binding fragment thereof is an anti-CGRP antagonist antibody or an anti-CGRP receptor antibody.