Use of anti-CGRP antibodies and antibody fragments to prevent or inhibit photophobia or light aversion in subjects in need thereof, especially migraine sufferers
The present invention is directed to methods of inhibiting or preventing photophobia in subjects in need thereof using anti-CGRP antibodies or antibody fragments that inhibit photophobia, especially CGRP-associated photophobia. These antibodies and fragments are useful in treating different disorders associated with photophobia such as migraine, cluster headaches and the like. The present invention also provides assays using transgenic Nestin/Ramp1 rodents, utilizing a CGRP model light aversive behavior model for identifying therapeutically effective anti-CGRP antibodies and fragments thereof having binding specificity for CGRP which inhibit or prevent photophobia in subjects in need thereof. The present invention is specifically directed to methods for identifying therapeutically effective antibodies and fragments thereof having binding specificity for CGRP that may be used to treat CGRP associated disorders such as migraine. Specifically, this invention relates to assays and therapies using the antibodies described herein to inhibit or prevent photophobia, and binding fragments thereof, comprising the sequences of the V H , V L and CDR polypeptides described herein, and the polynucleotides encoding them.
1. A method of assessing the potential in vivo efficacy of a candidate anti-CGRP antibody or antibody fragment for treating a condition treatable by the administration of a CGRP antagonist associated with photophobia comprising determining whether the antibody or antibody fragment inhibits light aversive behavior in a nestin/Ramp1 rodent administered CGRP compared to a rodent administered CGRP in the absence of the candidate anti-CGRP antibody or antibody fragment, wherein said candidate anti-CGRP antibody or antibody fragment comprises a variable light chain comprising the complementarity determining region (CDR) 1 sequence of SEQ ID NO: 5, the CDR2 sequence of SEQ ID NO: 6, and the CDR3 sequence of SEQ ID NO: 7, and a variable heavy chain comprising the CDR1 sequence of SEQ ID NO: 8, the CDR2 sequence of SEQ ID NO: 9, and the CDR3 sequence of SEQ ID NO: 10.
2. The method of claim 1 wherein this assay is used to assess whether the antibody or antibody fragment may be used to treat a neurological condition characterized by increased CGRP levels.
3. The method of claim 1 wherein this assay is used to assess whether the anti-CGRP antibody or antibody fragment may be used to treat migraine, menstrual migraine, or chronic migraine.
4. The method of claim 1 wherein this assay is used to assess whether the anti-CGRP antibody or antibody fragment may be used to treat headache or migraine.