Treatment of most bothersome symptom (mbs) associated with migraine using anti-cgrp antibodies

Abstract

Methods for treatment of most bothersome symptom (MBS) associated with migraine are provided. Exemplary methods provide improvement in MBS associated with migraine within 1 month of administration og anti-CGRP antibodies of the invention. Also provided are methods for improvement of patient impression of change (PGIC) associated with migraine. Exemplary methods comprise administration of an anti-CGRP antagonistic antibody to a patient in need thereof.

What is claimed is: 
     
         1 . A method for improving most bothersome symptom (MBS) associated with migraine, comprising administering to a patient in need an effective amount of an anti-CGRP antibody; wherein optionally the patient suffers from chronic migraine or episodic migraine. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method of  claim 1 , comprising one or more of the following:
 (i) the patient's most bothersome symptom (MBS) associated with migraine is improved at 1-12 hours post-completion of administration or infusion, such as 1-5 hours post-completion of administration or infusion, 1-2 hours post-completion of administration or infusion, or about 2 hours post-completion of administration or infusion;   (ii) the patient's most bothersome symptom (MBS) associated with migraine is improved within 1 month from the first dosing with said anti-CGRP antibody;   (iii) the patient's most bothersome symptom (MBS) associated with migraine is improved within 6 months from the first dosing with said anti-CGRP antibody;   (iv) the improvement is sustained for at least 3 months from the first dosing with said anti-CGRP antibody;   (v) the improvement is sustained for at least 6 months from the first dosing with said anti-CGRP antibody;   (vi) the improvement is sustained for at least 3 months from the first dosing with said anti-CGRP antibody;   (vii) the improvement is sustained for at least 6 months from the first dosing with said anti-CGRP antibody;   (viii) the MBS is selected from the group consisting of: Sensitivity to light (photophobia), Nausea/vomiting, Headache, Sensitivity to sound (phonophobia), Aura, Pain with activity, Pain, Throbbing/pulsation, Cognitive disruption, Fatigue, Mood changes, Sensitivity to smell (osmophobia or olfactophobia), Visual impact, Pressure/tightness, Pain (anatomical), Eye pain, Neck pain, Dizziness, Allodynia, Inactivity, Sensory disturbance, Sleep disturbance and Speech difficulty; or   (ix) the MBS is selected from the group consisting of: Sensitivity to light (photophobia), Nausea/vomiting, Headache, Sensitivity to sound (phonophobia), Aura, Pain with activity, Pain, Throbbing/pulsation, Cognitive disruption, Fatigue, Mood changes and Sensitivity to smell (osmophobia or olfactophobia).   
     
     
         5 - 11 . (canceled) 
     
     
         12 . A method of improving patient global impression of change (PGIC) associated with migraine, comprising administering to a patient in need an effective amount of an anti-CGRP antibody; wherein optionally the patient suffers from chronic migraine or episodic migraine. 
     
     
         13 - 14 . (canceled) 
     
     
         15 . The method of  claim 12 , comprising one or more of the following:
 (i) the improvement of patient global impression of change (PGIC) associated with migraine is observed within 1 month from the first dosing with said anti-CGRP antibody;   (ii) the improvement of patient global impression of change (PGIC) associated with migraine is observed within 3 months from the first dosing with said anti-CGRP antibody;   (iii) the improvement of patient global impression of change (PGIC) associated with migraine is observed within 6 months from the first dosing with said anti-CGRP antibody;   (iv) the improvement is sustained for at least 3 months from the first dosing with said anti-CGRP antibody;   (v) the improvement is sustained for at least 6 months from the first dosing with said anti-CGRP antibody;   (vi) said administration is done by infusion, such as intravenous or subcutaneous infusion;   (vii) said administration is done by intravenous infusion;   (viii) said patient is headache free 2 hours post-completion of administration or infusion;   (ix) said anti-CGRP antibody comprises Ab6;   (x) said anti-CGRP antibody comprises the light chain complementarity-determining region (CDR) 1, 2, and 3 polypeptide sequences of SEQ ID NO: 224; SEQ ID NO: 226; and SEQ ID NO: 228, respectively;   (xi) said anti-CGRP antibody comprises the light chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 234; SEQ ID NO: 236; and SEQ ID NO: 238, respectively;   (xii) said anti-CGRP antibody comprises the heavy chain CDR 1, 2, and 3 polypeptide sequences of SEQ ID NO: 204; SEQ ID NO: 206; and SEQ ID NO: 208, respectively;   (xiii) said anti-CGRP antibody comprises the heavy chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 214; SEQ ID NO: 216; and SEQ ID NO: 218, respectively;   (xiv) said anti-CGRP antibody comprises the light chain CDR 1, 2, and 3 polypeptide sequences of SEQ ID NO: 224; SEQ ID NO: 226; and SEQ ID NO: 228, respectively and heavy chain CDR 1, 2, and 3 polypeptide sequences of SEQ ID NO: 204; SEQ ID NO: 206; and SEQ ID NO: 208, respectively;   (xv) said anti-CGRP antibody comprises the light chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 234; SEQ ID NO: 236; and SEQ ID NO: 238, respectively and heavy chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 214; SEQ ID NO: 216; and SEQ ID NO: 218, respectively;   (xvi) said anti-CGRP antibody comprises the variable light chain polypeptide of SEQ ID NO: 222;   (xvii) said anti-CGRP antibody comprises the variable light chain polypeptide encoded by SEQ ID NO: 232;   (xviii) said anti-CGRP antibody comprises the variable heavy chain polypeptide of SEQ ID NO: 202;   (xix) said anti-CGRP antibody comprises the variable heavy chain polypeptide encoded by SEQ ID NO: 212;   (xx) said anti-CGRP antibody comprises the variable light chain polypeptide of SEQ ID NO: 222 and the variable heavy chain polypeptide of SEQ ID NO: 202;   (xxi) said anti-CGRP antibody comprises the variable light chain polypeptide encoded by SEQ ID NO: 232 and the variable heavy chain polypeptide encoded by SEQ ID NO: 212;   (xxii) said anti-CGRP antibody comprises the light chain polypeptide of SEQ ID NO: 221;   (xxiii) said anti-CGRP antibody comprises the light chain polypeptide encoded by SEQ ID NO: 231;   (xxiv) said anti-CGRP antibody comprises the heavy chain polypeptide of SEQ ID NO: 201 or SEQ ID NO: 566;   (xxv) said anti-CGRP antibody comprises the heavy chain polypeptide encoded by SEQ ID NO: 211 or SEQ ID NO: 567;   (xxvi) said anti-CGRP antibody comprises the light chain polypeptide of SEQ ID NO: 221 and the heavy chain polypeptide of SEQ ID NO: 201 or SEQ ID NO: 566;   (xxvii) said anti-CGRP antibody comprises the light chain polypeptide encoded by SEQ ID NO: 231 and the heavy chain polypeptide encoded by SEQ ID NO: 211 or SEQ ID NO: 567;   (xxviii) the administered amount of said anti-CGRP antibody is between about 100 mg and about 300 mg, or is about 100 mg, or is about 300 mg;   (xxix) the administered amount of said anti-CGRP antibody is 100 mg;   (xxx) the method further comprises intravenously administering 100 mg of said anti-CGRP antibody every 10-14 weeks, preferably every 11-13 weeks, more preferably every 12 weeks;   (xxxi) the administered amount of said anti-CGRP antibody is 100 mg;   (xxxii) the method further comprising intravenously administering 300 mg of said anti-CGRP antibody every 10-14 weeks, preferably every 11-13 weeks, more preferably every 12 weeks;   (xxxiii) prior to said administration, the patient exhibits between 1-10 migraine attacks per month in the month or in the 3 months prior to administration;   (xxxiv) prior to said administration, the patient exhibits between 2-8 migraine attacks per month in the month or in the 3 months prior to administration;   (xxxv) prior to said administration, the patient exhibits between 3-7 migraine attacks per month in the month or in the 3 months prior to administration;   (xxxvi) prior to said administration, the patient exhibits less than 25 headache days per month in the month or in the 3 months prior to administration;   (xxxvii) prior to said administration, the patient exhibits less than 20 headache days per month in the month or in the 3 months prior to administration;   (xxxviii) prior to said administration, the patient exhibits less than 15 headache days per month in the month or in the 3 months prior to administration;   (xxxix) prior to said administration, the patient exhibits less than 10 headache days per month in the month or in the 3 months prior to administration;   (xl) said patient was diagnosed with migraine at least 10 or at least 15 years prior to said administration;   (xli) said patient was diagnosed with migraine at least 18 or at least 19 years prior to said administration;   (xlii) said patient has a reduction in the number of migraine days by at least 50% in the one month period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xliii) said patient has a reduction in the number of migraine days by at least 75% in the one month period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xliv) said patient has a reduction in the number of migraine days by 100% in the one month period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xlv) said patient has a reduction in the number of migraine days by at least 50% in the 12 week period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xlvi) said patient has a reduction in the number of migraine days by at least 75% in the 12 week period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xlvii) said patient has a reduction in the number of migraine days by 100% in the 12 week period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xlvii) the method further comprises administering a second dose of said anti-CGRP antibody to said patient about 10-14 weeks, preferably 11-13 weeks, more preferably about 12 weeks or about 3 months after said administration;   (xlix) said administration comprises administering about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg of said anti-CGRP antibody;   (l) said anti-CGRP antibody is aglycosylated or if glycosylated only contains only mannose residues;   (li) said anti-CGRP antibody consists of the light chain polypeptide of SEQ ID NO: 221 and the heavy chain polypeptide of SEQ ID NO: 201 or SEQ ID NO: 566;   (lii) said anti-CGRP antibody consists of the light chain polypeptide encoded by SEQ ID NO: 231 and the heavy chain polypeptide encoded by SEQ ID NO: 211 or SEQ ID NO: 567;   (liii) said headache or said migraine is diagnosed according to the third edition of the International Classification of Headache Disorders;   (liv) said anti-CGRP antibody is expressed in or obtained by expression in  Pichia pastoris;      (lv) said anti-CGRP antibody is expressed in or obtained by expression in CHO cells;   (lvi) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of histidine (L-histidine), sorbitol, polysorbate 80, and water;   (lvii) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−10% of said values, and having a pH of 5.8 or within +/−10% of said value;   (lviii) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−5% of said values, and/or having a pH of 5.8 or within +/−5% of said value;   (lix) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−1% of said values, and/or having a pH of 5.8 or within +/−1% of said value;   (lx) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−0.5% of said values, and/or having a pH of 5.8 or within +/−0.5% of said value;   (lxi) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−0.1% of said values, and/or having a pH of 5.8 or within +/−0.1% of said value;   (lxii) said anti-CGRP antibody has a dissociation constant of less than or equal to 10 pM, such as 2-8 pM, such as 3-6 pM, such as less than or equal to about 5 pM, optionally when measured by surface plasmon resonance, which is optionally carried out at 25° C. or 37° C.; or   (lxiii) the method improves both MBS and PGIC in said patient.   
     
     
         16 - 78 . (canceled) 
     
     
         79 . The method of  claim 1 , comprising one or more of the following:
 (i) the improvement is sustained for at least 3 months from the first dosing with said anti-CGRP antibody;   (ii) the improvement is sustained for at least 6 months from the first dosing with said anti-CGRP antibody;   (iii) said administration is done by infusion, such as intravenous or subcutaneous infusion;   (iv) said administration is done by intravenous infusion;   (v) said patient is headache free 2 hours post-completion of administration or infusion;   (vi) said anti-CGRP antibody comprises Ab6;   (vii) said anti-CGRP antibody comprises the light chain complementarity-determining region (CDR) 1, 2, and 3 polypeptide sequences of SEQ ID NO: 224; SEQ ID NO: 226; and SEQ ID NO: 228, respectively;   (viii) said anti-CGRP antibody comprises the light chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 234; SEQ ID NO: 236; and SEQ ID NO: 238, respectively;   (ix) said anti-CGRP antibody comprises the heavy chain CDR 1, 2, and 3 polypeptide sequences of SEQ ID NO: 204; SEQ ID NO: 206; and SEQ ID NO: 208, respectively;   (x) said anti-CGRP antibody comprises the heavy chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 214; SEQ ID NO: 216; and SEQ ID NO: 218, respectively;   (xi) said anti-CGRP antibody comprises the light chain CDR 1, 2, and 3 polypeptide sequences of SEQ ID NO: 224; SEQ ID NO: 226; and SEQ ID NO: 228, respectively and heavy chain CDR 1, 2, and 3 polypeptide sequences of SEQ ID NO: 204; SEQ ID NO: 206; and SEQ ID NO: 208, respectively;   (xii) said anti-CGRP antibody comprises the light chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 234; SEQ ID NO: 236; and SEQ ID NO: 238, respectively and heavy chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 214; SEQ ID NO: 216; and SEQ ID NO: 218, respectively;   (xiii) said anti-CGRP antibody comprises the variable light chain polypeptide of SEQ ID NO: 222;   (xiv) said anti-CGRP antibody comprises the variable light chain polypeptide encoded by SEQ ID NO: 232;   (xv) said anti-CGRP antibody comprises the variable heavy chain polypeptide of SEQ ID NO: 202;   (xvi) said anti-CGRP antibody comprises the variable heavy chain polypeptide encoded by SEQ ID NO: 212;   (xvii) said anti-CGRP antibody comprises the variable light chain polypeptide of SEQ ID NO: 222 and the variable heavy chain polypeptide of SEQ ID NO: 202;   (xviii) said anti-CGRP antibody comprises the variable light chain polypeptide encoded by SEQ ID NO: 232 and the variable heavy chain polypeptide encoded by SEQ ID NO: 212;   (xix) said anti-CGRP antibody comprises the light chain polypeptide of SEQ ID NO: 221;   (xx) said anti-CGRP antibody comprises the light chain polypeptide encoded by SEQ ID NO: 231;   (xxi) said anti-CGRP antibody comprises the heavy chain polypeptide of SEQ ID NO: 201 or SEQ ID NO: 566;   (xxii) said anti-CGRP antibody comprises the heavy chain polypeptide encoded by SEQ ID NO: 211 or SEQ ID NO: 567;   (xxiii) said anti-CGRP antibody comprises the light chain polypeptide of SEQ ID NO: 221 and the heavy chain polypeptide of SEQ ID NO: 201 or SEQ ID NO: 566;   (xxiv) said anti-CGRP antibody comprises the light chain polypeptide encoded by SEQ ID NO: 231 and the heavy chain polypeptide encoded by SEQ ID NO: 211 or SEQ ID NO: 567;   (xxv) the administered amount of said anti-CGRP antibody is between about 100 mg and about 300 mg, or is about 100 mg, or is about 300 mg;   (xxvi) the administered amount of said anti-CGRP antibody is 100 mg;   (xvii) the method further comprises intravenously administering 100 mg of said anti-CGRP antibody every 10-14 weeks, preferably every 11-13 weeks, more preferably every 12 weeks;   (xxviii) the administered amount of said anti-CGRP antibody is 100 mg;   (xxix) the method further comprising intravenously administering 300 mg of said anti-CGRP antibody every 10-14 weeks, preferably every 11-13 weeks, more preferably every 12 weeks;   (xxx) prior to said administration, the patient exhibits between 1-10 migraine attacks per month in the month or in the 3 months prior to administration;   (xxxi) prior to said administration, the patient exhibits between 2-8 migraine attacks per month in the month or in the 3 months prior to administration;   (xxxii) prior to said administration, the patient exhibits between 3-7 migraine attacks per month in the month or in the 3 months prior to administration;   (xxxiii) prior to said administration, the patient exhibits less than 25 headache days per month in the month or in the 3 months prior to administration;   (xxxiv) prior to said administration, the patient exhibits less than 20 headache days per month in the month or in the 3 months prior to administration;   (xxxv) prior to said administration, the patient exhibits less than 15 headache days per month in the month or in the 3 months prior to administration;   (xxxvi) prior to said administration, the patient exhibits less than 10 headache days per month in the month or in the 3 months prior to administration;   (xvii) said patient was diagnosed with migraine at least 10 years or at least 15 prior to said administration;   (xviii) said patient was diagnosed with migraine at least 18 or at least 19 years prior to said administration;   (xxxix) said patient has a reduction in the number of migraine days by at least 50% in the one month period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xl) said patient has a reduction in the number of migraine days by at least 75% in the one month period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xli) said patient has a reduction in the number of migraine days by 100% in the one month period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xlii) said patient has a reduction in the number of migraine days by at least 50% in the 12 week period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xliii) said patient has a reduction in the number of migraine days by at least 75% in the 12 week period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xliv) said patient has a reduction in the number of migraine days by 100% in the 12 week period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xlv) the method further comprises administering a second dose of said anti-CGRP antibody to said patient about 10-14 weeks, preferably 11-13 weeks, more preferably about 12 weeks or about 3 months after said administration;   (xlvi) said administration comprises administering about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg of said anti-CGRP antibody;   (xlvii) said anti-CGRP antibody is aglycosylated or if glycosylated only contains only mannose residues;   (xlviii) said anti-CGRP antibody consists of the light chain polypeptide of SEQ ID NO: 221 and the heavy chain polypeptide of SEQ ID NO: 201 or SEQ ID NO: 566;   (xlix) said anti-CGRP antibody consists of the light chain polypeptide encoded by SEQ ID NO: 231 and the heavy chain polypeptide encoded by SEQ ID NO: 211 or SEQ ID NO: 567;   (l) said headache or said migraine is diagnosed according to the third edition of the International Classification of Headache Disorders;   (li) said anti-CGRP antibody is expressed in or obtained by expression in  Pichia pastoris;      (lii) said anti-CGRP antibody is expressed in or obtained by expression in CHO cells;   (liii) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of histidine (L-histidine), sorbitol, polysorbate 80, and water;   (liv) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−10% of said values, and having a pH of 5.8 or within +/−10% of said value;   (lv) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−5% of said values, and/or having a pH of 5.8 or within +/−5% of said value;   (lvi) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−1% of said values, and/or having a pH of 5.8 or within +/−1% of said value;   (lvii) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−0.5% of said values, and/or having a pH of 5.8 or within +/−0.5% of said value;   (lviii) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−0.1% of said values, and/or having a pH of 5.8 or within +/−0.1% of said value;   (lix) said anti-CGRP antibody has a dissociation constant of less than or equal to 10 pM, such as 2-8 pM, such as 3-6 pM, such as less than or equal to about 5 pM, optionally when measured by surface plasmon resonance, which is optionally carried out at 25° C. or 37° C.; or   (lx) the method improves both MBS and PGIC in said patient.   
     
     
         80 . The method of  claim 4 , comprising one or more of the following:
 (i) the improvement is sustained for at least 3 months from the first dosing with said anti-CGRP antibody;   (ii) the improvement is sustained for at least 6 months from the first dosing with said anti-CGRP antibody;   (iii) said administration is done by infusion, such as intravenous or subcutaneous infusion;   (iv) said administration is done by intravenous infusion;   (v) said patient is headache free 2 hours post-completion of administration or infusion;   (vi) said anti-CGRP antibody comprises Ab6;   (vii) said anti-CGRP antibody comprises the light chain complementarity-determining region (CDR) 1, 2, and 3 polypeptide sequences of SEQ ID NO: 224; SEQ ID NO: 226; and SEQ ID NO: 228, respectively;   (viii) said anti-CGRP antibody comprises the light chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 234; SEQ ID NO: 236; and SEQ ID NO: 238, respectively;   (ix) said anti-CGRP antibody comprises the heavy chain CDR 1, 2, and 3 polypeptide sequences of SEQ ID NO: 204; SEQ ID NO: 206; and SEQ ID NO: 208, respectively;   (x) said anti-CGRP antibody comprises the heavy chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 214; SEQ ID NO: 216; and SEQ ID NO: 218, respectively;   (xi) said anti-CGRP antibody comprises the light chain CDR 1, 2, and 3 polypeptide sequences of SEQ ID NO: 224; SEQ ID NO: 226; and SEQ ID NO: 228, respectively and heavy chain CDR 1, 2, and 3 polypeptide sequences of SEQ ID NO: 204; SEQ ID NO: 206; and SEQ ID NO: 208, respectively;   (xii) said anti-CGRP antibody comprises the light chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 234; SEQ ID NO: 236; and SEQ ID NO: 238, respectively and heavy chain CDR 1, 2, and 3 polypeptide sequences encoded by SEQ ID NO: 214; SEQ ID NO: 216; and SEQ ID NO: 218, respectively;   (xiii) said anti-CGRP antibody comprises the variable light chain polypeptide of SEQ ID NO: 222;   (xiv) said anti-CGRP antibody comprises the variable light chain polypeptide encoded by SEQ ID NO: 232;   (xv) said anti-CGRP antibody comprises the variable heavy chain polypeptide of SEQ ID NO: 202;   (xvi) said anti-CGRP antibody comprises the variable heavy chain polypeptide encoded by SEQ ID NO: 212;   (xvii) said anti-CGRP antibody comprises the variable light chain polypeptide of SEQ ID NO: 222 and the variable heavy chain polypeptide of SEQ ID NO: 202;   (xviii) said anti-CGRP antibody comprises the variable light chain polypeptide encoded by SEQ ID NO: 232 and the variable heavy chain polypeptide encoded by SEQ ID NO: 212;   (xix) said anti-CGRP antibody comprises the light chain polypeptide of SEQ ID NO: 221;   (xx) said anti-CGRP antibody comprises the light chain polypeptide encoded by SEQ ID NO: 231;   (xxi) said anti-CGRP antibody comprises the heavy chain polypeptide of SEQ ID NO: 201 or SEQ ID NO: 566;   (xxii) said anti-CGRP antibody comprises the heavy chain polypeptide encoded by SEQ ID NO: 211 or SEQ ID NO: 567;   (xxiii) said anti-CGRP antibody comprises the light chain polypeptide of SEQ ID NO: 221 and the heavy chain polypeptide of SEQ ID NO: 201 or SEQ ID NO: 566;   (xxiv) said anti-CGRP antibody comprises the light chain polypeptide encoded by SEQ ID NO: 231 and the heavy chain polypeptide encoded by SEQ ID NO: 211 or SEQ ID NO: 567;   (xxv) the administered amount of said anti-CGRP antibody is between about 100 mg and about 300 mg, or is about 100 mg, or is about 300 mg;   (xxvi) the administered amount of said anti-CGRP antibody is 100 mg;   (xvii) the method further comprises intravenously administering 100 mg of said anti-CGRP antibody every 10-14 weeks, preferably every 11-13 weeks, more preferably every 12 weeks;   (xxviii) the administered amount of said anti-CGRP antibody is 100 mg;   (xxix) the method further comprising intravenously administering 300 mg of said anti-CGRP antibody every 10-14 weeks, preferably every 11-13 weeks, more preferably every 12 weeks;   (xxx) prior to said administration, the patient exhibits between 1-10 migraine attacks per month in the month or in the 3 months prior to administration;   (xxxi) prior to said administration, the patient exhibits between 2-8 migraine attacks per month in the month or in the 3 months prior to administration;   (xxxii) prior to said administration, the patient exhibits between 3-7 migraine attacks per month in the month or in the 3 months prior to administration;   (xxxiii) prior to said administration, the patient exhibits less than 25 headache days per month in the month or in the 3 months prior to administration;   (xxxiv) prior to said administration, the patient exhibits less than 20 headache days per month in the month or in the 3 months prior to administration;   (xxxv) prior to said administration, the patient exhibits less than 15 headache days per month in the month or in the 3 months prior to administration;   (xxxvi) prior to said administration, the patient exhibits less than 10 headache days per month in the month or in the 3 months prior to administration;   (xvii) said patient was diagnosed with migraine at least 10 years or at least 15 prior to said administration;   (xviii) said patient was diagnosed with migraine at least 18 or at least 19 years prior to said administration;   (xxxix) said patient has a reduction in the number of migraine days by at least 50% in the one month period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xl) said patient has a reduction in the number of migraine days by at least 75% in the one month period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xli) said patient has a reduction in the number of migraine days by 100% in the one month period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xlii) said patient has a reduction in the number of migraine days by at least 50% in the 12 week period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xliii) said patient has a reduction in the number of migraine days by at least 75% in the 12 week period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xliv) said patient has a reduction in the number of migraine days by 100% in the 12 week period after being administered said antibody relative to the baseline number of migraine days experienced by that patient prior to said administration;   (xlv) the method further comprises administering a second dose of said anti-CGRP antibody to said patient about 10-14 weeks, preferably 11-13 weeks, more preferably about 12 weeks or about 3 months after said administration;   (xlvi) said administration comprises administering about 100 mg, about 125 mg, about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, or about 300 mg of said anti-CGRP antibody;   (xlvii) said anti-CGRP antibody is aglycosylated or if glycosylated only contains only mannose residues;   (xlviii) said anti-CGRP antibody consists of the light chain polypeptide of SEQ ID NO: 221 and the heavy chain polypeptide of SEQ ID NO: 201 or SEQ ID NO: 566;   (xlix) said anti-CGRP antibody consists of the light chain polypeptide encoded by SEQ ID NO: 231 and the heavy chain polypeptide encoded by SEQ ID NO: 211 or SEQ ID NO: 567;   (l) said headache or said migraine is diagnosed according to the third edition of the International Classification of Headache Disorders;   (li) said anti-CGRP antibody is expressed in or obtained by expression in  Pichia pastoris;      (lii) said anti-CGRP antibody is expressed in or obtained by expression in CHO cells;   (liii) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of histidine (L-histidine), sorbitol, polysorbate 80, and water;   (liv) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−10% of said values, and having a pH of 5.8 or within +/−10% of said value;   (lv) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−5% of said values, and/or having a pH of 5.8 or within +/−5% of said value;   (lvi) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−1% of said values, and/or having a pH of 5.8 or within +/−1% of said value;   (lvii) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−0.5% of said values, and/or having a pH of 5.8 or within +/−0.5% of said value;   (lviii) said anti-CGRP antibody or anti-CGRP antibody fragment is comprised in a formulation comprising or consisting of, per 1 mL volume, 100 mg anti-CGRP antibody, 3.1 mg L-Histidine, 40.5 mg Sorbitol, and 0.15 mg Polysorbate 80, or having amounts of each constituent within +/−0.1% of said values, and/or having a pH of 5.8 or within +/−0.1% of said value;   (lix) said anti-CGRP antibody has a dissociation constant of less than or equal to 10 pM, such as 2-8 pM, such as 3-6 pM, such as less than or equal to about 5 pM, optionally when measured by surface plasmon resonance, which is optionally carried out at 25° C. or 37° C.; or   (lx) the method improves both MBS and PGIC in said patient.