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20-May-2019 13:41

, European Journal of Pharmacology, 2001,419 (I) :47-54)是这样的。 In extreme cases related to the treatment of prostate cancer hormone loss (: in the case of age-associated androgen decline (129-35 Katovich, et al, Proceedings of the Society for Experimental Biology & Medicine, 1990,193 (2).) Berendsen, et al, European Journal of Pharmacology, 2001,419 (I):. [0006] CGRP is a vasodilator active, the symptoms such as all forms of vascular headache and pathology of other vasomotor-related symptoms, including migraine headache (with or without aura aura) and cluster headache.[0007] CGRP and base may be correlated to develop and test a large number of migraine of the following compounds, the compound to inhibit release of CGRP (e.g.In some embodiments, affinity is any of the following: about 200 n M, about IOOn MJ ^] 50n M, approximately IOn Mj ^] In Mj ^ J 500p M, about ΙΟΟρΜ, about 60 p M, about 50 p M, about 20 p M, about 15p M, about 10 p M, about 5p M or about 2p M.Means any administration of anti-CGRP antagonist antibody may be known in the art: oral, intravenous, subcutaneous, intraarterial, intramuscular, cardiac, spinal, intrathecal, intraperitoneal, intraventricular, sublingual, skin and / or via inhalation.In some other embodiments, the antibody comprises a human heavy chain Ig G2 constant region, the constant region comprising the following mutations:.A330P331 to S330S331 (amino acid reference sorting wildtype Ig G2 sequence) Eur J. 2613- 2624.在一些实施方案中,抗体的重链恒定区是具有任何以下突变的人重链Ig Gl :1)A327A330P331到G327S330S331 ;2)E233L234L235G236 到P233V234A235, G236 被删除;3)E233L234L235 到P233V234A235 ;4) E233L234L235G236A327A330P331 到P233V234A235G327S330S331,G236 被删除;5)E233L234L235A327A330P331 到P233V234A235G327S330S331 和6)N297 到A297 或除N 以外的任何其它氨基酸。 In some embodiments, the heavy chain constant region of the antibody is a human heavy chain Ig Gl with any of the following mutations: 1) A327A330P331 to G327S330S331; 2) E233L234L235G236 to P233V234A235, G236 deleted; 3) E233L234L235 to P233V234A235; 4) E233L234L235G236A327A330P331 to P233V234A235G327S330S331 , G236 deleted; 5) E233L234L235A327A330P331 to P233V234A235G327S330S331 and 6) N297 to A297 or any other amino acid other than the N.Relatively More recently, the serotonin 5HT-1B / 1D and / or 5HT-la receptor agonists (e.g., Sumatriptan) successful in some patients has drawn researchers have proposed the condition of serotonin You can etiology.One form of migraine (familial hemiplegic migraine) has been shown to associated with missense mutations α I subunit of voltage-gated P / Q- type calcium channels in, it is likely that other patient populations are found in other ion channel mutations.

[0012] More recently, it has been the treatment of some patients with migraine, topiramate voltage dependent sodium channels are closed and certain glutamate receptors (kainate of AMPA), enhanced the activity of GABA-A receptor and blocked with topiramate carbonic anhydrase anticonvulsant.

[0002] The present invention relates to anti-CGRP antagonist antibody for the prevention, amelioration or treatment of vasomotor symptoms, such as CGRP related headaches (e.g., migraine) and hot flushes use. psychological and emotional symptoms observed (such as nervousness, fatigue, irritability, insomnia, depression , memory loss, headache, anxiety, nervousness or inability to concentrate) is considered to be a lack of sleep after hot flashes and sleep sweat caused (Kramer et al, in:.

CGRP is a neurotransmitter in the central nervous system, and has been shown to be effective in the outer peripheral vasodilator, CGRP-containing neurons in close connection with the outer periphery of the blood vessel. Murphy et al, 3 sup rd Int ' I Symposium on Recent...

[0018] another aspect, the present invention provides for improvement in an individual, control, reduction of headache (e.g., migraine and cluster headache) the onset or development or progression of headache delay, said method comprising administering an effective amount of the anti-CGRP antagonist antibody.

[0019] In another embodiment, the present invention provides for improvement in an individual, control, reduction of headache (e.g., migraine and cluster headache) the onset or delaying the development or progression of headache, the methods comprising administering an effective amount of an anti-CGRP antagonist antibody in combination with at least one other agent useful in the treatment of headache.Although the blood vessels to dilate and increase the pain and migraine-related symptoms, but this type of neurovascular events currently considered to be the result of the disease rather than the cause.



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