	US 12,139,528 B2
	Treating refractory migraine
Marcelo Bigal, Doylestown, PA (US); and Ernesto Aycardi, Andover, MA (US)
Assigned to Teva Pharmaceuticals International GmbH, Jona (CH)
Filed by Teva Pharmaceuticals International GmbH, Jona (CH)
Filed on Feb. 17, 2023, as Appl. No. 18/111,172.
Application 18/111,172 is a continuation of application No. 17/308,580, filed on May 5, 2021.
Application 17/308,580 is a continuation of application No. 17/076,759, filed on Oct. 21, 2020, granted, now 11,028,160, issued on Jun. 8, 2021.
Application 17/076,759 is a continuation of application No. 16/508,574, filed on Jul. 11, 2019, abandoned.
Application 16/508,574 is a continuation of application No. 15/712,444, filed on Sep. 22, 2017, granted, now 10,392,434, issued on Aug. 27, 2019.
Claims priority of provisional application 62/558,557, filed on Sep. 14, 2017.
Claims priority of provisional application 62/399,180, filed on Sep. 23, 2016.
Prior Publication US 2023/0242631 A1, Aug. 3, 2023
Int. Cl. C07K 16/18 (2006.01); A61K 9/00 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); A61P 25/06 (2006.01); A61K 39/00 (2006.01)

CPC C07K 16/18 (2013.01) [A61K 9/0019 (2013.01); A61K 39/3955 (2013.01); A61K 45/06 (2013.01); A61P 25/06 (2018.01); A61K 2039/505 (2013.01); A61K 2039/54 (2013.01); A61K 2039/545 (2013.01); C07K 2317/21 (2013.01); C07K 2317/24 (2013.01); C07K 2317/33 (2013.01); C07K 2317/34 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01)]

19 Claims

1. A method of treating or preventing migraine in a subject, the method comprising:

selecting a subject that has had inadequate responses to at least two preventive medications, wherein the inadequate responses were (i) no clinically meaningful improvement after at least three months, or (ii) treatment had to be interrupted because of adverse events that made it intolerable to the subject, wherein the at least two preventive medications are selected from two or more different clusters, wherein the clusters are defined as follows:

cluster A: topiramate, carbamazepine, divalproex sodium, and sodium valproate

cluster B: flunarizine and pizotifen

cluster C: amitriptyline, venlafaxine, nortriptyline, and duloxetine

cluster D: atenolol, nadolol, metoprolol, propranolol, and timolol

cluster E: onabotulinumtoxinA;

and

administering to the subject a therapeutically effective amount of a humanized monoclonal anti-calcitonin gene-related peptide (CGRP) antagonist antibody comprising the amino acid sequence of the heavy chain variable region set forth in SEQ ID NO: 1 and the amino acid sequence of the light chain variable region set forth in SEQ ID NO: 2.