US010392434B2 (12 ) United States Patent (10 ) Patent No. : US 10 , 392 ,434 B2 Bigal et al. (45 ) Date of Patent: Aug . 27 , 2019 ( 54 ) TREATING REFRACTORY MIGRAINE 5 ,851 , 556 A 12 / 1998 Breton et al. 5 , 932 ,215 A 8 / 1999 De Lacharriere et al. 5 , 935 , 586 A 8 / 1999 De Lacharriere et al . ( 71 ) Applicant: Teva Pharmaceuticals International 5 , 938 , 586 A 8 / 1999 De Lacharriere et al. GmbH , Jona (CH ) 6 , 168 , 809 B1 1 /2001 De Lacharriere et al. 6 , 180 ,370 B1 1 /2001 Queen et al. (72 ) Inventors : Marcelo Bigal, Doylestown , PA (US ) ; 6 ,313 ,097 B1 11 / 2001 Eberlein et al. Ernesto Aycardi, Andover, MA (US ) 6 , 344 , 438 B1 2 /2002 De Lacharriere et al. 6 , 344 ,449 B1 2 / 2002 Rudolf et al. 6 , 509 ,014 B1 1 / 2003 De Lacharriere et al. ( 73 ) Assignee : Teva Pharmaceuticals International 6 , 521 ,609 B1 2 / 2003 Doods et al . GmbH , Jona ( CH ) 6 ,552 ,043 B1 4 / 2003 Patchett et al. 6 ,586 ,458 B1 7 / 2003 Plachetka ( * ) Notice : Subject to any disclaimer , the term of this 6 ,737 ,056 B1 5 / 2004 Presta patent is extended or adjusted under 35 6 , 767 ,056 B2 5 /2004 Presta 7 , 109 , 214 B2 9 / 2006 Zimmer et al . U . S . C . 154 (b ) by 0 days . 7 , 384 . 930 B2 6 / 2008 Chaturvedula et al. 7 ,479 , 488 B2 1 / 2009 Mueller et al. ( 21) Appl. No .: 15 /712 ,444 7 ,772 ,224 B2 8 / 2010 Paone et al . 8 , 007 , 794 B2 8 / 2011 Zeller et al. 8 , 168 , 592 B2 5 / 2012 Gegg , Jr. et al . ( 22) Filed : Sep . 22 , 2017 8 , 293 , 239 B2 10 / 2012 Poulsen et al. 8 , 298 , 536 B2 10 /2012 Poulsen et al. (65 ) Prior Publication Data 8 ,586 ,045 B2 11 / 2013 Zeller et al . US 2018 /0127490 A1 May 10 , 2018 8 , 597 ,649 B2 12 /2013 Zeller et al . 8 ,623 ,366 B2 1 /2014 Pios et al . 8 ,669 , 368 B2 3 / 2014 Leahy et al . Related U . S . Application Data 8 ,734 , 802 B1 5 / 2014 Zeller et al . 9 , 115 , 194 B2 8 / 2015 Zeller et al . (60 ) Provisional application No. 62/ 399, 180 , filed on Sep . 9 , 266 , 951 B2 2 /2016 Zeller et al. 23 , 2016 , provisional application No . 62 / 558 , 557 , 9 , 328 , 167 B2 5 /2016 Poulsen et al . 9 , 328 , 168 B2 5 /2016 Zeller et al. filed on Sep . 14 , 2017 . 9 , 340 ,614 B2 5 / 2016 Zeller et al. 9 , 346 ,881 B2 5 /2016 Zeller et al . (51 ) Int . CI. 9 , 365 ,648 B1 6 / 2016 Zeller et al . A61K 9 / 00 ( 2006 .01 ) 9 , 505 , 838 B2 11 /2016 Allan et al. A61K 39 / 00 ( 2006 . 01 ) A61K 45 / 06 ( 2006 .01 ) (Continued ) A61P 25 / 06 ( 2006 . 01 ) FOREIGN PATENT DOCUMENTS CO7K 16 / 18 ( 2006 .01 ) A61K 39 /395 ( 2006 . 01) CA 2563687 11 / 2005 U . S . CI. CN 1308676 8 / 2001 CPC .. .. COZK 16 / 18 ( 2013 . 01 ) ; A61K 9 / 0019 (Continued ) ( 2013 .01 ) ; A61K 39 / 3955 ( 2013 .01 ) ; A61K 45 / 06 ( 2013 .01 ) ; A61P 25 / 06 (2018 .01 ) ; A61K OTHER PUBLICATIONS 2039 / 505 ( 2013 .01 ) ; A61K 2039 / 54 ( 2013 .01 ) ; A61K 2039 /545 (2013 . 01) ; COZK 2317 / 21 Chen “ Enhancement and destruction of antibody function by somatic (2013 .01 ) ; COZK 2317 / 24 (2013 .01 ) ; COOK mutation : unequal occurrence is controlled by V gene combinatorial 2317 / 33 (2013 .01 ) ; CO7K 2317 /34 (2013 .01 ) ; associations ” EMBO Journal vol . 14 No . 1 2 pp . 2784 - 2794 ( Year : CO7K 2317 /55 (2013 .01 ) ; CO7K 2317/ 56 1995 ) . * (2013 .01 ) ; C07K 2317 /565 ( 2013 . 01 ) ; CO7K (Continued ) 2317 /76 (2013 .01 ) ; CO7K 2317 /92 (2013 . 01 ) ; CO7K 2317 / 94 (2013 .01 ) Primary Examiner — Adam Weidner (58 ) Field of Classification Search None ( 74 ) Attorney, Agent, or Firm — Fish & Richardson P . C . See application file for complete search history . ( 57 ) ABSTRACT ( 56 ) References Cited Disclosed herein are methods of treating or reducing inci U . S . PATENT DOCUMENTS dence of migraine and / or at least one secondary symptom associated with refractory migraine in a subject having 4 ,816 , 567 A 3 / 1989 Cabilly et al. refractory migraine comprising administering to the subject 5 , 116 , 964 A 5 / 1992 Capon et al. 5 , 500 , 362 A 3 / 1996 Robinson et al. a monoclonal antibody that modulates the CGRP pathway . 5 , 545 , 806 A 8 / 1996 Longberg et al . Compositions for use in the disclosed methods are also 5 , 545 , 807 A 8 / 1996 Surani et al. provided . Antagonist antibody G1 and antibodies derived 5 , 569 , 825 A 10 / 1996 Longberg et al. from G1 directed to CGRP are also described . 5 ,625 , 126 A 4 / 1997 Longberg et al . 5 ,633 , 425 A 5 / 1997 Longberg et al . 5 ,661 , 016 A 8 / 1997 Longberg et al. 5 , 750 , 373 A 5 / 1998 Garrard et al. 13 Claims, 8 Drawing Sheets 5 , 821 , 337 A 10 / 1998 Carter et al . 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