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Cha Kuna Taiteit Uit En Una Man Unita Ant In CHA KUNA TAITEIT US009974774B2UIT EN UNA MAN UNITA ANT IN (12 ) United States Patent (10 ) Patent No. : US 9 , 974 , 774 B2 Garner et al. ( 45) Date of Patent: May 22, 2018 ( 54 ) COMBINATORIAL METHODS TO IMPROVE 5 ,077 , 282 A 12 / 1991 Murdock et al . THE THERAPEUTIC BENEFIT OF 5 , 077 , 283 A 12 / 1991 Murdock et al. 5 , 116 ,827 A 5 / 1992 Murdock et al . BISANTRENE AND ANALOGS AND 5 , 143 , 661 A 9 / 1992 Lawter et al. DERIVATIVES THEREOF 5 ,212 ,291 A 5 / 1993 Murdock et al . 5 , 378 ,456 A 1 / 1995 Tsou @( 71) Applicant : UPDATE PHARMA INC ., Lebanon , 5 , 387 , 584 A 2 / 1995 Schnur 5 , 436 , 243 A 7 / 1995 Sachs et al . NJ (US ) 5 , 550 , 149 A 8 / 1996 Powell et al. 5 , 561, 141 A 10 / 1996 Powell et al. @(72 ) Inventors : William J . Garner, San Francisco , CA 5 , 573 , 781 A 11/ 1996 Brown et al. 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(60 ) Provisional application No. 61/ 858 ,729 , filed on Jul. (Continued ) 26 , 2013 . FOREIGN PATENT DOCUMENTS (51 ) Int. Cl. EP 1332755 AL 8 /2003 A61K 31/ 4178 ( 2006 . 01 ) WO 199739768 A1 10 / 1997 A61K 45 /06 ( 2006 .01 ) (Continued ) A61K 31 /4168 ( 2006 .01 ) A61K 31/ 473 ( 2006 .01 ) A61K 47 / 48 ( 2006 .01 ) OTHER PUBLICATIONS (52 ) U .S . Ci. Alberts et al CAS : 115 : 41444 , 1991. * CPC . A61K 31/ 4178 ( 2013 .01 ) ; A61K 31/ 4168 ( 2013 .01 ) ; A61K 31/ 473 ( 2013 .01 ) ; A61K (Continued ) 45 /06 ( 2013 . 01 ) ; A61K 47/ 48 (2013 . 01 ) Primary Examiner — Rei Tsang Shiao (58 ) Field of Classification Search (74 ) Attorney , Agent, or Firm — Ditthavong & Steiner , ??? . .. .. .. .. .. A61K 31 /4178 ; A61K 47 / 48 See application file for complete search history. P . C . (56 ) References Cited (57 ) ABSTRACT The present invention describes methods and compositions U . S . PATENT DOCUMENTS for improving the therapeutic efficacy of therapeutic agents 4 ,258 ,181 A * 3 / 1981 Murdock .. .. .. .. C07C 17 /32 previously limited by suboptimal therapeutic performance 540 /467 by either improving efficacy as monotherapy or reducing 4 , 261, 989 A 4 / 1981 Sasaki et al . side effects . Such methods and compositions are particularly 4 ,784 , 845 A 11/ 1988 Desai et al. applicable to bisantrene or derivatives, analogs , or prodrugs 4 , 816 , 247 A 3 / 1989 Desai et al . 4 , 900 , 838 A 2 / 1990 Murdock thereof. 5 , 000 , 886 A 3 / 1991 Lawter et al. 5 , 070 ,082 A 12 / 1991 Murdock et al. 7 Claims , No Drawings US 9 ,974 , 774 B2 Page 2 (56 ) References Cited 8 , 008 , 281 B2 8 / 2011 Prendergast et al. 8 ,008 , 318 B2 8 / 2011 Beckmann et al. U . S . 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