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(12) United States Patent (10) Patent No.: US 8,580,814 B2 Adelman Et Al

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(12) United States Patent (10) Patent No.: US 8,580,814 B2 Adelman Et Al USOO858O814B2 (12) United States Patent (10) Patent No.: US 8,580,814 B2 Adelman et al. (45) Date of Patent: *Nov. 12, 2013 (54) METHODS OF USING 5,528,823. A 6/1996 Rudy, Jr. et al. (+)-1,4-DIHYDRO-7-(3S4S)-3-METHOXY-4- 3.43wk A E. E. St.Ola tala (METHYLAMINO)-1-PYRROLIDINYL-4- 6,171,857 B1 1/2001 Hendrickson OXO-1-(2-THIAZOLYL)-1.8- 6,291643 B1 9/2001 Zou et al. NAPHTHYRIDNE-3-CARBOXYLIC ACID 6,570,002 B1 5/2003 Hardwicket al. FORTREATMENT OF CANCER 6,641,810 B2 11/2003 Gold 6,641,833 B2 * 1 1/2003 Dang ............................ 424/426 (75) Inventors: Daniel CAdelman, Redwood City, CA 6,696,4836,670,144 B2B1 12/20032/2004 CraigSingh et al. (US); Jeffrey A. Silverman, 6,723,734 B2 4/2004 Kim et al. Burlingame, CA (US) 7,211,562 B2 5/2007 Rosen et al. 7.989,468 B2 * 8/2011 Adelman et al. .............. 514,300 (73) Assignee: Sunesis Pharmaceuticals, Inc., South 3.9. A. S. idaran-Ghera Gh et al.1 San Francisco, CA (US) 2003/0232334 A1* 12/2003 Morris et al. ..................... 435/6 c - r 2004/0106605 A1 6/2004 Carboni et al. .... 514/226.8 (*) Notice: Subject to any disclaimer, the term of this 2004/0132825 A1* 7/2004 Bacopoulos et al. ......... 514/575 patent is extended or adjusted under 35 2005/0203120 A1 9, 2005 Adelman et al. U.S.C. 154(b) by 201 days. 2005/0215583 A1 9, 2005 Arkin et al. 2006, OO25437 A1 2/2006 Adelman et al. This patent is Subject to a terminal dis- 2006, OO63795 A1 3, 2006 Arkin et al. claimer. 2006/0247267 A1 11/2006 Adelman et al. 2008, OO63642 A1 3/2008 Adelman et al. (21) Appl. No.: 11/991,349 FOREIGN PATENT DOCUMENTS (22) PCT Filed: Sep. 5, 2006 JP O9-221424 8, 1997 (86). PCT No.: PCT/US2O06/034699 wo wiseS 12. WO WOO 1/74395 10, 2001 S 371 (CI), WO WOO2,20500 3, 2002 (2), (4) Date: Jun. 18, 2009 WO WO2004/085418 10, 2004 WO WO2007 O28171 3/2007 (87) PCT Pub. No.: WO2007/028171 WO WO2007/1463.35 12/2007 WO WO2008/O16678 2, 2008 PCT Pub. Date: Mar. 8, 2007 WO WO2009/O54935 4/2009 WO WO2009,075841 6, 2009 (65) Prior Publication Data OTHER PUBLICATIONS “Harrison's Principles of Internal Medicine.” 15th Ed., by Braunwald US 2009/0263393 A1 Oct. 22, 2009 et al. (Eds.), McGraw-Hill (New York), pp. 706-727 (2001).* “Treatment of platinum-resistant ovarian cancer' by Trimble et al., O O Expert Opin. Pharmacother. 2, 1299-306 (2001).* Related U.S. Application Data Allen, J.C., Database MEDLINE Accession No. 92345081, “Com lications of Chemotherapy in Patients with Brain and Spinal Cord (60) Provisional application No. 60789,093, filed on Apr. Ration Ped. liters 17, No. 4, pp. 218-224, RE 1-1992. 3, 2006, provisional application No. 60/788,927, filed Chiba, et al., “Practical Synthesis of AG-7352, Optically Active New on Apr. 3, 2006, provisional application No. Antitumor Agent.” Abstract, 218". ACS National Meeting, Aug. 60/810,285, filed on Jun. 1, 2006. Cleton,22-26, 1999.F.J., “History of the Development of Anticancer Drugs'. 51) Int. C Oxford Textbook of Oncology, vol. 1. pp. 445-453, 1995. (51) Int. Cl. Emens, et al., Curr. Opinion Mol. Ther. 3(1):77-84, 2001. A6 IK3I/4375 (2006.01) Evanchik, et al., “Non-Clinical Admet, PK, and Biological Activity CO7D 46L/00 (2006.01) of SNS-595, a Novel Cell Cycle Inhibitory Antineoplastic Agent.” (52) U.S. Cl Drug metabolism reviews, Marcel Dekker.New York, NY, US, vol. AV e. we 36, NO. SUPPL1 Aug. 2004 (2004-2008), p. 103. USPC ........... 514/300: 514/299; 514/279:514/277; , No Aug ( ), p 54.6/123:546/122:546/113:546/112:546/26 (Continued) (58) Field of Classification Search Primary Examiner — Brandon Fetterolf None Assistant Examiner — Theodore R West See application file for complete search history. (74) Attorney, Agent, or Firm — Jones Day (56) References Cited (57) ABSTRACT Methods of treating, preventing or managing cancer, includ U.S. PATENT DOCUMENTS ing certain leukemias are disclosed. The methods encompass the administration of enantiomerically pure (+)-1,4-dihydro 4,261,989 A 4, 1981 Sasaki et al. 7-(3S4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl-4- 4,810,643 A 3, 1989 Souza oxo-1-(2-thiazolyl)-1.8-naphthyridine-3-carboxylic acid. 4,999.291 A 3, 1991 Souza Also provided are methods of treatment using this compound 5,078,966 A 1/1992 Strong et al. with chemotherapy, radiation therapy, hormonal therapy, bio 5,134,127 A 7, 1992 Stella et al. logical therapy or immunotherapy. Pharmaceutical composi 5,229,496 A 7/1993 Deeley et al. tions and single unit dosage forms suitable for use in the 5,391,485 A 2/1995 Deeley et al. methods are also disclosed. 5,393,870 A 2/1995 Deeley et al. 5,489,519 A * 2/1996 Deeley et al. ................ 435/69.1 24 Claims, 20 Drawing Sheets US 8,580,814 B2 Page 2 (56) References Cited oxo-1-2(2-thiazolyl)-1,8-naphthyridine-3-carobxylic Acids”, BK Abstracts, 217' ACS Nat Mtd., Mar. 21-25, 1999. Tsuzuki, et al., “Practical Synthesis of (3S4S)-3-Methoxy-4- OTHER PUBLICATIONS Methylaminopyrrolidine.” Tetrahedron: Asymmetry 12(2001) 2989 2997. Freireich, et al., “Quantitative Comparison of Toxicity of Anticancer Tsuzuki, et al., “Process Research of a Novel Quinolone Antitumor Agents in Mouse, Rat, Hamster, Dog, Monkey, and Man', Cancer Agent, AG-7352.” English Abstract. The Japanese Society for Pro Chemotherapy Reports, vol. 50, No. 4, pp. 219-244, May 1966. cess Chemstry, 2004 Summer Symposium. 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