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(12) United States Patent (10) Patent No.: US 9,301.962 B2 Bradner Et Al

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(12) United States Patent (10) Patent No.: US 9,301.962 B2 Bradner Et Al USOO930 1962B2 (12) United States Patent (10) Patent No.: US 9,301.962 B2 Bradner et al. (45) Date of Patent: Apr. 5, 2016 (54) MALE CONTRACEPTIVE COMPOSITIONS 5,854.238 A 12/1998 Kempen AND METHODS OF USE 6,444,664 B1 9, 2002 Princen et al. 7,015,213 B1 3/2006 Bigg et al. 7,589,167 B2 9, 2009 Zhou et al. (75) Inventors: James Elliott Bradner, Weston, MA 8,044,042 B2 * 10/2011 Adachi et al. ................. 514,219 (US); Martin Matzuk, Houston, TX 8,476,260 B2 * 7/2013 Miyoshi et al. ............... 514, 220 (US); Jun Qi, Sharon, MA (US) 8,981,083 B2 3/2015 Bradner et al. 2002fO169158 A1 1 1/2002 Hunt, III et al. (73) Assignees: Baylor College of Medicine, Houston, 2003. O130268 A1 7/2003 Sagara et al. 2006, O142257 A1 6/2006 Nieschlag et al. TX (US); Dana Farber Cancer 2006/0223055 A1 10/2006 Howley et al. Institute, Inc., Boston, MA (US) 2007/0218135 A1 9/2007 Mukharya et al. 2008.0004308 A1 1/2008 Dhanak et al. (*) Notice: Subject to any disclaimer, the term of this 2008/0081781 A1 4/2008 Lippa et al. patent is extended or adjusted under 35 2009/0012064 A1 1/2009 Sagara et al. U.S.C. 154(b) by 0 days. 2010/0286127 A1 1 1/2010 Miyoshi et al. 2012/0202798 A1 8/2012 Sagara 2013, O184264 A1 7/2013 Bradner et al. (21) Appl. No.: 13/698,006 2013,0252331 A1 9/2013 Bradner et al. (22) PCT Filed: May 16, 2011 2014/0011862 A1 1/2014 Bradner et at. (86). PCT No.: PCT/US2O11AO366.67 FOREIGN PATENT DOCUMENTS CA 2020806 A1 1, 1991 S371 (c)(1), CA 271074.0 A1 T 2009 (2), (4) Date: Apr. 26, 2013 CH 622O19 A5 3, 1981 CN 1227.555 A 9, 1999 (87) PCT Pub. No.: WO2011/143657 DE 3724164 A1 2, 1988 EP O 087 850 A1 9, 1983 PCT Pub. Date: Nov. 17, 2011 EP O 368 175 A1 5, 1990 EP O 387 613 A1 9, 1990 (65) Prior Publication Data EP O 93494.0 A1 8, 1999 EP O 989 131 A1 3, 2000 US 2013/0210813 A1 Aug. 15, 2013 EP 1297 836 A1 4/2003 EP 2 239264 A1 10, 2010 Related U.S. Application Data FR T532815 A1 5, 1977 JP 1-299231 12/1989 (60) Provisional application No. 61/334,991, filed on May JP 6-157316 6, 1994 14, 2010, provisional application No. 61/370,745, JP 11-228576 8, 1999 JP 3OO1979 11, 1999 filed on Aug. 4, 2010, provisional application No. JP 3096,299 8, 2000 61/375,863, filed on Aug. 22, 2010, provisional WO WO 97/47622 A1 12/1997 application No. 61/467,376, filed on Mar. 24, 2011, WO WO 98.11111 A1 3, 1998 provisional application No. 61/467,299, filed on Mar. WO WOO1,959 12 A1 12/2001 24, 2011. WO WO 2008/083056 A2 T 2008 WO WO 2008/137081 A1 11, 2008 WO WO 2009/084693 A1 T 2009 (51) Int. Cl. WO WO 2010/O15387 A1 2, 2010 AOIN 43/00 (2006.01) WO WO 2010/04946.6 A1 5, 2010 A 6LX3/553 (2006.01) A6 IK3I/554 (2006.01) (Continued) A6 IK3I/55 (2006.01) CO7D 495/4 (2006.01) OTHER PUBLICATIONS A 6LX3/557 (2006.01) Patani et al. Bioisosterism: A Rational Approach to Drug Design, (52) U.S. Cl. Chemical Reviews, 1996, vol. 96, No. 8.* CPC ........... A61K3I/551 (2013.01); A61 K3I/5517 (2013.01); C07D 495/14 (2013.01) (Continued) (58) Field of Classification Search None See application file for complete search history. Primary Examiner — Craig Ricci Assistant Examiner — Jared D Barsky (56) References Cited (74) Attorney, Agent, or Firm — Foley Hoag LLP U.S. PATENT DOCUMENTS 3,681,343 A 8, 1972 Hester, Jr. (57) ABSTRACT 3,709,898 A 1/1973 Hester, Jr. 3,812,259 A 5, 1974 Collins The invention relates to compositions and methods for effect 4,621,083. A 11, 1986 Casals-Stenzel et al. 5,104.543 A 4, 1992 Brandt et al. ing male contraception. 5,593.988 A 1/1997 Tahara et al. 5,712,274 A * 1/1998 Sueoka et al. ................ 514,219 5,753,649 A 5, 1998 Tahara et al. 22 Claims, 19 Drawing Sheets US 9,301.962 B2 Page 2 (56) References Cited Cellai, C., et al., “Mechanistic Insight Into Web-2170-induced Apoptosis in Human Acute Myelogenous Leukemia Cells: the Cru FOREIGN PATENT DOCUMENTS cial Role of PTEN,” Exp Hematol, 37(10): 1176-1185 (2009). Cole, P. A., “Chemical probes for histone-modifying enzymes.” Nat WO WO 2011/143651 A1 11/2011 Chem Biol 4, 590-597, (2008). WO WO 2011/143657 A1 11/2011 Crawford, N. P. et al., “Bromodomain 4 activation predicts breast WO WO 2011/143660 A2 11/2011 cancer survival.” Proc Natl AcadSci, 105,6380-6385, (2008). 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