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(12) United States Patent (10) Patent No.: US 9,597,335 B2 Tuiten Et Al

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(12) United States Patent (10) Patent No.: US 9,597,335 B2 Tuiten Et Al USO09597335B2 (12) United States Patent (10) Patent No.: US 9,597,335 B2 Tuiten et al. (45) Date of Patent: *Mar. 21, 2017 (54) USE OF TESTOSTERONE AND A 5-HT1A 5,015,646 A 5/1991 Simms AGONST IN THE TREATMENT OF SEXUAL 5,250,534 A 10, 1993 Bell et al. 5,389,687 A 2f1995 Schaus et al. DYSFUNCTION 5,565,466 A 10, 1996 Gioco et al. 5,731,339 A 3/1998 Lowrey (71) Applicant: EMOTIONAL BRAIN B.V., Almere 5,877,216 A 3, 1999 Place et al. (NL) 6,165.975 A 12/2000 Adams et al. 6,242,436 B1 6/2001 Llewellyn 6,246,436 B1 6/2001 Lin et al. (72) Inventors: Jan Johan Adriaan Tuiten, Almere 6,251,436 B1 6/2001 Drizen et al. (NL); Johannes Martinus Maria 6,294.550 B1 9, 2001 Place et al. Bloemers, Almere (NL); Robertus 6,306,841 B1 10/2001 Place et al. Petrus Johannes De Lange, Hilversum 6,423,683 B1 7/2002 Heaton et al. (NL) 6,428,769 B1 8/2002 Rubsamen et al. 6,469,012 B1 10/2002 Ellis et al. 6,469,016 B1 10/2002 Place et al. (73) Assignee: EB IP LYBRIDOS B.V., Almere (NL) 6,472.434 B1 10/2002 Place et al. 6,541,536 B2 4/2003 Weikard et al. (*) Notice: Subject to any disclaimer, the term of this 6,593,313 B2 7/2003 Place et al. patent is extended or adjusted under 35 6,608,065 B1 8/2003 Daugan U.S.C. 154(b) by 0 days. 6,610,652 B2 8/2003 Adams et al. 6,632,419 B2 10/2003 Rubsamen et al. This patent is Subject to a terminal dis 6,964,780 B1 11/2005 King et al. claimer. 7,151,103 B2 12/2006 Borsini et al. 7,198.801 B2 4/2007 Carrara et al. 2002fOOO2973 A1 1/2002 Rubsamen et al. (21) Appl. No.: 14/960,204 2003/0022877 A1 1/2003 Dudley 2003/00278O1 A1 2/2003 McBurney (22) Filed: Dec. 4, 2015 2003/0027804 A1 2/2003 Van der Hoop 2003. O104980 A1 6/2003 Borsini et al. (65) Prior Publication Data 2003. O139384 A1 7/2003 Dudley 2004/OO 14761 A1 1/2004 Place et al. US 2016/OO82O18 A1 Mar. 24, 2016 2004/O186086 A1 9/2004 Bunschoten et al. 2004O2O8829 A1 10/2004 RubSamen et al. 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A6 IK 3/496 (2006.01) Ansel, “The Prescription,” in Remington's Pharmaceutical Sci A 6LX 3/59 (2006.01) ences, 17th Ed. (1985), Gennaro, (ed.), Chapter 101, pp. 1778-1787. A6 IK 45/06 (2006.01) Belikov et al., Pharmaceutical Chemistry (1993) 43-47 (machine translation provided). (52) U.S. Cl. Berman et al., “Safety and Efficacy of Sildenafil Citrate for the CPC .......... A6 IK3I/568 (2013.01); A61K 31/496 Treatment of Female Sexual Arousal Disorder: A Double-Blind, (2013.01); A61 K3I/519 (2013.01); A61 K Placebo Controlled Study,” Journal of Urology (2003) 170(6):2333 45/06 (2013.01) 2338. (58) Field of Classification Search USPC ......................................... 514/656, 657, 171 (Continued) See application file for complete search history. Primary Examiner — San-Ming Hui (74) Attorney, Agent, or Firm — Morrison & Foerster (56) References Cited LLP U.S. PATENT DOCUMENTS (57) ABSTRACT 3,976,776 A 8, 1976 Wu et al. The invention relates to the field of male and/or female 4,521,421 A 6, 1985 Foreman 4,596,795 A 6, 1986 Pitha sexual dysfunction. The invention specifically relates to the 4,640,921 A 2f1987. Othmer et al. use of testosterone and a 5-HT1A agonist. 4,833,142 A 5/1989 Hartog et al. 4,877,774 A 10, 1989 Pitha et al. 8 Claims, No Drawings US 9,597,335 B2 Page 2 (56) References Cited Haensel et al., “Flesinoxan: A Prosexual Drug for Male Rats.” European Journal of Pharmacology (1997) 330: 1-9. U.S. PATENT DOCUMENTS Holterhus et al., “Anabolic steroids, testosterone-precursors and virilizing androgens induce distinct activation profiles of androgen 2005.0245539 A1 11/2005 Mendla et al. responsive promoter constructs,” J Steroid Biochem Mol Biol 2006,004.0935 A1 2/2006 Maytornet al. (2002) 82:269-275. 2006/027O642 A1 1 1/2006 Lehman et al. 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JP 11-504902 5, 1999 International Search Report for International Patent Application No. JP 2001-520999 11 2001 PCT/NO2007/050535, mailed Feb. 24, 2009, 3 pages. JP 2002-543,128 12/2002 International Search Report for International Patent Application No. JP 2003-530430 10, 2003 JP 2004-520320 T 2004 PCT/NL2005/000355, mailed Dec. 18, 2006, 5 pages. JP 2005-50O347 1, 2005 International Search Report for International Patent Application No. JP 2005-503374 2, 2005 PCT/NL2006/000542, mailed Jul. 17, 2007, 5 pages. NZ 524601 4/2006 Kharkevich et al., Pharmacology (3" ed. 1987) 41-42 (machine RU 2130776 5, 1999 translation provided). RU 97117167 10, 1999 Koolman et al., Biochemistry (1998) 365 (machine translation RU 2152.787 T 2000 provided). RU 2180591 3, 2002 Kuhn, "Anabolic Steroids.” Rec. Progress Hormone Research RU 2285519 10, 2006 (2002) Academic Press vol. 57, pp. 411-434. 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WO WO-O2/O69.906 9, 2002 WO WO-037011300 2, 2003 Rendell et al., “Sildenafil for Treatment of Erectile Dysfunction in WO WO-037011301 2, 2003 Men with Diabetes a Randomized Controlled Trial,” JAMA (1999) WO WO-03/002123 9, 2003 281(5):421-426. WO WO-2004/O37173 5, 2004 Sher et al., “Vaginal Sildenafil (Viagra): A Preliminary Report of a WO WO-2004/O37262 5, 2004 Novel Method to Improve Uterine Artery Blood Flow and Endo WO WO-2005/007166 1, 2005 metrial Development in Patients Undergoing IVF,” Human Repro WO WO-2005/039530 5, 2005 duction (2000) 15(4):805-809. WO WO-2005/094827 10/2005 Shields et al., “Use of Sildenafil for Female Sexual Dysfunction.” WO WO-2005,102342 11/2005 Ann. Pharmacother. (2006) 40:931-934. WO WO-2005,107810 11/2005 Shifren et al., “Transdermal Testosterone Treatment in Women with WO WO-2006/127057 11 2006 Impaired Sexual Function after Oophorectomy,” New England WO WO-2007/0547.91 5/2007 Journal of Medicine (2000) 343:682-688. 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