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United States Patent (10) Patent No.: US 7,863,261 B2 Frincke (45) Date of Patent: Jan

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United States Patent (10) Patent No.: US 7,863,261 B2 Frincke (45) Date of Patent: Jan USOO786.3261 B2 (12) United States Patent (10) Patent No.: US 7,863,261 B2 Frincke (45) Date of Patent: Jan. 4, 2011 (54) BREAST AND PROSTATE CANCER 2,308,834. A 1/1943 Ruzicka et al. TREATMENT METHOD 2,318, 105 A 5, 1943 Ruzicka 2,357,364 A 9/1944 Stavely (75) Inventor: James M. Frincke, Carlsbad, CA (US) 3,029.263 A 4/1962 Campbell et al. 3,210,249 A 10, 1965 BeerStecher et al. (73) Assignee: Hah Biosciences, Inc., San Diego, 3,336,347 A 8/1967 Engelfried et al. (US) 3.459,739 A 8/1969 Borrevang et al. (*) Notice: Subject to any disclaimer, the term of this 3,654,320 A 4/1972 Ayer et al. patent is extended or adjusted under 35 3,734,935 A 5.1973 Husbands et al. U.S.C. 154(b) by 543 days. 3,869,467 A 3, 1975 Guthrie et al. 3,935,245 A 1/1976 Engelfried et al. (21) Appl. No.: 11/835,397 (22) Filed: Aug. 7, 2007 (Continued)Ont1nue (65) Prior Publication Data FOREIGN PATENT DOCUMENTS US 2008/O176823 A1 Jul. 24, 2008 CA 1054143 5, 1979 Related U.S. Application Data (63) Continuation of application No. 09/675,323, filed on Sep. 28, 2000, now abandoned. (Continued) (60) Provisional application No. 60/157.275, filed on Sep. OTHER PUBLICATIONS 30, 1999, now abandoned, provisional application No. 60/157.347, filed on Sep. 30, 1999, now abandoned, Ben-David et al., Anti-hypocholterolemic effects of provisional application No. 60/166,116, filed on Nov. yspiandersterone in rats Proc. Soc. Exp. Biol. Med., 125:1136 16, 1999, now abandoned. (51) Int. Cl. (Continued) A6 IK3I/56 (2006.01) Primary Examiner San-ming Hui C07 L/00 (2006.01) (74) Attorney, Agent, or Firm Daryl D. Muenchau (52) U.S. Cl. ....................................... 514/182:552/502 (58) Field of Classification Search ................. 514/182; (57) ABSTRACT 552/5O2 See application file for complete search history. The invention provides methods to treating conditions such as (56) References Cited prostate cancer, or for ameliorating one or more symptoms U.S. PATENT DOCUMENTS associated with prostate cancer, or for agents that modulate the biological activity of the androgen receptor. The invention 2,243,887 A 6, 1941 Serini et al. also provides methods and compositions suitable for thera 2,251,939 A 8, 1941 Kathol peutic applications. 2,266,778 A 12/1941 Logemann et al. 2,267,257 A 12/1941 Ruzicka 2,308,833. A 1, 1943 Ruzicka et al. 24 Claims, 6 Drawing Sheets Ethanol DHT (1 nM) No.4 1,3,5(10)-Estratriene-17o-ethynyl-3,17-diol No.6 17o-Ethynyl-androstene-diol No.8 3,3,17B-Dihydroxy-androst-5-en-16-one No. 10 3-Methylcarbonate-androst-5-en-7,17-dione No.18 17-Methyl-marrianotic acid No.15 3B-Methoxy-17B-hydroxyandrost-5-en-7-one No.22 7-oxo-androstene-diol No.13 3,3,17B-Acetoxy-androst-5-ene-7o, 173-diol No.O 7-oxo-dehydroepiandrosterone No.5 Androst-5-ene-3B, 11B,173-triol No.18 33-Methoxy-androst-5-ene-73, 173-diol No.11 3B,173-Dihydroxy-androst-5-en-11-one No. 17 173-Methoxy-androst-3,5-dien-7-One No.19 17-Hydroxy-androst-3,5-dien-7-one No.2 17a-Ethynyl-17B-hydroxy-4-estren-3-one No.7 17o-Ethynyl-17B-hydroxy-4-androsten-3-one No. 14 33,17B-Diacetoxy-androst-5-en-7-one No. 1 17o-Ethynyl-17B-hydroxy-4-estren-3-one No.3 17o-Ethynyl-7-hydroxy-5(1-0)-estren-3-one No.9 33,173-Dihydroxy-androst-4-ene No.23 19-nor-Androst-5-ene-3,17-diol No.21 5o-Androstane-3c, 173-diol US 7,863,261 B2 Page 2 U.S. PATENT DOCUMENTS WO WO99.63.973 12/1999 3,944,576 A 3, 1976 Van den Broek OTHER PUBLICATIONS 3,962,275 A 6, 1976 Guthrie et al. 4,898,694 A 2f1990 Schwartz et al. 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A 4/1996 Lardy et al. 3O-androstanediol in naturally occurring and androgen-induced 5,532,230 A 7, 1996 Daynes et al. .............. 514,178 prostatic hyperplasia in the dog J. Clin. Invest. 64: 1003-1010 1979. 5,567,830 A 10/1996 Upasani Ranney et al Hypocholesterolemic effect of an androsterone analog 5,593.981 A 1, 1997 Labrie Proc. Soc. Exp. Biol. Med. 166:569-9 1964. 5,656,621 A 8, 1997 Schwartz et al. Rao, et al., Chemoprevention of rat prostate carcinogenesis by early 5,686,438 A 1 1/1997 Daynes et al. and delayed administration of dehydroepiandrosterone, Cancer Res. 5,744.462 A 4, 1998 Schwartz et al. 59(13):3084-3089, 1999. 5,763.433 A 6, 1998 Morfin Schwarz, Concerning Steroid Derivatives XIV Preparation of 5,859,000 A 1/1999 Dowell et al. Methylandrostenediol Derivatives with an Oxygen Function at the 7 5,912,240 A 6, 1999 Loria Position Coll. Czech. Chem. Comm. 26:1958-1966 1961 (translated 5,922,701 A 7, 1999 Araneo from German). 5,925,630 A 7/1999 Upasani et al. Chang, et al., Suppression of Al-Androstenediol-induced androgen 5,981,744 A 1 1/1999 Ng et al. receptor transactlvation by selective steroids in human prostate can 5,994,335 A 11/1999 Brodie et al. cer cells, Proc. Natl. Acad. Sci. USA., 96(20): 11173-11177, Sep. 28, 6,440,966 B1 8/2002 Barrett et al. 1999. 6,573.289 B1 6/2003 Tasaka et al. Hackenberg et al., Estrogen and androgen receptor mediated Stimu 6,667,299 B1 12/2003 Ahlem et al. lation and inhibition of proliferation by androst-5-ene-3B,17B-diol in 6,696.459 B1 2/2004 Jones et al. human mammary cancer cells, J. Steroid Biochem. Molec. Biol. 6,767,903 B1 7/2004 Cleve et al. 46(5):597-603 1993. 6,770,639 B2 8, 2004 Snow et al. Henderson, Dehydroepiandrosterone and 16O-bromo 6,770,641 B2 8/2004 Hayakawa et al. epiandrosterone: Inhibitors of Epstein-Barr virus-induced transfor 6,790,842 B1 9, 2004 Bohlmann et al. mation of human lymphocytes, Carcinogenesis, 2(7):683-686 1981. 6,962.923 B2 11/2005 Banks et al. 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