Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Reexamination Certificate
2000-03-23
2003-12-23
Badio, Barbara P. (Department: 1616)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
C552S536000
Reexamination Certificate
active
06667299
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to methods to make and use steroids, such as 16&agr;-bromo-3&bgr;-hydroxy-5&agr;-androstane-17-one (16&agr;-bromoepiandrosterone or hereafter “BrEA”) and new analogs thereof. The steroids are useful for a number of therapeutic and non-therapeutic applications, including their use as immune modulators. The present invention also relates to methods to make the compounds, compositions and formulations.
BrEA and its preparation from the steroid compound 3&bgr;-hydroxyandrost-5-en-17-one (dehydroepiandrosterone or “DHEA”) have been described (see, e.g.,
J. Org. Chem.
1962 27:2937-2938). Methods to prepare DHEA and other steroids and their biological properties have been described, see, e.g., U.S. Pat. Nos. 2,833,793, 2,911,418, 3,148,198, 3,471,480, 3,976,691, 4,268,441, 4,427,649, 4,542,129, 4,666,898, 4,956,355, 5,001,119, 5,043,165, 5,077,284, 5,028,631, 5,110,810, 5,157,031, 5,162,198, 5,175,154, 5,277,907, 5,292,730, 5,296,481, 5,372,996, 5,387,583, 5,407,684, 5,424,463, 5,461,042, 5,478,566, 5,506,223, 5,518,725, 5,527,788, 5,527,789, 5,532,230, 5,559,107, 5,562,910, 5,583,126, 5,585,371, 5,587,369, 5,591,736, 5,593,981, 5,610,150, 5,635,496, 5,641,766, 5,641,768, 5,656,621, 5,660,835, 5,686,438, 5,696,106, 5,700,793, 5,707,983, 5,709,878, 5,710,143, 5,714,481, 5,728,688, 5,736,537, 5,744,462, 5,753,237, 5,756,482, 5,776,921, 5,776,923, 5,780,460, 5,795,880, 5,798,347, 5,798,348, 5,804,576, 5,807,848, 5,807,849, 5,811,418, 5,824,313, 5,824,668, 5,824,671, 5,827,841, 5,837,269, 5,837,700, 5,843,932, 5,846,963, 5,859,000, 5,872,114 and 5,872,147; German patent numbers 2035738 and 2705917; PCT publication numbers WO 95/21617, WO 97/48367, WO 98/05338, WO 98/50040, WO 98/50041, WO 98/58650; European publication number 0020029; Ben-David, et al.,
Proc. Soc. Expt. Biol. Med.
1967 125:1136-1140, Coleman et al.,
Diabetes
1982 31:830, Oertel, et al.,
J. Steroid Biochem.
1972 3:493-496, Pashko, et al.,
Carcinogenesis
1981 2:717-721, Schwartz et al.,
Nutr. Cancer
1981 3:46-53; Dyner et al.,
J. Acquired Immune Deficiency Syndromes
1993 6:459-465; A. A. Afanasii and Y. A. Titov,
Total Steroid Synthesis,
Plenum Press, New York, 1970, see, e.g., p 1-304.
The use DHEA and other steroids in various applications, e.g., modulating immune responses have been described, e.g., U.S. Pat. Nos. 5,869,090, 5,863,910, 5,856,340, 5,824,668, 5,804,576, 5,753,237, 5,714,481, 5,709,878, 5,407,684, 5,206,008, 5,077,284, 4,978,532, 4,898,694, 4,542,129, 3,711,606 and 3,710,795. U.S. Pat. No. 4,956,355 and PCT publication number WO 97/48367, have described the use of BrEA and certain steroid compounds to treat certain virus or bacterial infections, such as human immunodeficiency virus (“HIV”) infection.
Various biological effects and/or metabolic conversions of steroid compounds have been described, e.g., Batta et al.,
J. Biol. Chem.
1986 25:127-133, Belli et al.,
Liver
1991 11:162-169, Bhattacharjee et al.,
Anal. Biochem.
1992 201:233-236, Blake et al.,
Int. J. Peptide Protein Res.
1982 20:97-101, 1986 25:127-133, Bonaventura,
Am. J. Obstet. Gynecol.
1978 131:403-409, Bucala et al.,
J. Steroid Biochem.
1986 25:127-133, Carey et al.,
Biochem.
1981 20:3637-3648, Chen et al.,
Carcinogenesis
1999 20:249-254, Chen et al.,
Carcinogenesis
1998 19:2187-2193, Chow et al.,
Antisense Res. Dev.
1994 4:81-86, Citro et al.,
Dis. Colon Rectum
1994 37(2 Suppl):S127-S132, Cleary,
Proc. Soc. Exp. Biol. Med.
1991 196:8-16, Cleary,
Int. J. Biochem.
1990 22:205-210, Crawford et al.,
Lab. Invest.
1994 71:42-51, Danenberg et al.,
Antimicrob. Agents Chemother.
1992 36:2275-2279, Dotzlaw et al.,
Cancer Res.
1999 59:529-532, Falany et al.,
J. Steroid Biochem. Mol. Biol.
1994 48:369-375, Faredin et al.,
J. Investigative Dermatol.
1969 52:357-361, Galigniana et al.,
Mol. Pharmacol.
1999 55:317-323, Goto et al.,
J. Chromatogr.
1983 276:289-300,
Grenot Biochem.
1992 31:7609-7621, Hofbauer et al.,
Life Sci.
1999 64:671-679, Huijghebaert et al.,
J. Lipid Res.
1986 27:742-752, Hurd et al.,
Oncogene
1999 18:1067-1072, Iida et al.,
J. Lipid Res.
1995 36:628-638, Jellinck et al.,
Steroids
1967 10:329-346, Jonsson et al.,
J. Pediatr. Gastroenterol. Nutr.
1995 20:394-402, Kalimi et al,
Mol. Cell. Biochem.
1994 131:99-108, Kramer et al.,
J. Biol. Chem.
1994 269:10621-10627, LaRochelle et al.,
Steroids
1984 43: 209-217, Liao et al.,
Carcinogenesis
1998 19:2173-2180, Lillienau et al.,
J. Clin. Invest.
1992 89:420-431, Loria,
Psychoneuroendocrinology
1997 22:S103-S108, Luscher et al
Mol. Immunol.
1983 20:1099-1105, Manna et al.,
J. Biol. Chem.
1999 274:5909-5918, Marschall et al.,
J. Biol. Chem.
1989 264:12989-12993, Medh et al.,
Cancer Res.
1998 15:3684-3693, Mohan et al.,
Steroids
1992 57:244-247, Munoz de Toro et al.,
J. Steroid Biochem. Mol. Biol.
1998 67:333-339, Padgett et al.,
J. Neuroimmunol.
1998 84:61, Padgett et al.,
Ann. N.Y. Acad. Sci.
1995 774:323, Padgett et al.,
J. Immunol.
1994 153:1544-1552, Pashko et al.,
Carcinogenesis
1984 5:463-466, Pashko et al.,
Carcinogenesis
1981 2:717, Petrylak et al.,
J. Clin. Oncology
1999 17:958-967, Podesta et al.,
Steroids
1996 61:622-626, Regelson et al.,
Ann. N.Y. Acad. Sci.
1994 719:564, Schmassmann et al.,
Gastroenterology
1993 104:1171-1181, Schmassmann et al.,
Hepatology
1990 11:989-996, Schreiber et al.,
Lancet
353:459-461, Schreiber,
Neth. J. Med.
1998 53:S24-31, Schwartz et al.,
Cancer Res.
1988 48:4817, Shahidi et al.,
Biochem. Biophys. Res. Commun.
1999 254:559-565, Steer et al.,
Ann. Rheum. Dis.
1998 57:732-737, Suzuki et al.,
Steroids
1998 63:672-677, Suzuki et al.,
Steroids
1996 61:296-301, Swaan et al.,
Bioconjugate Chem.
1997 8:520-525, Tang et al,
Anticancer Drug Res.
1998 13:815-824, Thomas et al.,
J. Steroid Biochem.
1986 25:103-108, Utsumi et al.,
Cancer Res.
1999 59:377-381, Vanden Heuvel,
J. Nutr.
1999 129(2S Suppl.):575S-580S, Wang et al.,
Endocrinology
1998 139:3903-3912, Wong et al.,
J. Biol. Chem.
1999 274:5443-5453, Xie et al.,
Endocrinology
1999 140:219-227, Yen et al.,
Lipids
1977 12:409-413, Zackheim et al.,
Arch. Dermatology
1998 134:949-954, Zhang et al.,
Biochim. Biophys. Acta
1991 1096:179-186, Zhu et al.,
Carcinogenesis
1988 19:2101-2106.
Compositions containing BrEA that were used to deliver the compound to cells or cell extracts usually included a significant amount of water. Such compositions contained solvents such as dioxane or dimethylsulfoxide (“DMSO”), which contained water, or an aqueous cyclodextrin solutions to facilitate compound delivery to cells, see, e.g.,
J. Pharmacol Exp. Ther.
1998, 285:876-83,
Cancer Res.
1986 46:3389-95,
Carcinogenesis
1985 6:333-35,
Carcinogenesis
1981 2:717-721,
Carcinogenesis
1981 2:683-86. Such compositions are typically delivered to animals by injection or to cells in tissue culture by addition to cell culture medium. European publication number EP 429 187 describes formulations that contain DHEA or BrEA and polyvinylpyrrolidone and crosslinked polyvinylpyrrolidone. Some of these compositions may have undesired or suboptimal properties. For example, solvents such as dioxane, DMSO or chloroform are generally not preferred or suitable parenteral excipients, particularly for human use. Formulations that contain BrEA or related steroids and that have improved properties, e.g., lower toxicity, improved chemical stability or desirable characteristics for large-scale synthesis are needed.
Mammalian immune responses to infections or other conditions are often characterized by responses mediated by different effector cell populations. In some situations, helper T cells designated Th1 in the murine system, facilitate immune effector functions that are typically dominated by cell-mediated responses. In other cases, helper T cells designated Th2 cells facilitate immune effector functions that are typically dominated by humoral responses. A vigorous Th1 response is usually needed to clear infections or to slow the progression of
Ahlem Clarence Nathaniel
de Carvalho Luis Daniel dos Anjos
Heggie William
Badio Barbara P.
Hollis-Eden Pharmaceuticals, Inc.
Muenchau Daryl D.
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