(12) United States Patent (10) Patent N0.: US 7,265,155 B2 Artman Et A1

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(12) United States Patent (10) Patent N0.: US 7,265,155 B2 Artman Et A1 US007265155B2 (12) United States Patent (10) Patent N0.: US 7,265,155 B2 Artman et a1. (45) Date of Patent: *Sep. 4, 2007 (54) TREATING A VARIETY OF PATHOLOGICAL W0 98 08498 A 3/1998 CONDITIONS, INCLUDING SPASTICITY WO WO98/08498 3/1998 AND CONVULSIONS, BY EFFECTING A WO WO99/44623 3/1999 MODULATION OF CNS ACTIVITY WITH W0 WO 01/28516 10/2000 ISOVALERAMIDE, ISOVALERIC ACID, OR A RELATED COMPOUND OTHER PUBLICATIONS Schon and Blau, J Neurol Neurosurg Psychiatry, Sep. 1987: (75) Inventors: Linda D. Artman, Salt Lake City, UT 50(9):1148-1152.* (US); Manuel Balandrin, Sandy, UT Dorland’s Medical Dictionary 27th ed. p. 379* (US); Robert L. Smith, Lansdale, PA Pharmacotherapy, A Pathophysiologic Approach, Dipiro et al.2nd (Us) ed. 1991, pp. 1232, 1238).* Drug facts and comparisons 1999 ed. pp. 1595-1597(“Drug (73) Assignee: NBS Pharmaceuticals, Inc., Salt Lake Facts”).* City, UT (US) Pharmacotherapy, A Pathophysiologic Approach, Dipiro et al. 2nd ed. 1991, pp. 1232 & 1238* Notice: Subject to any disclaimer, the term of this Drug Facts and Comparisons. 1999 ed. pp. 1595-1597 (“Drug patent is extended or adjusted under 35 Facts”).* Julius A. Vida “Advances in Anticonvulsant Drug Development”; USC 154(b) by 0 days. Anticonvulsants (1997) pp. 1-9; Academic Press. Julius A. Vida “Noncyclic Anticonvulsants”; Anticonvulsants This patent is subject to a terminal dis (1977) pp. 577-619; Academic Press. claimer. Salim Hadad, et al. “Pharmacokinetic Analysis and Antiepileptic Activity of N-Valproyl Deriatives of GABA and Glycine”; Phar (21) Appl. N0.: 10/614,344 maceutical Research (1995), pp. 905-907; Plenum Publishing Cor poration. (22) Filed: Jul. 8, 2003 Abdulla Haj -Yehia, et al. “Structure-Pharmacokinetic Relationships in a Series of Short Fatty Acid Amides that Possess Anticonvulsant (65) Prior Publication Data Activity”; Journal Of Pharmaceutical Sciences; (Aug. 1990); pp. 719-724; vol. 79, No. 8. US 2004/0072900 A1 Apr. 15, 2004 Abdulla Haj-Yehia, et a1. “Pharmacokinetic Analysis of the Struc tural Requirements for Forming “Stable” Analogues of Related US. Application Data Valpromide”; Pharmaceutical Research; (1992) pp. 1058-1063; vol. (60) Division of application No. 09/258,882, ?led on Mar. 9, No. 8; Plenum Publishing Corporation. 1, 1999, noW Pat. No. 6,589,994, Which is a continu Georges Taillandier, et al. “Recherches dans la série dipropylacétique XII. Acides et alcools aliphatiques rami?és ation-in-part of application No. PCT/US97/ 15272, anticonvulsivants”; Eur. J. Med. ChemiChemical Therapeutica; ?led on Aug. 29, 1997. (Sep.-Oct. 1975-10); N° 5; pp. 453-462. (60) Provisional application No. 60/025,050, ?led on Aug. Joel G. Hardman, Ph.D., et al. “The Pharmacological Basis of 30, 1996. Therapeutics” 10th Edition; (2001). H. Steve White, et al. “Experimental Selection, Quanti?cation, and Int. Cl. Evaluation of Antiepileptic Drugs” Antiepileptic Drugs, Fourth (51) Edition; (1995); pp. 99-110; Raven Press, New York. A61K 31/155 (2006.01) Walter Sneader “Drug Discovers: The Evolution of Modern Medi (52) US. Cl. ..................................... .. 514/629; 514/923 cines” (1985), pp. 24-47; John Wil y & Sons. (58) Field of Classi?cation Search .............. .. 514/629, Julius A. Vida “Anticonvulsants”; Principles Of Modern Chemistry, 5 14/923 4th Edition; (1995); pp. 182-198; Williams and Wilkins. See application ?le for complete search history. (Continued) References Cited (56) Primary ExamineriSreeni Padmanabhan U.S. PATENT DOCUMENTS Assistant ExamineriRenee Claytor (74) Attorney, Agent, or F irmiTraskBritt 3,485,851 A 12/1969 Thies .................... .. 260/3452 4,933,324 A 6/1990 Shashoua 514/17 4,939,174 A 7/1990 Shashoua ..... .. 514/549 (57) ABSTRACT 5,506,268 A * 4/1996 Balandrin et al. 514/629 5,763,494 A 6/1998 Balandrin et al. 514/629 Preparations and extracts of valerian, as Well as isovalera 5,994,392 A 11/1999 Shashoua ................... .. 514/78 mide, isovaleric acid, and certain structurally related com 6,107,499 A 8/2000 Shashoua ................... .. 554/78 pounds, exhibit clinically signi?cant pharmacological prop 6,258,836 B1 7/2001 Shashoua 526/437 erties that implicate a treatment for a variety of pathological 6,589,994 B1 * 7/2003 Altman et al. ............ .. 514/629 conditions, including spasticity and convulsions, Which are FOREIGN PATENT DOCUMENTS ameliorated by e?cecting a modulation of CNS activity. The compositions in question generally are non-cytotoxic and do 94/28888 12/1994 not elicit Weakness or sedative activity at doses that are 94 28888 A 12/1994 e?‘ective for the symptomatic treatment of such pathological WO94/28888 12/1994 97/34596 9/1997 conditions. WO97/34596 9/1997 98/08498 3/1998 2 Claims, 7 Drawing Sheets US 7,265,155 B2 Page 2 OTHER PUBLICATIONS V. E. Tyler et al., Pharmacognosy, 9th ed. (Lea and Febiger 1988), pp. 456-494. David A. Williams, et al. (Table of Contents) “Foye’s Principles of H. A. Hare et al., The National Standard Dispensatory, 1905, pp. 93, Medicinal Chemistry” 5th Edition (2002). 94, 159, 160, 169, 256, 642, 692-694, 766, 767, 1031, 1383, 1384, W. Loscher, et al. “Strategies in antiepileptic drug development: is 1426, 1479, 1480, 1571, 1572, 1619-1620, 1631-1633, 1661-1662. rational drug design superior to random screening and structural D. Hoffman, The Herbal Handbook: A User’s Guide to Medical variation?” Epilepsy Research; (1994) pp. 95-134. 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