(12) United States Patent (10) Patent No.: US 7,678,808 B2 Barlow Et Al

(12) United States Patent (10) Patent No.: US 7,678,808 B2 Barlow Et Al

USOO7678808B2 (12) United States Patent (10) Patent No.: US 7,678,808 B2 Barlow et al. (45) Date of Patent: Mar. 16, 2010 (54) 5 HT RECEPTOR MEDIATED 3,960,927 A 6, 1976 Metcalfetal. NEUROGENESIS 4,007,196 A 2f1977 Christensen et al. 4,024, 175 A 5/1977 Satzinger et al. (75) Inventors: Carrolee Barlow, Del Mar, CA (US); 4,036,840 A 7, 1977 O'Brien et al. Todd Carter, San Diego, CA (US); 4,051.236 A 9, 1977 Harris et al. 4,062,848 A 12/1977 Van der Burg Andrew Morse, San Diego, CA (US); 4,085.225Ww - A 4, 1978 W.elle et al. Kai Treuner, San Diego, CA (US); Kym 4,093,617 A 6/1978 Robins et al. I. Lorrain, San Diego, CA (US) 4,094.992 A 6/1978 Kaplanet al. 4,096,257 A 6, 1978 Menschik et al. (73) Assignee: BrainCells, Inc., San Diego, CA (US) 4,107,307 A 8, 1978 Paul et al. 4,107,309 A 8, 1978 Paul et al. (*) Notice: Subject to any disclaimer, the term of this 4,123,534. A 10/1978 Credner et al. patent is extended or adjusted under 35 4,136,193 A 1/1979 Bogeso et al. U.S.C. 154(b) by 27 days. 4,146,718 A 3, 1979 Jenks et al. 4,172,074 A 10, 1979 Eriksoo et al. (21) Appl. No.: 11/746,008 4,188,391 A 2/1980 Campbell et al. 9 4,194,009 A 3/1980 Molloy et al. 1-1. 4,220,646 A 9, 1980 Cotrel et al. (22) Filed: May 8, 2007 4,229,449 A 10/1980 Melloni et al. O O RE30,511 E 2f1981 Paul et al. (65) Prior Publication Data 4.278,676 A 7/1981 Krogsgaard-Larsen US 2007/O270449 A1 Nov. 22, 2007 4,280,957 A 7/1981 Walser et al. 4,289,772 A 9/1981 Campbell et al. Related U.S. Application Data (60) Provisional application No. 60/746,878, filed on May (Continued) 9, 2006, provisional application No. 60/805,436, filed FOREIGN PATENT DOCUMENTS 3. A 2. pal application No. 60/882, EP 00505:51 4f1982 , Illed On Dec. ZRS, EP OO50563 4f1982 EP O356.128 2, 1990 (51) Int. Cl. EP O362001 4f1990 A6 IK 3/44 (2006.01) EP O461986 12/1991 A 6LX 3L/395 (2006.01) EP O463969 1, 1992 A 6LX 3L/2197 (2006.01) EP O503411 9, 1992 A6 IK3I/50 I (2006.01) EP O579496 1, 1994 (52) U.S. Cl. ............. 514/280: 514/210.01: 514/210.21; EP O685479 12/1995 514/222.2: 514/229.8: 514/247; 514/252.16; EP O7O2555 3, 1996 514/359; 514/415 (58) Field of Classification Search ................. 514/280, (Continued) 514/282 OTHER PUBLICATIONS See application file for complete search history. Adachi et al., Selective activation of vitamin D receptor by (56) References Cited lithocholic acid acetate, abile acid derivative, J. Lipid Res.46(1):46 57, 2005. U.S. PATENT DOCUMENTS Adams et al., Omega-Conotoxin CVID inhibits a pharmacologically 1,873,732 A 8, 1932 Adams distinct voltage-sensitive calcium channel associated with transmit 3,109,843. A 11, 1963 Reeder et al. ter release from preganglionic nerve terminals, J. Biol. Chem. 3,116,203 A 12/1963 Kariss et al. 278(6):4057-62, 2003. 3,121,076 A 2f1964 Keller et al. 3,136,815 A 6, 1964 Reeder et al. (Continued) 3.242,190 A 3/1966 Hafliger et al. 3,296,249 A 1, 1967 Bell Primary Examiner Sreeni Padmanabhan 3,371,085 A 2f1968 Reeder et al. Assistant Examiner Sahar Javanmard 3,397.209 A 8/1968 Hafliger (74) Attorney, Agent, or Firm Sughrue Mion PLLC 3,454,554 A 7, 1969 Biel 3,471.548 A 10, 1969 Keberle et al. (57) ABSTRACT 3,534,041 A 10/1970 Van der Burg et al. 3,758,528 A 9, 1973 Malen et al. The instant disclosure describes methods for treating diseases 3,814,812 A 6/1974 Eynard and conditions of the central and peripheral nervous system 3,819,631 A 6/1974 Broughton et al. by stimulating or increasing neurogenesis. The disclosure 3,819,706 A 6, 1974 Mehta et al. 3,821,249 A 6, 1974 Malen et al. includes compositions and methods based on use of a 5HTR 3,862,149 A 1/1975 Cotrel et al. agent, optionally in combination with one or more other 3,885,046 A 5, 1975 Mehta neurogenic agents, to stimulate or activate the formation of 3,912,743 A 10, 1975 Christensen et al. new nerve cells. 3,932,407 A 1/1976 Beverung, Jr. et al. 3,941,785 A 3, 1976 Clarke et al. 3 Claims, 53 Drawing Sheets US 7,678,808 B2 Page 2 U.S. PATENT DOCUMENTS 5,130,154 A 7, 1992 Liu et al. 5,130,430 A 7, 1992 Shaw 4.298,734. A 1 1/1981 Temple, Jr. 5,137,895 A 8/1992 Munson, Jr. et al. 4,301,176 A 11, 1981 Grabowski et al. 5,139,802 A 8, 1992 Liu et al. 4,314,081 A 2/1982 Molloy et al. 5,149,817 A 9, 1992 Matsumura et al. 4,316,839 A 2f1982 Gerecke et al. 5,158,947 A 10/1992 Tatsuoka et al. 4.338,317 A 7/1982 Temple, Jr. et al. 5,162.341 A 11/1992 Cook 4,361,583. A 1 1/1982 Kaplan 5,169,855. 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