US007572600B2 (12) United States Patent (10) Patent No.: US 7,572,600 B2 Berahovich et al. (45) Date of Patent: Aug. 11, 2009 (54) ENZYMATIC ACTIVITIES IN WO WO90, 13332 11, 1990 CHEMOKNE-MEDIATED INFLAMMATION WO WO 91/12779 9, 1991 WO WO 91f17271 11, 1991 (75) WO WO91, 1898O 12/1991 Inventors: Robert D. Berahovich, Berkeley, CA WO WO92fO1047 1, 1992 (US); Zhenhua Miao, San Jose, CA WO WO93,06121 4f1993 (US); Brett Premack, San Francisco, WO WO93, 17706 9, 1993 CA (US); Thomas J. Schall, Palo Alto, WO WO93/24640 12/1993 CA (US) WO WO94,08051 4f1994 WO WO94/20142 9, 1994 (73) Assignee: Chemocentryx, Inc., Mt. View, CA (US) WO WO95/12608 5, 1995 WO WO95/30642 11, 1995 (*) Notice: Subject to any disclaimer, the term of this WO WO95/35503 12/1995 patent is extended or adjusted under 35 WO WO 98.04554 2, 1998 U.S.C. 154(b) by 486 days. OTHER PUBLICATIONS (21) Appl. No.: 11/198,935 Al-Obeidi (1998), Mol. Biotechnol. 9:205-223. Aoyama, Y. et al. (2001), Bioorg Med. Chem. Lett. 11: 1691-4. 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Truncated chemokines lacking an N-terminal region that acti 6,329,510 B1* 12/2001 Qin et al. ............... 530,38822 vate CCR1 and/or FPRL1 and compositions containing the 6,723,538 B2 * 4/2004 Macket al. ................ 435/69.7 truncated chemokines are provided. Methods of identifying 6,756,035 B2 6/2004 Qin et al. agents that modulate CCR1 and/or FPRL1 activity either by 6,770,729 B2 8/2004 Van Antwerp modulating the production of the truncated chemokines or the 2003/0096.260 A1* 5/2003 Miao et al. ..................... 435/6 ability of the truncated chemokines to activate CCR1 and/or 2004/0243225 A1 12/2004 Ragheb et al. FPRL1 are also disclosed. Methods using the truncated chemokines to inhibit or activate CCR1 and/or FPRL1 medi FOREIGN PATENT DOCUMENTS ated biological activities are also disclosed. GB 2276.169 9, 1994 WO WO90, 11092 10, 1990 10 Claims, 25 Drawing Sheets US 7,572,600 B2 Page 2 OTHER PUBLICATIONS Poltorak, A.N. et al. (1995), J Inflamm 45:207-219. Queen, et al. 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CCL15/MP-18 VINSFHFAADCC . -- eastase VLNSFHFAADCC. ... + PMN sup #1 VLNSFHFAADCC. ... + PMN sup #2 SFHFAADCC. ... + synovial AADCC. ... + cathepsin G AADCC. -- chymase Figure 1B s costa cosa cks CCs CCL15thyrise CCL15+ chyrase oc1st PMN split CCS cathepsin-G ocCl5synonial Cis- easts ue PMN sup alone war CCL154 PNNsus 2 syrosiastone PAN2 one a. s 2 s Figure 1C U.S. Patent US 7,572,600 B2 U.S. Patent 000; 0 t g a r N re (s sun 03uoso on) nauts unbrea U.S. Patent Aug. 11, 2009 Sheet 6 of 25 US 7,572,600 B2 (9L:ON (LI:ON (8L:ON (6T:ON (ÜZ:ON {IZ:ON (6:ON (£I:ON (GI:ONCII (OI:ONCII (II:ONQI (ZT:ONCII CII CII CII QI CII QI ÕES) SI?9InáH U.S. Patent Aug. 11, 2009 Sheet 7 Of 25 US 7,572,600 B2 U.S. Patent Aug. 11, 2009 Sheet 8 of 25 US 7,572,600 B2 rycznoo þzyoSZTOO e.