USOO8663633B2 (12) United States Patent (10) Patent No.: US 8,663,633 B2 Madison (45) Date of Patent: *Mar. 4, 2014 (54) PROTEASE SCREENING METHODS AND 4,925,648 A 5/1990 Hansen et al. ............... 424,153 PROTEASESIDENTIFIED THEREBY 4,932,412 A 6/1990 Goldenberg .................. 600,431 4,952.496 A 8, 1990 Studier et al. 435,2141 5,033,252 A 7, 1991 Carter ........ 53.425 (75) Inventor: Edwin L. Madison, San Francisco, CA 5,052,558 A 10, 1991 Carter . ... 206,439 (US) 5,059,595 A 10/1991 Le Grazie ..... ... 424/468 5,073,543 A 12/1991 Marshall et al. .. ... 514/21 (73) Assignees: Torrey Pines Institute for Molecular 5, 120,548 A 6/1992 McClelland et al. ... 424/473 Studies, San Diego, CA (US); Catalyst 5,223,409 A 6/1993 Ladner et al. ................. 506.1 Biosciences, Inc.. 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No.: 13/507,480 5,637.288 A 6/1997 Goldenberg et al. 424,149 5,639,476 A 6/1997 OShlack et al. ... ... 424/468 (22)22) Filed: Jul. 2,9 2012 5,658,727 A 8/1997 Barbas et al. ..................... 506.9 5,674,533 A 10, 1997 Santus et al. ...... ... 424/493 O O 5,677.427 A 10/1997 Goldenberg et al. 530,387.3 (65) Prior Publication Data 5,686,578 A 1 1/1997 Goldenberg ...... 530,387.3 US 2012/O3O8551A1 Dec. 6, 2012 5,698,178 A 12/1997 Goldenberg ...... ... 424/1.49 s 5,728,564 A 3, 1998 Sambrook et al. 435,215 5,733,566 A 3/1998 Lewis ........................... 424/426 Related U.S. Application Data (Continued) (63) Continuation of application No. 1 1/825,627, filed on Jul. 5, 2007, now Pat. No. 8,211,428. FOREIGN PATENT DOCUMENTS (60) Provisional application No. 60/818,804, filed on Jul. 5, EP O O92182 10, 1983 2006, provisional application No. 60/818,910, filed on EP O 238 473 9, 1987 Jul. 5, 2006. (Continued) (51) Int. Cl. OTHER PUBLICATIONS A6 IK38/48 (2006.01) CI2O I/37 (2006.01) U.S. Appl. No. 13/506,845, filed Jul. 2, 2012. U.S. Appl. No. 13/506,603, filed Apr. 30, 2012. 52 tprol (2006.01) U.S. Appl.pp No. 13/373, 118, filed Nov. 3, 2011. (52) AV e. we Adams et al., “The c-myc oncogene driven by immunoglobulin USPC ....... 424/94.64; 424/94.63; 435/23: 435/226; enhancers induces lymphoid malignancy in transgenic mice.” Nature 435/320.1; 435/252.33: 536/23.2 318:533-538 (1985). (58) Field of Classification Search Alexander et al., “Expression of the c-myc oncogene under control of USPC ......... 424/94.64, 94.63; 435/23, 226, 252.33, an immunoglobulin enhancer in E mu-myc transgenic mice.” Mol. 435/320.1; 536/23.2 Cell Biol. 7:1436-1444 (1987). See application file for complete search history. (Continued) (56) References Cited Primary Examiner — Chih-Min Kam U.S. PATENT DOCUMENTS (74) Attorney, Agent, or Firm — McKenna Long & Aldridge 3,536,809 A 10/1970 Appelzweig .................. 424/435 LLP; Stephanie Seidman 3,598,123 A 8, 1971 Zaffaroni ..... ... 128,268 3,630,200 A 12/1971 Higuchi ... ... 128,260 3,845,770 A 11, 1974 Eyes ... 128,260 (57) ABSTRACT 3,916,899 A 1 1/1975 Theeuwes ... ... 128,260 Methods for identifying modified proteases with modified 4,046.7224,008,719 A 9,2f1977 1977 TheeuwesRowland...... .... ...... 424/427530,362 substrate specificity- Y - or other properties are provided. The 4.33647 A 5/1982 Goldenberg . ... 424/1.37 methods screen candidate and modified proteases by contact 4,348,376 A 9/1982 Goldenberg . ... 424/1.49 ing them with a Substrate. Such as a serpin, an alpha macro 4,361,544. 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