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(12) United States Patent (10) Patent No.: US 8,663,633 B2 Madison (45) Date of Patent: *Mar

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(12) United States Patent (10) Patent No.: US 8,663,633 B2 Madison (45) Date of Patent: *Mar 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.. South San Francisco 5,283,187 A 2f1994 Aebischer et al. ... 435, 182 9 es s 5,304,482 A 4, 1994 Sambrook et al. ... 435,226 CA (US) 5,323,907 A 6/1994 Kalvelage ......... ... 206,531 5,332,567 A 7/1994 Goldenberg . 424,149 (*) Notice: Subject to any disclaimer, the term of this 5,443,953. A 8, 1995 Hansen et al. ... 424/1.49 patent is extended or adjusted under 35 3.283sys- A l E. Skeat."aOOK a 4:3 U.S.C. 154(b) by 0 days. 5,541,297 A 7/1996 Hansen et al. ............. 530/391.7 This patent is Subject to a terminal dis- 5,550,042 A 8, 1996 Sambrook et al. ... 435,212 claimer 5,591,767 A 1/1997 Mohr et al. ....... 514,413 5,601,825 A 2f1997 Hansen et al. ... 424,183.1 5,635,603 A 6/1997 Hansen et al. .... 530.391.5 (21) Appl. 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. A 1 1/1982 Goldenberg . ... 424/1.49 globulins or a p35 family protein or modified serpins and 4,444,744 A 4, 1984 Goldenberg . ... 424/1.49 modified p35 family members or modified alpha macroglo 4,468.4574,460,561 A 7/19848/1984 Goldenberg et... al. ........... 435/68.1424/1.49 bulins.uns, thatunal, upon cleavage1 orfth the substrate,bstrate, trapst thuneprotease t 4,624,846 A 11/1986 Goldenberg ... ... 424/1.1 by forming a stable complex. Also provided are modified 4,671,958 A 6, 1987 Rodwell et al. ... 424,153 proteases. 4,769,027 A 9, 1988 Baker et al. ..... ... 424/493 4,818,709 A 4, 1989 Primus et al. ... 435/723 4,892,538 A 1/1990 Aebischer et al. ......... 604/891.1 20 Claims, 1 Drawing Sheet US 8,663,633 B2 Page 2 (56) References Cited FOREIGN PATENT DOCUMENTS U.S. PATENT DOCUMENTS EP O 266 032 5, 1988 EP O 277 313 8, 1988 5,766,842 A 6, 1998 Melnick ............................ 435/5 EP O3O8716 3, 1989 5,789,208 A 8, 1998 Sharon ..... 506,14 EP O 336 508 10, 1989 5,789,554 A 8/1998 Leung et al. ...................... 435/6 EP O 387 380 9, 1990 5,821,047 A 10, 1998 Garrard et al. .................... 435.5 EP O 613 683 12/1999 5,849,500 A 12/1998 Breitling et al. ... 435/7.1 EP 1361,284 11, 2003 5,866,413 A 2f1999 Sambrook et al. ......... 435/320.1 EP 1726 643 11, 2006 5,922,302 A 7/1999 Goldenberg et al. ........ 424/1.41 EP 1504. 117 7/2007 6,077,697 A 6/2000 Hadlaczky et al. ... 435/6 EP 1633 865 9, 2011 6,168,919 B1 1/2001 Short ............. ... 435/69 EP 1676 860 4/2012 6,187,287 B1 2/2001 Leung et al. ....... ... 424/9.1 JP A-5-503211 6, 1993 6,271,012 B1 8/2001 Van Eekelen et al. 435,221 WO WO90,02809 3, 1990 6,319,500 B1 1 1/2001 Goldenberg ............ 424,178.1 WO WO91,05048 4f1991 6,383,775 B1 5/2002 Duffet al. .................... 435/69.1 WO WO 91f17271 11, 1991 6,423.538 B1 7/2002 Wittrup et al. 435/320.1 WO WO92fO1047 1, 1992 6,867,010 B1 3/2005 Pedersen et al. ............... 435.74 WO WO92,062O3 4f1992 7,030,231 B1 4/2006 Craik et al. ... 536,231 WO WO92.09690 6, 1992 7,227,009 B2 6/2007 Craik et al. 536,231 WO WO92, 15679 9, 1992 7.335,504 B2 2/2008 Haupts et al. 435,226 WO WO92, 18619 10, 1992 7,439,226 B2 10/2008 Roller et al. ... 514/10 WO WO92/2O791 11, 1992 7,939,304 B2 5/2011 Ruggles ... 435, 183 WO WO93/O1288 1, 1993 8,211,428 B2 7/2012 Madison ..... 424/94.64 WO WO93,25221 12/1993 2002/0022243 A1 2/2002 Harris et al. .................... 435/23 WO WO94, 17784 8, 1994 2002/0031801 A1 3/2002 Kapeller-Libermann ... 435/69.1 W. 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