United States Patent (10) Patent No.: US 8,859,256 B2 Szalay Et Al
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US008859256B2 (12) United States Patent (10) Patent No.: US 8,859,256 B2 Szalay et al. (45) Date of Patent: Oct. 14, 2014 (54) METHOD FOR DETECTING REPLICATION 6,759,038 B2 7/2004 Tan et al. ................... 424.93.21 OR COLONIZATION OF A BIOLOGICAL 6,863,894 B2 3/2005 Bermudes et al. ... 424,335.1 6,897,045 B2 5/2005 Engelhardt et al. 435/69.6 THERAPEUTC 6,916,462 B2 7/2005 Contag et al. ..... ... 424/9.6 6,923,972 B2 8, 2005 Bermudes et al. ... 424,235.1 (71) Applicants: Aladar A. Szalay, Highland, CA (US); 6,962,696 B1 1 1/2005 Bermudes et al. ... 424/93.4 Jochen Stritzker, La Jolla, CA (US); 7,001,765 B2 2/2006 Maass ............... ... 435/320.1 Michael Hess, Wuerzburg (DE) 7,033,826 B2 4/2006 Perricaudet et al. ... 435/320.1 7,153,510 B1 12/2006 Rose .................... ... 424,199.1 7,172,893 B2 2/2007 Rabinowitz et al. 435/235.1 (72) Inventors: Aladar A. Szalay, Highland, CA (US); 7,238,526 B2 7/2007 Wilson et al. ..... ... 435/.382 Jochen Stritzker, La Jolla, CA (US); 7,241,447 B1 7/2007 Engelhardt et al. 424, 1931 Michael Hess, Wuerzburg (DE) 7,255,851 B2 8/2007 Contaget al. .................. 4249.1 7,354,592 B2 4/2008 Bermudes et al. 424,235.1 Assignee: Genelux Corporation, San Diego, CA 7,452,531 B2 11/2008 Bermudes et al. ........... 424/93.2 (73) 7,514,089 B2 4/2009 Bermudes et al. ......... 424/258.1 (US) 7,537,924 B2 5/2009 Coffin et al. ...... 435/235.1 7.550,296 B2 6/2009 Hermiston et al. ........... 435/473 (*) Notice: Subject to any disclaimer, the term of this 7,588,767 B2 9/2009 Szalay et al. ...... ... 424,199.1 patent is extended or adjusted under 35 7,588,771 B2 9/2009 Szalay et al. .. ... 424,232.1 U.S.C. 154(b) by 30 days. 7,662,398 B2 2/2010 Szalay et al. .. ... 424,232.1 7,662.627 B2 2/2010 Johnson et al. 435/367 7,687,474 B2 3/2010 Matin et al. ... ... 514/44 (21) Appl. No.: 13/573,845 7,731,952 B2 6, 2010 Mohr et al. 424/93.2 7,731,974 B2 6, 2010 Bell et al. ...... ... 424,199.1 (22) Filed: Oct. 5, 2012 7,754.221 B2 7/2010 Szalay et al. .. ... 424,199.1 7,763.420 B2 7/2010 Stritzker et al. .................. 435/4 (65) Prior Publication Data 7,811,814 B2 10/2010 Bohn et al. ........ ... 435/320.1 7,820, 184 B2 10/2010 Stritzker et al. ........... 424,241.1 US 2013/O13O292 A1 May 23, 2013 (Continued) Related U.S. Application Data FOREIGN PATENT DOCUMENTS (60) Provisional application No. 61/627,255, filed on Oct. EP 1 281 767 2, 2003 5, 2011. EP 1 281 772 2, 2003 (51) Int. C. (Continued) CI2N 15/52 (2006.01) OTHER PUBLICATIONS CI2N 15/86 (2006.01) GOIN33/569 (2006.01) Iankov et al. 2009; Converting tumor-specific markers into reporters GOIN 2L/64 (2006.01) of oncolytic nirus invention. Molecular Therapy, 17(8): 1395-1403.* Kanervaetal. 2005; Noninvasive dual modality in vivo monitoring of CI2O I/68 (2006.01) the persistence and potency of a tumor targeted conditionally repli (52) U.S. C. cating adenovirus. Gene Therapy. 12: 87-94.* CPC. G0IN 21/6428 (2013.01); G0IN33/56911 Kelly et al. 2008; Novel oncolytic agent GLV-1hó8 is effective (2013.01); G0IN 2800/52 (2013.01); G0IN against malignant pleural mesothelioma. Human Gene Therapy 19:774-782.* 33/56983 (2013.01); C12O 1/6897 (2013.01) Mastrangelo et al. 1998; Intratumoral ecombinant GM-CSF-encod USPC ........................................ 435/210; 435/320.1 ing virus as gene thereapy in patients with cutaneous melanoma. (58) Field of Classification Search Cancer Gene Therapy. 6(5): 409-422.* CPC ................................ C12N 15/52, C12N 15/86 Peng et al. 2002; Non-invasive in vivo monitoring of trackable USPC ............................................... 435/210, 320.1 viruses expressing soluble marker peptides. Nature Medicine 8(5): See application file for complete search history. 527-531* (56) References Cited (Continued) U.S. PATENT DOCUMENTS Primary Examiner — Karen Cochrane Carlson (74) Attorney, Agent, or Firm — McKenna Long & Aldridge 4,952.496 A 8, 1990 Studier et al. ... 435/91 LLP; Stephanie Seidman 5,716,613 A 2f1998 Guber et al. .... ... 424/93.2 5,716,826 A 2f1998 Gruber et al. 435/320.1 5,851,529 A 12/1998 Guber et al. 424,188.1 (57) ABSTRACT 5,976,796 A 11/1999 Szalay et al. ...................... 435/6 Methods for detecting replication in or colonization of a host 6,428,968 B1 8, 2002 Molnar-Kimber et al. .. 435/723 6,447,784 B1 9/2002 Bermudes et al. ......... 424,235.1 by a biological therapeutic, such as an oncolytic virus, cells 6,475,482 B1 11/2002 Bermudes et al. .. ... 424/93.4 administered for cell therapy and gene therapy vectors, are 6,632,670 B1 10/2003 Wadsworth et al. 435/455 provided. In the methods, a product produced by the biologi 6,635,472 B1 10/2003 Lauermann ..... 435/320.1 cal therapeutic is detected in a sample of tissue or body fluid 6,638,752 B2 10/2003 Contaget al. 435/252.3 6,649,159 B2 11/2003 Yang et al. ... 424.93.21 distinct from the administered therapy or locus thereof, 6,653,103 B2 11/2003 Peterson et al. ... 435/69.1 thereby permitting assessment of the therapy and/or monitor 6,685,935 B1 2/2004 Pawelek et al. ... 424/93.2 ing its progress. 6,689,871 B1 2/2004 Wolfe et al. ..... ... 530,412 6,723,316 B2 4/2004 Lacquerre et al. ............. 424.93.2 20 Claims, 6 Drawing Sheets US 8,859,256 B2 Page 2 (56) References Cited 2012fO244068 A1 9/2012 Chen et al. ................... 424/1.11 2012/0276010 A1 1 1/2012 Szalay et al. ................... 4249.1 U.S. PATENT DOCUMENTS 2012/0308484 A1 12/2012 Szalay et al. ................... 4249.3 2013/0129614 A9 5/2013 Szalay et al. ................. 424/1.11 7,897,146 B2 3, 2011 Brown et al. 424,931 2013/0273.007 A1 10/2013 Szalay et al. ................. 424.93.2 7,906,111 B2 3, 2011 Wilson et al. ... 424/93.2 2013/0280170 A1 10/2013 Szalay ........................... 424.92 7,927,585 B2 4, 2011 Snyder ......................... 424.93.2 2014/OO86976 A1 3/2014 Szalay et al. 424,445 7,943,374 B2 5, 2011 Hildinger ................... 435/320.1 2014/OO87362 A1 3/2014 Szalay et al. ...................... 435/5 7968,340 B2 6, 2011 Hallek et al. ... 435/.440 8,007,780 B2 8, 2011 Arbetman ... ... 424/93.2 FOREIGN PATENT DOCUMENTS 8,021,662 B2 9, 2011 Szalay et al. 424,138.1 8,052,968 B2 11, 2011 Szalay et al. 424,199.1 EP 1385 466 2, 2004 8,066,984 B2 11, 2011 Szalay et al. 424/93.21 EP 1414994 5, 2004 8,221,769 B2 T/2012 Szalay et al. 424,232.1 EP 152O 175 4/2005 8.323,959 B2 12, 2012 Szalay et al. ... 435/320.1 EP 1606 411 12/2005 8,357,486 B2 1, 2013 Stritzker et al. .................. 435/4 WO WO93/O1296 1, 1993 8,568,707 B2 10, 2013 Szalay et al. ................... 4249.3 WO WO 98,14605 4f1998 8,586,022 B2 11, 2013 Szalay et al. 424.93.2 WO WOO3,O1438O 2, 2003 8,642,257 B2 2, 2014 Szalay et al. ...................... 435/5 WO WOO3/O57OO7 T 2003 2002fOO28195 A1 3, 2002 Coffey et al. 424,131.1 WO WO 2005/047458 5, 2005 2003, OO31628 A1 2, 2003 Zhao et al. ... 424/9.6 WO WO 2007/075879 7/2007 2003/00594.00 A1 3, 2003 Szalay ..... 424.93.2 WO WO 2008/073148 6, 2008 2003/O161788 A1 8, 2003 Zhao et al. .. ... 424/9.6 WO WO 2008/10O292 8, 2008 2003/0228261 A1 12, 2003 Szalay et al. 424,934 WO WO 2009/O54996 4/2009 2004/OOO9604 A1 1, 2004 Zhang et al. 435/.456 WO WO 2008,156655 6, 2009 2004/0213741 A1 10, 2004 Szalay et al. ... 424/9.6 WO WO 2009/126189 10/2009 2004/O234455 A1 11, 2004 Szalay et al. ... 424/9.6 2005, OO31643 A1 2, 2005 Szalay et al. 424,199.1 OTHER PUBLICATIONS 2005, OO69491 A1 3, 2005 Yu et al. ....................... 424/1.11 Rajeckietal. 2007: Treatment of prostate cancer with Ad5/3D24hCG 2005/022O818 A1 10, 2005 Lorence ..................... 424,214.4 allows non-invasive deterection of the magnitude and persistence of 2005/0249670 A1 11/2005 Szalay et al. 424,932 2005/0260601 A1 11/2005 Whitt et al. ....................... 435/6 virus replication in vivo. Mol. Cancer Ther. 6(2): 742-751.* 2006/0039894 A1 2, 2006 Mohr et al. 424,936 Letter/Written Disclosure of the Information Disclosure Statement, 2006/005.1370 A1 3, 2006 Szalay et al. ... 424,199.1 mailed Feb. 22, 2013, for the above-referenced application U.S. Appl. 2007/OOO9489 A1 1/2007 Bermudes etal ... 424/93.4 No. 13/573,845, 2 pages. 2007/0O25981 A1 2, 2007 Szalay et al. ... 424,130.1 Search Report, issued Jan. 30, 2013, in connection with correspond 2007/OO98743 A1 5/2007 Bell et al. .... 424,224.1 ing International Patent Application No. PCT/US2012/059126, 8 2007/01 10720 A1 5/2007 Brown et al.