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(12) United States Patent (10) Patent No.: US 8,911,786 B2 Desai Et Al US00891. 1786B2 (12) United States Patent (10) Patent No.: US 8,911,786 B2 Desai et al. (45) Date of Patent: Dec. 16, 2014 (54) NANOPARTICLE COMPRISING RAPAMYCIN A61K 45/06 (2013.01); A61K 47/42 (2013.01); AND ALBUMINAS ANTICANCERAGENT A61N 5/10 (2013.01); A61N 7700 (2013.01) (75) Inventors: Neil P. Desai, Los Angeles, CA (US); USPC ............ 424/491; 424/489: 424/490; 424/500 Patrick Soon-Shiong, Los Angeles, CA (58) Field of Classification Search (US); Vuong Trieu, Calabasas, CA (US) USPC .......... 424/465-489, 490, 491, 500: 514/19.3 See application file for complete search history. (73) Assignee: Abraxis Bioscience, LLC, Los Angeles, CA (US) (56) References Cited (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S. PATENT DOCUMENTS U.S.C. 154(b) by 344 days. 5,206,018 A * 4/1993 Sehgal et al. ................. 424,122 5,362.478 A 11/1994 Desai et al. (21) Appl. No.: 12/530,188 5.439,686 A 8, 1995 Desai et al. 5,498.421 A 3, 1996 Grinstaffet al. (22) PCT Filed: Mar. 7, 2008 5,505,932 A 4/1996 Grinstaffet al. 5,508,021 A 4/1996 Grinstaffet al. (86). PCT No.: PCT/US2O08/OO3O96 5,512,268 A 4/1996 Grinstaffet al. 5,540,931 A 7/1996 Hewitt et al. S371 (c)(1), 5,560,933 A 10/1996 Soon-Shiong et al. (2), (4) Date: Mar. 4, 2010 5,635,207 A 6/1997 Grinstaffet al. 5,639,473 A 6/1997 Grinstaffet al. (87) PCT Pub. No.: WO2008/109163 5,650,156 A 7/1997 Grinstaffet al. PCT Pub. Date: Sep. 12, 2008 5,665,382 A 9, 1997 Grinstaffet al. 5,665,383 A 9, 1997 Grinstaffet al. (65) Prior Publication Data 5,916,596 A 6/1999 Desai et al. US 2010/O183728A1 Jul. 22, 2010 (Continued) FOREIGN PATENT DOCUMENTS Related U.S. Application Data (60) Provisional application No. 60/905,669, filed on Mar. EP 1683 S17 A1 T 2006 7, 2007, provisional application No. 60/905,734, filed JP 2004-525950 A 8, 2004 on Mar. 7, 2007, provisional application No. (Continued) 60/905,662, filed on Mar. 7, 2007, provisional application No. 60/905,735, filed on Mar. 7, 2007, OTHER PUBLICATIONS provisional application No. 60/905,672, filed on Mar. 7, 2007, provisional application No. 60/905,787, filed Adnot, S. etal. (Jan. 1991). “Loss of Endothelium-Dependent Relax on Mar. 7, 2007, provisional application No. ant Activity in the Pulmonary Circulation of Rats Exposed to Chronic 60/905,663, filed on Mar. 7, 2007, provisional Hypoxia.” J. Clin. Invest. 87(1): 155-162. application No. 60/905,767, filed on Mar. 7, 2007, provisional application No. 60/905,750, filed on Mar. (Continued) 7, 2007, provisional application No. 60/923,248, filed on Apr. 13, 2007, provisional application No. Primary Examiner — Michael G. Hartley 60/923,456, filed on Apr. 13, 2007. Assistant Examiner — Micah-Paul Young (51) Int. Cl. (74) Attorney, Agent, or Firm — Morrison & Foerster LLP A 6LX 9/50 (2006.01) A6 IK3I/675 (2006.01) A6 IK9/00 (2006.01) (57) ABSTRACT A 6LX 9/19 (2006.01) A 6LX 9/5 (2006.01) The present invention features methods for treating, stabiliz A6 IK3I/436 (2006.01) ing, preventing, and/or delaying cancer by administering A 6LX3/57 (2006.01) nanoparticles that comprise rapamycin or a derivative A6 IK3I/685 (2006.01) thereof. The invention also provides compositions (e.g., unit A6 IK 45/06 (2006.01) dosage forms) comprising nanoparticles that comprise a car A6 IK 47/42 (2006.01) rier protein and rapamycin or a derivative thereof. The inven A6IN 5/10 (2006.01) tion further provides combination therapy methods of treat A61N 7700 (2006.01) ing cancer comprising administering to an individual an (52) U.S. Cl. effective amount of nanoparticles that comprise rapamycin or CPC ............. A6 IK3I/675 (2013.01); A61 K9/0019 a derivative thereof and a second therapy. (2013.01); A61 K9/19 (2013.01); A61 K9/5169 (2013.01); A61 K3I/436 (2013.01); A61 K 31/517 (2013.01); A61 K3I/685 (2013.01); 37 Claims, 7 Drawing Sheets US 8,911,786 B2 Page 2 (56) References Cited 2013/0202709 A1 8, 2013 Desai et al. 2013/0209518 A1 8, 2013 Desai et al. U.S. PATENT DOCUMENTS 2013,0244952 A1 9/2013 Desai et al. 2013/0266659 A1 10, 2013 Desai et al. 5.997,904 A 12, 1999 Magdassi et al. 2013/0280336 A1 10, 2013 Desai et al. 6,096,331 A 8, 2000 Desai et al. 2013/0280337 A1 10, 2013 Desai et al. 6,506.405 B1 1, 2003 Desai et al. 2014, OO17315 A1 1/2014 Desai et al. 6,528,067 B1 3, 2003 Magdassi et al. 2014, OO1731.6 A1 1/2014 Desai et al. 6,537,579 B1 3, 2003 Desai et al. 2014, OO17323 A1 1/2014 Desai et al. 6,652,884 B2 11, 2003 Falciani 2014/OO23717 A1 1/2014 Desai et al. 6,749,868 B1 6, 2004 Desai et al. 2014/OO39069 A1 2/2014 Desai et al. 6,753,006 B1 6, 2004 Desai et al. 2014/OO39070 A1 2/2014 Desai et al. 7.771751 B2 8, 2010 Desai et al. 2014.0056986 A1 2/2014 Desai et al. 7,820,788 B2 10, 2010 Desai et al. 2014f0072630 A1 3/2014 Tao et al. 7,923,536 B2 4, 2011 Desai et al. 2014f0072631 A1 3/2014 Trieu et al. 7,981445 B2 T/2011 De et al. 2014f0072643 A1 3/2014 Desai et al. 8,034,375 B2 10, 2011 Desai et al. 2014/OO79787 A1 3/2014 Yeo et al. 8,034,765 B2 10, 2011 De et al. 2014/OO79788 A1 3/2014 Desai et al. 8,137,684 B2 3/2012 Desai et al. 2014/OO79793 A1 3/2014 Desai et al. 8,138,229 B2 3/2012 Desai et al. 2014f0080901 A1 3/2014 Desai et al. 8,257,733 B2 9, 2012 Desai et al. 2014/01342.57 A1 5, 2014 Desai et al. 8,268,348 B2 9, 2012 Desai et al. 8,314,156 B2 11, 2012 Desai et al. FOREIGN PATENT DOCUMENTS 2003, OO54042 A1 3, 2003 Liversidge et al. 2003/O1994.25 A1 10, 2003 Desai et al. WO WO-94, 18954 A1 9, 1994 2004/O126400 A1 T/2004 Iversen et al. ................. 424/400 WO WO-98,14174 A1 4f1998 2005/OOO40O2 A1 1/2005 Desai et al. ....................... 514/2 WO WO-98, 14175 A1 4f1998 2005/OO38498 A1 2, 2005 Dubrow et al. WO WO-99/00113 A1 1, 1999 2005/01 19330 A1 6, 2005 Kao et al. WO WO-00,64437 A1 11, 2000 2005/O152979 A1 7/2005 Besman et al. WO WO-OOf71079 A2 11/2000 2005/02O3O13 A1 9, 2005 Soker et al. WO WO-OOf71079 A3 11, 2000 2005/0209266 A1 9, 2005 Garvey WO WO-01f89522 A1 11, 2001 2005/0244339 A1 11/2005 Jauernigh et al. WO WO-O2/O80975 A1 10, 2002 2006, OO73182 A1 4, 2006 Wong et al. ................... 424/426 WO WO-O2/O87545 A1 11, 2002 2006/0210638 A1 9, 2006 Liversidge et al. WO WO-03/096944 A1 11, 2003 2007/0066522 A1 3, 2007 McCormicket al. ........... 514/12 WO WO-2004/052401 A2 6, 2004 2007/0O87022 A1 4, 2007 Desai et al. WO WO-2004/0524O1 A3 6, 2004 2007/0092.563 A1 4, 2007 Desai et al. WO WO 2005.117952 A2 * 12/2005 2007/0093547 A1 4, 2007 Desai et al. WO WO-2006/053754 A1 5, 2006 2007/0116774 A1 5/2007 Desai et al. WO WO-2006/0892O7 A2 8, 2006 2007/0117744 A1 5/2007 Desai et al. 514/11 WO WO-2006/0892O7 A3 8, 2006 2007/0129448 A1 6, 2007 Desai et al. WO WO-2006/08929.0 A1 8, 2006 2007/O166388 A1 7/2007 Desai et al. WO WO 20060892.90 A1 * 8, 2006 2008, OO63724 A1 3, 2008 Desai et al. WO WO-2006,124739 A1 11, 2006 2008. O153738 A1 6, 2008 Desai et al. WO WO-2007/027819 A2 3, 2007 2008. O161382 A1 T/2008 Desai et al. WO WO-2007/027941 A2 3, 2007 2008/0213370 A1 9, 2008 Desai et al. WO WO-2007/027941 A3 3, 2007 2008/0280939 A1 11, 2008 Izumo et al. WO WO-2008/O2.7055 A1 3, 2008 2008/028O987 A1 11, 2008 Desai et al. WO WO-2008/057562 A1 5, 2008 2009/0098.210 A1 4, 2009 Desai et al. WO WO-2008.076373 A1 6, 2008 2009/0175951 A1 T/2009 Liversidge WO WO-2008,109 163 A1 9, 2008 2009,0263.483 A1 10, 2009 Desai et al. WO WO-2008,137148 A2 11/2008 2009/0304805 A1 12, 2009 Desai et al. WO WO-2008,137148 A3 11 2008 2010.0035.800 A1 2, 2010 Desai et al. WO WO-2008,150532 A1 12/2008 2010.0048499 A1 2, 2010 Desai et al. 2010/01 12077 A1 5, 2010 Desai et al. OTHER PUBLICATIONS 2010, 0166869 A1 T/2010 Desai et al. 2010/0215751 A1 8, 2010 Desai et al. Al Housseini. A et al. (Mar. 1, 2008). “A Phase II. Non-Randomized 2010, O297243 A1 11, 2010 Desai et al. Study of Abraxane plus Carboplatin in Patents With Recurrent Plati 2011/0052708 A1 3, 2011 Soon-Shiong et al.
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