US 9,808,524 B2
Combination of local and systemic immunomodulative therapies for melanoma and liver cancer
Craig J. Eagle, New York, NY (US); H. Craig Dees, Knoxville, TN (US); Eric A. Wachter, Oak Ridge, TN (US); and Jamie Singer, Knoxville, TN (US)
Assigned to Provectus Pharmatech, Inc., Knoxville, TN (US); and Pfizer, Inc., New York, NY (US)
Filed by Provectus Pharmaceuticals, Inc., Knoxville, TN (US); and Pfizer, Inc., New York, NY (US)
Filed on Jun. 24, 2015, as Appl. No. 14/748,634.
Application 14/748,634 is a continuation of application No. 13/416,494, filed on Mar. 9, 2012, granted, now 9,107,887.
Claims priority of provisional application 61/451,395, filed on Mar. 10, 2011.
Prior Publication US 2015/0290318 A1, Oct. 15, 2015
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/395 (2006.01); A61K 31/352 (2006.01); A61K 38/21 (2006.01); C07K 16/30 (2006.01); A61K 31/365 (2006.01); A61K 38/19 (2006.01); A61K 38/20 (2006.01); A61K 39/00 (2006.01); A61K 39/245 (2006.01); A61K 45/06 (2006.01); A61K 47/02 (2006.01); A61K 47/60 (2017.01); C12N 7/00 (2006.01)
CPC A61K 39/3955 (2013.01) [A61K 31/352 (2013.01); A61K 31/365 (2013.01); A61K 38/193 (2013.01); A61K 38/20 (2013.01); A61K 38/204 (2013.01); A61K 38/2006 (2013.01); A61K 38/2013 (2013.01); A61K 38/21 (2013.01); A61K 38/212 (2013.01); A61K 38/217 (2013.01); A61K 39/0005 (2013.01); A61K 39/0011 (2013.01); A61K 39/245 (2013.01); A61K 39/39558 (2013.01); A61K 45/06 (2013.01); A61K 47/02 (2013.01); A61K 47/60 (2017.08); C07K 16/30 (2013.01); C12N 7/00 (2013.01); A61K 2039/505 (2013.01); C12N 2710/16021 (2013.01); C12N 2710/16034 (2013.01)] 25 Claims
 
1. A method of treatment of a melanoma, or a primary or metastatic liver cancer tumor in a human comprising separately administering a therapeutically effective amount of: (1) an intralesional chemoablative pharmaceutical composition to elicit ablation of at least one melanoma, or primary or metastatic liver cancerous tumor; and (2) a therapeutically effective amount of a systemic immunomodulatory anticancer agent that comprises anti-CTLA-4 antibodies, anti-PD-L1 antibodies or anti-PD-1 antibodies,
wherein said intralesional chemoablative pharmaceutical composition comprises an intralesional (IL) chemoablative agent comprising rose bengal (4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein) in an appropriate pharmaceutical composition, including a 0.1% (w/v) or higher concentration aqueous solution of rose bengal, or a physiologically acceptable salt of rose bengal, said intralesional chemoablative pharmaceutical composition being administered intralesionally into said at least one melanoma, or primary or metastatic liver cancerous tumor at about 0.1 mL/cc lesion volume to about 2 mL/cc lesion volume.