US 12,350,318 B2
Combination therapy to treat brain cancer
Amy-Lee Bredlau, Mahopac, NY (US); Israel Lowy, Dobbs Ferry, NY (US); Jeffrey Skolnik, Cherry Hill, NJ (US); Jian Yan, Wallingford, PA (US); Bernadette Ferraro, San Diego, CA (US); Jewell Walters, Poway, CA (US); Albert J. Sylvester, III, Croydon, PA (US); Kimberly A. Kraynyak, Norristown, PA (US); Matthew P. Morrow, Malvern, PA (US); and Elisabeth Gillespie, Horsham, PA (US)
Assigned to Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA (US); and Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed by Inovio Pharmaceuticals, Inc., Plymouth Meeting, PA (US); and Regeneron Pharmaceuticals, Inc., Tarrytown, NY (US)
Filed on Aug. 12, 2022, as Appl. No. 17/819,401.
Claims priority of provisional application 63/232,966, filed on Aug. 13, 2021.
Prior Publication US 2023/0070723 A1, Mar. 9, 2023
Int. Cl. A61K 38/20 (2006.01); A61K 31/495 (2006.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01); A61K 41/00 (2020.01); A61N 5/10 (2006.01); A61P 35/00 (2006.01); C12Q 1/6869 (2018.01); C12Q 1/6886 (2018.01)
CPC A61K 38/208 (2013.01) [A61K 31/495 (2013.01); A61K 39/001153 (2018.08); A61K 39/001157 (2018.08); A61K 39/001195 (2018.08); A61K 39/3955 (2013.01); A61K 41/0047 (2013.01); A61P 35/00 (2018.01); C12Q 1/6886 (2013.01); A61N 5/10 (2013.01); C12Q 1/6869 (2013.01); C12Q 2600/158 (2013.01); C12Q 2600/178 (2013.01)] 23 Claims
 
1. A method of treating glioblastoma characterized by an unmethylated 06-methylguanine methyltransferase (MGMT) gene promoter in a subject having an increased pre-treatment expression level of a miR-331-3p miRNA or isomiRs thereof and a miR-1537-3p miRNA or isomiRs thereof relative to a control population of subjects, comprising:
administering to said subject:
an anti-programmed cell death receptor 1 (PD-1) antibody;
interleukin-12 (IL-12); and
an immunogenic composition comprising a DNA plasmid comprising a nucleic acid sequence encoding human telomerase reverse transcriptase (hTERT) antigen, a DNA plasmid comprising a nucleic acid sequence encoding Wilms Tumor-1 (WT-1) antigen, and a DNA plasmid comprising a nucleic acid sequence encoding prostate specific membrane antigen (PSMA) antigen,
wherein the control population of subjects is a population of subjects having glioblastoma characterized by an unmethylated MGMT promoter administered IL-12; the immunogenic composition comprising a DNA plasmid comprising a nucleic acid sequence encoding hTERT antigen, a DNA plasmid comprising a nucleic acid sequence encoding WT-1 antigen, and a DNA plasmid comprising a nucleic acid sequence encoding PSMA antigen; and the anti-PD-1 antibody that is deceased at 18 months post tumor resection.