Claims for Patent: 9,907,849

Summary for Patent: 9,907,849

Title:	Combination of a PD-1 antagonist and a listeria-based vaccine for treating prostate cancer
Abstract:	The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a Listeria based strain that expresses prostate-tissue specific antigen (PSA), and the use of the combination therapies for the treatment of prostate cancer.
Inventor(s):	Petit; Robert (Newtown, PA), Mauro; David J. (Washington Crossing, PA), Perini; Rodolfo F. (North Wales, PA)
Assignee:	Advaxis, Inc. (Princeton, NJ) Merck Sharp & Dohme Corp. (Rahway, NJ)
Application Number:	14/802,607
Patent Claims:	1. A method for treating prostate cancer in a patient comprising administering to the patient a combination therapy which comprises an antagonist of a Programmed Death 1 protein (PD-1) and a bioengineered live-attenuated Listeria monocytogenes strain transformed with an expression vector to express a PSA antigen fused to a truncated Listeriolysin O (tLLO), and wherein the live-attenuated Listeria monocytogenes strain stimulates Antigen Presenting Cells (APCs) capable of driving a cellular immune response to PSA expressing cells. 2. A method for treating prostate cancer in a patient comprising administering to the patient a combination therapy which comprises an anti-PD-1 monoclonal antibody, comprising a heavy chain and a light chain, wherein the heavy and light chains comprise SEQ ID NO:21 and SEQ ID NO:22, respectively, and a bioengineered live-attenuated Listeria monocytogenes strain transformed with an expression vector to express a PSA antigen fused to a truncated Listeriolysin O (tLLO), wherein the live-attenuated Listeria monocytogenes strain stimulates Antigen Presenting Cells (APCs) capable of driving a cellular immune response to PSA expressing cells. 3. The method of claim 1, wherein the PD-1 antagonist and the live-attenuated Listeria monocytogenes strain are administered simultaneously. 4. The method of claim 1 or 2, wherein said tLLO-PSA fusion polypeptide consists of the sequence of SEQ ID NO: 54 or a sequence at least 99% homologous thereto, wherein said tLLO enhances the immunogenicity of the fusion polypeptide. 5. The method of claim 1 or 2, wherein the live-attenuated Listeria monocytogenes strain comprises an LmddA-142 (10403S dal.sup.(-) dat.sup.(-) actA.sup.(-) pADV142) strain. 6. A method for treating prostate cancer in a patient comprising administering to the patient a combination therapy which comprises, an anti-PD-1 monoclonal antibody comprising a heavy chain and a light chain, wherein the heavy and light chains comprise SEQ ID NO:21 and SEQ ID NO:22, respectively, and a live-attenuated Listeria monocytogenes strain comprising a LmddA-143 (10403S dal.sup.(-) dat.sup.(-) actA.sup.(-) with klk3 fused to the hly gene in the chromosome) strain, wherein the live-attenuated Listeria monocytogenes strain stimulates Antigen Presenting Cells (APCs) capable of driving a cellular immune response to PSA expressing cells. 7. The method of claim 2 or 6, wherein the anti-PD-1 monoclonal antibody and the live-attenuated Listeria monocytogenes strain are administered simultaneously. 8. The method of claim 1, 2 or 6, wherein the prostate cancer is metastatic Castration-Resistant Prostate Cancer (mCRPC). 9. The method of claim 1, 2 or 6, wherein said live attenuated Listeria monocytogenes strain is administered with an adjuvant, wherein said adjuvant comprises Montanide ISA 51, GM-CSF, KLH, a cytokine, a growth factor, a cell population, QS21, Freund's incomplete adjuvant, aluminum phosphate, aluminum hydroxide, BCG, alum, an interleukin, an unmethylated CpG oligonucleotide, quill glycosides, monophosphoryl lipid A, a liposomes, a bacterial mitogen, a bacterial toxin, or a chemokine, or any combination thereof. 10. The method of claim 2 or 6, wherein the antibody is formulated as a liquid medicament which comprises 7% (w/v) sucrose, 0.02% (w/v) polysorbate 80 in 10 mM histidine buffer pH 5.5. 11. The method of claims 1, 2 or 6, wherein the prostate cancer tests positive for PD-L1 expression. 12. The method of claims 1, wherein the PD-1 antagonist is pembrolizumab. 13. The method of claim 2 or 6, wherein the anti-PD 1 monoclonal antibody is pembrolizumab. 14. The method of claim 1, wherein the PD-1 antagonist and the live-attenuated Listeria monocytogenes strain are administered sequentially. 15. The method of claim 2 or 6, wherein the anti-PD-1 monoclonal antibody and the live-attenuated Listeria monocytogenes strain are administered sequentially.

Details for Patent 9,907,849

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	For Injection	125514	09/04/2014		2034-07-18
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	Injection	125514	01/15/2015		2034-07-18