Claims for Patent: 7,662,396

Summary for Patent: 7,662,396

Title:	Compositions and methods for enhancing the immunogenicity of antigens
Abstract:	The present invention provides recombinant polypeptides comprising an N-terminal fragment of an ActA protein or LLO protein fused to an antigen or a fragment thereof, nucleotides encoding same, recombinant vectors comprising same, and immunogenic and therapeutic methods utilizing same.
Inventor(s):	Paterson; Yvonne (Philadelphia, PA), Souders; Nicholas (Philadelphia, PA), Sewell; Duane (Cheltenham, PA), Pan; Zhen-kun (Wynnewood, PA), Singh; Reshma (Philadelphia, PA)
Assignee:	The Trustees of the University of Pennsylvania (Philadelphia, PA)
Application Number:	11/373,528
Patent Claims:	1. A recombinant nucleotide encoding a recombinant polypeptide comprising an N-terminal fragment of an ActA protein consisting of the first 390 amino acids of the Listeria monocytogenes ActA protein fused to a tumor antigen or a fragment thereof, wherein said ActA fragment comprises a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5 and wherein said tumor antigen is a self antigen. 2. The recombinant nucleotide of claim 1, wherein said self antigen is selected from the group consisting of Her-2/Neu, tyrosinase-related protein (TRP)-2, melanoma antigen (MAGE)-1, MAGE-3, gp-100, tyrosinase, melanoma antigen recognized by T-cells (MART)-1, heat shock protein (HSP)-70, beta-human chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA), the ras protein, the p53 protein, Muc1, and prostate specific antigen (PSA). 3. The recombinant nucleotide of claim 1, wherein said self antigen and said N-terminal fragment of an ActA protein are expressed from a promoter selected from the group consisting of an hly promoter, a prfA promoter, and a p60 promoter. 4. The recombinant nucleotide of claim 1, wherein said Listeria monocytogenes is the 10403s strain. 5. A recombinant vector expressing a recombinant polypeptide comprising an N-terminal fragment of an ActA protein consisting of the first 390 amino acids of the Listeria monocytogenes ActA protein fused to a tumor antigen or a fragment thereof, wherein said ActA fragment comprises a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5 and wherein said tumor antigen is a self antigen. 6. The recombinant vector of claim 5, wherein said self antigen is selected from the group consisting of Her-2/Neu, tyrosinase-related protein (TRP)-2, melanoma antigen (MAGE)-1, MAGE-3, gp-100, tyrosinase, melanoma antigen recognized by T-cells (MART)-1, heat shock protein (HSP)-70, beta-human chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA), the ras protein, the p53 protein, Muc1, and prostate specific antigen (PSA). 7. The recombinant vector of claim 5, wherein said self antigen and said N-terminal fragment of an ActA protein are expressed from a promoter selected from the group consisting of an hly promoter, a prfA promoter, and a p60 promoter. 8. The recombinant vector of claim 5, wherein said Listeria monocytogenes is the 10403s strain. 9. A recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide comprising an N-terminal fragment of an ActA protein consisting of the first 390 amino acids of the Listeria monocytogenes ActA protein fused to a tumor antigen or a fragment thereof, wherein said ActA fragment comprises a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5 and wherein said tumor antigen is a self antigen. 10. The recombinant Listeria strain of claim 9, wherein said self antigen is selected from the group consisting of Her-2/Neu, tyrosinase-related protein (TRP)-2, melanoma antigen (MAGE)-1, MAGE-3, gp-100, tyrosinase, melanoma antigen recognized by T-cells (MART)-1, heat shock protein (HSP)-70, beta-human chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA), the ras protein, the p53 protein, Muc1, and prostate specific antigen (PSA). 11. The recombinant Listeria strain of claim 9, wherein said self antigen and said N-terminal fragment of an ActA protein are expressed from a promoter selected from the group consisting of an hly promoter, a prfA promoter, and a p60 promoter. 12. The recombinant Listeria strain of claim 9, wherein said Listeria monocytogenes is the 10403s strain. 13. A method of killing a cell of a Her-2 transformed tumor comprising administering a recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide comprising an N-termninal fragment of an ActA protein consisting of the first 390 amino acids of the Listeria monocytogenes ActA protein fused to Her-2/Neu tumor antigen or a fragment thereof, wherein said ActA fragment comprises a PEST-like sequence selected from the sequences set forth in SEQ ID NO: 2-5, thereby killing the cell of a Her-2 transformed tumor. 14. A method of reducing the size of a Her-2 transformed tumor comprising administering a recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide comprising an N-terminal fragment of an ActA protein consisting of the first 390 amino acids of the Listeria monocytogenes ActA protein fused to a Her-2/Neu tumor antigen or a fragment thereof, wherein said ActA fragment comprises a PEST-like sequence selected from the sequences set forth in SEQ ID NO: 2-5, thereby reducing the size of said Her-2 transformed tumor. 15. A method of treating a subject having a Her-2 transformed tumor comprising administering to said subject a recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide comprising an N-terminal fragment of an ActA protein consisting of the first 390 amino acids of the Listeria monocytogenes ActA protein fused to a Her-2/Neu tumor antigen or a fragment thereof, wherein said ActA fragment comprises a PEST-like sequence selected from the sequences set forth in SEQ ID NO: 2-5, thereby treating said subject having said Her-2 transformed tumor. 16. A method for overcoming the immune tolerance of a subject to a self antigen-expressing tumor comprising administering to said subject a composition comprising a recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide comprising an N-terminal fragment of an ActA protein consisting of the first 390 amino acids of the Listeria monocytogenes ActA protein fused to a tumor antigen or a fragment thereof, wherein said ActA fragment comprises a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5 and wherein said tumor antigen is a self antigen, whereby said subject mounts an immune response against said self-antigen-expressing tumor, thereby overcoming the immune tolerance of said subject to said self-antigen-expressing tumor. 17. A method of suppressing the formation of a self antigen-expressing tumor in a subject comprising administering to said subject a composition comprising a recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide comprising an N-terminal fragment of an ActA protein consisting of the first 390 amino acids of the Listeria monocytogenes ActA protein fused to a tumor antigen or a fragment thereof, wherein said ActA fragment comprises a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5 and wherein said tumor antigen is a self antigen, whereby said subject mounts an immune response against said self-antigen-expressing tumor, thereby suppressing the formation of said self-antigen-expressing tumor. 18. A recombinant nucleotide encoding a recombinant polypeptide consisting of a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5 fused to a tumor antigen or a fragment thereof, wherein said tumor antigen is a self antigen. 19. The recombinant nucleotide of claim 18, wherein said self antigen is selected from the group consisting of Her-2/Neu, tyrosinase-related protein (TRP)-2, melanoma antigen (MAGE)-1 MAGE-3, gp-100, tyrosinase, melanoma antigen recognized by T-cells (MART)-1, heat shock protein (HSP)-70, beta-human chorionic gonadotropin (HCG), carcinoembryonic antigen (CEA), the ras protein, the p53 protein, Muc1, and prostate specific antigen (PSA). 20. The recombinant nucleotide of claim 18, wherein said self antigen and said PEST-like sequence are expressed from a promoter selected from the group consisting of an hly promoter, a prfA promoter, and a p60 promoter. 21. A recombinant vector expressing a recombinant polypeptide, consisting of a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5 fused to a tumor antigen or a fragment thereof, wherein said tumor antigen is a self antigen. 22. The recombinant vector of claim 21, wherein said self antigen is selected from the group consisting of Her-2/Neu, tyrosinase-related protein (TRP)-2, melanoma antigen (MAGE)-1, MAGE-3, gp-100, tyrosinase, melanoma antigen recognized by T-cells (MART)-1, heat shock protein (HSP)-70, beta-human chorionic gonadotropin (HCG) carcinoembryonic antigen (CEA) the ras protein, the p53 protein, Muc1, and prostate specific antigen (PSA). 23. The recombinant vector of claim 21, wherein said self antigen and said PEST-like sequence are expressed from a promoter selected from the group consisting of an hly promoter, a prfA promoter, and a p60 promoter. 24. A recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide consisting of a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5 fused to a tumor antigen or a fragment thereof, wherein said tumor antigen is a self antigen. 25. The recombinant Listeria strain of claim 24, wherein said self antigen is selected from the group consisting of Her-2/Neu, tyrosinase-related protein (TRP)-2, melanoma antigen (MAGE)-1, MAGE-3, gp-100, tyrosinase, melanoma antigen recognized by T-cells (MART)-1, heat shock protein (HSP)-70, beta-human chorionic gonadotropin (HCG) carcinoembryonic antigen (CEA) the ras protein, the p53 protein, Muc1, and prostate specific antigen (PSA). 26. The recombinant Listeria strain of claim 24, wherein said self antigen and said N-terminal fragment of an ActA protein are expressed from a promoter selected from the group consisting of an hly promoter, a prfA promoter, and a p60 promoter. 27. A method of killing a cell of a Her-2 transformed tumor comprising administering a recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide consisting of a PEST-like sequence selected from the sequences set forth in SEQ ID NO: 2-5 fused to a Her-2/Neu tumor antigen or a fragment thereof, thereby killing said cell of said Her-2 transformed tumor. 28. A method of reducing the size of a Her-2 transformed tumor comprising administering a recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide consisting of a PEST-like sequence selected from the sequences set forth in SEQ ID NO: 2-5 fused to a Her-2/Neu tumor antigen or a fragment thereof, thereby reducing the size of said Her-2 transformed tumor. 29. A method of treating a subject having a Her-2 transformed tumor comprising administering to said subject a recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide consisting of a PEST-like sequence selected from the sequences set forth in SEQ ID NO: 2-5 fused to a Her-2/Neu tumor antigen or a fragment thereof, thereby treating said subject having said Her-2 transformned tumor. 30. A method for overcoming the immune tolerance of a subject to a self antigen-expressing tumor, comprising administering to said subject a composition comprising a recombinant Listeria strain comprising a recombinant nucleotide, said recombinant nucleotide encoding a recombinant polypeptide consisting of a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5 fused to a tumor antigen or a fragment thereof, wherein said tumor antigen is a self antigen, whereby said subject mounts an immune response against said self-antigen-expressing tumor, thereby overcoming the immune tolerance of said subject to said self-antigen-expressing tumor. 31. A method of suppressing a formation of a self antigen-expressing tumor in a subject, comprising administering to said subject a composition comprising a recombinant Listeria strain comprising a recombinant nucleotide said recombinant nucleotide encoding a recombinant polypeptide consisting of a PEST-like sequence selected from the sequences set forth in SEQ ID No: 2-5 fused to a tumor antigen or a fragment thereof, wherein said tumor antigen is a self antigen, whereby said subject mounts an immune response against said self-antigen-expressing tumor, thereby suppressing the formation of said self-antigen-expressing tumor in the subject.

Details for Patent 7,662,396

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	January 15, 1974	7,662,396	2026-03-13
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	December 27, 1984	7,662,396	2026-03-13
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 15, 1985	7,662,396	2026-03-13
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 16, 1990	7,662,396	2026-03-13
Bel-mar Laboratories, Inc.	CHORIONIC GONADOTROPIN	chorionic gonadotropin	Injection	017054	March 26, 1974	7,662,396	2026-03-13
Fresenius Kabi Usa, Llc	CHORIONIC GONADOTROPIN	chorionic gonadotropin	For Injection	017067	March 05, 1973	7,662,396	2026-03-13