Claims for Patent: 9,345,754

Summary for Patent: 9,345,754

Title:	Allogeneic tumor therapeutic agent, a vaccine using allogeneic tumor cells for the therapeutic treatment of tumor diseases, and a method for the making of such a vaccine, and transfected human tumor cells for use as a vaccine
Abstract:	A vaccine on the basis of allogeneic tumor cells for the therapeutic treatment of defined tumor diseases, and a method for the making of such vaccine is disclosed. The tumor cells were previously transfected ex vivo with expression constructs encoding cytokines and co-stimulatory factors.
Inventor(s):	Dobric; Tomislav (Berlin, DE), Wittig; Burghardt (Berlin, DE), Schmidt; Manuel (Berlin, DE)
Assignee:	Mologen AG (Berlin, DE)
Application Number:	12/614,985
Patent Claims:	1. A vaccine for the treatment of patients who suffer from tumor diseases, said vaccine containing transfected tumor cells of a genetically not identical (different) donor of the same species (allogeneic), wherein the tumor cells were transfected ex-vivo with nucleic acid molecules encoding: interleukin-7 (IL-7), granulocyte-macrophage colony stimulating factor (GM-CSF), CD40L/CD154 and B7.1/CD80. 2. The vaccine according to claim 1, wherein the encoding nucleic acid molecules are present in one or more expression constructs. 3. The vaccine according to claim 2, wherein the expression construct is one of: a) a plasmid; or b) a linear double stranded, covalently closed expression cassette comprising essentially solely a CMV promoter, an intron, the encoding gene sequence and a polyadenylation sequence being closed on both ends of the double strand by a short loop of single stranded nucleotide residues. 4. The vaccine according to claim 3, wherein: said vaccine comprises additionally an immune modulating oligodeoxyribonucleotide as an adjuvant; and the immune modulating oligodeoxynucleotide: a) comprises a sequence of the base sequence N.sup.1N.sup.2CGN.sup.3N.sup.4, where N.sup.1N.sup.2 is an element selected from the group comprising GT, GG, GA, AT or AA, N.sup.3N.sup.4 is an element selected from the group comprising CT or TT, and C is desoxycytosine, G is desoxyguanosine, A is desoxyadenosine and T is desoxythymidine, b) and comprises a circular strand deoxyribonucleic acid with a partially complementary antiparallel base sequence and is of a dumbbell shape. 5. The vaccine according to claim 4, wherein the sequence with the base sequence N.sup.1N.sup.2CGN.sup.3N.sup.4 is positioned in the single stranded region of the oligodeoxyribonucleotide and comprises 40 to 200 nucleotides; and said vaccine comprises a pharmaceutically acceptable carrier. 6. The vaccine according to claim 1, wherein the allogeneic tumor cells are selected from colorectal carcinoma, small cell or non-small cell lung carcinoma, prostate carcinoma, mamma carcinoma, ovarian carcinoma, renal cell carcinoma and malign melanoma. 7. The vaccine according to claim 5, wherein the tumor cells are derived from the renal cell carcinoma cell line deposited under accession number DSM ACC 2635 at the DSMZ. 8. A method of making a vaccine according to claim 1 for the treatment of patients who suffer from tumor diseases, wherein tumor cells of a genetically not identical (different) donor of the same species (allogeneic) are transfected ex-vivo with nucleic acid molecules encoding: interleukin-7 (IL-7), granulocyte-macrophage colony stimulating factor (GM-CSF), CD40L/CD154 and B7.1/CD80 and subsequently are transferred into a an applicable pharmaceutical composition. 9. The method according to claim 8, wherein: additionally, an immune modulating oligodeoxyribonucleotide is employed as an adjuvant; and the immune modulating oligodeoxyribonucleotide comprises a circular strand of deoxyribonucleic acid with a partially complementary, antiparallel base sequence and is of a dumbbell shape. 10. The method according to claim 9, wherein: the immune modulating oligodeoxyribonucleotide comprises a sequence of the base sequence N.sup.1N.sup.2CGN.sup.3N.sup.4, where N.sup.1N.sup.2 is an element selected from the group comprising GT, GG, GA, AT or AA, N.sup.3N.sup.4 is an element selected from the group comprising CT or TT, and C is desoxycytosine, G is desoxyguanosine, A is desoxyadenosine and T is desoxythymidine; and the sequence with the base sequence N.sup.1N.sup.2CGN.sup.3N.sup.4 is positioned in the single stranded region of the oligodeoxyribonucleotide and comprises 40 to 200 nucleotides. 11. The method according to claim 8, wherein at least one of: the nucleic acid molecules are present in one or several expression constructs; and the allogeneic tumor cells are selected from colorectal carcinoma, small cell or non-small cell lung carcinoma, prostate carcinoma, mamma carcinoma, ovarian carcinoma, renal cell carcinoma and malign melanoma. 12. The method according to claim 8, wherein the transfection method being ballistic transfer, polycation, transfection, calcium phosphate precipitation, microinjection, protoplast fusion, liposome fusion, viral transfection systems, lipofection and/or electroporation. 13. The method according to claim 9, wherein the tumor cells are derived from several patients with the same disease picture. 14. The method according to claim 8, wherein the tumor cells of the renal cell carcinoma cell line deposited under accession number DSM ACC 2635at the DSMZ are employed. 15. A human tumor cell transfected ex-vivo with nucleic acid molecules encoding: interleukin-7 (IL-7), granulocyte-macrophage colony stimulating factor (GM-CSF), CD40L/CD154 and B7.1/CD80. 16. The human tumor cell according to claim 15, wherein the expression construct is: a) a plasmid; or b) a linear double stranded, covalently closed expression cassette comprising essentially solely a CMV promoter, an intran, the encoding gene sequence and a polyadenylation sequence being closed on both ends of the double strand by a short loop of single stranded nucleotide residues. 17. The human tumor cell according to claim 16, wherein said tumor cell is an allogeneic tumor cell of a renal cell carcinoma cell line. 18. The human tumor cell according to claim 17, wherein the tumor cells are from the renal cell carcinoma cell line deposited under accession number DSM ACC 2635 at the DSMZ. 19. A composition comprising tumor cells of a genetically not identical (different) donor of the same species (allogeneic), wherein the tumor cells comprise ex-vivo-transfected, encoding nucleic acid molecules which encode: interleukin-7 (IL-7), granulocyte-macrophage colony stimulating factor (GM-CSF), CD40L1CD154 and B7.1/CD80. 20. A human tumor cell for use as a vaccine in the treatment of tumor diseases comprising: tumor cells from the renal cell carcinoma cell line deposited under accession number DSM ACC 2635 at the DSMZ that has been transfected ex-vivo with nucleic acid molecules encoding: interleukin-7 (IL-7), granulocyte-macrophage colony stimulating factor (GM-CSF), CD40L/CD154 and B7.1/CD80 and a corresponding expression construct, wherein the expression construct is a plasmid or a linear double stranded, covalently closed expression cassette comprising essentially solely a CMV promoter, an intron, the encoding gene sequence and a polyadenylation sequence being closed on both ends of the double strand by a short loop of single stranded nucleotide residues.

Details for Patent 9,345,754

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2023-12-30
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2023-12-30
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2023-12-30