Claims for Patent: 9,132,146

Summary for Patent: 9,132,146

Title:	Furin-knockdown and GM-CSF-augmented (FANG) cancer vaccine
Abstract:	Compositions and methods for cancer treatment are discloses herein. More specifically the present invention describes an autologous cancer vaccine genetically modified for Furin knockdown and GM-CSF expression. The vaccine described herein attenuates the immunosuppressive activity of TGF-.beta. through the use of bi-functional shRNAs to knock down the expression of furin in cancer cells, and to augment tumor antigen expression, presentation, and processing through expression of the GM-CSF transgene.
Inventor(s):	Nemunaitis; John J. (Cedar Hill, TX), Senzer; Neil (Dallas, TX), Maples; Phillip B. (Pilot Point, TX), Rao; Donald (Dallas, TX)
Assignee:	GRADALIS, INC. (Dallas, TX)
Application Number:	12/973,823
Patent Claims:	1. An autologous cell vaccine comprising: a bishRNAfurin/GMCSF expression vector plasmid, wherein the vector plasmid comprises a first nucleic acid insert operably linked to a promoter, wherein the first insert encodes a Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) cDNA; a second nucleic acid insert operably linked to the promoter, wherein the second insert encodes one or more short hairpin RNAs (shRNA) capable of hybridizing to a region of a mRNA transcript encoding furin, thereby inhibiting furin expression via RNA interference wherein the shRNA incorporates cleavage dependent siRNA and cleavage independent miRNA motifs, wherein the shRNA comprises SEQ ID NO:2; and one or more optional vaccine adjuvants. 2. The composition of claim 1, wherein the GM-CSF is human. 3. The composition of claim 1, wherein a nucleotide sequence encoding a picornaviral 2A ribosomal skip peptide sequence is intercalated between the first and the second nucleic acid inserts. 4. The composition of claim 1, wherein the promoter is a CMV mammalian promoter. 5. The composition of claim 4, wherein the CMV mammalian promoter contains a CMV IE 5' UTR enhancer sequence and a CMV IE Intron A. 6. An autologous furin-knockdown and Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) augmented (FANG) cancer vaccine composition comprising: an autologous cancer cell transfected with a vector comprising: a first nucleic acid insert operably linked to a promoter, wherein the first insert encodes the GM-CSF cDNA; and a second nucleic acid insert operably linked to the promoter, wherein the second insert encodes one or more short hairpin RNAs (shRNA) capable of hybridizing to a region of a mRNA transcript encoding furin, thereby inhibiting furin expression via RNA interference wherein the shRNA incorporates cleavage dependent siRNA and cleavage independent miRNA motifs of SEQ ID NO: 2. 7. An autologous cell vaccine composition for cancer treatment by inhibition of furin expression via RNA interference comprising: a bishRNAfurin/GMCSF expression vector plasmid, wherein the vector plasmid comprises a first nucleic acid insert operably linked to a promoter, wherein the first insert encodes a Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) cDNA; a second nucleic acid insert operably linked to the promoter, wherein the second insert encodes one or more bi-functional short hairpin RNAs (shRNAfurin) providing a single targeted site for both a cleavage and a sequestering mechanism of RNA interference, wherein the bi-functional shRNAfurin comprises a first stem-loop structure comprising a complete complementary guide strand and a passenger strand and a second stem-loop structure comprising one or more basepair mismatches of the passenger strand capable of hybridizing to a region of a mRNA transcript encoding furin, wherein the shRNA comprises SEQ ID NO: 2, thereby inhibiting furin expression via RNA interference; and one or more vaccine adjuvants.

Details for Patent 9,132,146

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		2029-12-23
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2029-12-23
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2029-12-23