Claims for Patent: 10,695,415

Summary for Patent: 10,695,415

Title:	Live attenuated oral vaccine against shigellosis and typhoid fever
Abstract:	Disclosed is the attenuated Salmonella typhi vaccine Ty21a utilized as a vector for Shigella and/or enterotoxogenic E. coli genes stably integrated in the Ty21a chromosome. These genes include a heterologous Shigella sonnei O-antigen biosynthetic gene region that comprises the wzz gene and expresses Shigella sonnei form 1 O-antigen, as well as a heterologous acid resistance biosynthetic gene system comprising a YbaS gene, which enables increased stability of the Ty21a vector at pH 2.5 relative to Ty21a without the integrated acid resistance biosynthetic gene system.
Inventor(s):	Wu; Yun (Rockville, MD), Kopecko; Dennis J. (Silver Spring, MD), Sim; B. Kim Lee (Gaithersburg, MD), Hoffman; Stephen L. (Gaithersburg, MD)
Assignee:	Protein Potential, LLC (Rockville, MD)
Application Number:	15/742,459
Patent Claims:	1. A transgenic Salmonella typhi Ty21a comprising a heterologous Shigella sonnei O-antigen biosynthetic gene region and a heterologous acid resistance biosynthetic gene system comprising one or more heterologous Shigella acid resistance enzymes, wherein said heterologous Shigella sonnei O-antigen biosynthetic gene region and said heterologous acid resistance biosynthetic gene system both being integrated into the Salmonella typhi Ty21a chromosome, wherein said heterologous Shigella sonnei O-antigen biosynthetic gene region comprises a wzz gene, which comprises (i) a DNA sequence that shares at least 95% sequence identity with the DNA sequence of nucleic acids 4,511,904 to 4,513,010 of SEQ ID NO: 4; or (ii) the DNA sequence of nucleic acids 4,511,904 to 4,513,010 of SEQ ID NO: 4, and wherein: a. a heterologous Shigella sonnei 0-antigen is stably expressed; b. one or more heterologous Shigella acid resistance enzymes comprising a YbaS gene are stably expressed; c. said transgenic Salmonella typhi Ty21a is more acid stable at pH 2.5 than Salmonella typhi Ty21a without the integrated acid resistance biosynthetic gene system; d. an immune response is elicited against virulent Shigella sonnei challenge; and e. an immune response is elicited against virulent Salmonella typhi challenge. 2. The transgenic Ty21a of claim 1, wherein said heterologous Shigella sonnei 0-antigen biosynthetic gene region comprises (i) a DNA sequence that shares at least 95% sequence identity with the DNA sequence of nucleic acids 4,500,076 to 4,513,461 of SEQ ID NO: 4; or (ii) the DNA sequence of nucleic acids 4,500,076 to 4,513,461 of SEQ ID NO: 4. 3. The transgenic Ty21a of claim 2, wherein the YbaS gene comprises (i) a DNA sequence that shares at least 95% sequence identity with the DNA sequence of nucleic acids 4,503,240 to 4,504,172 of SEQ ID NO: 1; or (ii) the DNA sequence of nucleic acids 4,503,240 to 4,504,172 of SEQ ID NO: 1. 4. The transgenic Ty21a of claim 3, additionally comprising an O-antigen biosynthetic gene region from a bacterial strain selected from the group consisting of: Shigella dysenteriae, Shigella flexneri, Shigella boydii, Escherichia coli, Salmonela enterica serovars, Vibrio cholera serotypes, Enterobacter species, Yersinia species, and Pseudomonas species. 5. A composition comprising the transgenic Ty21a of claim 4 and a carrier. 6. A vaccine comprising the composition of claim 5 which is suitable for oral administration. 7. The vaccine of claim 6, wherein administration of said vaccine to a human population reduces the incidence of shigellosis in said human population subsequently exposed to pathogenic Shigella sonnei. 8. The vaccine of claim 6, wherein administration of said vaccine to a human population reduces the incidence of typhoid fever in said human population subsequently exposed to pathogenic S. typhi. 9. The vaccine of claim 6, wherein administration of said vaccine to a human population reduces the incidence of both shigellosis and typhoid fever in said human population subsequently exposed to both pathogenic Shigella sonnei and pathogenic S. typhi. 10. The transgenic Ty21a of claim 1, wherein the one or more heterologous Shigella acid resistance enzymes comprise GadA and GadC genes. 11. The transgenic Ty21a of claim 1, wherein the one or more heterologous Shigella acid resistance enzymes comprise GadB and GadC genes. 12. The transgenic Ty21a of claim 1, wherein the one or more heterologous Shigella acid resistance enzymes comprise GadA, GadB, and GadC genes.

Details for Patent 10,695,415

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bavarian Nordic A/s	VIVOTIF	typhoid vaccine live oral ty21a	Capsule	103123	December 15, 1989		2036-07-06