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Last Updated: April 24, 2024

Claims for Patent: 6,309,878


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Summary for Patent: 6,309,878
Title: Glucose-inducible recombinant viral vector
Abstract:A defective recombinant virus including at least one heterologous gene controlled by a glucose-inducible expression signal, a pharmaceutical composition containing same, and cells transformed using said vector, are disclosed.
Inventor(s): Chen; Ruihuan (New York, NY), Doiron; Bruno (Champs sur Marne, FR), Kahn; Axel (Paris, FR)
Assignee: Institut National de la Sante et de la Recherche Medicale (Paris, FR)
Application Number:08/945,140
Patent Claims:1. A replication defective recombinant virus comprising at least one heterologous gene under the control of an expression signal, wherein the expression signal comprises a glucose-responsive L pyruvate kinase (L-PK) gene promoter sequence.

2. The replication defective recombinant virus according to claim 1, wherein the signal sequence comprises 183 base pairs located at the '5 end of the L-PK gene.

3. The replication defective recombinant virus according to claim 1, wherein the expression signal comprises all or part of the L4 element in SEQ ID NO: 1.

4. A replication defective recombinant virus comprising at least one heterologous gene under the control of an expression signal, wherein the expression signal comprises an L4 element of a promoter of an L-PK gene.

5. The replication defective recombinant virus according to claim 4, wherein the L4 element comprises SEQ ID NO: 2, or a sequence that hybridizes with SEQ ID NO: 2 and interacts with factor MLTF/USF.

6. The replication defective recombinant virus according to claim 4, wherein the L4 element is present as four consecutive repeats.

7. The replication defective recombinant virus according to claim 4, further comprising an L3 element of the promoter of the L-PK gene.

8. The replication defective recombinant virus according to claim 7, wherein the L3 element comprises SEQ ID NO: 3, or a sequence that hybridizes with SEQ ID NO: 3 and interacts with factor HNF4.

9. The replication defective recombinant virus according to claim 1, wherein the expression signal comprises an L4-L3 oligomer comprising an L4 element of the promoter of the L-PK gene fused upstream of an L3 element of the promoter of the L-PK gene.

10. The replication defective recombinant virus according to claim 9, wherein the expression signal comprises four successive L4-L3 oligomers.

11. The replication defective recombinant virus according to claim 1, wherein the expression signal further comprises a minimal promoter.

12. The replication defective recombinant virus according to claim 11, wherein the promoter comprises base pairs -119 to 11 located at the 5' end of the L-PK gene.

13. The replication defective recombinant virus according to claim 1, wherein the expression signal comprises SEQ ID NO: 4, or a derivative thereof.

14. The replication defective recombinant virus according to claim 1, wherein the expression signal further comprises a transcriptional enhancer.

15. The replication defective recombinant virus according to claim 14, wherein the transcriptional enhancer comprises a first intron of a rat aldolase B gene.

16. The replication defective recombinant virus according to claim 1, wherein said virus has a genome lacking at least one region necessary for replication in a target cell.

17. The replication defective recombinant virus according to claim 1, wherein the virus is an adenovirus.

18. The replication defective recombinant virus according to claim 17, wherein the adenovirus is selected from a group consisting of human adenovirus type Ad 2, human adenovirus type Ad 5, and canine adenovirus type CAV-2.

19. The replication defective recombinant virus according to claim 1, wherein the virus is a retrovirus.

20. The replication defective recombinant virus according to claim 19, wherein the retrovirus is a MoMuLV family retrovirus.

21. The replication defective recombinant virus according to claim 1, wherein the heterologous gene encodes insulin or a variant thereof.

22. An isolated mammalian cell infected with at least one replication defective recombinant virus according to claim 1.

23. The isolated mammalian cell according to claim 22, wherein said cell is a human cell.

24. The isolated mammalian cell according to claim 23, wherein said cell is a hepatocyte of a pancreatic .beta. cell.

Details for Patent 6,309,878

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 ⤷  Try a Trial 2015-04-14
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 ⤷  Try a Trial 2015-04-14
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b Injection 103132 ⤷  Try a Trial 2015-04-14
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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