IP Library › Granted Patent US 9,657,311
Granted Patent B2
US 9,657,311 · App. 14/287,699 · Granted May 23, 2017

Lentiviral vectors containing an MHC class I, MHC class II, or B2 microglobulin upstream promoter sequence

Inventors: Cecile Bauche (Paris, FR); Emeline Sarry (Malakoff, FR)
Assignee: THERAVECTYS
C12N15/86C12N2740/16043C12N2830/30C12N2830/85
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Quick Facts
Patent No.
US 9,657,311
App. No.
14/287,699
Granted
May 23, 2017
Kind
B2
Abstract

The present invention relates to the insertion of an MHC class I, MHC Class II, or β2 microglobulin upstream promoter sequence into a lentiviral vector to increase viral titers. The invention encompasses these vectors, methods of making the vectors, and methods of using them, including medicinal uses.

Claims (26)

1. A lentiviral expression vector comprising:

(i) 300-1100 nucleotides of an MHC class I, MHC Class II, or β2 microglobulin upstream promoter sequence, and

(ii) a transgene sequence under control of an MHC class I or β2 microglobulin promoter,

wherein the MHC class I, MHC Class II, or β2 microglobulin upstream promoter sequence is selected from the group consisting of a β2 microglobulin upstream promoter sequence, an HLA-A2 upstream promoter sequence, HLA-B7 upstream promoter sequence, an HLA-E upstream promoter sequence and an HLA-DRα upstream promoter sequence.

2. The lentiviral vector of claim 1 , comprising 300-600 nucleotides of an MHC class I or β2 microglobulin upstream promoter sequence.

3. The lentiviral vector of claim 1 , comprising 300-400 nucleotides of an MHC class I or β2 microglobulin upstream promoter sequence.

4. The lentiviral vector of claim 1 , wherein the upstream promoter sequence is in the same orientation as the MHC class I or β2 microglobulin promoter.

5. The lentiviral vector of claim 1 , wherein the upstream promoter sequence is an MHC class I upstream promoter sequence selected from the group consisting of an HLA-A2 upstream promoter sequence, an HLA-B7 upstream promoter sequence and an HLA-E upstream promoter sequence.

6. The lentiviral vector of claim 1 , wherein the upstream promoter sequence is a β2 microglobulin upstream promoter sequence.

7. The lentiviral vector of claim 6 , wherein the upstream promoter sequence comprises the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:27.

8. The lentiviral vector of claim 1 , wherein the promoter is an MHC class I promoter.

9. The lentiviral vector of claim 1 , wherein the promoter is a β2 microglobulin promoter.

10. An isolated host cell comprising the lentiviral vector of claim 1 .

11. The lentiviral vector of claim 1 , wherein the upstream promoter sequence comprises the nucleotide sequence of any one of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36.

12. A method for producing the lentiviral expression vector of claim 1 comprising inserting 300-1100 nucleotides of an MHC class I, MHC Class II, or β2 microglobulin upstream promoter sequence into a lentiviral vector,

wherein the MHC class I, MHC Class II, or β2 microglobulin upstream promoter sequence is selected from the group consisting of a β2 microglobulin upstream promoter sequence, an HLA-A2 upstream promoter sequence, HLA-B7 upstream promoter sequence, an HLA-E upstream promoter sequence and an HLA-DRα upstream promoter sequence,

and wherein the lentiviral vector comprises a transgene sequence under control of an MHC class I or β2 microglobulin promoter.

13. The method of claim 12 , comprising inserting 300-600 nucleotides of an MHC class I or β2 microglobulin upstream promoter sequence into a lentiviral vector.

14. The method of claim 12 , comprising inserting 300-400 nucleotides of an MHC class I or β2 microglobulin upstream promoter sequence into a lentiviral vector.

15. The method of claim 12 , wherein the upstream promoter sequence is inserted in the same orientation as the MHC class I or β2 microglobulin promoter.

16. The method of claim 12 , wherein the upstream promoter sequence is an MHC class I upstream promoter sequence selected from the group consisting of an HLA-A2 upstream promoter sequence, an HLA-B7 upstream promoter sequence and an HLA-E upstream promoter sequence.

17. The method of claim 12 , wherein the upstream promoter sequence is a β2 microglobulin upstream promoter sequence.

18. The method of claim 17 , wherein the upstream promoter sequence comprises the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:27.

19. The method of claim 12 , wherein the promoter is an MI-IC class I promoter.

20. The method of claim 12 , wherein the promoter is a β2 microglobulin promoter.

21. The method of claim 12 , wherein the upstream promoter sequence comprises the nucleotide sequence of any one of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 28, 2014
From: BAUCHE, CECILE; SARRY, EMELINE
To: THERAVECTYS
Reel/Frame 032980/0475 →
Priority Claims (1)
EP 13305738 · Jun 3, 2013 · regional
Continuity (1)
Related Publication 20140356946A1 · Dec 4, 2014