Claims for Patent: 8,329,462
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Summary for Patent: 8,329,462
Title: | Methods and compositions relating to improved lentiviral vectors and their applications |
Abstract: | The present invention provides HIV-derived lentivectors which are safe, highly efficient, and very potent for expressing transgenes for human gene therapy, especially, in human hematopoietic progenitor cells as well as in all other blood cell derivatives. The lentiviral vectors comprise a self-inactivating configuration for biosaftey and promoters such as the EF1.alpha. promoter as one example. Additional promoters are also described. The vectors can also comprise additional transcription enhancing elements such as the wood chuck hepatitis virus post-transcriptional regulatory element. These vectors therefore provide useful tools for genetic treatments such as inherited and acquired lympho-hematological disorders, gene-therapies for cancers especially the hematological cancers, as well as for the study of hematopoiesis via lentivector-mediated modification of human HSCs. |
Inventor(s): | Trono; Didier (Collonge, CH), Salmon; Patrick (Arenthon, FR) |
Assignee: | Research Development Foundation (Carson City, NV) |
Application Number: | 12/537,789 |
Patent Claims: | 1. A recombinant lentiviral vector comprising: (a) an expression cassette comprising a transgene positioned under the control of a promoter, other than a CMV promoter, that
is active to promote detectable transcription of the transgene at a signal-to-noise ratio of between about 10 and about 200 in both a human hematopoietic progenitor cell and a differentiated hematopoietic cell; and (b) an LTR region that has reduced
promoter activity relative to wild-type LTR, wherein the LTR region has been rendered substantially transcriptionally inactive by virtue of deletions in the U3region of the 3' LTR.
2. The vector of claim 1, wherein the promoter is capable of promoting expression of the transgene at a signal-to-noise ratio of between about 40 and about 200. 3. The vector of claim 2, wherein the promoter is capable of promoting expression of the transgene at a signal-to-noise ratio of between about 150 and about 200. 4. The vector of claim 1, wherein the promoter is an EF1-.alpha. promoter, a PGK promoter, a gp91hox promoter, a MHC classII promoter, a clotting Factor IX promoter, a clotting Factor V111 promoter, an insulin promoter, a PDX1 promoter, a CD11 promoter, a CD4 promoter, a CD2 promoter or a gp47 promoter. 5. The vector of claim 4, wherein the transgene is positioned under the control of the EF1-.alpha. promoter. 6. The vector of claim 4, wherein the transgene is positioned under the control of the PGK promoter. 7. The vector of claim 1, wherein the transgene is erythropoietin, an interleukin, a colony-stimulating factor, integrin .alpha.IIb.beta., a multidrug resistance gene, gp91hox, gp 47, an antiviral gene, a gene coding for blood coagulation factor VIII, a gene coding for blood coagulation factor IX, a T cell antigen receptor, a B cell antigen receptor, a single chain antibodies (ScFv), TNF, gamma interferon, CTLA4, B7, Melana, MAGE. 8. The vector of claim 7, wherein the transgene is gp91hox. 9. The vector of claim 7, wherein the transgene is gp 47. 10. The vector of claim 7, wherein the transgene is Interleukin-2. 11. The vector of claim 7, wherein the transgene is Interleukin-12. 12. The vector of claim 7, wherein the transgene is a gene coding for blood coagulation factor VIII. 13. The vector of claim 7, wherein the transgene is a gene coding for blood coagulation factor IX. 14. The vector of claim 1, further comprising a posttranscriptional regulatory sequence positioned to promote the expression of the transgene. 15. The vector of claim 14, wherein the posttranscriptional regulatory sequence is an intron positioned within the expression cassette. 16. The vector of claim 15, wherein the intron is positioned in an orientation opposite the vector genomic transcript. 17. The vector of claim 14, wherein the posttranscriptional regulatory sequence is a posttranscriptional regulatory element. 18. The vector of claim 17, wherein the posttranscriptional regulatory element is woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). 19. The vector of claim 17, wherein the posttranscriptional regulatory element is hepatitis B virus posttranscriptional regulatory element (HPRE). 20. A host cell transduced with a vector in accordance with claim 1. 21. The host cell of claim 20, wherein the cell is a virus producer cell. 22. The host cell of claim 20, wherein the cell is a stem cell. 23. The host cell of claim 20, wherein the cell is a 293T cell. 24. The host cell of claim 20, wherein the cell is a human hematopoietic progenitor cell. 25. The host cell of claim 24, wherein the human hematopoietic progenitor cell is a CD34.sup.+ cell. |
Details for Patent 8,329,462
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 | 2020-11-13 |
Merck Sharp & Dohme Corp. | INTRON A | interferon alfa-2b | For Injection | 103132 | ⤷ Try a Trial | 2020-11-13 | |
Merck Sharp & Dohme Corp. | INTRON A | interferon alfa-2b | Injection | 103132 | ⤷ Try a Trial | 2020-11-13 | |
>Applicant | >Tradename | >Biologic Ingredient | >Dosage Form | >BLA | >Approval Date | >Patent No. | >Expiredate |
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