You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 29, 2024

Claims for Patent: 9,303,078


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 9,303,078
Title:Nucleic acid molecules and methods for exchanging exon(s) by transsplicing
Abstract: The present invention provided methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated simple or double trans-splicing. The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and to mediate a simple or double trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (Chimeric RNA).
Inventor(s): Garcia; Luis (Bailly, FR), Lorain; Stephanie (Vincennes, FR)
Assignee: ASSOCIATION INSTITUT DE MYOLOGIE (Paris, FR) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) (Paris, FR) INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) (Paris, FR) UNIVERSITE PIERRE ET MARIE CURRIE (PARIS 6) (Paris, FR)
Application Number:13/500,612
Patent Claims:1. A nucleic acid molecule comprising: a) two target binding domains AS and AS' that target the binding of the nucleic acid molecule to a target pre-mRNA, wherein said two target binding domains AS and AS' are located respectively at the 5'-end and at the 3'-end of the nucleic acid molecule, b) a 3' splice region comprising a branch point, a polypyrimidine tract and a 3' splice acceptor site, c) a 5' splice region comprising a 5' splice donor site, d) a spacer sequence that separates said 3' splice region from said 5'-end target binding domain AS, e) a spacer sequence that separates said 5' splice region from said 3'-end target binding domain AS', said spacer comprising a downstream intronic splice enhancer (DISE) and f) a nucleotide sequence to be trans-spliced to said target pre-mRNA, wherein said nucleotide sequence encodes at least a part of a polypeptide, and is located between said 3' splice region and said 5' splice region of said nucleic acid.

2. The nucleic acid molecule according to claim 1, wherein said two target binding domains AS and AS' target binding of said nucleic acid molecule to the pre-mRNA of the dystrophin (DMD) gene, and wherein the nucleotide sequence to be trans-spliced encodes at least a part of the dystrophin polypeptide.

3. The nucleic acid molecule according to claim 2, wherein said nucleotide sequence to be trans-spliced comprises at least one exon of the DMD gene.

4. The nucleic acid molecule according to claim 2, wherein said nucleotide sequence to be trans-spliced comprises at least the sequence of exon 23 of the DMD gene, or the sequence of exon 70 of the DMD gene.

5. The nucleic acid molecule according to claim 4, wherein said nucleotide sequence to be trans-spliced comprises the nucleotide sequence of exon 23 of the human DMD gene as set forth in SEQ ID NO 60.

6. The nucleic acid molecule according to claim 1, wherein each of said target binding domains AS and AS' comprises between 100 and 200 nucleotides.

7. The nucleic acid molecule according to claim 6, wherein each of said target binding domains AS and AS' comprises 150 nucleotides.

8. The nucleic acid molecule according to claim 1, wherein said 5'-end target binding domain AS targets the binding of the nucleic acid to the intron 22 of the pre-mRNA of a DMD gene.

9. The nucleic acid molecule according to claim 1, wherein said 3'-end target binding domain AS' targets the binding of the nucleic acid to the intron 23 of the pre-mRNA of a DMD gene.

10. The nucleic acid molecule according to claim 1, wherein said 5'-end target binding domain AS comprises at least 20 successive nucleotides of at least one nucleotide sequence chosen among: SEQ ID NO 13 and SEQ ID NO 14.

11. The nucleic acid molecule according to claim 1, wherein said 3'-end target binding domain AS' targets the binding of the nucleic acid to a nucleotide sequence located in said 5'-half of the nucleotide sequence of intron 23.

12. The nucleic acid molecule according to claim 11, wherein said 3'-end target binding domain AS' comprises at least 20 successive nucleotides of at least one nucleotide sequence chosen among: SEQ ID NO 16, SEQ ID NO 19, and SEQ ID NO 20.

13. The nucleic acid molecule according to claim 1, wherein said 3'-end target binding domain AS' comprises at least 20 successive nucleotides of the nucleotide sequence as set forth in SEQ ID NO 21.

14. The nucleic acid molecule according to claim 1, wherein each of the two spacers comprises from 10 to 100 nucleotides.

15. The nucleic acid molecule according to claim 14, wherein each of the two spacers comprises from 30 to 50 nucleotides.

16. The nucleic acid molecule according to claim 1, wherein said branch point is a conserved yeast branch point sequence.

17. The nucleic acid molecule according to claim 16, wherein said branch point has the nucleic acid sequence of SEQ ID NO: 25.

18. A recombinant vector comprising said nucleic acid of claim 1.

19. The vector according to claim 18, wherein said vector is an eukaryotic expression vector.

20. A cell comprising said nucleic acid molecule according to claim 1.

21. The cell according to claim 18, wherein said cell is an eukaryotic cell.

22. The nucleic acid molecule according to claim 1, wherein said spacer separating said 5' splice donor site and said 3'-end target binding domain AS' comprises the DISE sequence from the rat FGFR2 gene having the nucleic acid sequence of SEQ ID NO: 27.

Details for Patent 9,303,078

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 2029-10-08
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 ⤷  Try a Trial 2029-10-08
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b Injection 103132 ⤷  Try a Trial 2029-10-08
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.