Phosphate replacement mRNA cap analogs

Patent metadata

Field	Value
Publication number	US-10563195-B2
Application number	US-201816008662-A
Country	US
Kind code	B2
Filing date	Jun 14, 2018
Priority date	Oct 16, 2015
Publication date	Feb 18, 2020
Grant date	Feb 18, 2020

Abstract

The present disclosure relates to cap analogs, which can result in high levels of capping efficiency and transcription and improved translation efficiencies. The present disclosure also relates to methods useful for preparing cap analogs and using mRNA species containing such analogs, as well as kits containing the cap analogs.

First claim

What is claimed is:

1. An RNA molecule having a 5′ end comprising a compound of formula (III):

wherein
B 1 is

R a , R b , and R c are H;
R 1 is CH 3 ;
B 2 is

R d , R e , and R f are H;
X 1 is N or N + (CH 3 );
X 2 is O;
R 20 , R 21 , R 22 , and R 23 are H;
R 27 and R 28 are OH;
R 2 is OR 3 ;
R 3 is H or CH 3 ; and
Y 2 is

wherein

indicates an attachment point.

2. The RNA molecule of claim 1 , wherein X 1 is N.

3. The RNA molecule of claim 1 , wherein R 3 is CH 3 .

4. The RNA molecule of claim 1 , wherein X 1 is N + (CH 3 ).

5. The RNA molecule of claim 1 , wherein R 3 is H.

6. The RNA molecule of claim 1 , wherein R 3 is H and X 1 is N.

7. The RNA molecule of claim 1 , wherein R 3 is H and X 1 is N + (CH 3 ).

8. The RNA molecule of claim 1 , wherein R 3 is CH 3 and X 1 is N + (CH 3 ).

9. The RNA molecule of claim 1 , having a 5′ end comprising

wherein

indicates the attachment point.

10. The RNA molecule of claim 9 , wherein X 1 is N.

11. The RNA molecule of claim 9 , wherein R 3 is CH 3 .

12. The RNA molecule of claim 9 , wherein X 1 is N + (CH 3 ).

13. The RNA molecule of claim 9 , wherein R 3 is H.

14. The RNA molecule of claim 9 , wherein R 3 is H and X 1 is N.

15. The RNA molecule of claim 9 , wherein R 3 is H and X 1 is N + (CH 3 ).

16. The RNA molecule of claim 9 , wherein R 3 is CH 3 and X 1 is N + (CH 3 ).

17. The RNA molecule of claim 1 , having a 5′ end comprising

wherein

indicates the attachment point.

Assignees

• Modernatx Inc

Inventors

• Butora Gabor
• Stanton Matthew
• Steele Thomas

Classifications

• C07H21/02

  with ribosyl as saccharide radical · CPC title

• C12N15/1089 Primary

  Design, preparation, screening or analysis of libraries using computer algorithms · CPC title

• C12N2310/313

  Phosphorodithioates · CPC title

• C07H21/00

  Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids · CPC title

• C12N2310/317

  with an inverted bond, e.g. a cap structure · CPC title