Polynucleotides containing a stabilizing tail region

Patent metadata

Field	Value
Publication number	US-12109274-B2
Application number	US-201615760686-A
Country	US
Kind code	B2
Filing date	Sep 19, 2016
Priority date	Sep 17, 2015
Publication date	Oct 8, 2024
Grant date	Oct 8, 2024

Abstract

The invention features polynucleotides encoding a polypeptide including a 3′-stabilizing region and having increased stability compared to wild-type polynucleotides.

First claim

What is claimed:

1. A polynucleotide encoding a polypeptide, wherein said polynucleotide comprises:
(a) a 5′-cap structure;
(b) a 5′-UTR;
(c) a coding region encoding the polypeptide;
(d) a 3′-UTR; and
(e) a 3′-stabilizing region comprising 1 to 500 nucleosides, wherein one or more of said nucleosides is an inverted thymidine.

2. The polynucleotide of claim 1 , wherein said polynucleotide further comprises (f) a poly-A region.

3. The polynucleotide of claim 1 , wherein said stabilizing region comprises at least two different nucleosides.

4. The polynucleotide of claim 1 , wherein said stabilizing region comprises 10 nucleosides.

5. The polynucleotide of claim 1 , wherein the 3′-stabilizing region comprises a 5′-terminus, wherein said 5′-terminus of said 3′-stabilizing region is conjugated to the 3′-terminus of said poly-A region.

6. The polynucleotide of claim 1 , wherein said polynucleotide comprises a 3′-terminus, wherein said 3′-stabilizing region comprises said 3′-terminus of said polynucleotide.

7. The polynucleotide of claim 2 , wherein said poly-A region comprises at least one alternative nucleoside.

8. The polynucleotide of claim 3 , wherein at least one nucleoside is 2′-O-methyl-adenosine.

9. The polynucleotide of claim 8 , wherein said stabilizing region comprises the structure:

or a salt thereof;
wherein each X is, independently O or S; and
A represents adenine and T represents thymine.

Assignees

• Modernatx Inc

Inventors

• Butora Gabor
• Fraley Andrew W
• Miracco Edward John
• Nelson Jennifer
• Rhoden Smith Amy
• Stanton Matthew
• Fritz Brian R

Classifications

• C12N15/67

  General methods for enhancing the expression · CPC title

• C07H21/02

  with ribosyl as saccharide radical · CPC title

• C07F9/65586 Primary

  at least one of the hetero rings does not contain nitrogen as ring hetero atom · CPC title

• C07F9/65616

  containing the ring system [IMAGE cpc-sch-C07F-1006.gif] having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs · CPC title

• A61K48/0066 Primary

  Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid · CPC title