# US 12,109,274 B2 · Polynucleotides containing a stabilizing tail region

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- Number: US 12,109,274 B2
- Document ID: US12109274B2
- Status: Granted
- Kind: B2
- Application number: 15/760,686
- Filed: 2016-09-19
- Published: 2018-09-13
- Granted: 2024-10-08
- Earliest claimed: 2015-09-17
- Assignees: ModernaTX, Inc.
- Applicants: ModernaTX, Inc.
- Inventors: Gabor Butora; Andrew W. Fraley; Edward John Miracco; Jennifer Nelson; Amy Rhoden Smith; Matthew Stanton; Brian R. Fritz
- Web page: https://patentgrep.com/patent/US12109274B2

## CPC

- A61K 48/0066: {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}
- C07F 9/65586: {at least one of the hetero rings does not contain nitrogen as ring hetero atom}
- C07F 9/65616: {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}
- C07H 21/02: with ribosyl as saccharide radical
- C12N 15/67: General methods for enhancing the expression
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

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

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 2)

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

### Claim 8 (depends on 3)

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

### Claim 9 (depends on 8)

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.