IP Library › Granted Patent US 12,480,117
Granted Patent B2
US 12,480,117 · App. 17/442,212 · Granted Nov 25, 2025

Compositions comprising modified circular polyribonucleotides and uses thereof

Inventors: Avak Kahvejian (Lexington, MA); Nicholas McCartney Plugis (Cohasset, MA); Alexandra Sophie De Boer (Somerville, MA); Ki Young Paek (Brighton, MA)
Assignee: Flagship Pioneering Innovations VI, LLC
C12N15/113C12N15/85C12N2310/113C12N2310/532C12N2840/203
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Quick Facts
Patent No.
US 12,480,117
App. No.
17/442,212
Granted
Nov 25, 2025
Kind
B2
Abstract

This invention relates generally to pharmaceutical compositions and preparations of modified circular polyribonucleotides and uses thereof.

Claims (18)

1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and a hybrid modified circular polyribonucleotide, wherein the hybrid modified circular polyribonucleotide comprises a first portion of contiguous nucleotides comprising an internal ribosome entry site (IRES) consisting of unmodified nucleotides and a second portion of contiguous nucleotides consisting of cytidines, adenine, guanine, and modified uridines.

2 . The pharmaceutical composition of claim 1 , wherein the circular polyribonucleotide is translationally competent.

3 . The pharmaceutical composition of claim 1 , wherein the hybrid modified circular polyribonucleotide has a higher half-life than a corresponding unmodified circular polyribonucleotide.

4 . The pharmaceutical composition of claim 1 , wherein the modified uridines comprise 5-aza-uridine, 2-thio-5-aza-uridine, 2-thiouridine, 4-thio-pseudouridine, 2-thio-pseudouridine, 5-hydroxyuridine, 3-methyluridine, 5-carboxymethyl-uridine, 1-carboxymethyl-pseudouridine, 5-propynyl-uridine, 1-propynyl-pseudouridine, 5-taurinomethyluridine, 1-taurinomethyl-pseudouridine, 5-taurinomethyl-2-thio-uridine, 1-taurinomethyl-4-thio-uridine, 5-methyl-uridine, 1-methyl-pseudouridine, 4-thio-1-methyl-pseudouridine, 2-thio-1-methyl-pseudouridine, 1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-1-deaza-pseudouridine, dihydrouridine, dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxyuridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, or 4-methoxy-2-thio-pseudouridine.

5 . The pharmaceutical composition of claim 1 , wherein the hybrid modified circular polyribonucleotide comprises a binding site consisting of unmodified nucleotides configured to bind to a protein, peptide, biomolecule, DNA, RNA, or a cell target.

6 . The pharmaceutical composition of claim 1 , wherein the hybrid modified circular polyribonucleotide comprises one or more expression sequences.

7 . The pharmaceutical composition of claim 1 , wherein the hybrid modified circular polyribonucleotide has a lower immunogenicity than a corresponding unmodified circular polyribonucleotide.

8 . The pharmaceutical composition of claim 1 , wherein the modified uridines are pseudouridine.

9 . The pharmaceutical composition of claim 8 , wherein the modified uridines are N1-methyl-pseudouridine.

10 . A method of decreasing immunogenicity of a circular polyribonucleotide in a subject comprising:

administering the pharmaceutical composition of claim 1 to the subject; and

obtaining decreased immunogenicity for the hybrid modified circular polyribonucleotide compared to a corresponding unmodified circular polyribonucleotide in a cell or tissue of the subject.

11 . A method of expressing one or more expression sequences in a subject comprising:

administering the pharmaceutical composition of claim 1 to the subject; and

obtaining increased expression of the one or more expression sequences compared to expression of a corresponding one or more expression sequences in a fully modified circular polyribonucleotide counterpart in a cell or tissue of the subject.

12 . A method of increasing stability of a circular polyribonucleotide in a subject comprising:

administering the pharmaceutical composition of claim 1 to the subject; and

obtaining increased stability for the hybrid modified circular polyribonucleotide compared to a corresponding unmodified circular polyribonucleotide in a cell or tissue of the subject.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2022
From: FLAGSHIP PIONEERING, INC.
To: FLAGSHIP PIONEERING INNOVATIONS VI, LLC
Reel/Frame 060001/0253 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2022
From: CIFUENTES-ROJAS, CATHERINE; PAEK, KI YOUNG
To: VL50, INC.
Reel/Frame 060000/0986 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2022
From: KAHVEJIAN, AVAK; PLUGIS, NICHOLAS MCCARTNEY; DE BOER, ALEXANDRA SOPHIE
To: FLAGSHIP PIONEERING, INC.
Reel/Frame 060001/0087 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2022
From: VL50, INC.
To: FLAGSHIP PIONEERING, INC.
Reel/Frame 060001/0123 →
Continuity (2)
Provisional Application 62823573 · Mar 25, 2019
Related Publication 20230072532A1 · Mar 9, 2023
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