Granted Patent
B2
US 12,539,309 · App. 17/898,947 · Granted Feb 3, 2026
Compositions comprising circular polyribonucleotides and uses thereof
Inventors:
Avak Kahvejian (Lexington, MA); Nicholas McCartney Plugis (Duxbury, MA); Alexandra Sophie De Boer (Somerville, MA)
Assignee:
Flagship Pioneering Innovations VI, LLC
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Abstract
This invention relates generally to pharmaceutical compositions and preparations of circular polyribonucleotides and uses thereof.
Claims (69)
1 . A pharmaceutical composition for expression of a first hormone and a second hormone comprising:
(a) a lipid nanoparticle carrier;
(b) a covalently closed polyribonucleotide that comprises, in the following order:
(i) a first internal ribosome entry site (IRES);
(ii) a first expression sequence that encodes the first hormone;
(iii) a second IRES; and
(iv) a second expression sequence that encodes the second hormone; and
(c) a pharmaceutically acceptable excipient.
2 . The pharmaceutical composition of claim 1 wherein the covalently closed polyribonucleotide:
(a) lacks one or both of a 5′ cap and a 3′ poly A sequence;
(b) is detectable in-vivo for at least 7 days after administration of the composition to the human; or
(c) further comprises a miRNA target sequence, a miRNA binding site, or a protein binding site.
3 . The pharmaceutical composition of claim 1 , wherein the first IRES is an encephalomyocarditis virus (EMCV) IRES or a coxsackievirus B3 (CVB3) IRES.
4 . The pharmaceutical composition of claim 1 , wherein the second IRES is an EMCV IRES or a CVB3 IRES.
5 . The pharmaceutical composition of claim 1 , wherein the first hormone and the second hormone are the same.
6 . The pharmaceutical composition of claim 1 , wherein the first hormone and the second hormone are different.
7 . The pharmaceutical composition of claim 1 , wherein the first hormone or the second hormone is less than 300 amino acids in length.
8 . The pharmaceutical composition of claim 1 , wherein the covalently closed polyribonucleotide comprises, in the following order:
(i) a first spacer sequence;
(ii) the first IRES;
(iii) the first expression sequence that encodes the first hormone;
(iv) a second spacer;
(v) the second IRES; and
(vi) the second expression sequence that encodes the second hormone.
9 . The pharmaceutical composition of claim 8 , wherein the covalently closed polyribonucleotide comprises, in the following order:
(i) the first spacer sequence;
(ii) the first IRES;
(iii) the first expression sequence that encodes the first hormone;
(iv) the second spacer;
(v) the second IRES;
(vi) the second expression sequence that encodes the second hormone; and
(vii) a third spacer.
10 . The pharmaceutical composition of claim 1 , wherein the covalently closed polyribonucleotide comprises, in the following order:
(i) a first spacer sequence;
(ii) the first IRES;
(iii) the first expression sequence that encodes the first hormone;
(iv) the second IRES;
(v) the second expression sequence that encodes the second hormone; and
(vi) a second spacer.
11 . A pharmaceutical composition for expression of a first hormone and a second hormone, comprising:
(a) a lipid nanoparticle carrier;
(b) a covalently closed polyribonucleotide comprising, in the following order:
(i) an IRES;
(ii) a first expression sequence that encodes the first hormone;
(iii) a stagger element; and
(iv) a second expression sequence that encodes the second hormone; and
(c) a pharmaceutically acceptable excipient.
12 . The pharmaceutical composition of claim 11 , wherein the covalently closed polyribonucleotide comprises, in the following order:
(i) the IRES;
(ii) a first translation initiation sequence;
(iii) the first expression sequence that encodes the first hormone;
(iv) the stagger element;
(v) a second translation initiation sequence; and
(vi) the second expression sequence that encodes the second hormone.
13 . The pharmaceutical composition of claim 11 , wherein the covalently closed polyribonucleotide comprises, in the following order:
(i) a first spacer sequence;
(ii) the IRES;
(iii) the first expression sequence that encodes the first hormone;
(iv) a second spacer;
(v) the stagger element; and
(vi) the second expression sequence that encodes the second hormone.
14 . The pharmaceutical composition of claim 13 , wherein the covalently closed polyribonucleotide comprises, in the following order:
(i) the first spacer sequence;
(ii) the IRES;
(iii) the first expression sequence that encodes the first hormone;
(iv) the second spacer;
(v) the stagger element;
(vi) the second expression sequence that encodes the second hormone; and
(vii) a third spacer.
Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 12, 2022
From: STEWART, MORAG HELEN; CIFUENTES-ROJAS, CATHERINE; PAEK, KI YOUNG
To: VL50, INC.
Reel/Frame 062051/0522 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 12, 2022
From: KAHVEJIAN, AVAK; PLUGIS, NICHOLAS MCCARTNEY; DE BOER, ALEXANDRA SOPHIE; WEINSTEIN, ERICA GABRIELLE; TROUSIL, SEBASTIAN
To: FLAGSHIP PIONEERING, INC.
Reel/Frame 062051/0529 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 12, 2022
From: VL50, INC.
To: FLAGSHIP PIONEERING, INC.
Reel/Frame 062051/0560 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 12, 2022
From: FLAGSHIP PIONEERING, INC.
To: FLAGSHIP PIONEERING INNOVATIONS VI, LLC
Reel/Frame 062051/0565 →
Continuity (8)
Continuation
PCTUS2018065836
· Dec 14, 2018
Provisional Application
62676688
· May 25, 2018
Provisional Application
62599547
· Dec 15, 2017
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