Granted Patent
B2
US 12,686,711 · App. 18/595,641 · Granted Jul 21, 2026
DARIC interleukin receptors
Assignee:
Regeneron Pharmaceuticals, Inc.
C07K14/7155A61K35/17A61K38/00A61K40/11A61K40/4217A61P35/00C07K14/70517C07K14/70575C12N5/0636C07K2319/70
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Abstract
The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.
Claims (28)
1 . A polynucleotide encoding a fusion polypeptide, wherein the fusion polypeptide comprises:
(a) a first polypeptide comprising, in the following order:
(i) a first extracellular multimerization domain;
(ii) a first transmembrane domain; and
(iii) an IL-18R1 immune receptor intracellular signaling domain;
(b) a polypeptide cleavage signal; and
(c) a second polypeptide comprising, in the following order:
(i) a second extracellular multimerization domain;
(ii) a second transmembrane domain; and
(iii) an IL-18RAP immune receptor intracellular signaling domain;
wherein the first extracellular multimerization domain comprises an FKBP12-rapamycin binding (FRB) polypeptide and the second extracellular multimerization domain comprises an FK506 binding protein (FKBP12) polypeptide; or
wherein the first extracellular multimerization domain comprises an FKBP12 polypeptide and the second extracellular multimerization domain comprises an FRB polypeptide; and
wherein the fusion polypeptide has a sequence having at least 95% identity to SEQ ID NO: 5.
2 . The polynucleotide of claim 1 , wherein the first multimerization domain and the second multimerization domain associate with a bridging factor, wherein the bridging factor is rapamycin or a rapalog thereof.
3 . The polynucleotide of claim 1 , wherein the FRB polypeptide is FRB T2098L or FRB T89L.
4 . The polynucleotide of claim 1 , wherein:
a) the first transmembrane domain and the second transmembrane domain are independently selected from the group consisting of: a CD4 transmembrane domain, a CD8a transmembrane domain, an amnionless (AMN) transmembrane domain, a CD28 transmembrane domain, a CD154 transmembrane domain, and a CD71 transmembrane domain; or
b) the first transmembrane domain and the second transmembrane domain are independently selected from the group consisting of: a CD4 transmembrane domain and a CD8a transmembrane domain.
5 . The polynucleotide of claim 1 , wherein the polypeptide cleavage signal is a viral self-cleaving polypeptide selected from the group consisting of: a foot-and-mouth disease virus (FMDV) (F2A) peptide, an equine rhinitis A virus (ERAV) (E2A) peptide, a Thosea asigna virus (TaV) (T2A) peptide, a porcine teschovirus-1 (PTV-1) (P2A) peptide, a Theilovirus 2A peptide, and an encephalomyocarditis virus 2A peptide.
6 . The polynucleotide of claim 1 , wherein the first multimerization domain localizes extracellularly when the first polypeptide is expressed and the second multimerization domain localizes extracellularly when the second polypeptide is expressed.
7 . A polynucleotide encoding a fusion polypeptide comprising the amino acid sequence of SEQ ID NO: 5.
8 . A vector comprising the polynucleotide of claim 1 .
9 . A vector comprising the polynucleotide of claim 2 .
10 . A vector comprising the polynucleotide of claim 3 .
11 . A vector comprising the polynucleotide of claim 4 .
12 . A vector comprising the polynucleotide of claim 5 .
13 . A vector comprising the polynucleotide of claim 6 .
14 . A vector comprising the polynucleotide of claim 7 .
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 29, 2024
From: 2SEVENTY BIO, INC.
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 067254/0623 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 26, 2024
From: LEUNG, WAI-HANG
To: BLUEBIRD BIO, INC.
Reel/Frame 067233/0157 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 26, 2024
From: BLUEBIRD BIO, INC.
To: 2SEVENTY BIO, INC.
Reel/Frame 067240/0063 →
Continuity (3)
Provisional Application
62598923
· Dec 14, 2017
Related Publication
20240287157A1
· Aug 29, 2024
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