Granted Patent
B2
US 12,577,547 · App. 17/311,455 · Granted Mar 17, 2026
PDCD-1 homing endonuclease variants
Inventors:
Jordan Jarjour (Seattle, WA); Kyle Havens (Seattle, WA); Jasdeep Mann (Lake Forest Park, WA)
Assignee:
REGENERON PHARMACEUTICALS, INC.
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Abstract
The present disclosure provides improved homing endonuclease variants and megaTALs reprogrammed to bind and cleave the PDCD-1 gene.
Claims (18)
1 . A polypeptide comprising an I-OnuI homing endonuclease (HE) variant, wherein the polypeptide comprises an amino acid sequence at least 98% identical to the amino acid sequence set forth in SEQ ID NO: 6.
2 . The polypeptide of claim 1 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 6.
3 . The polypeptide of claim 1 , wherein the polypeptide binds and cleaves a target site in the human programmed cell death 1 (PDCD-1) gene, and wherein the target site is SEQ ID NO: 8.
4 . The polypeptide of claim 2 , wherein the polypeptide binds and cleaves a target site in the human programmed cell death 1 (PDCD-1) gene, and wherein the target site is SEQ ID NO: 8.
5 . The polypeptide of claim 1 , further comprising a TALE DNA binding domain, wherein the polypeptide binds and cleaves a target site in the human PDCD-1 gene, wherein the target site is SEQ ID NO: 10.
6 . The polypeptide of claim 5 , wherein the TALE DNA binding domain comprises about 9.5 TALE repeat units to about 15.5 TALE repeat units.
7 . The polypeptide of claim 5 , wherein the TALE DNA binding domain binds the polynucleotide sequence set forth in SEQ ID NO: 9.
8 . The polypeptide of claim 5 , wherein the I-OnuI HE variant comprises the amino acid sequence set forth in SEQ ID NO: 6.
9 . The polypeptide of claim 5 , wherein the polypeptide comprises an amino acid sequence at least 98% identical to the amino acid sequence set forth in SEQ ID NO: 7.
10 . The polypeptide of claim 9 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 7.
11 . The polypeptide of claim 1 , wherein the I-Onul HE variant comprises the following amino acid residues: 14T, 26G, 28S, 30L, 32R, 34R, 35G, 36T, 37A, 38R, 40H, 42R, 44S, 46T, 48M, 68S, 70L, 72N, 75H, 76Y, 80V, 82Y, 83A, 138M, 143N, 153V, 156R, 159P, 168G, 178D, 180S, 184R, 186R, 189N, 190V, 191N, 192A, 193R, 195R, 201E, 203S, 207R, 223H, 225Y, 227G, 232R, 236Q, 238R, 240E, 261M, and 300R in relation to the amino acid sequence set forth in SEQ ID NO: 6.
12 . The polypeptide of claim 11 , wherein the polypeptide comprises an amino acid sequence at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 6.
13 . The polypeptide of claim 11 , wherein the polypeptide binds and cleaves a target site in the human programmed cell death 1 (PDCD-1) gene, and wherein the target site is SEQ ID NO: 8.
14 . The polypeptide of claim 11 , further comprising a TALE DNA binding domain.
15 . The polypeptide of claim 14 , wherein the polypeptide comprises an amino acid sequence at least 98% identical to the amino acid sequence set forth in SEQ ID NO: 7.
16 . The polypeptide of claim 14 , wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 7.
17 . The polypeptide of claim 14 , wherein the polypeptide binds and cleaves a target site in the human PDCD-1 gene, wherein the target site is SEQ ID NO: 10.
18 . The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 6.
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 25, 2024
From: 2SEVENTY BIO, INC.
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 067822/0847 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 14, 2021
From: BLUEBIRD BIO, INC.
To: 2SEVENTY BIO, INC.
Reel/Frame 057683/0099 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 1, 2021
From: JARJOUR, JORDAN; HAVENS, KYLE; MANN, JASDEEP
To: BLUEBIRD BIO, INC.
Reel/Frame 056738/0293 →
Continuity (2)
Provisional Application
62777471
· Dec 10, 2018
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