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US 2025/0034224 A1Published application
Novel il2 agonists and methods of use thereof
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsJiaxi WU, Tong ZHANG, Maria del Pilar MOLINA-PORTELA, Eric Smith, Chia-Yang LIN, Thomas Craig Meagher
Life of this patent
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Abstract
The present disclosure relates to IL2 agonists with improved therapeutic profiles.
Claims21
1-80. (canceled)
A nucleic acid or a plurality of nucleic acids encoding a heterodimer, the heterodimer comprising:
- (a) a first polypeptide chain comprising, in N- to C-terminal orientation:
- (i) a peptide-MHC (pMHC) complex comprising a class I α heavy chain human HLA-A2 sequence and a viral peptide, the viral peptide comprising the amino acid sequence of HPV 16E7 (11-19), HPV 16E7 (82-90), CMV pp65 (495-503), NY-ESO-1 (157-165) mutant C165V, WT-1 (126-134), or Tyrosinase (369-377);
- and
- (ii) a first Fc domain;
- and
- (b) a second polypeptide chain comprising, in N- to C-terminal orientation:
- (i) an IL2 domain comprising an amino acid sequence having at least about 90% sequence identity to SEQ ID NO:2;
- and
- (ii) a second Fc domain capable of heterodimerizing with the first Fc domain.
6 more elements
A host cell engineered to express a heterodimer, the heterodimer comprising:
- (a) a first polypeptide chain comprising, in N- to C-terminal orientation:
- (i) a peptide-MHC (pMHC) complex comprising a class I α heavy chain human HLA-A2 sequence and a viral peptide, the viral peptide comprising the amino acid sequence of HPV 16E7 (11-19), HPV 16E7 (82-90), CMV pp65 (495-503), NY-ESO-1 (157-165) mutant C165V, WT-1 (126-134), or Tyrosinase (369-377);
- and
- (ii) a first Fc domain;
- and
- (b) a second polypeptide chain comprising, in N- to C-terminal orientation:
- (i) an IL2 domain comprising an amino acid sequence having at least about 90% sequence identity to SEQ ID NO:2;
- and
- (ii) a second Fc domain capable of heterodimerizing with the first Fc domain.
6 more elements
A method of treating cancer, comprising administering to a subject in need thereof:
- (a) chimeric antigen receptor (“CAR”) T cells (“CAR-T cells”);
- and
- (b) a heterodimer comprising:
- (i) a first polypeptide chain comprising, in N- to C-terminal orientation:
- (1) a peptide-MHC (pMHC) complex comprising a class I α heavy chain human HLA-A2 sequence and a viral peptide, the viral peptide comprising the amino acid sequence of HPV 16E7 (11-19), HPV 16E7 (82-90), CMV pp65 (495-503), NY-ESO-1 (157-165) mutant C165V, WT-1 (126-134), or Tyrosinase (369-377);
- and (2) a first Fc domain;
- and
- (ii) a second polypeptide chain comprising, in N- to C-terminal orientation:
- (1) an IL2 domain comprising an amino acid sequence having at least about 90% sequence identity to SEQ ID NO:2;
- and (2) a second Fc domain capable of heterodimerizing with the first Fc domain.
7 more elements
Dependencies are inferred from the claim text.