Heteromultimeric proteins and methods of use thereof
AssigneeAb Studio Inc.
InventorsYue Liu, Jianbo Dong, Bo Wang
Life of this patent
Estimating the term…
Abstract
The present application provides heteromultimeric proteins, such as bispecific antibodies, comprising a first antibody heavy chain constant domain 3 (CH3)-containing polypeptide having a substitution relative to a wildtype CH3 domain at amino acid position 354 with a bulky hydrophobic amino acid, and/or a second CH3-containing polypeptide comprising a substitution relative to a wildtype CH3 domain at ammo acid position 347 with a negatively charged amino acid residue. Also provided are polypeptides, nucleic acids and vectors encoding such polypeptides, pharmaceutical compositions, methods of preparation and methods of treatment using the heteromultimeric proteins.
Claims19
A heteromultimeric protein comprising a first polypeptide comprising a first IgG heavy chain constant domain 3 (CH3) domain and a second polypeptide comprising a second IgG CH3 domain, wherein the first IgG CH3 domain comprises a substitution relative to a wildtype IgG CH3 domain at position 354 with an aromatic hydrophobic amino acid, and the second IgG CH3 domain comprises a substitution relative to a wildtype IgG CH3 domain at amino acid position 347 with a negatively charged amino acid, wherein the first IgG CH3 domain comprises a lysine (K) at amino acid position 360, and wherein the amino acid residue numbering is based on EU numbering.
A method of generating a heteromultimeric protein that specifically binds to a first target and a second target, comprising:
- (a) providing a first polypeptide comprising a first binding domain that specifically binds to the first target, and a first IgG CH3 domain;
- and
- (b) providing a second polypeptide comprising a second binding domain that specifically binds to the second target, and a second IgG CH3 domain;
- wherein:
- (i) the first IgG CH3 domain comprises a substitution relative to a wildtype IgG CH3 domain at position 354 with an aromatic hydrophobic amino acid, wherein the first IgG CH3 domain comprises a lysine (K) at amino acid position 360, and the second IgG CH3 domain comprises a substitution relative to a wildtype IgG CH3 domain at amino acid position 347 with a negatively charged amino acid;
- or
- (ii) the first IgG CH3 domain comprises a substitution relative to a wildtype IgG CH3 domain at position 347 with a negatively charged amino acid, and the second IgG CH3 domain comprises a substitution relative to a wildtype IgG CH3 domain at amino acid position 354 with an aromatic hydrophobic amino acid, wherein the second IgG CH3 domain comprises a lysine (K) at amino acid position 360;
- and wherein the amino acid residue numbering is based on EU numbering.
Dependencies are inferred from the claim text.