Patent ID: 11965019
Assignee: ZYMEWORKS BC INC.
Field: Biotechnology (Chemistry)
Classification: CPC A  C | IPC C

Claim 0:
1. A chimeric heterodimer comprising:
a) a first immunoglobulin heavy chain polypeptide construct (H1) comprising a human heavy chain constant domain 1 (CH1) sequence and a human or mouse heavy chain variable domain (VH) sequence, and
b) a first chimeric immunoglobulin light chain polypeptide construct (L1) comprising a human kappa light chain constant domain (Ckappa) IGKC*01 sequence having the amino acid sequence set forth in SEQ ID NO: 31 and a human or mouse lambda light chain variable domain (Vlambda) sequence,
the Vlambda sequence comprising one or more stabilizing amino acid modifications that increase the melting temperature of the chimeric heterodimer compared to a corresponding wild-type chimeric heterodimer without the stabilizing amino acid modifications, as measured by differential scanning calorimetry (DSC) or differential scanning fluorimetry (DSF),
wherein H1 and L1 form a first Fab region that binds to a first epitope,
wherein the melting temperature of the first Fab region without the stabilizing amino acid modifications is decreased compared to the Fab region of a corresponding parental wild-type antibody,
wherein the one or more stabilizing amino acid modifications comprise a substitution at residue 83, residue 85, or at both residues, wherein residue 83 is substituted with F, V, I, or A, and residue 85 is substituted with T or V; and
wherein the numbering of amino acid residues is according to Kabat.