US 11,879,004 B2
Modified binding polypeptides for optimized drug conjugation
Qun Zhou, Ashland, MA (US); Sunghae Park, Waban, MA (US); Huawei Qiu, Westborough, MA (US); Marie-Priscille Brun, Paris (FR); and Francis Duffieux, Paris (FR)
Assigned to GENZYME CORPORATION, Cambridge, MA (US)
Filed by GENZYME CORPORATION, Cambridge, MA (US)
Filed on Feb. 26, 2021, as Appl. No. 17/187,039.
Claims priority of provisional application 62/982,943, filed on Feb. 28, 2020.
Prior Publication US 2021/0292391 A1, Sep. 23, 2021
Int. Cl. C07K 16/00 (2006.01); A61K 47/68 (2017.01)
CPC C07K 16/00 (2013.01) [A61K 47/6803 (2017.08); C07K 2317/14 (2013.01); C07K 2317/52 (2013.01); C07K 2317/56 (2013.01); C07K 2317/94 (2013.01)] 26 Claims
1. An antigen-binding protein or an antigen-binding fragment thereof, comprising an antigen-binding domain and an antibody heavy chain constant (CH) domain comprising a double-engineered cysteine reactive amino acid residue at positions selected from the group consisting of: K274C and A339C, K274C and K360C, K274C and N384C, K274C and G385C, K274C and V422C, and K274C and S440C, according to the numbering of the EU index of Kabat, wherein the cysteine reactive amino acid residue is conjugated to a ligand via a linker, wherein the ligand comprises polyethylene glycol (PEG), a diagnostic agent, or a drug, and wherein the antigen-binding protein comprises a ligand to antibody ratio (LAR) of at least 3.0.