US 12,227,591 B2
Antigen-binding constructs targeting HER2
Eric Escobar-Cabrera, Burnaby (CA); and Leonard G. Presta, San Francisco, CA (US)
Assigned to Zymeworks BC Inc., Vancouver (CA)
Filed by Zymeworks BC Inc., Vancouver (CA)
Filed on May 3, 2021, as Appl. No. 17/306,241.
Application 17/306,241 is a division of application No. 15/572,364, granted, now 11,028,182, previously published as PCT/CA2016/050546, filed on May 13, 2016.
Claims priority of provisional application 62/161,114, filed on May 13, 2015.
Claims priority of provisional application 62/267,247, filed on Dec. 14, 2015.
Prior Publication US 2021/0395388 A1, Dec. 23, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/32 (2006.01); A61P 35/00 (2006.01); G01N 33/574 (2006.01)
CPC C07K 16/32 (2013.01) [A61P 35/00 (2018.01); G01N 33/57415 (2013.01); G01N 33/57446 (2013.01); G01N 33/57492 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/35 (2013.01); C07K 2317/526 (2013.01); C07K 2317/55 (2013.01); C07K 2317/565 (2013.01); C07K 2317/567 (2013.01); C07K 2317/64 (2013.01); C07K 2317/73 (2013.01); C07K 2317/77 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01); G01N 2333/71 (2013.01)] 19 Claims
 
1. An antigen-binding construct comprising a variant first antigen-binding polypeptide construct which monovalently binds a first HER2 ECD2 (human epidermal growth factor receptor 2 extracellular domain 2) antigen, the variant first antigen-binding polypeptide construct comprising
a variable heavy (VH) domain comprising a complementary determining region (CDR) 1 (CDR-H1) comprising the sequence as set forth in SEQ ID NO: 956, a CDR-H2 comprising the sequence as set forth in SEQ ID NO: 957, and a CDR-H3 comprising the sequence as set forth in SEQ ID NO: 958; and
a variable light (VL) domain comprising a CDR-L1 comprising the sequence as set forth in SEQ ID NO: 959, a CDR-L2 comprising the sequence as set forth in SEQ ID NO: 960, and a CDR-L3 comprising the sequence as set forth in SEQ ID NO: 609;
and wherein the Glycine at position 56 of CDR-H2 has been substituted with a Tyrosine (H_G56Y) or a Phenylalanine (H_G56F), or the Serine at position 99 of CDR-H3 has been substituted with a Tryptophan (H_S99W), numbering according to Kabat numbering system;
optionally wherein the variant first antigen-binding polypeptide construct comprises H_G56Y and further comprises the following substitution or set of substitutions relative to the VH domain as set forth in SEQ ID NO: 2 and the VL domain as set forth in SEQ ID NO: 11, numbering according to Kabat numbering system;
H_K75W; or
H_T30Q; or
H_T30Y; or
H_S99W; or
L_Y49W; or
L_Y96G; or
H_S99W and L_Y49W; or
L_Y49W and L_Y96G; or
H_T30Q and L_Y49W; or
H_T30Q and H_S99W; or
H_T30Q and L_Y96G; or
H_T30Y and L_Y49W; or
H_T30Q and H_S99W and L_Y49W; or
H_T30Q and L_Y49W and L_Y96G; and
 optionally wherein the variant first antigen-binding polypeptide construct comprises H_S99W and further comprises the following substitution or set of substitutions relative to the VH domain as set forth in SEQ ID NO: 2 and the VL domain as set forth in SEQ ID NO: 11, numbering according to Kabat numbering system;
H_K75W; or
H_T30Q; or
H_K75E; or
H_T30Y; or
H_K75W and L_Y49W; or
H_T30Q and H_K75W; or
H_T30Q and L_Y49W; or
H_T30Q and H_K75W and L_Y49W; or
H_K75W and L Y49W and L_Y96G; or
H_T30Q and H_K75W and L_Y96G; or
H_T30Q and L_Y49W and L_Y96G; or
H_T30Q and H_G56Y and L_Y49W.