US 12,304,945 B2
Engineered immunoglobulin heavy chain-light chain pairs and uses thereof
Adam Louis Corper, Vancouver (CA); Dunja Urosev, Vancouver (CA); Stacey A. L. Tom-Yew, Coquitlam (CA); Dustin Weyland Blue Bleile, Vancouver (CA); Thomas Spreter Von Kreudenstein, Vancouver (CA); Surjit Dixit, Richmond (CA); Paula Irene Lario, South Vancouver (CA); and Mario Sanches, Vancouver (CA)
Assigned to Zymeworks BC Inc., Vancouver (CA)
Filed by ZYMEWORKS BC INC., Vancouver (CA)
Filed on Jan. 24, 2022, as Appl. No. 17/648,747.
Application 17/648,747 is a division of application No. 16/122,417, filed on Sep. 5, 2018, granted, now 11,286,293.
Application 16/122,417 is a division of application No. 14/648,222, granted, now 10,077,298, previously published as PCT/CA2013/050914, filed on Nov. 28, 2013.
Claims priority of provisional application 61/730,906, filed on Nov. 28, 2012.
Claims priority of provisional application 61/761,641, filed on Feb. 6, 2013.
Claims priority of provisional application 61/818,874, filed on May 2, 2013.
Claims priority of provisional application 61/869,200, filed on Aug. 23, 2013.
Claims priority of application No. PCT/CA2013/050914 (WO), filed on Nov. 28, 2013.
Prior Publication US 2022/0227840 A1, Jul. 21, 2022
Int. Cl. C07K 16/00 (2006.01); C07K 16/28 (2006.01); C07K 16/32 (2006.01); C07K 16/36 (2006.01); G16B 40/00 (2019.01); G16B 40/10 (2019.01)
CPC C07K 16/00 (2013.01) [C07K 16/2863 (2013.01); C07K 16/32 (2013.01); C07K 16/36 (2013.01); G16B 40/00 (2019.02); G16B 40/10 (2019.02); C07K 2317/10 (2013.01); C07K 2317/31 (2013.01); C07K 2317/35 (2013.01); C07K 2317/51 (2013.01); C07K 2317/515 (2013.01); C07K 2317/52 (2013.01); C07K 2317/522 (2013.01); C07K 2317/524 (2013.01); C07K 2317/526 (2013.01); C07K 2317/53 (2013.01); C07K 2317/55 (2013.01); C07K 2317/72 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01)] 20 Claims
 
1. An isolated antigen binding polypeptide construct comprising at least a first heterodimer and a second heterodimer,
the first heterodimer comprising a first immunoglobulin G (IgG) heavy chain polypeptide sequence (H1) and a first immunoglobulin light chain polypeptide sequence (L1), and binding to a first epitope; and
the second heterodimer comprising a second immunoglobulin G (IgG) heavy chain polypeptide sequence (H2) and a second immunoglobulin light chain polypeptide sequence (L2), and binding to a second epitope,
wherein at least one of the H1 or L1 sequences of the first heterodimer is distinct from the corresponding H2 or L2 sequence of the second heterodimer, H1 and H2 each comprise a heavy chain variable domain (VH domain) and a heavy chain constant domain (CH1 domain), and L1 and L2 each comprise a light chain variable domain (VL domain) and a light chain constant domain (CL domain);
wherein H1 preferentially pairs with L1 as compared to L2, and H2 preferentially pairs with L2 as compared to L1;
wherein:
a) H1 comprises amino acid substitution 139W; L1 comprises amino acid substitution 116A, and L2 comprises amino acid substitution 135W;
b) H1 comprises amino acid substitution 139W; L1 comprises amino acid substitutions 116A and 135A; H2 comprises amino acid substitutions 139G and 145L and 179E and 190A, and L2 comprises amino acid substitutions 131R and 135W;
c) H1 comprises amino acid substitution 139W; L1 comprises amino acid substitutions 116S and 135A; H2 comprises amino acid substitutions 139G and 145L and 179E and 190A, and L2 comprises amino acid substitutions 131R and 135W;
d) H1 comprises amino acid substitution 139W; L1 comprises amino acid substitutions 116A and 135A; H2 comprises amino acid substitutions 139G and 190A, and L2 comprises amino acid substitutions 135W and 137A;
e) H1 comprises amino acid substitutions 37W and 139W; L1 comprises amino acid substitutions 98A and 116A and 135A; H2 comprises amino acid substitutions 37A and 103H and 139G and 190A, and L2 comprises amino acid substitutions 44W and 135W;
f) H1 comprises amino acid substitutions 37W and 103H and 139W; L1 comprises amino acid substitutions 98L and 116A and 135A; H2 comprises amino acid substitutions 139G and 190A, and L2 comprises amino acid substitutions 98W and 135W;
g) H1 comprises amino acid substitutions 39R and 139W; L1 comprises amino acid substitutions 38E and 116A and 135V; H2 comprises amino acid substitutions 39E and 139G and 190A, and L2 comprises amino acid substitutions 38R and 135W;
h) H1 comprises amino acid substitution 139W; L1 comprises amino acid substitutions 98W and 116A and 135A; H2 comprises amino acid substitutions 37W and 103H and 139G and 190A, and L2 comprises amino acid substitutions 98L and 135W;
i) H1 comprises amino acid substitutions 39R and 139W; L1 comprises amino acid substitutions 38D and 116A and 135A; H2 comprises amino acid substitutions 39D and 139G and 190A, and L2 comprises amino acid substitutions 38R and 135W;
j) H1 comprises amino acid substitutions 39D and 139W; L1 comprises amino acid substitution 38R and 116A and 135A; H2 comprises amino acid substitutions 39R and 139G and 190A, and L2 comprises amino acid substitutions 38D and 135W;
k) H1 comprises amino acid substitutions 139W and 145Y and 179E; L1 comprises amino acid substitution 116A and 131K and 135A; H2 comprises amino acid substitutions 139G and 190A, and L2 comprises amino acid substitution 135W, or
l) H1 comprises amino acid substitutions 139W and 186K; L1 comprises amino acid substitution 116A and 124E and 135A and 180E; H2 comprises amino acid substitutions 139G and 145T and 146G and 179E and 190A, and L2 comprises amino acid substitution 135W;
wherein when both L1 and L2 are co-expressed with at least one of H1 and H2, the amount of H1-L1 compared to H1-L2 and the amount of H2-L2 compared to H2-L1 is greater than the amount of H1-L1 compared to H1-L2 and the amount of H2-L2 compared to H2-L1 in the absence of the amino acid substitutions,
and wherein the numbering of amino acid residues is according to Kabat.