US 12,357,701 B2
Anti-HER2 biparatopic antibody-drug conjugates and methods of use
Kevin Hamblett, Seattle, WA (US); Rupert H. Davies, Seattle, WA (US); James R. Rich, Vancouver (CA); Gerald J. Rowse, New Westminster (CA); Vincent K. C. Fung, Vancouver (CA); and Stuart D. Barnscher, Vancouver (CA)
Assigned to Zymeworks BC Inc., Vancouver (CA)
Filed by Zymeworks BC Inc., Vancouver (CA)
Filed on Mar. 23, 2021, as Appl. No. 17/210,081.
Application 17/210,081 is a division of application No. 16/594,728, filed on Oct. 7, 2019, granted, now 11,000,598.
Application 16/594,728 is a continuation of application No. PCT/CA2019/050303, filed on Mar. 12, 2019.
Claims priority of provisional application 62/743,884, filed on Oct. 10, 2018.
Claims priority of provisional application 62/658,477, filed on Apr. 16, 2018.
Claims priority of provisional application 62/642,483, filed on Mar. 13, 2018.
Prior Publication US 2021/0346508 A1, Nov. 11, 2021
Int. Cl. A61K 47/64 (2017.01); A61K 47/65 (2017.01); A61K 47/68 (2017.01); A61P 35/00 (2006.01); C07K 16/30 (2006.01); C07K 16/32 (2006.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01)
CPC A61K 47/6425 (2017.08) [A61K 47/65 (2017.08); A61K 47/6817 (2017.08); A61K 47/6855 (2017.08); A61K 47/6857 (2017.08); A61K 47/6863 (2017.08); A61K 47/6869 (2017.08); A61P 35/00 (2018.01); C07K 16/3015 (2013.01); C07K 16/3023 (2013.01); C07K 16/3046 (2013.01); C07K 16/3069 (2013.01); C07K 16/32 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/526 (2013.01); C07K 2317/55 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01)] 33 Claims
OG exemplary drawing
 
1. A method of treating a HER2-expressing cancer comprising administering to a subject having a HER2-expressing cancer an effective amount of an antibody-drug conjugate comprising an anti-HER2 biparatopic antibody conjugated to an auristatin analogue via a linker (L) at a low average drug-to-antibody ratio (DAR),
wherein the anti-HER2 biparatopic antibody comprises a first antigen-binding polypeptide construct comprising the CDR sequences set forth in SEQ ID NOs: 67, 68, 69, 70, 71 and 72, and a second antigen-binding polypeptide construct comprising the CDR sequences set forth in SEQ ID NOs: 27, 28, 29, 39, 40 and 41, wherein the auristatin analogue and linker have general Formula (X):

OG Complex Work Unit Chemistry
wherein:
R1 is

OG Complex Work Unit Chemistry
L is a protease-cleavable linker, and
custom character represents the point of attachment of the linker to the anti-HER2 biparatopic antibody, and
wherein the low average DAR is an average DAR of between 1.5 and 2.5.