	US 12,128,102 B2
	Constrained conditionally activated binding proteins
Patrick Baeuerle, Gauting (DE); Robert B. DuBridge, Belmont, CA (US); Holger Wesche, San Francisco, CA (US); Luke Evnin, San Francisco, CA (US); Jeanmarie Guenot, San Francisco, CA (US); Anand Panchal, San Francisco, CA (US); and Maia Vinogradova, San Francisco, CA (US)
Assigned to Takeda Pharmaceutical Company Limited, Osaka (JP)
Filed by Takeda Pharmaceutical Company Limited, Osaka (JP)
Filed on Jul. 21, 2023, as Appl. No. 18/357,013.
Application 17/743,995 is a division of application No. 16/124,556, filed on Sep. 7, 2018, granted, now 11,406,710.
Application 17/743,995 is a division of application No. 15/727,423, filed on Oct. 6, 2017, abandoned.
Application 18/357,013 is a continuation in part of application No. 17/743,995, filed on May 13, 2022, granted, now 11,744,893.
Application 16/124,556 is a continuation of application No. PCT/US2017/021435, filed on Mar. 8, 2017.
Claims priority of provisional application 62/587,318, filed on Nov. 16, 2017.
Claims priority of provisional application 62/586,627, filed on Nov. 15, 2017.
Claims priority of provisional application 62/555,943, filed on Sep. 8, 2017.
Claims priority of provisional application 62/305,092, filed on Mar. 8, 2016.
Prior Publication US 2023/0414752 A1, Dec. 28, 2023
Int. Cl. G01N 31/00 (2006.01); A61K 39/395 (2006.01); A61P 35/00 (2006.01); C07K 16/18 (2006.01); C07K 16/28 (2006.01); C07K 16/30 (2006.01); C07K 16/46 (2006.01); G01N 33/53 (2006.01); A61K 39/00 (2006.01)

CPC A61K 39/39558 (2013.01) [A61P 35/00 (2018.01); C07K 16/18 (2013.01); C07K 16/28 (2013.01); C07K 16/2809 (2013.01); C07K 16/2827 (2013.01); C07K 16/2863 (2013.01); C07K 16/30 (2013.01); C07K 16/468 (2013.01); A61K 2039/505 (2013.01); C07K 2317/31 (2013.01); C07K 2317/565 (2013.01); C07K 2317/569 (2013.01); C07K 2317/62 (2013.01); C07K 2317/622 (2013.01); C07K 2317/94 (2013.01); C07K 2319/00 (2013.01); C07K 2319/50 (2013.01)]

15 Claims

1. A pair of polypeptides comprising:

a) a first polypeptide comprising a first target antigen binding domain linked using a first domain linker to a first single chain Fv (scFv) domain directed to a CD-3 antigen, wherein the first polypeptide further comprises a half-life extension domain, and

b) a second polypeptide comprising a second target antigen binding domain linked using a second domain linker to a second single chain Fv (scFv) domain directed to a CD-3 antigen, wherein the second polypeptide further comprises a half-life extension domain;

wherein the first scFv domain comprises an inactive VH domain and an active VL domain joined through a first cleavable linker between the inactive VH domain and the active VL domain, the inactive VH domain and the active VL domain interact to form a first VH/VL pair that does not specifically bind the CD-3 antigen; and

wherein the second scFv domain comprises an active VH domain and an inactive VL domain joined through a second cleavable linker between the active VH domain and the inactive VL domain, the active VH domain and the inactive VL domain interact to form a second VH/VL pair that does not specifically bind the CD-3 antigen.