	US 11,981,716 B2
	Activatable interleukin-2 polypeptides and methods of use thereof
William Winston, West Newton, MA (US); Daniel Hicklin, Montclair, NJ (US); Vinay Bhaskar, San Francisco, CA (US); Luke Evnin, San Francisco, CA (US); Patrick Baeuerle, Gauting (DE); Jose Andres Salmeron Garcia, Westminster, MA (US); Heather Brodkin, West Newton, MA (US); and Cynthia Seidel-Dugan, Belmont, MA (US)
Assigned to Werewolf Therapeutics, Inc., Watertown, MA (US)
Filed by Werewolf Therapeutics, Inc., Cambridge, MA (US)
Filed on May 14, 2021, as Appl. No. 17/320,779.
Application 17/320,779 is a continuation of application No. 16/880,606, filed on May 21, 2020, granted, now 11,352,403.
Application 16/880,606 is a continuation of application No. 16/438,156, filed on Jun. 11, 2019, granted, now 10,696,724, issued on Jun. 30, 2020.
Application 16/438,156 is a continuation in part of application No. PCT/US2019/032321, filed on May 14, 2019.
Claims priority of provisional application 62/756,504, filed on Nov. 6, 2018.
Claims priority of provisional application 62/756,507, filed on Nov. 6, 2018.
Claims priority of provisional application 62/671,225, filed on May 14, 2018.
Prior Publication US 2021/0403524 A1, Dec. 30, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/55 (2006.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01); A61K 38/00 (2006.01)

CPC C07K 14/55 (2013.01) [A61P 35/00 (2018.01); C07K 16/2809 (2013.01); A61K 38/00 (2013.01); C07K 2317/90 (2013.01); C07K 2319/31 (2013.01); C07K 2319/50 (2013.01)]

13 Claims

1. A conditionally active cytokine comprising:

a) a half-life extension domain which is an immunoglobulin Fc;

b) an IL-2 binding moiety, wherein the IL-2 binding moiety comprises a ligand-binding domain or fragment of a cognate receptor for the IL-2 polypeptide or an antibody or antigen binding fragment of an antibody that binds the IL-2 polypeptide; and

c) an IL-2 polypeptide;

wherein the IL-2 binding moiety and the IL-2 polypeptide are operably linked to the immunoglobulin Fc, and the IL-2 binding moiety is linked operably linked to the immunoglobulin Fc through a linker that comprises a cleavable peptide; and

wherein the IL-2 polypeptide has attenuated IL-2-receptor activating activity at least about 10 fold less than the IL-2-receptor activating activity of the polypeptide that comprises the IL-2 polypeptide that is produced by cleavage of the cleavable linker.