	US 12,275,769 B2
	Activatable interleukin 12 polypeptides and methods of use thereof
William Winston, West Newton, MA (US); Daniel Hicklin, Boston, MA (US); Vinay Bhaskar, San Francisco, CA (US); Luke Evnin, San Francisco, CA (US); Patrick Baeuerle, Gauting (DE); Jose Andres Salmeron Garcia, Acton, 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 Apr. 11, 2022, as Appl. No. 17/717,783.
Application 17/717,783 is a continuation of application No. 16/880,624, filed on May 21, 2020, granted, now 11,453,710.
Application 16/880,624 is a continuation of application No. 16/438,166, filed on Jun. 11, 2019, granted, now 10,696,723, issued on Jun. 30, 2020.
Application 16/438,166 is a continuation in part of application No. PCT/US2019/032322, filed on May 14, 2019.
Claims priority of provisional application 62/756,507, filed on Nov. 6, 2018.
Claims priority of provisional application 62/756,504, filed on Nov. 6, 2018.
Claims priority of provisional application 62/756,515, filed on Nov. 6, 2018.
Claims priority of provisional application 62/671,225, filed on May 14, 2018.
Prior Publication US 2022/0324930 A1, Oct. 13, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/54 (2006.01); C07K 16/28 (2006.01)

CPC C07K 14/5434 (2013.01) [C07K 16/2866 (2013.01); C07K 2317/55 (2013.01); C07K 2317/569 (2013.01); C07K 2317/622 (2013.01); C07K 2319/31 (2013.01); C07K 2319/50 (2013.01)]

14 Claims

1. A conditionally active IL-12 comprising at least one of each of:

a) interleukin 12 (IL-12) [A];

b) a half-life extension domain [B], wherein the half-life extension element is human serum albumin or an antigen-binding polypeptide that binds human serum albumin;

c) an IL-12 blocking moiety [D] wherein the IL-12 blocking moiety comprises an antibody or antigen-binding fragment of an antibody that binds the IL-12; and

d) a protease-cleavable polypeptide linker [L]; and

wherein the IL-12 and the IL-12 blocking moiety are operably linked by the protease-cleavable polypeptide linker and the conditionally active IL-12 has attenuated IL-12-receptor activating activity, wherein the IL-12-receptor activating activity of the conditionally active IL-12 is at least about 10 fold less than the IL-12-receptor activating activity of the IL-12 that is produced by cleavage of the protease-cleavable polypeptide linker, and wherein the serum half-life of the IL-12 comprising fragment that is produced by protease cleavage of the protease-cleavable polypeptide linker is comparable to the half-life of naturally occurring IL-12.