Nektar Therapeutics

Takahiro Miyazaki

Neel Kumar Anand

Bo-Liang Deng

Zhongxu Ren

Haiying Cai

Bhalchandra V Joshi

Saul Kivimae

Jonathan Zalevsky

Provided are multi-arm polymer conjugates of Toll-Like Receptor (“TLR”) agonists such as TLR 7/8 agonists, as well as related compositions, and methods of making and using such conjugates. Exemplary conjugates are encompassed by Formula I: or a pharmaceutically acceptable salt form thereof, where R, taken together with each Q, is a residue of a polyol, polythiol, or polyamine bearing from 3 to about 50 hydroxyl, thiol, or amino groups; each Q is a linker selected from oxygen, sulfur and —NH; each POLY is independently a water-soluble, non-peptidic polymer; each Xis independently a linkage-containing spacer moiety; q is a positive integer from 3 to about 50; and each TLR 7/8 AG is a Toll-like receptor 7/8 agonist. Also provided is a method of administering to a patient having cancer (a) an IL-2Rβ-activating amount of a long-acting, IL-2Rβ-selective agonist; and (b) a Toll-like receptor agonist such as a conjugate as described above, as well as related compositions, kits and methods.

Multi-arm polymer conjugates of TLR agonist compounds and related immunotherapeutic treatment methods

Provided are multi-arm polymer conjugates of Toll-Like Receptor ('TLR') agonists such as TLR 7/8 agonists, as well as related compositions, and methods of making and using such conjugates. Exemplary conjugates are encompassed by Formula I: (I) or a pharmaceutically acceptable salt form thereof, where R, taken together with each Q, is a residue of a polyol, polythiol, or polyamine bearing from 3 to about 50 hydroxyl, thiol, or amino groups; each Q is a linker selected from oxygen, sulfur and &#x2014;NH; each POLY is independently a water-soluble, non-peptidic polymer; each Xr is independently a linkage-containing spacer moiety; q is a positive integer from 3 to about 50; and each TLR 7/8 AG is a Toll-like receptor 7/8 agonist. Also provided is a method of administering to a patient having cancer (a) an IL-2R&#x3b2;-activating amount of a long-acting, IL-2R&#x3b2;-selective agonist; and (b) a Toll-like receptor agonist such as a conjugate as described above, as well as related compositions, kits and methods.RQ-POLY-Xr-TLR7/8 AG)&#x2003;&#x2003;(I)

Growing community of inventors

San Francisco, CA, United States of America

Takahiro Miyazaki