US 12,214,045 B2
Multi-arm polymer conjugates of TLR agonist compounds and related immunotherapeutic treatment methods
Zhongxu Ren, Foster City, CA (US); Neel K. Anand, San Mateo, CA (US); Haiying Cai, Cupertino, CA (US); Bo-Liang Deng, San Ramon, CA (US); Bhalchandra V. Joshi, Madison, AL (US); Jonathan Zalevsky, Chinnor (GB); Takahiro Miyazaki, San Francisco, CA (US); and Saul Kivimae, San Francisco, CA (US)
Assigned to Nektar Therapeutics, San Francisco, CA (US)
Filed by Nektar Therapeutics, San Francisco, CA (US)
Filed on Jul. 12, 2023, as Appl. No. 18/221,300.
Application 18/221,300 is a continuation of application No. 16/475,972, granted, now 11,744,898, previously published as PCT/US2018/013199, filed on Jan. 10, 2018.
Claims priority of provisional application 62/510,024, filed on May 23, 2017.
Claims priority of provisional application 62/510,019, filed on May 23, 2017.
Claims priority of provisional application 62/488,407, filed on Apr. 21, 2017.
Claims priority of provisional application 62/488,251, filed on Apr. 21, 2017.
Claims priority of provisional application 62/467,945, filed on Mar. 7, 2017.
Claims priority of provisional application 62/444,735, filed on Jan. 10, 2017.
Claims priority of provisional application 62/444,756, filed on Jan. 10, 2017.
Prior Publication US 2023/0372500 A1, Nov. 23, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/60 (2017.01); A61K 9/00 (2006.01); A61K 47/54 (2017.01); A61K 47/64 (2017.01); A61P 35/00 (2006.01)
CPC A61K 47/60 (2017.08) [A61K 9/0029 (2013.01); A61K 47/54 (2017.08); A61K 47/642 (2017.08); A61P 35/00 (2018.01)] 24 Claims
 
1. A method of treating cancer comprising administering a conjugate comprising a Toll-like Receptor (TLR) 7/8 agonist covalently attached, via a linkage-containing spacer moiety, to a multi-arm, water-soluble, non-peptidic polymer having a formula in accordance with Formula III:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: L is —(CH2)m—, —(CH2)m—NH—C(O)—(CH2)m—, —CHF—(CH2)m—NH—C(O)—(CH2)m—, —CH(CH3)—NH—C(O)—(CH2)m—, —CH(CH(CH3)2)—NH—C(O)—(CH2)m—, —CH(CH2CH(CH3)2)—NH—C(O)—(CH2)m—, —C(CH3)2—NH—C(O)—(CH2)m—, a single bond, or —NH—(CH2)m—,
each m is independently an integer from 1 to 5, inclusive;
each n is independently an integer from 40 to 350, inclusive;
R1 is hydrogen or —CH2—O—CH2—CH3; and
R2 is hydrogen or hydroxyl
to a subject in need thereof.