US 12,357,705 B2
Negatively charged peg-lipid conjugates
James Heyes, Vancouver (CA); Kieu Mong Lam, Richmond (CA); and Mark Wood, Port Moody (CA)
Assigned to ARBUTUS BIOPHARMA CORPORATION, Vancouver (CA)
Appl. No. 17/291,908
Filed by ARBUTUS BIOPHARMA CORPORATION, Burnaby (CA)
PCT Filed Nov. 8, 2019, PCT No. PCT/US2019/060518
§ 371(c)(1), (2) Date May 6, 2021,
PCT Pub. No. WO2020/097493, PCT Pub. Date May 14, 2020.
Claims priority of provisional application 62/758,099, filed on Nov. 9, 2018.
Prior Publication US 2022/0072154 A1, Mar. 10, 2022
Int. Cl. A61K 48/00 (2006.01); A61K 9/16 (2006.01); A61K 31/7105 (2006.01); A61K 47/54 (2017.01); A61K 47/60 (2017.01)
CPC A61K 48/0033 (2013.01) [A61K 9/1617 (2013.01); A61K 31/7105 (2013.01); A61K 47/543 (2017.08); A61K 47/60 (2017.08)] 20 Claims
 
1. A compound of formula (I):
A-B-C  (I)
wherein:
A is (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylthio, or (C2-C6)alkanoyloxy, wherein any (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylthio, and (C2-C6)alkanoyloxy is substituted with one or more anionic precursor groups, and wherein any (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C6)alkyl, C1-C6)alkoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylthio, and (C2-C6)alkanoyloxy is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxyl, (C1-C3)alkoxy, (C1-C6)alkanoyl, (C1-C3)alkoxycarbonyl, (C1-C3)alkylthio, and(C2-C3)alkanoyloxy;
each anionic precursor group is capable of forming an anion at physiological pH;
A is linked to B directly or via a linker moiety selected from the group consisting of —C(O)NRb—, —NRb—, —C(O)—, —NRbC(O)O—, —NRbC(O)NRb—, —S—S—, —O—, —(O)CCH2CH2C(O)—, and —NHC(O)CH2CH2C(O)NH—;
B is a polyethylene glycol chain having a molecular weight of from about 550 daltons to about 10,000 daltons;
C is -L-Ra
L is selected from the group consisting of a direct bond, —C(O)O—, —C(O)NRb—, —NRb—, —C(O)—, —NRbC(O)O—, —NRbC(O)NRb—, —S—S—, —O—, —(O)CCH2CH2C(O)—, and —NHC(O)CH2CH2C(O)NH—;
Ra is a branched (C10-C50)alkyl or branched (C10-C50)alkenyl wherein one or more carbon atoms of the branched (C10-C50)alkyl or branched (C10-C50)alkenyl have been replaced with —O—; and
each Rb is independently H or (C1-C6)alkyl.