US 12,134,630 B2
Compositions and methods for liquid phase oligonucleotide synthesis
Gaomai Yang, Davis, CA (US); Jingshe Song, Union City, CA (US); Shengdong Wang, Fremont, CA (US); Yun-Chiao Yao, Union City, CA (US); Hongrong Yang, Union City, CA (US); David Yu, Union City, CA (US); and Aldrich N.K. Lau, Palo Alto, CA (US)
Assigned to Hongene Biotech Corporation, Union City, CA (US)
Filed by Hongene Biotech Corporation, Union City, CA (US)
Filed on Jun. 19, 2023, as Appl. No. 18/337,233.
Claims priority of provisional application 63/354,150, filed on Jun. 21, 2022.
Claims priority of provisional application 63/382,691, filed on Nov. 7, 2022.
Prior Publication US 2024/0002420 A1, Jan. 4, 2024
Int. Cl. C07H 1/00 (2006.01); C08F 120/68 (2006.01); C08F 220/28 (2006.01); C08F 220/56 (2006.01); C08F 265/10 (2006.01)
CPC C07H 1/00 (2013.01) [C08F 120/68 (2013.01); C08F 220/286 (2020.02); C08F 220/56 (2013.01); C08F 265/10 (2013.01)] 38 Claims
 
1. A polymer for liquid phase oligonucleotide synthesis, having the structure of Formula (I):

OG Complex Work Unit Chemistry
 wherein:
R is H, or unsubstituted or substituted C1-C6 alkyl;
W is C1-C20 alkylene, a 2 to 20 membered heteroalkylene, or a bond;
Q is

OG Complex Work Unit Chemistry
L1 is C1-C20 alkylene, 2 to 20 membered heteroalkylene, optionally substituted phenylene, optionally substituted 5 to 6 membered heteroarylene, or optionally substituted C3-C10 cycloalkylene, or C1-C20 alkylene or 2 to 20 membered heteroalkylene in which one or more methylene repeating units is each independently replaced by a group selected from the group consisting of optionally substituted phenylene, optionally substituted 5 to 6 membered heteroarylene, optionally substituted C3-C10 cycloalkylene, —C(═O)—, —CH═CH—, and —C≡C—;
each of R1 and R2 is independently —OR3 or —NR4aR4b;
R3 is H, a hydroxy protecting group, or

OG Complex Work Unit Chemistry
each R4a and R4b is independently H, —C(═O)(C1-C6 alkyl), —C(═O) phenyl, an amino protecting group, or

OG Complex Work Unit Chemistry
 or R4a and R4b taken together is a divalent amino protecting group;
each of L2a and L2b is independently C1-C20 alkylene, 2 to 20 membered heteroalkylene, optionally substituted phenylene, optionally substituted 5 to 6 membered heteroarylene, or optionally substituted C3-C10 cycloalkylene, or C1-C20 alkylene or 2 to 20 membered heteroalkylene in which one or more methylene repeating units is each independently replaced by a group selected from the group consisting of optionally substituted phenylene, optionally substituted 5 to 6 membered heteroarylene, optionally substituted C3-C10 cycloalkylene, —C(═O)—, —CH═CH—, and —C≡C—:
each of R5a, R5b, R6a and R6b is independently H, —OR7 or —NR8aR8b;
each of R7 is independently H, a hydroxy protecting group, or

OG Complex Work Unit Chemistry
each of R8a and R8b is independently H, —C(═O)(C1-C6 alkyl), —C(═O) phenyl, an amino protecting group, or

OG Complex Work Unit Chemistry
 or R8a and R8b taken together is a divalent amino protecting group;
each of L3a and L3b is independently C1-C20 alkylene, 2 to 20 membered heteroalkylene, optionally substituted phenylene, optionally substituted 5 to 6 membered heteroarylene, or optionally substituted C3-C10 cycloalkylene, or C1-C20 alkylene or 2 to 20 membered heteroalkylene in which one or more methylene repeating units is each independently replaced by a group selected from the group consisting of optionally substituted phenylene, optionally substituted 5 to 6 membered heteroarylene, optionally substituted C3-C10 cycloalkylene, —C(═O)—, —CH═CH—, and —C≡C—:
each of R9a, R9b, R10a and R10b is independently H, —OR11 or —NR12aR12b;
each of R11 is independently H, a hydroxy protecting group, or

OG Complex Work Unit Chemistry
each of R12a and R12b is independently H, —C(═O)(C1-C6 alkyl), —C(═O) phenyl, an amino protecting group, or

OG Complex Work Unit Chemistry
 or R12a and R12b taken together is a divalent amino protecting group;
each of L4a and L4b is independently C1-C20 alkylene, 2 to 20 membered heteroalkylene, optionally substituted phenylene, optionally substituted 5 to 6 membered heteroarylene, or optionally substituted C3-C10 cycloalkylene, or C1-C20 alkylene or 2 to 20 membered heteroalkylene in which one or more methylene repeating units is each independently replaced by a group selected from the group consisting of optionally substituted phenylene, optionally substituted 5 to 6 membered heteroarylene, optionally substituted C3-C10 cycloalkylene, —C(═O)—, —CH═CH—, and —C≡C—:
each of R13a, R13b, R14a and R14b is independently H, —OH, protected hydroxy, —NH2, —NH (optionally substituted C1-C6 alkyl), or protected amino;
each of m1, m2, m3, m4, m5, m6 and m7 is independently 0 or 1; and
j is an integer from 150 to 1500.