Trialkyne Linking Agents and Methods of Use
AssigneeArrowhead Pharmaceuticals, Inc.
InventorsZhen Li, Erich Altenhofer, Jeffrey Carlson, Matthew Fowler-Watters, Bo Chen
Life of this patent
Estimating the term…
Abstract
Described are improved linking agents that are useful for facilitating the attachment of targeting groups, pharmacokinetic (PK) enhancers or modifiers, or other delivery agents to oligonucleotides. The described linking agents may exhibit improved reaction yields, stability, and biological activity, particularly when used in connection with oligonucleotide-based compounds, such as RNA interference (RNAi) agents.
Claims18
1-17. (canceled)
A compound of Formula II,
- or a pharmaceutically acceptable salt thereof,
- wherein,
- L1, L2, and L3 are each independently linkers comprising optionally substituted alkylene;
- L4 is a linker comprising optionally substituted alkylene, optionally substituted arylene, and optionally substituted cycloalkylene;
- each instance of R1 is optionally substituted alkyl;
- R2 is optionally substituted alkyl;
- and
- R4 is H or optionally substituted alkyl.
19-24. (canceled)
A compound of Formula III,
- or a pharmaceutically acceptable salt thereof,
- wherein,
- L1, L2, and L3 are each independently linkers comprising optionally substituted alkylene;
- L4 is a linker comprising optionally substituted alkylene, optionally substituted arylene, and optionally substituted cycloalkylene;
- R4 is H or optionally substituted alkyl;
- X is O or S;
- and
- RNA comprises or consists of an RNAi agent.
26-31. (canceled)
33-40. (canceled)
A compound of Formula V,
- or a pharmaceutically acceptable salt thereof,
- wherein,
- L1, L2 and L3 are each independently linkers comprising optionally substituted alkylene;
- L4 is a linker comprising optionally substituted alkylene, optionally substituted arylene, or optionally substituted cycloalkylene;
- R4 is H or optionally substituted alkyl;
- TL is a targeting ligand;
- Y is O or S;
- and
- RNA comprises or consists of an RNAi agent.
47-66. (canceled)
A compound of Formula IX
- or a pharmaceutically acceptable salt thereof,
- wherein,
- L1, L2 and L3 are each independently linkers comprising optionally substituted alkylene;
- L4 is a linker comprising optionally substituted alkylene, optionally substituted arylene, or optionally substituted cycloalkylene;
- TL is a targeting ligand;
- each instance of R4 is H or optionally substituted alkyl;
- and
- RNA comprises or consists of an RNAi agent.
68-71. (canceled)
73-76. (canceled)
Dependencies are inferred from the claim text.