Poly(oxazoline) conjugates with pendant cationic groups and lipid nanoparticles and polyplexes including same
AssigneeSerina Therapeutics (AL), Inc.
InventorsRandall Moreadith, J Milton Harris, Kunsang Yoon, Zhihao Fang, Rebecca Weimer, Wookhyun Kim, Kelley Smith
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Abstract
Poly(oxazoline) conjugates with pendant cationic groups (cationic POZ) and lipid nanoparticles (LNPs) including cationic POZ used to facilitate delivery of an encapsulated payload. LNPs and polyplexes including cationic POZ and a nucleic acid payload such as, but not limited to, mRNA or modified mRNA are disclosed. Such LNPs have no immunogenicity or reduced immunogenicity as compared to a corresponding LNP containing an ionizable lipid.
Claims20
A lipid nanoparticle comprising:
- a cationic POZ;
- a helper lipid;
- a polymer lipid;
- and
- a sterol lipid, wherein the cationic POZ is selected from the group consisting of one cationic POZ of Formulae I-IV:
- R-POZ1-cation (I)
- wherein R comprises an initiating group and POZ1 comprises a polyoxazoline polymer;
- wherein R comprises an initiating group, n ranges from 1 to 10, R2 is independently selected for each repeating unit from an unsubstituted or substituted alkyl, alkenyl, aralkyl, heterocyclylalkyl, or active functional group, m ranges from 1 to 100, a is ran, which indicates a random copolymer, or block, which indicates a block copolymer, and T comprises a terminating group;
- wherein R comprises an initiating group, n ranges from 1 to 10, R2 is independently selected for each repeating unit from an unsubstituted or substituted alkyl, alkenyl, aralkyl, heterocyclylalkyl, or active functional group, m ranges from 1 to 100, a is ran, which indicates a random copolymer, or block, which indicates a block copolymer, and T comprises a terminating group;
- and
- wherein R comprises an initiating group, n ranges from 1 to 10, R2 is independently selected for each repeating unit from an unsubstituted or substituted alkyl, alkenyl, aralkyl, heterocyclylalkyl, or active functional group, m ranges from 1 to 100, a ranges from 3 to 20, and T comprises a terminating group.
A lipid nanoparticle comprising:
- a cationic POZ of Formula I
- R-POZ1-cation (I)
- wherein R comprises an initiating group and POZ1 comprises a polyoxazoline polymer;
- a helper lipid;
- a polymer lipid;
- and
- a sterol lipid.
A lipid nanoparticle comprising:
- a cationic POZ of Formula II
- wherein R comprises an initiating group, n ranges from 1 to 10, R2 is independently selected for each repeating unit from an unsubstituted or substituted alkyl, alkenyl, aralkyl, heterocyclylalkyl, or active functional group, m ranges from 1 to 100, a is ran, which indicates a random copolymer, or block, which indicates a block copolymer, and T comprises a terminating group;
- a helper lipid;
- a polymer lipid;
- and
- a sterol lipid.
Dependencies are inferred from the claim text.