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US 12,668,572 B2Granted
Degradable lipid for active molecule delivery and lipid nanoparticle thereof
AssigneeBeijing Carrius Bio Ltd.
InventorMing Wang
Life of this patent
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Abstract
The present invention provides an ionizable lipid compound having an optimized carbon chain length and an amine head so that the ionizable lipid compound has increased delivery efficiency for an active molecule including, but not limited to, nucleic acids, proteins, small molecule drugs and the like. The present invention further relates to a lipid nanoparticle (LNP) comprising the ionizable lipid compound and the active molecule, and a pharmaceutical composition comprising the lipid nanoparticle.
Claims19
A lipid compound of formula (I),
- wherein
- R2a and R3a are each independently selected from the group consisting of hydrogen, a monovalent aliphatic group, a monovalent heteroaliphatic group, a monovalent aromatic group, a monovalent heteroaromatic group, and Ht;
- t and s are each independently 0 or 1, and when t or s is zero, it means that the part is directly a single bond, provided that t and s are not both 0;
- A1, A2, and A3 are each independently selected from the group consisting of a single bond, a divalent aliphatic group, a divalent heteroaliphatic group, a divalent aromatic group, and a divalent heteroaromatic group;
- each Ht is independently at each occurrence —R1—X—R2—Y—R3—Z—R4,
- wherein
- each R1 is independently at each occurrence selected from the group consisting of a divalent aliphatic group, a divalent heteroaliphatic group, a divalent aromatic group, and a divalent heteroaromatic group;
- each X is independently at each occurrence
- wherein
- m is 1-6;
- W is selected from the group consisting of O, S, and NRc;
- L1 is directly connected to R1 and is selected from the group consisting of a single bond, O, S, and NRd;
- L2 is selected from the group consisting of a bond, O, S, and NRe;
- wherein Rc, Rd, and Re are each independently selected from the group consisting of hydrogen, hydroxy, an oxyaliphatic group, a monovalent aliphatic group, a monovalent heteroaliphatic group, a monovalent aromatic group, and a monovalent heteroaromatic group;
- Y and Z are both S;
- each R2 is independently at each occurrence selected from the group consisting of a single bond, a divalent aliphatic group, a divalent heteroaliphatic group, a divalent aromatic group, and a divalent heteroaromatic group;
- R3 is independently at each occurrence
- each R4 is independently at each occurrence a hydrophobic group selected from the group consisting of —(CH2CH2O)y—C3-8 alkyl, —(CH2CH2O)y—C3-8 alkenyl and —(CH2CH2O)y—C3-8 alkynyl, wherein y is 0 or 1 or 2.
15 more elements
A lipid compound selected from the group consisting of
- YX17
- YX31
- YX27
- YX28
- YX35
- YX29
- and
- YX33
5 more elements
Dependencies are inferred from the claim text.