Nanomaterials
AssigneeGuide Therapeutics, LLC
InventorsGregory Lawrence Hamilton, Neeraj Narendra Patwardhan, Cory Dane Sago, Mina Fawzy Gaballa Shehata, Milloni Balwantkumar Chhabra
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Abstract
Lipid nanoparticle compositions for delivery of nucleic acids are described. In various embodiments the lipid nanoparticle contains an ionizable lipid of the Formula (I). Methods of using such lipid nanoparticle compositions to achieve targeted delivery of therapeutic cargo without the need for a targeting ligand are also provided.
Claims46
A compound of Formula (I):
- wherein:
- R1 is C9-C20 alkyl or C9-C20 alkenyl with 1-3 units of unsaturation;
- X1 and X2 are each independently absent or selected from —O—, —NR2— and
- wherein each R2 is independently hydrogen or C1-C6 alkyl;
- each a is independently an integer between 1 and 6;
- X3 and X4 are each independently absent or selected from the group consisting of:
- 4- to 8-membered heterocyclyl optionally substituted with 1 or 2 C1-C6 alkyl groups, 5- to 6-membered heteroaryl optionally substituted with 1 or 2 C1-C6 alkyl groups, 5- to 6-membered aryl optionally substituted with 1 or 2 C1-C6 alkyl groups, 4- to 7-membered cycloalkyl optionally substituted with 1 or 2 C1-C6 alkyl groups, —O— and —NR3 wherein each R3 is a independently a hydrogen atom or C1-C6 alkyl and wherein X1-X2—X3—X4 does not contain any oxygen-oxygen, oxygen-nitrogen or nitrogen-nitrogen bonds;
- X5 is —(CH2)b—, wherein b is an integer between 0 and 6;
- X6 is hydrogen, C1-C6 alkyl, 5- to 6-membered heteroaryl optionally substituted with 1 or 2 C1-C6 alkyl groups, or —NR4R5, wherein R4 and R5 are each independently hydrogen or C1-C6 alkyl;
- or alternatively R4 and R5 join together with the nitrogen to which they are bound to form a 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C1-C6 alkyl groups, wherein the heterocyclyl optionally includes an additional heteroatom selected from oxygen, sulfur, and nitrogen;
- each X7 is independently hydrogen, hydroxyl or —NR6R7, wherein R6 and R7 are each independently hydrogen or C1-C6 alkyl;
- or alternatively R6 and R7 join together with the nitrogen to which they are bound to form a 4- to 7-membered heterocyclyl optionally substituted with 1 or 2 C1-C6 alkyl groups, wherein the heterocyclyl optionally includes an additional heteroatom selected from oxygen, sulfur, and nitrogen;
- at least one of X1, X2, X3, X4, and X5 is present;
- A1 and A2 are each independently selected from the group consisting of:
- C5-C12 haloalkyl, C5-C12 alkenyl, C5-C12 alkynyl, (C5-C12 alkoxy)-(CH2)n2—, (C5-C10 aryl)-(CH2)n3— optionally ring substituted with one or two halo, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 alkoxy groups, and (C3-C8 cycloalkyl)-(CH2)n4— optionally ring substituted with 1 or 2 C1-C6 alkyl groups;
- or alternatively A1 and A2 join together with the atoms to which they are bound to form a 5- to 6-membered cyclic acetal substituted with 1 or 2 C4-C10 alkyl groups;
- n1, n2 and n3 are each individually an integer between 1 and 4;
- and
- n4 is an integer between zero and 4.
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Dependencies are inferred from the claim text.