Rna formulations and lipids
AssigneeImmorna (Hangzhou) Biotechnology Co., Ltd.
InventorsZihao Wang, Yuanqing Liu, Yanni Chen, Qizhi Hu, Zhijun Guo, Hongyue Wu
Life of this patent
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Abstract
The disclosure relates to the method of lyophilizing RNA and mixing with a liquid LNP solution, e.g., to make an RNA vaccine or therapeutic. Included are methods for preparing and administering the vaccine or therapeutic.
Claims34
A composition or set of compositions separately comprising each of (1) a lyophilized polynucleotide composition and (2) a liquid lipid nanoparticle (LNP) solution,
- wherein the LNP comprises an ionizable lipid of
- (i) Formula II:
- wherein:
- R1 and R2 are each independently C1 to C6 alkyl;
- R3 is C1 to C5 alkyl;
- R4 and R5 are each independently C1 to C18 alkyl group
- Q1 and Q2 are each independently —O—C(O)—, —C(O)—O—, —O—C(S)—, —C(S)—O—;
- —S—S—, and
- R6 and R7 are each independently C1 to C32 alkyl;
- or
- (ii) Formula I
- wherein:
- R1 and R2 are each, independently C1-C6 alkyl;
- R3 is C1-C5 alkyl;
- Q1, Q2 and Q3 are each independently —O—, —S—, —C(O)O—, —OC(O)—, —S—S—, —C(O)S—, —SC(O)—, —OC(S)—, or —C(S)O—;
- L is C1-C3 alkyl;
- R4 and R5 are each, independently C1-C10 alkyl;
- R6 and R7 are each, independently C1-C10 alkyl, C1-C10 alkenyl;
- A1 and A2 are each independently a bond, —O—, —S—, —C(O)O—, —OC(O)—, —S—S—, —C(O)S—, —SC(O)—, —OC(S)—, or —C(S)O—;
- and
- R8 and R9 are each, independently C1-C30 alkyl.
-4. (canceled)
-18. (canceled)
-29. (canceled)
A self-replicating RNA (srRNA) vector comprising in 5′ to 3′ order:
- a) a Cap1 cap;
- b) a 5′ UTR;
- c) one or more structural genes;
- d) a gene of interest (GOI);
- e) a 3′ UTR comprising about 100 to about 400 nucleotides;
- and
- f) a poly A tail comprising about 30 to about 100 nucleotides.
-33. (canceled)
-46. (canceled)
-52. (canceled)
-62. (canceled)
-71. (canceled)
A liquid composition comprising a lyophilized RNA electrostatically adsorbed to at least one exterior portion of or encapsulated in a lipid nanoparticle (LNP) comprising an ionizable lipid, with an ionizable lipid:RNA (N/P) molar ratio ranging from 5:1 to 12:1,
- wherein the LNP comprises an ionizable lipid of
- (i) Formula I:
- wherein:
- R1 and R2 are each, independently C1-C6 alkyl;
- R3 is C1-C5 alkyl;
- Q1, Q2 and Q3 are each independently —O—, —S—, —C(O)O—, —OC(O)—, —S—S—, —C(O)S—, —SC(O)—, —OC(S)—, or —C(S)O—;
- L is C1-C3 alkyl;
- R4 and R5 are each, independently C1-C10 alkyl;
- R6 and R7 are each, independently C1-C10 alkyl, C1-C10 alkenyl;
- A1 and A2 are each independently a bond, —O—, —S—, —C(O)O—, —OC(O)—, —S—S—, —C(O)S—, —SC(O)—, —OC(S)—, or —C(S)O—;
- and
- R8 and R9 are each, independently C1-C30 alkyl;
- or
- (ii) Formula II
- wherein:
- R1 and R2 are each independently C1 to C6 alkyl;
- R3 is C1 to C5 alkyl;
- R4 and R5 are each independently C1 to C18 alkyl group
- Q1 and Q2 are each independently —O—C(O)—, —C(O)—O—, —O—C(S)—, —C(S)—O—;
- —S—S—, and
- R6 and R7 are each independently C1 to C32 alkyl.
-76. (canceled)
-85. (canceled)
-92. (canceled)
-111. (canceled)
A lipid or a lipid nanoparticle (LNP) comprising an ionizable lipid of
- (i) Formula I:
- wherein:
- R1 and R2 are each, independently C1-C6 alkyl;
- R3 is C1-C5 alkyl;
- Q1, Q2 and Q3 are each independently —O—, —S—, —C(O)O—, —OC(O)—, —S—S—, —C(O)S—, —SC(O)—, —OC(S)—, or —C(S)O—;
- L is C1-C3 alkyl;
- R4 and R5 are each, independently C1-C10 alkyl;
- R6 and R7 are each, independently C1-C10 alkyl, C1-C10 alkenyl;
- A1 and A2 are each independently a bond, —O—, —S—, —C(O)O—, —OC(O)—, —S—S—, —C(O)S—, —SC(O)—, —OC(S)—, or —C(S)O—;
- and
- R8 and R9 are each, independently C1-C30 alkyl;
- (ii) Formula II:
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 and R2 are each, independently, C1-C6 alkyl;
- R3 is C1-C5 alkyl;
- R4 and R5 are each independently C1-C18 alkyl;
- Q1 and Q2 are each independently —O—C(O)—, —C(O)—O—, —O—C(S)—, —C(S)—O—;
- —S—S—,
- R6 and R7 are each independently a C18-C32 alkyl;
- or
- (iii) selected from the group consisting of
- wherein the LNP further comprises a phospholipid, a structural lipid, and a pegylated lipid.
-116. (canceled)
118-122. (canceled)
Dependencies are inferred from the claim text.