Lipid nanoparticle

Patent metadata

Field	Value
Publication number	US-12458605-B2
Application number	US-202118247612-A
Country	US
Kind code	B2
Filing date	Oct 1, 2021
Priority date	Oct 2, 2020
Publication date	Nov 4, 2025
Grant date	Nov 4, 2025

Abstract

The present invention addresses the problem of providing lipid nanoparticles which function as gene transfer carriers capable of selective transfer to the liver or spleen. Lipid nanoparticles which contain a pH-sensitive cationic lipid represented by formula (I) [a represents an integer of 3-5; b represents 0 or 1; R 1 and R 2 each independently represent a group represented by general formula (A) (R 11 and R 12 each independently represent a linear or branched C 2-15 alkyl group; c represents 0 or 1; v represents an integer of 4-12); and X represents a group represented by general formula (B)(d represents an integer of 0-3; and R 3 and R 4 each independently represent a C 1-4 alkyl group or C 2-4 alkenyl group, while R 3 and R 4 may form a 5- to 7-membered non-aromatic heterocycle) or represents a 5- to 7-membered non-aromatic heterocyclic group]. (I) (R 1 )(R 2 )C(OH)—(CH 2 )a-(O—CO)b-X. (A): (R 11 )(R 12 )—CH—(CO—O)c-(CH 2 )v-. (B):—(CH 2 )d-N(R 3 )(R 4 ).

(R 1 )(R 2 )C(OH)—(CH 2 ) a —(O—CO) b -X  (I)

(R 11 )(R 12 )—CH—(CO—O) c —(CH 2 ) v -  (A)

—(CH 2 ) d -N(R 3 )(R 4 )  (B)

First claim

What is claimed is:

1. A lipid nanoparticle which comprises a pH-sensitive cationic lipid represented by formula (I):
[Chem. 1]
(R 1 )(R 2 )C(OH)—(CH 2 ) a —(O—CO) b -X  (I)

wherein:
a represents an integer of 3-5;
b represents 0 or 1;
R 1 and R 2 each independently represent a group represented by general formula (A):
[Chem. 2]
(R 11 )(R 12 )—CH—(CO—O) c —(CH 2 ) v -  (A)

wherein:
R 11 and R 12 each independently represent a linear or branched C 2-15 alkyl group;
c represents 0 or 1;
V represents an integer of 4-12; and
X represents a group represented by general formula (B):
[Chem. 3]
—(CH 2 ) d -N(R 3 )(R 4 )  (B)

wherein:
d represents an integer of 0-3; and
R 3 and R 4 each independently represent a C 1-4 alkyl group or C 2-4 alkenyl group (in said C 1-4 alkyl group or C 2-4 alkenyl group, one or two hydrogen atoms may be replaced with phenyl group(s)), while R 3 and R 4 may be bound to each other to form a 5- to 7-membered non-aromatic heterocycle (one or two hydrogen atoms of said ring may be replaced with C 1-4 alkyl group or C 2-4 alkenyl group) or represents a 5- to 7-membered non-aromatic heterocyclic group (wherein, said group is bound to (O—CO)b- by a carbon atom and one or two hydrogen atoms of said ring may be replaced with C 1-4 alkyl group or C 2-4 alkenyl group).

2. The lipid nanoparticle of claim 1 , further comprising a sterol and a polyalkylene glycol-modified lipid.

3. The lipid nanoparticle of claim 1 , containing a nucleic acid.

4. The lipid nanoparticle of claim 3 , wherein the nucleic acid is siRNA.

5. The lipid nanoparticle of claim 3 , wherein the nucleic acid is mRNA or plasmid DNA.

6. The lipid nanoparticle of claim 3 , wherein the nucleic acid is a gene to be expressed in liver cells.

7. A pharmaceutical composition comprising the lipid nanoparticle of claim 1 as an active ingredient.

8. The pharmaceutical composition of claim 7 , used for gene therapy.

9. A method for expressing a foreign gene of interest to be expressed in liver cells, the method comprising:
administering the lipid nanoparticle of claim 3 encapsulating the foreign genes to a human or a test animal in need of gene therapy; and
expressing the foreign gene in the liver of the human or the test animal.

10. A method for expressing a foreign gene of interest to be expressed in liver cells, the method comprising:
administering the lipid nanoparticle of claim 4 encapsulating the foreign genes to a human or a test animal in need of gene therapy; and
expressing the foreign gene in the liver of the human or the test animal.

11. A method for expressing a foreign gene of interest to be expressed in liver cells, the method comprising:
administering the lipid nanoparticle of claim 5 encapsulating the foreign genes to a human or a test animal in need of gene therapy; and
expressing the foreign gene in the liver of the human or the test animal.

12. A method for expressing a foreign gene of interest to be expressed in liver cells, the method comprising:
administering the lipid nanoparticle of claim 5 encapsulating the foreign genes to a human or a test animal in need of gene therapy; and
expressing the foreign gene in the liver of the human or the test animal.

13. A pharmaceutical composition comprising the lipid nanoparticle of claim 2 as an active ingredient.

14. A pharmaceutical composition comprising the lipid nanoparticle of claim 3 as an active ingredient.

15. A pharmaceutical composition comprising the lipid nanoparticle of claim 4 as an active ingredient.

16. A pharmaceutical composition comprising the lipid nanoparticle of claim 5 as an active ingredient.

17. A pharmaceutical composition comprising the lipid nanoparticle of claim 6 as an active ingredient.

Assignees

• Univ Hokkaido Nat Univ Corp
• Nitto Denko Corp

Inventors

• Sato Yusuke
• Harashima Hideyoshi
• Hashiba Kazuki
• Taguchi Masamitsu
• Sakamoto Sachiko
• Shishido takuya
• Otsu Ayaka
• Maeda Yoshiki

Classifications

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• C12N15/88

  using microencapsulation, e.g. using {amphiphile} liposome vesicle · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• A61K48/0041

  the non-active part being polymeric · CPC title