Cationic lipid

Patent metadata

Field	Value
Publication number	US-9845306-B2
Application number	US-201514828751-A
Country	US
Kind code	B2
Filing date	Aug 18, 2015
Priority date	Apr 28, 2010
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

Abstract

The present invention provides a cationic lipid, which allow nucleic acids to be easily introduced into cells, represented by formula (I)
(wherein: R 1 and R 2 are, the same or different, alkenyl, etc, and X 1 and X 3 are hydrogen atoms, or are combined together to form a single bond or alkylene, and X 3 is absent or is alkyl, etc, Y is absent or anion, a and b are, the same or different, 0 to 3, and L 3 is a single bond, etc, R 3 is alkyl, etc, L 1 and L 2 are —O—, —CO—O— or —O—CO—), a composition comprising the cationic lipid and a nucleic acid, and a method for introducing a nucleic acid into a cell by using the composition comprising the cationic lipid and the nucleic acid, and the like.

First claim

The invention claimed is:

1. A cationic lipid represented by formula (I):

wherein:
R 1 and R 2 are, the same or different, each linear or branched alkyl, alkenyl or alkynyl having: 12 to 24 carbon atoms, or R 1 and R 2 are combined together to form dialkylmethylene, dialkenylmethylene, dialkynylmethylene or alkylalkenylmethylene;
X 1 and X 2 are hydrogen atoms, or combined together to form a single bond or alkylene;
X 3 and Y are absent;
a and b are, the same or different, 1 to 3;
L 3 is a single bond;
R 3 is a hydrogen atom; and
L 1 and L 2 are, the same or different, —O— or

2. The cationic lipid according to claim 1 , wherein L 1 and L 2 are —O—, and R 1 and R 2 are dodecyl, tetradecyl, hexadecyl, octadecyl, icosyl, docosyl, tetracosyl, (Z)-tetradec-9-enyl, (Z)-hexadec-9-enyl, (Z)-octadec-6-enyl, (Z)-octadec-9-enyl, (E)-octadec-9-enyl, (Z)-octadec-11-enyl, (9Z,12Z)-octadec-9,12-dienyl, (9Z, 12Z, 15Z)-octadec-9, 12, 15-trienyl, (Z)-icos-11-enyl, (11Z,14Z)-icos-11,14-dienyl, 3,7, 11-trimethyldodeca-2,6,10-trienyl or 3,7, 11,15-tetramethylhexadec-2-enyl.

3. The cationic lipid according to claim 1 , wherein L 1 and L 2 are

and R 1 and R 2 are tridecyl, pentadecyl, heptadecyl, nonadecyl, heneicosyl, tricosyl, (Z)-tridec-8-enyl, (Z)-pentadec-8-enyl, (Z)-heptadec-5-envl, (Z)-heptadec-8-enyl, (E)-heptadec-8-enyl, (Z)-heptadec-10-enyl, (8Z,11Z)-heptadec-8,11-dienyl, (8Z, 11Z,14Z)-octadec-8, 11,14-trienyl, (Z)-nonadec-10-enyl, (10Z,13Z)-nonadec-10,13-dienyl, (11Z,14Z)-icos-11,14-dienyl, 2,6,10-trimethylundec-1,5,9-trienyl or 2,6,10,14-tetramethylpentadec-1-enyl.

4. The cationic lipid according to anyone of claims 1 to 3 , wherein a and b are both 1.

5. A composition that comprises the cationic lipid according to anyone of claims 1 to 3 , and a nucleic acid.

6. A composition comprising a complex particle of the cationic lipid according to any one of claims 1 to 3 and a nucleic acid, or a complex particle of a nucleic acid and a combination of the cationic lipid and a neutral lipid and/or a polymer.

7. A composition comprising a lipid particle constituted of a complex particle of the cationic lipid according to anyone of claims 1 to 3 and a nucleic acid, or a complex particle of a nucleic acid and a combination of the cationic lipid and a neutral lipid and/or a polymer, and a lipid membrane that encapsulates the complex particle.

8. The composition according to claim 6 , wherein the nucleic acid is a nucleic acid having an activity of suppressing the expression of the target gene by utilizing RNA interference (RNAi).

9. The composition according to claim 8 , wherein the target gene is a gene associated with tumor or inflammation.

10. A method for introducing the nucleic acid into a cell with the composition according to claim 6 wherein the method of the introduction into a cell is a method of introduction into a cell by intravenous administration.

11. The method according to claim 10 , wherein the cell is a cell at a tumor or inflammation site of a mammal.

12. The method according to claim 10 , wherein the cell is a cell in the liver, lungs, kidneys or spleen of a mammal.

Assignees

• Kyowa Hakko Kirin Co Ltd

Inventors

• Kuboyama Takeshi
• Era Tomohiro
• Naoi Tomoyuki

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/1272

  comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C12N2320/30

  Special therapeutic applications · CPC title

• C07C2601/08

  the ring being saturated · CPC title