Lipids, lipid complexes and use thereof

Patent metadata

Field	Value
Publication number	US-9486538-B2
Application number	US-201514838791-A
Country	US
Kind code	B2
Filing date	Aug 28, 2015
Priority date	May 5, 2004
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

The present invention is related to uses of a composition comprising a pharmaceutically active component and a compound according to formula (I),

wherein R 1 and R 2 are each and independently selected from the group comprising alkyl;
n is any integer between 1 and 4;
R 3 is an acyl selected from the group comprising lysyl, ornithyl, 2,4-diaminobutyryl, histidyl and an acyl moiety according to formula (II),

wherein m is any integer from 1 to 3 and
Y − is a pharmaceutically acceptable anion.

First claim

We claim:

1. A composition comprising a carrier and a liposome comprising at least one helper lipid component selected from the group consisting of phospholipids and steroids and a compound according to formula (I),

wherein R 1 and R 2 are each and independently selected from the group comprising alkyl;
n is any integer between 1 and 4;
R 3 is an acyl selected from the group comprising lysyl, ornithyl, 2,4-diaminobutyryl, histidyl and an acyl moiety according to formula (II)

wherein m is any integer from 1 to 3 and
Y − is a pharmaceutically acceptable anion.

2. The composition according to claim 1 , wherein R 1 and R 2 are each and independently selected from the group comprising lauryl, myristyl, palmityl and oleyl.

3. The composition according to claim 1 , wherein R 1 is lauryl and R 2 is myristyl or R 1 is palmityl and R 2 is oleyl.

4. The composition according to claim 1 , wherein m is 1 or 2.

5. The composition according to claim 1 , wherein Y − is selected from the group consisting of halogenids, acetate and trifluoroacetate.

6. The composition according to claim 1 , wherein the compound is selected from the group consisting of:

7. The composition according to claim 1 , wherein the carrier is a pharmaceutically acceptable carrier.

8. The composition according to claim 1 , wherein the liposome is associated with a nucleic acid.

9. The composition according to claim 8 , wherein the nucleic acid is an oligonucleotide, polynucleotide or siRNA.

10. The composition according to claim 1 , wherein the helper lipid component is selected from the group comprising 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine and 1,2-dioleyl-sn-glycero-3-phosphoethanolamine.

11. The composition according to claim 10 , wherein the content of the helper lipid component is from about 20 mol % to about 80 mol % of the overall lipid content of the liposome.

12. The composition according to claim 1 , wherein said at least one helper lipid comprises a moiety which is selected from the group comprising a PEG moiety, a HEG moiety, a polyhydroxyethyl starch (polyHES) moiety and a polypropylene moiety.

13. The composition according to claim 12 , wherein the helper lipid comprising the PEG moiety is selected from the group comprising 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, 1,2-dialkyl-sn-glycero-3-phosphoethanolamine; and Ceramide-PEG.

14. The composition according to claim 1 , said liposome comprising:
a) 50 mol % of β-arginyl-2,3-diamino propionic acid-N-palmityl-N-oleyl-amide trihydrochloride,
48 mol % of 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine; and
2 mol % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG2000; or

b) 50 mol % of β-L-arginyl-2,3-L-diamino propionic acid-N-palmityl-N-oleyl-amide trihydrocloride,
49 mol % 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine; and
1 mol % N(Carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine.

Assignees

• Silence Therapeutics Gmbh

Inventors

• Keil Oliver
• Kaufmann Jörg
• Santel Ansgar

Classifications

• C12N2310/14

  interfering nucleic acids [NA] · 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

• 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

• C12N2320/32

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

• C07C279/14

  being further substituted by carboxyl groups · CPC title