Coated lipid complexes and their use

• US 9,387,262 B2
• Filed: 10/06/2014
• Issued: 07/12/2016
• Est. Priority Date: 12/27/2004
• Status: Expired due to Fees

• Current Assignee: Silence Therapeutics Gmbh (Silence Therapeutics plc)
• Original Assignee: Silence Therapeutics Gmbh (Silence Therapeutics plc)
• Inventors: Keil, Oliver, Kaufmann, Jorg
• Primary Examiner(s): Kelly, Robert M
• Application Number:
  US14/507,045
• Publication Number:
  US 20150031752A1
• Time in Patent Office: 645 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 47/543 Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 48/0033 the non-active part being non-polymeric
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y10S 977/907 Liposome
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

The present invention is related to a lipid composition comprising at least a first lipid component, at least a first helper lipid, and a shielding compound which is removable from the lipid composition under in vivo conditions.

Claims

1. A lipid composition comprising:

a nucleic acid selected from the group consisting of an RNAi, an siRNA, an siNA,

a cationic lipid component that is a compound according to formula (I),

2. The lipid composition according to claim 1, wherein said shielding compound is PEG2000 or PEG5000.

3. The lipid composition according to claim 1, wherein the shielding compound is a conjugate of PEG and ceramide.

4. The lipid composition according to claim 3, wherein the ceramide comprises at least one short carbon chain substituent of from 6 to 10 carbon atoms.

5. The lipid composition according to claim 1, wherein said first helper lipid is ceramide, and wherein said ceramide is conjugated to PEG.

6. The lipid composition according to claim 1, further comprising a ceramide conjugated to PEG.

7. The lipid composition according to claim 1, wherein said shielding compound is covalently linked to said nucleic acid.

8. The lipid composition according to claim 7, wherein the linker moiety is selected from the group consisting of an ssRNA, an ssDNA, a dsRNA, a dsDNA, a peptide, an S-S-linker and a pH sensitive linker.

9. The lipid composition according to claim 7, wherein the nucleic acid is selected an RNAi molecule, the first strand having the following sequence:

UaAgUuCuAgCuGuGgUgG-P (SEQ ID NO;

     1); and

the second strand having the sequence CcAcCaCaGcUaGaAcUuA-P (SEQ ID NO;

     2), whereby the modification pattern is such that the nucleotides which are capitalized are 2′

-O-methyl nucleotides and P is a phosphate group.

10. The lipid composition according to claim 1, wherein R₁ and R₂ are each independently selected from the group consisting of lauryl, myristyl, palmityl and oleyl.

11. The lipid composition according to claim 1, wherein R₁ is lauryl and R₂ is myristyl, or R₁ is palmityl and R₂ is oleyl.

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

13. The lipid composition according to claim 1, wherein Y⁻

is selected from the group consisting of halide, acetate and trifluoroacetate.

14. The lipid composition according to claim 1, wherein said cationic lipid component is selected from the group consisting of:

β

-arginyl-2,3-diamino propionic acid-N-palmityl-N-oleyl-amide trihydrochloride

15. The lipid composition according to claim 1, further comprising a pharmaceutically acceptable carrier.