Polyethyleneglycol-modified lipid compounds and uses thereof

• US 7,803,397 B2
• Filed: 09/15/2004
• Issued: 09/28/2010
• Est. Priority Date: 09/15/2003
• Status: Active Grant

• Current Assignee: Arbutus Biopharma Corporation
• Original Assignee: Protiva Biotherapeutics Inc (Arbutus Biopharma Corporation)
• Inventors: Ambegia, Ellen Grace, Heyes, James, MacLachlan, Ian
• Primary Examiner(s): Epps-Smith; Janet
• Application Number:
  US10/942,379
• Publication Number:
  US 20050175682A1
• Time in Patent Office: 2,204 Days
• Field of Search: None
• US Class Current: 424/450
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 47/543 Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07C 233/18 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 235/08 having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 271/16 to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
• CPC Class Codes: C08L 2203/02 for biomedical use

Abstract

The present invention provides compositions comprising polytheylyene-dialkyloxypropyl conjugates (PEG-DAA), liposomes, SNALP, and SPLP comprising such compositions, and methods of using such compositions, liposomes, SNALP, and SPLP.

Claims

1. A compound of Formula I:

wherein;

R¹ and R² are independently selected and are alkyl groups having from about 10 to about 20 carbon atoms;

PEG is a polyethyleneglycol, wherein the terminal hydroxyl group is substituted with a methyl group; and

L is a carbamate linker moiety.

2. The compound in accordance with claim 1, wherein R¹ and R² are selected from the group consisting of lauryl (C12), myristyl (C14), palmityl (C16), stearyl (C18) and icosyl (C20).

3. The compound in accordance with claim 1, wherein R¹ and R² are the same.

4. The compound in accordance with claim 3, wherein R¹ and R² are both myristyl (C14).

5. The compound in accordance with claim 3, wherein R¹ and R² are both palmityl (C16).

6. The compound in accordance with claim 3, wherein R¹ and R² are both stearyl (C18).

7. The compound in accordance with claim 1, wherein said alkyl groups are saturated.

8. The compound in accordance with claim 1, wherein said alkyl groups are unsaturated.

9. The compound in accordance with claim 1, wherein said PEG has an average molecular weight ranging from about 550 daltons to about 10,000 daltons.

10. The compound in accordance with claim 9, wherein said PEG has an average molecular weight ranging from about 750 to about 5,000 daltons.

11. The compound in accordance with claim 9, wherein said PEG has an average molecular weight ranging from about 1,000 to about 5,000 daltons.

12. The compound in accordance with claim 9, wherein said PEG has an average molecular weight ranging from about 1,500 to about 3,000 daltons.

13. The compound in accordance with claim 9, wherein said PEG has an average molecular weight of about 2,000 daltons.

14. The compound in accordance with claim 1, having the formula

wherein PEG is a polyethyleneglycol, wherein the terminal hydroxyl group is substituted with a methyl group.

15. The compound in accordance with claim 14, wherein L has a formula selected from the group consisting of:

wherein the dashed line indicates the point of attachment to the PEG terminal oxygen and the wavy line indicates the point of attachment to the rest of the compound.