Cationic lipids

• US 5,334,761 A
• Filed: 08/28/1992
• Issued: 08/02/1994
• Est. Priority Date: 08/28/1992
• Status: Expired due to Term

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Incorporated (Thermo Fisher Scientific Incorporated)
• Inventors: Jessee, Joel A., Chytil, Anna, Gebeyehu, Gulilat, Hawley-Nelson, Pamela, Ciccarone, Valentina C.
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US07/937,508
• Time in Patent Office: 704 Days
• Field of Search: 260/404, 560/222, 560/251, 564/292, 564/197, 564/504, 554/105, 554/106, 554/107, 206/569
• US Class Current: 564/197
• CPC Class Codes: A61K 47/543 Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
• 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: C07C 217/28 having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
• CPC Class Codes: C07C 237/10 having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups

Abstract

The present invention discloses cationic lipids useful for making lipid aggregates for delivery of macromolecules and other compounds into cells. They are especially useful for the DNA-dependent transformation of cells. Also disclosed are lipids useful both for the delivery of macromolecules and also useful as intermediates for making other such lipids.

Claims

1. A composition having the structure

wherein

R₁ and R₂ independently of another, are C_1-23 alkyl or alkenyl, or ##STR12## alkyl or alkenyl, Z₁ and Z₂ independently of one another, are H or unbranched alkyl C_1-6, q is 1 to 6,

X is selected from any of X₁ -X₈, X₁₅ and X₁₆ where

X₁ is --(CH₂)_n Br, (CH₂)_n Cl, (CH₂)_n F, (CH₂)_n F or (CH₂)_n I where n=0-6 or

X₂ is --(CH₂)_n NH₂ n=0-6 or

X₃ is --NH--(CH₂)_m --NH₂ m=2-6 or

X₄ is --NH--(CH₂)₃ --NH--(CH₂)₄ --NH₂ or

X₅ is --NH--(CH₂)₃ --NH--(CH₂)₄ --NH(CH₂)₃ --NH₂ or

X₆ is ##STR13## X₇ is ##STR14## X₈ is ##STR15## X₁₅ is --(CH₂)_r --SH where r is 0-6 or X₁₆ is --(CH₂)_s --S--S--(CH₂)_t --NH₂ where s is 0-6 and t is 2-6.

2. A compound according to claim 1 wherein X is X₂.

3. A compound according to claim 1 wherein X is X₂, and n is 2.

4. A compound according to claim 1 wherein X is X₂, n is 1, R₁ =R₂ is C₁₈ alkenyl and Z₁ =Z₂ is methyl.

5. A compound according to claim 1 wherein X is X₁.

6. A compound according to claim 1 wherein X is X₁ is (CH₂)_n Br where n is 1.

7. A compound according to claim 1 wherein X is X₁ is (CH₂)_n Br where n is 1, R₁ =R₂ is C₁₈ alkenyl and Z₁ =Z₂ is methyl.

8. A compound according to claim 1 wherein X is X₃.

9. A compound according to claim 1 wherein X is X₃, q is 2, and m is 3.

10. A compound according to claim 1 wherein X is X₃, q is 2, m is 3, Z₁ =Z₂ is methyl and R₁ =R₂ is C₁₈ alkenyl.

11. A compound according to claim 1 wherein X is X₅.

12. A compound according to claim 1 wherein X is X₅ and q is 2.

13. A compound according to claim 1 wherein X is X₅, q is 2, Z₁ =Z₂ is methyl, and R₁ =R₂ is C₁₈ alkenyl.

14. A compound according to claim 1 wherein X is X₆.

15. A compound according to claim 1 wherein X is X₆ and q is 2.

16. A compound according to claim 1 wherein X is X₆, q is 2, Z₁ =Z₂ is methyl and R₁ =R₂ is C₁₈ alkenyl.

17. A lipid aggregate comprising a compound of claim 1.

18. A kit for preparing a lipid aggregate comprising a cationic lipid according to claim 1.