Eric Ronald Rowe

US Patent:

57670994, Jun 16, 1998

Filed:

Oct 20, 1995

Appl. No.:

8/546086

Inventors:

David J. Harris - Lexington MA
Edward R. Lee - Quincy MA
Craig S. Siegel - Woburn MA
Eric A. Rowe - Malden MA
Shirley C. Hubbard - Belmont MA

Assignee:

Genzyme Corporation - Cambridge MA

International Classification:

A61K 3170
A61K 1728
A61K 3156
A61K 4800
B61F 1728

US Classification:

514 44

Abstract:

Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation.

US Patent:

57474710, May 5, 1998

Filed:

Oct 11, 1995

Appl. No.:

8/540867

Inventors:

Craig S. Siegel - Woburn MA
David J. Harris - Lexington MA
Edward R. Lee - Quincy MA
Shirley C. Hubbard - Belmont MA
Seng H. Cheng - Wellesley MA
Simon J. Eastman - Marlboro MA
John Marshall - Milford MA
Ronald K. Scheule - Hopkinton MA
Mathieu B. Lane - Cambridge MA
Eric A. Rowe - Malden MA

Assignee:

Genzyme Corporation - Cambridge MA

International Classification:

A61K 4800
A61K 3156
A61K 3170
B01F 1728

US Classification:

514 44

Abstract:

Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from ether or ester-linked alkyl groups, and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation.