Simon J Eastman

US Patent:

6383814, May 7, 2002

Filed:

Jan 11, 1999

Appl. No.:

09/228232

Inventors:

Edward R. Lee - Natick MA
David J. Harris - Lexington MA
Craig S. Siegel - Woburn MA
Mathieu B. Lane - Cambridge MA
Shirley C. Hubbard - Belmont MA
Seng H. Cheng - Wellesley MA
Simon J. Eastman - Marlborough MA
John Marshall - Milford MA
Ronald K Scheule - Hopkinton MA
Nelson S. Yew - West Upton MA

Assignee:

Genzyme Corporation - Cambridge MA

International Classification:

C12N 1588

US Classification:

435458, 4353201, 424450, 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:

6465007, Oct 15, 2002

Filed:

Jul 1, 1999

Appl. No.:

09/340509

Inventors:

Simon J. Eastman - Hudson MA
Quiming Chu - Melrose MA
Jennifer D. Tousignant - Cambridge MA
Seng H. Cheng - Wellesley MA
Ronald K. Scheule - Hopkinton MA

Assignee:

Genzyme Corporation - Framingham MA

International Classification:

A61K 4800

US Classification:

424450, 514 2, 514 44, 424 931, 424 932, 424 936, 435455, 435456, 435325, 4353201

Abstract:

The well-differentiated airway epithelium is the principal target tissue for gene therapy for the treatment of CF. However, recent studies have shown that gene delivery vehicles, such as cationic lipid:DNA complexes, can be inefficient at binding to and internalizing into polarized epithelial cells. The present invention provides a method to improve gene therapy by using a compound capable of disrupting tight junctions. In the practice of the invention, the transfection of a biologically active molecule by a cationic amphiphile:biologically active molecule complex or other lipid or viral or nonviral vectors is improved by treating the cells with a class of compounds known in the art as absorption enhancers or tight junction disrupting compounds.

US Patent:

20010048940, Dec 6, 2001

Filed:

Jun 18, 1999

Appl. No.:

09/335689

Inventors:

JENNIFER D. TOUSIGNANT - CAMBRIDGE MA, US
SIMON J. EASTMAN - HUDSON MA, US
EDWARD R. LEE - NATICK MA, US
RONALD K. SCHEULE - HOPKINTON MA, US
SENG H. CHENG - WELLESLEY MA, US
J. NIETUPSKI - MILLBURY MA, US
QIUMING CHU - MELROSE MA, US
JOHN MARSHALL - HOPEDALE MA, US

International Classification:

A61K048/00
A61K009/22
A61K009/127

US Classification:

424/450000, 424/468000, 514/044000, 435/458000

Abstract:

The effective introduction of foreign genes and other biologically active molecules into targeted mammalian cells is a challenge still facing those skilled in the art. Gene therapy, for example, requires successful transfection of target cells in a patient. The present invention relates to novel micellar complexes of cationic amphiphilic compounds that facilitate delivery of biologically active molecules to the targeted cells of a mammal. The novel micellar complexes are comprised of a cationic amphiphile, a biologically active molecule, a derivative of polyethylene glycol (PEG), and optionally, a co-lipid. A further aspect of the invention is the use of targeting agents in any of the methods that effectuate the delivery of biologically active molecules into the cells of mammals. A targeting agent is usually any molecule, peptide sequence, or large protein that preferentially targets or binds to specific mammalian cells.

US Patent:

20020013282, Jan 31, 2002

Filed:

Oct 5, 1998

Appl. No.:

09/166074

Inventors:

JOHN MARSHALL - MILFORD MA, US
DAVID J. HARRIS - LEXINGTON MA, US
EDWARD R. LEE - QUINCY MA, US
CRAIG S. SIEGEL - WOBURN MA, US
SIMON J. EASTMAN - MARLBORO MA, US
RONALD K. SCHEULE - HOPKINTON MA, US
SENG H. CHENG - WELLESLEY MA, US

International Classification:

A61K048/00
A61K009/127

US Classification:

514/044000, 514/002000, 424/450000

Abstract:

Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. By this invention, such cationic amphiphile is used in a state in which it is capable of accepting additional protons, i.e., it is not fully protonated. For purposes of this invention, cationic amphiphiles may be considered to encompass four general categories: (A) T-shaped/steroid-based amphiphiles; (B) T-shaped/non steroid-based amphiphiles; (C) non T-shaped/steroid based amphiphiles and (D) non T-shaped/non steroid-based amphiphiles.

US Patent:

20030143266, Jul 31, 2003

Filed:

Nov 22, 2002

Appl. No.:

10/301867

Inventors:

Jennifer Tousignant - Cambridge MA, US
Simon Eastman - Hudson MA, US
Edward Lee - Natick MA, US
Ronald Scheule - Hopkinton MA, US
Seng Cheng - Wellesley MA, US
J. Nietupski - Millbury MA, US
Quiming Chu - Melrose MA, US
John Marshall - Hopedale MA, US

Assignee:

GENZYME CORPORATION

International Classification:

A61K009/127
C12N015/88

US Classification:

424/450000, 435/458000

Abstract:

The effective introduction of foreign genes and other biologically active molecules into targeted mammalian cells is a challenge still facing those skilled in the art. Gene therapy, for example, requires successful transfection of target cells in a patient. The present invention relates to novel micellar complexes of cationic amphiphilic compounds that facilitate delivery of biologically active molecules to the targeted cells of a mammal. The novel micellar complexes are comprised of a cationic amphiphile, a biologically active molecule, a derivative of polyethylene glycol (PEG), and optionally, a co-lipid. A further aspect of the invention is the use of targeting agents in any of the methods that effectuate the delivery of biologically active molecules into the cells of mammals. A targeting agent is usually any molecule, peptide sequence, or large protein that preferentially targets or binds to specific mammalian celis.

US Patent:

59359366, Aug 10, 1999

Filed:

Jun 3, 1996

Appl. No.:

8/657238

Inventors:

Allen J. Fasbender - Solon IA
Michael J. Welsh - Riverside IA
Craig S. Siegel - Woburn MA
Edward R. Lee - Lincoln Heights MA
John Marshall - Milford MA
Seng H. Cheng - Wellesley MA
David J. Harris - Lexington MA
Simon J. Eastman - Marlboro MA
Shirley C. Hubbard - Belmont MA
Mathieu B. Lane - Cambridge MA
Eric A. Rowe - Malden MA
Ronald K. Scheule - Hopkinton MA
Nelson S. Yew - West Upton MA

Assignee:

Genzyme Corporation - Cambridge MA
University of Iowa - Iowa City IA

International Classification:

A01N 4304

US Classification:

514 44

Abstract:

Novel compositions are provided. Typically, the compositions comprise one or more neutral co-lipids and also a cationic amphiphile. Therapeutic compositions are prepared according to the practice of the invention by contacting a therapeutically active molecule with a dispersion of neutral co-lipid(s) and amphiphile(s).

US Patent:

60718900, Jun 6, 2000

Filed:

Oct 19, 1995

Appl. No.:

8/545473

Inventors:

Ronald K. Scheule - Hopkinton MA
Rebecca G. Bagley - Natick MA
Simon J. Eastman - Marlboro MA
Seng H. Cheng - Wellesley MA
John Marshall - Milford MA
Nelson S. Yew - West Upton MA
David J. Harris - Lexington MA
Edward R. Lee - Quincy MA
Craig S. Siegel - Woburn MA

Assignee:

Genzyme Corporation - Cambridge MA

International Classification:

A01N 4304

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:

63315246, Dec 18, 2001

Filed:

Apr 7, 1997

Appl. No.:

8/835213

Inventors:

Ronald K. Scheule - Hopkinton MA
Rebecca G. Bagley - Natick MA
Simon J. Eastman - Hudson MA
Seng H. Cheng - Wellesley MA
John Marshall - Hopedale MA
David J. Harris - Lexington MA
Edward R. Lee - Natick MA
Craig S. Siegel - Woburn MA
S. Catherine Hubbard - Belmont MA
Duane E. Johnson - Encinitas CA
Daniel C. Maneval - San Diego CA
H. Michael Shepard - Rancho Santa Fe CA
Richard J. Gregory - Westford MA

Assignee:

Genzyme Corporation - Framingham MA

International Classification:

A61K 4800
C12N 1588
C12N 1563

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.