Richard E Gregory

US Patent:

6358507, Mar 19, 2002

Filed:

Oct 12, 1999

Appl. No.:

09/416673

Inventors:

Johanne Kaplan - Sherborn MA
Donna Armentano - Belmont MA
Richard J. Gregory - Westford MA

Assignee:

Genzyme Corporation - Framingham MA

International Classification:

A61K 4800

US Classification:

424 932, 424 936, 4353201, 435 691, 435455, 435456, 435325, 435366, 435 911, 435 914, 435 9141, 435 9142, 435371

Abstract:

The present invention relates to transgene expression systems, related compositions comprising the transgene expression systems, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA encoding a transgene which codes for a desired product operably linked to expression control sequence, and at least a portion of the adenovirus E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E40RF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or âE4 cassetteâ) includes E40RF3 and at least one other portion selected from E40RF4, E40RF6/7 and E40RF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.

US Patent:

6485720, Nov 26, 2002

Filed:

Aug 8, 2001

Appl. No.:

09/924925

Inventors:

Johanne Kaplan - Sherborn MA
Donna Armentano - Belmont MA
Richard J. Gregory - Westford MA

Assignee:

Genzyme Corporation - Cambridge MA

International Classification:

A61K 4800

US Classification:

424 932, 424 931, 424 936, 4353201, 435455, 435456, 435457, 435 691, 435325, 435366

Abstract:

The present invention relates to transgene expression systems, related compositions comprising the transgene expression systems, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA encoding a transgene which codes for a desired product operably linked to expression control sequence, and at least a portion of the adenovirus E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E4ORF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or âE4 cassetteâ) includes E4ORF3 and at least one other portion selected from E4ORF4, E4ORF6/7 and E4ORF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.

US Patent:

8283331, Oct 9, 2012

Filed:

Oct 8, 2008

Appl. No.:

12/682149

Inventors:

Richard I Gregory - Brookline MA, US
George Q Daley - Weston MA, US
Srinivas R Viswanathan - Brookline MA, US

Assignee:

Children's Medical Center Corporation - Boston MA

International Classification:

C12N 15/11

US Classification:

514 44A

Abstract:

The present invention relates generally to methods to regulate microRNA (miRNA) biogenesis, in particular the regulation of the processing of pri-miRNA to mature miRNA by Lin-28 and/or variants such as Lin28B. In particular, the present invention relates to methods and compositions comprising at least one agent which inhibits Lin-28 function or activity and/or expression to increase the processing of pri-mRNA to mature miRNA. More specifically, one aspect of the invention is directed to treating and/or preventing cancer in a subject by administering an agent that inhibits Lin-28 activity or expression to a subject, preferably a human subject.

US Patent:

59817143, Nov 9, 1999

Filed:

Aug 15, 1996

Appl. No.:

8/691605

Inventors:

Seng H. Cheng - Bosaton MA
John Marshall - Milford MA
Richard J. Gregory - Ayer MA
Patrick W. Rafter - Natick MA

Assignee:

Genzyme Corporation - Cambridge MA

International Classification:

C07K 1628
C12N 518

US Classification:

5303882

Abstract:

Antibodies for binding epitopes of cystic fibrosis transmembrane conductance regulator (CFTR) and hybridomas which produce such antibodies are described. The antibodies of the present invention can be used in a method for detecting CFTR in a biological sample and/or in a method for purifying CFTR from an impure solution. In addition, the present invention includes a method for detecting CFTR in a biological sample from a nonhuman cystic fibrosis knockout animal wherein the the nonhuman cystic fibrosis knockout animal has been subjected to human CFTR replacement therapy. Another aspect of the present invention is a method for determining the orientation of CFTR in the membrane of a lipid vesicle. Yet another aspect of the invention is a kit for detecting CFTR in a biological sample.

US Patent:

58770119, Mar 2, 1999

Filed:

Nov 20, 1996

Appl. No.:

8/752760

Inventors:

Donna Armentano - Belmont MA
Richard J. Gregory - Westford MA
Alan E. Smith - Dover MA

Assignee:

Genzyme Corporation - Framingham MA

International Classification:

C12N 1586

US Classification:

4353201

Abstract:

A chimeric adenoviral vector is provided that comprises nucleotide sequence of a first adenovirus, wherein at least one gene of said first adenovirus encoding a protein that facilitates binding of said vector to a target mammalian cell, or internalization thereof within said cell, is replaced by the corresponding gene from a second adenovirus belonging to subgroup D, said vector further comprising a transgene operably linked to a eucaryotic promoter to allow for expression therefrom in a mammalian cell. Additionally, a method of delivering transgenes to target mammalian cells, particularly airway epithelial cells, is provided.

US Patent:

59812753, Nov 9, 1999

Filed:

Apr 14, 1997

Appl. No.:

8/839552

Inventors:

Donna Armentano - Belmont MA
John Marshall - Hopedale MA
Nelson S. Yew - West Upton MA
Seng H. Cheng - Wellesley MA
Richard J. Gregory - Westford MA

Assignee:

Genzyme Corporation - Cambridge MA

International Classification:

C12N 1500

US Classification:

4353201

Abstract:

The invention is directed to a transgene expression system comprising a transcription unit which contains a transgene operably linked to expression control sequences, preferably the CMV promoter, and which is delivered simultaneously with all or part of the adenovirus E4 genomic region to a cell in order to facilitate persistent expression of the transgene. The components of the transgene expression system can be delivered by vectors including plasmids and/or viruses and may be complexed with cationic amphiphiles to facilitate entry into a cell. The invention is also directed to methods for the production of the transgene expression system. The invention is further directed to compositions that contain the transgene expression system and to methods for the use of such compositions to deliver transgenes encoding biologically active proteins to cells.

US Patent:

61000868, Aug 8, 2000

Filed:

Apr 14, 1997

Appl. No.:

8/839679

Inventors:

Johanne Kaplan - Sherborn MA
Donna Armentano - Belmont MA
Richard J. Gregory - Westford MA

Assignee:

Genzyme Corporation - Cambridge MA

International Classification:

C12N 1586
C07J 900

US Classification:

4353201

Abstract:

The present invention relates to transgene expression systems, related pharmaceutical compositions, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA sequence encoding a transgene which codes for a desired product, expressibly contained within an adenovirus vector containing at least a portion of the E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E4ORF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or "E4 cassette") includes E4ORF3 and at least one other portion selected from E4ORF4, E4ORF6/7 and E4ORF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.

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.