Samuel C Wadsworth, 7610 Straw Hollow Ln, Shrewsbury, MA 01545

6541245, Apr 1, 2003

Nov 21, 2000

09/718034

Helen Romanczuk - Framingham MA
Samuel C. Wadsworth - Shrewsbury MA
Patricia Berthelette - Uxbridge MA

Genzyme Corporation - Cambridge MA

C12N 1573

4353201, 4352351, 4353251, 435440, 435455, 435 911, 435 914, 435 9141, 4241901, 424 936, 424 9321, 4241991, 5141723

The present invention is directed to improved helper vectors and cell lines for the production of pseudoadenoviral (PAV) vectors containing substantially reduced levels of contaminating helper vector. The invention provides for helper vectors for the production of substantially helper vector-free PAV stocks comprising phag C31 recombinase recognition sequences which, depending upon their arrangement within the helper vector, can prevent helper vector packaging. The invention also provides for improved cell lines for the production of substantially helper vector-free PAV stocks comprising a stably introduced novel circular PAV genome into the cell.

6632670, Oct 14, 2003

Nov 16, 1998

09/029705

Samuel C. Wadsworth - Shrewsbury MA
Karen Vincent - Arlington MA
Susan Piraino - Framingham MA

Genzyme Corporation - Cambridge MA

C12N 15864

435455, 4352351, 4353201, 435456, 435457

The present invention is directed to methods for generating high titer, contaminant free, recombinant AAV vectors, methods and genetic constructs for producing recombinant AAV vectors conveniently and in large quantities, methods for the delivery of all essential viral proteins required in trans for high yields of recombinant AAV, recombinant AAV vectors for use in gene therapy, novel packaging cell lines which obviate the need for cotransfection of vector and helper plasmids, helper plasmids and vector plasmid backbone constructs, a reporter assay for determining AAV vector yield. Further provided are recombinant AAV vectors in a pharmaceutically acceptable carrier, methods of delivering a transgene of interest to a cell, compositions and methods for delivering a DNA sequence encoding a desired polypeptide to a cell, and transgenic non-human mammals that express a human chromosome 19 AAV integration locus.

7312324, Dec 25, 2007

May 6, 2002

10/139763

David W. Souza - Waltham MA, US
Donna Armentano - Belmont MA, US
Samuel C. Wadsworth - Shrewsbury MA, US

Genzyme Corporation - Cambridge MA

C07H 21/04
C07H 21/02
A01N 63/00
A01N 65/00
A01N 43/04
A01N 31/70

536 241, 514 44, 424 931, 536 231

The invention is directed to novel combinations of liver specific enhancers and promoter elements for achieving persistent transgene expression in the liver. The liver specific enhancer elements may be derived from either the human serum albumin, prothrombin, α-1microglobulin or aldolase genes in single copies or in multimerized form linked to elements derived from the cytomegalovirus intermediate early (CMV), α-1-antitrypsin or albumin promoters. In a preferred embodiment of the invention, an adenoviral vector comprising a liver specific enhancer/promoter combination operably linked to a transgene is administered to recipient cells. In other embodiments of the invention, adeno-associated viral vectors, retroviral vectors, lentiviral vectors or a plasmid comprising the liver specific enhancer/promoter combination linked to a transgene is administered to recipient cells. Also within the scope of the invention are promoter elements derived from the human prothrombin gene and the β-fibrinogen gene.

7615537, Nov 10, 2009

Oct 25, 2001

10/057620

Abraham Scaria - Framingham MA, US
Samuel C. Wadsworth - Shrewsbury MA, US

Genzyme Corporation - Cambridge MA

A61K 48/00
C12N 15/63

514 44, 4353201

The present invention relates to a method of treating an individual having a blood coagulation defect (e. g. , hemophilia A, hemophilia B), comprising administering to the individual an effective amount of a DNA vector encoding modified Factor VII (FVII), wherein the modified Factor VII leads to generation of Factor VIIa in vivo. In a particular embodiment, the invention pertains to a method of treating an individual having a blood coagulation defect comprising administering to the individual an effective amount of a nucleic acid encoding a modified FVII wherein the modified FVII comprises a signal which codes for precursor cleavage by furin at the activation cleavage site of the modified FVII. The invention also relates to a method of treating an individual having a blood coagulation disorder comprising administering to the individual an effective amount of a nucleic acid encoding the light chain of human FVII and a nucleic acid encoding the heavy chain of human FVII operably linked to a leader sequence. Compositions, expression vectors and host cells comprising nucleic acid which encodes a modified Factor VII, wherein the modified Factor VII leads to generation of Factor VIIa in vivo is also encompassed by the present invention.

7928072, Apr 19, 2011

Mar 12, 2007

11/716794

Abraham Scaria - Framingham MA, US
Peter Pechan - Brookline MA, US
Samuel Wadsworth - Shrewsbury MA, US

Genzyme Corporation - Framingham MA

C12P 21/04
C12N 15/00
C12N 9/48
A61K 38/17
C07K 14/705
C07K 14/71
C07H 21/04

514 206, 435 697, 435212, 4353201, 536 234, 530350, 514 1

Multimeric fusion proteins of an Ig-like domain of Flt-1 are rendered functional by inclusion of a linker moiety. Vectors encoding the fusion proteins and host cells expressing the fusion proteins can be used therapeutically to block neovascularization in individuals with pathological conditions related to neovascularization. Such conditions include age-related macular degeneration, cancer, psoriasis, proliferative diabetic retinopathy, asthma, uveitis, osteoarthritis, and rheumatoid arthritis. The same means of multimerization used for an Iglike domain of Flt-1, i. e. , a linker and a multimerization domain, can be used for other polypeptides, including extracellular receptors, antibody variable regions, cytokines, chemokines, and growth factors.

2002004, Apr 18, 2002

Aug 28, 2001

09/941321

Samuel Wadsworth - Shrewsbury MA, US

C12N015/861
C12N007/01
C12N005/06

435/320100, 435/364000, 435/235100

The invention is directed to novel systems for the high level production of purified recombinant adeno-associated virus (rAAV) vector stocks comprising producer cell lines and helper adenoviruses. These systems provide high level production of rAAV vector stocks that are not contaminated by helper viruses or have very minimal contamination with helper virus. The invention is also directed to methods for the production of high yield, purified rAAV vector stocks using the systems of the invention.

2004000, Jan 1, 2004

Aug 7, 2002

10/215272

Samuel Wadsworth - Shrewsbury MA, US
Donna Armentano - Belmont MA, US
Richard Gregory - Westford MA, US
Geoffrey Parsons - Jamaica Plain MA, US

Genzyme Corporation - Cambridge MA

A61K048/00
C07H021/04
C12P021/02
C12N005/06
C07K014/605

514/044000, 536/023500, 435/069400, 435/320100, 435/325000, 530/399000

Compositions, expression vectors and host cells comprising nucleic acid which encodes a precursor glucagon-like peptide 1 (GLP-1) comprising mammalian GLP-1 linked to a heterologous signal sequence are encompassed by the present invention. The invention also relates to a method of promoting insulin production in an individual comprising administering to the individual an effective amount of a nucleic acid encoding a precursor GLP-1. The present invention also relates to a method of treating an individual having a blood sugar defect (e.g., type I or type II diabetes), comprising administering to the individual an effective amount of a nucleic acid encoding the precursor GLP-1. In a particular embodiment, the invention pertains to a method of treating an individual having a blood sugar defect comprising administering to the individual an effective amount of a nucleic acid encoding a precursor GLP-1 wherein the precursor GLP-1 comprises a signal sequence which codes for precursor cleavage at the activation cleavage site of the precursor GLP-1.

2004002, Feb 5, 2004

Nov 12, 2002

10/292893

Abraham Scaria - Framingham MA, US
Samuel Wadsworth - Shrewsbury MA, US

A61K048/00
C12N007/00
C12N015/861

435/456000, 435/235100, 435/320100, 424/093200

The invention relates to recombinant adenoviral vectors for use in delivering a nucleic acid(s) encoding an immunomodulatory molecule(s) to the cells of an individual that allows the vector to reduce or evade the host immune response from the cells of said individual. These vectors could be used to induce tolerance to an adenovirus antigen or transgenic products by transduction of antigen-presenting cells of an individual and/or increase the half-life of antigen-presenting cells in order to enhance immune response against tumor antigens. The invention further relates to recombinant adenoviral vectors for use in delivering desired therapeutic transgenes to cells in patients, said vectors containing at least one nucleic acid encoding an immunomodulatory molecule that allow the vectors containing said nucleic acid(s) to reduce or evade the host antiviral immune response to the adenovirus and one or more transgenes. These vectors are capable of increased persistence in the individual to whom they are administered, thereby facilitating longer term administration of transgenes and reduced immunologic response upon administration. The invention also relates to methods for the use of such vectors in delivering transgenes to patients for therapeutic uses.