Alison Jane O'Brien

US Patent:

6881411, Apr 19, 2005

Filed:

May 20, 2002

Appl. No.:

10/150058

Inventors:

Marian L. McKee - Great Falls VA, US
Alison D. O'Brien - Bethesda MD, US
Marian R. Wachtel - Albany CA, US

Assignee:

Henry M. Jackson Foundation for the Advancement of Military Medicine - Rockville MD

International Classification:

C12P021/06

US Classification:

4241841, 4242341, 4242523, 435 691, 435410, 435420, 435 693, 435 6, 435470, 536 231, 536 232, 536 237, 536 2371, 514 44

Abstract:

This invention satisfies needs in the art by providing intimin, the Enterohemorrhagic (EHEC) adherence protein, alone or as a fusion protein with one or more other antigens, expressed by transgenic plants and the use of those plants as vehicles for stimulating a protective immune response against EHEC and the one or more other antigens. Various plant species are transformed to protect various animal species and also humans against EHEC, against pathogens expressing intimin-like proteins, and against pathogens expressing any of the one or more other antigens to which intimin may be fused. The eae gene encoding intimin, a functional portion thereof, or a recombination that encodes a fusion protein is put under the control of a constitutive plant promoter in a plasmid and the plasmid is introduced into plants by the type of transformation appropriate for the particular plant species. The engineered plants expressing intimin or the intimin fusion protein are then fed to animals and/or humans to elicit the production of antibodies, which protect the animals/humans against EHEC colonization and infection, and against pathogens expressing the one or more other antigens and any cross-reactive antigens. The invention may also be practiced by expressing the intimin or intimin fusion protein in other host organisms such as bacteria, yeast, and fungi.

US Patent:

6942861, Sep 13, 2005

Filed:

Apr 18, 1997

Appl. No.:

08/837459

Inventors:

Marian L. McKee - Great Falls VA, US
Alison D. O'Brien - Bethesda MD, US
Marian R. Wachtel - Gaithersburg MD, US

Assignee:

Henry M. Jackson Foundation for the Advancement of Military Medicine - Rockville MD

International Classification:

A61K039/00

US Classification:

4241691, 4241641, 4241841, 4241851, 4242571, 4242341, 530350, 5303882, 5303871, 5303884, 4353201, 435 691, 435325, 43525233, 435 6, 435410, 435420

Abstract:

The present invention describes the isolation and purification of histidine-tagged functional portions of intimin (his-tagged intimin or his-intimin), a protein associated with the ability of certain strains of pathogenic bacteria to adhere to epithelial cells. The invention further describes the use of intimin as an antigen to promote a protective immune response. In addition, the invention describes the combination of intimin with one or more other antigens and administration of the combination to promote a protective immune response against intimin and the one or more antigens. One aspect of the invention is the administration of intimin to target specific epithelial cells to promote a protective immune response to intimin proteins. Additional aspects of the invention include the use of intimin or intimin combined with one or more antigens and administration of the combination to target gastrointestinal mucosa and stimulate an immune response. Additionally, the invention describes administration of the combination of intimin combined with drugs, to provide a means for targeted delivery of drugs to specific epithelial cells.

US Patent:

8293245, Oct 23, 2012

Filed:

Apr 20, 2007

Appl. No.:

11/788546

Inventors:

Michael Smith - Silver Spring MD, US
Alison O'Brien - Bethesda MD, US

Assignee:

The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. - Rockville MD

International Classification:

A61K 39/00

US Classification:

4241921, 530300, 530350

Abstract:

The invention is based on the discovery of the epitope in the Stx1 protein for the 13C4 antibody. The invention features non-full length Stx1 polypeptides that include the epitope for the 13C4 monoclonal antibody epitope. The invention also features methods of producing anti-Stx1 antibodies specific for the 13C4 epitope of the Stx1 protein. Additionally, the invention features methods for treating a subject having, or at risk of developing, a Shiga toxin associated disease (e. g. , hemolytic uremia syndrome and diseases associated with and infection) with a polypeptide that includes the 13C4 epitope or with an anti-Stx1 antibody developed using the methods of the invention. Furthermore, the invention features the detection of Stx1 in a sample using the antibodies developed using the methods of the invention.

US Patent:

20050244425, Nov 3, 2005

Filed:

Apr 19, 2005

Appl. No.:

11/108864

Inventors:

Marian McKee - Great Falls VA, US
Alison O'Brien - Bethesda MD, US
Marian Wachtel - Gaithersburg MD, US

International Classification:

A61K039/02
C12P021/06
C07K014/245

US Classification:

424190100, 530350000, 435069100

Abstract:

The present invention describes the isolation and purification of histidine-tagged functional portions of intimin (his-tagged intimin or his-intimin), a protein associated with the ability of certain strains of pathogenic bacteria to adhere to epithelial cells. The invention further describes the use of intimin as an antigen to promote a protective immune response. In addition, the invention describes the combination of intimin with one or more other antigens and administration of the combination to promote a protective immune response against intimin and the one or more antigens. One aspect of the invention is the administration of intimin to target specific epithelial cells to promote a protective immune response to intimin proteins. Additional aspects of the invention include the use of intimin or intimin combined with one or more antigens and administration of the combination to target gastrointestinal mucosa and stimulate an immune response. Additionally, the invention describes administration of the combination of intimin combined with drugs, to provide a means for targeted delivery of drugs to specific epithelial cells. Other aspects of the invention include the production of antibodies directed against his-intimin and methods of using such antibodies to provide passive immune protection, and in an assay system.

US Patent:

20090226469, Sep 10, 2009

Filed:

Feb 16, 2007

Appl. No.:

12/279423

Inventors:

Michael J. Smith - Silver Spring MD, US
Alison D. O'Brien - Bethesda MD, US
Louise D. Teel - Silver Spring MD, US

International Classification:

A61K 39/00
C07K 14/00
C07K 16/00
C07H 21/04
C12N 15/63
C12N 5/10
C12P 21/00
A61P 1/12

US Classification:

4241841, 530350, 5303891, 536 231, 4353201, 435325, 435 691

Abstract:

A chimeric Shiga toxoid according to the invention contains an enzymatically-inactivated StxA subunit and a native StxB subunit. This hybrid Shiga toxoid induces the production of broadly cross-reactive species of antibodies against Shiga toxin following immunization. The StxA subunit is modified so that it is enzymatically inactive. The invention thus encompasses the Shiga toxoid or fragments thereof and the nucleic acid sequence of the Shiga toxoid or fragments thereof. The invention further encompasses the production of a Shiga toxoid, the production of antibodies using the Shiga toxoid and methods of productions, and an immunogenic composition containing the Shiga toxoid.

US Patent:

20090258010, Oct 15, 2009

Filed:

May 31, 2007

Appl. No.:

12/302748

Inventors:

Marc Riviere - Saint Lambert, CA
Mariam Mehran - Blainville, CA
Alison O'Brien - Bethesda MD, US
Janique Sam-Pan - Laval, CA

Assignee:

Thallion Pharmaceuticals, Inc. - Montreal

International Classification:

A61K 39/395

US Classification:

4241331

Abstract:

The invention features methods, compositions, and kits for treating a subject having a Shiga toxin associated disease with chimeric anti-Shiga Toxin 1 (cαStx1) and anti-Shiga Toxin 2 (cαStx2) antibodies.

US Patent:

20110318357, Dec 29, 2011

Filed:

Jan 21, 2010

Appl. No.:

13/142556

Inventors:

Alison O'Brien - Bethesda MD, US
Michael Smith - Silver Spring MD, US
James Sinclair - Baltimore MD, US

Assignee:

The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. - Rockville MD

International Classification:

A61K 39/00
C12N 15/11
C12N 15/70
A61K 38/02
C07K 16/12
C12N 1/21
A61P 31/00
A61P 37/04
C12P 21/00
C12N 5/16
G01N 33/566
C07K 19/00
A61K 39/40

US Classification:

4241391, 530409, 536 231, 4353201, 4241851, 514 11, 5303879, 435 702, 435 703, 435331, 436501, 43525233

Abstract:

The invention is based on the discovery of the epitope in the Stx2 protein for the 11 E1O antibody. The invention features compositions containing non-full length Stx2 polypeptides that include the 11 E1O monoclonal antibody epitope. The invention also features methods of producing anti-Stx2 antibodies specific for the 11 E1O epitope of the Stx2 protein. Additionally, the invention features methods for treating a subject having, or at risk of developing, a Shiga toxin associated disease (e.g., hemolytic uremia syndrome and diseases associated with and infection) with a polypeptide that includes the 11 E1O epitope or with an anti-Stx2 antibody developed using the methods of the invention. Furthermore, the invention features the detection of Stx2 in a sample using the antibodies developed using the methods of the invention.

US Patent:

20120195891, Aug 2, 2012

Filed:

Mar 6, 2012

Appl. No.:

13/412735

Inventors:

Marc Riviere - Saint Lambert, CA
Mariam Mehran - Blainville, CA
Alison O'Brien - Bethesda MD, US
Janique Sam-Pan - Laval, CA

Assignee:

The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. - Rockville MD
Thallion Pharmaceuticals, Inc. - Dorval

International Classification:

A61K 39/40
A61P 31/04

US Classification:

4241331

Abstract:

The invention features methods, compositions, and kits for treating a subject having a Shiga toxin associated disease with chimeric anti-Shiga Toxin 1 (cαStx1) and anti-Shiga Toxin 2 (cαStx2) antibodies.