Thomas H Bugge

US Patent:

7947289, May 24, 2011

Filed:

Feb 9, 2005

Appl. No.:

11/055557

Inventors:

Stephen H. Leppla - Bethesda MD, US
Thomas H. Bugge - Bethesda MD, US

Assignee:

The United States of America as represented by the Secretary of the Department of Health and Human Services - Washington DC

International Classification:

A61K 39/02
A61K 39/00
A61K 39/07

US Classification:

4242341, 424 91, 424 92, 4241841, 4241851, 4241921, 4242461, 530300, 530350

Abstract:

The present invention provides compositions comprising modified bacterial toxins and methods for using the modified bacterial toxins for targeting particular cell populations and for treating diseases.

US Patent:

8388933, Mar 5, 2013

Filed:

Apr 15, 2011

Appl. No.:

13/088011

Inventors:

Stephen H. Leppla - Bethesda MD, US
Thomas H. Bugge - Bethesda MD, US

Assignee:

The United States of America as Represented by the Secretary of the Department of Health and Human Services - Washington DC

International Classification:

A61K 49/00
A61K 39/00
A61K 39/07

US Classification:

424 91, 424 92, 4241841, 4241851, 4241921, 4242341, 4242461, 530300, 530350

Abstract:

The present invention provides compositions comprising modified bacterial toxins and methods for using the modified bacterial toxins for targeting particular cell populations and for treating diseases.

US Patent:

20050123476, Jun 9, 2005

Filed:

Sep 5, 2002

Appl. No.:

10/488806

Inventors:

Thomas Bugge - Bethesda MD, US
Stephen Leppla - Bethesda MD, US
David Mitola - Baltimore MD, US

Assignee:

The Government of the United States as represented by the Secretary of the Department of Health and - Rockville MD

International Classification:

A61K051/00
A61K049/00
C12Q001/37

US Classification:

424001490, 424009340, 424009600, 435023000

Abstract:

This invention pertains to methods for imaging the activity of extracellular proteases in cells using the anthrax binary toxin-system to target cells expressing extracellular proteases with mutant anthrax toxin protective antigens (μPrAg) that bind to receptors on the cells and are cleaved by a specific extracellular protease expressed by the cells, and ligands that specifically bind to the cleaved μPrAg and are linked to a moiety that is detectable by an imaging procedure. The μPrAg proteins used in the methods comprise a protease cleavage site that is cleaved by a specific extracellular protease and is in place of the furin cleavage site of the native PrAg. The methods are useful for diagnosing and treating diseases and undesirable physiological conditions correlated with the activity of extracellular proteases, and for optimizing the therapeutic efficacy of drugs used to treat such diseases and conditions.

US Patent:

20080166375, Jul 10, 2008

Filed:

May 6, 2004

Appl. No.:

10/554076

Inventors:

Stephen H. Leppla - Bethesda MD, US
Jennifer Avallone - Flemington NJ, US
Thomas Bugge - Bethesda MD, US
Manuel Osorio - Bethesda MD, US

Assignee:

The Government of the United States of America, as rep. by the Secretary of Health and Human Service - Rockville MD

International Classification:

A61K 39/02
C07H 21/04
C12N 15/00
C07K 16/00
C12N 5/00

US Classification:

4242361, 536 234, 4353201, 530350, 435325

Abstract:

The present invention provides compositions and methods for inhibiting abnormal cell growth. In particular, the invention provides nucleic acids encoding Diphtheria toxin fusion proteins comprising residues 1-388 of Diphtheria toxin, wherein the native furin cleavage site has been substituted for a matrix metalloproteinase or plasminogen activator cleavage site, and a heterologous polypeptide and the polypeptides encoded by such nucleic acids. In addition, the invention provides methods of treating cancer by administering such polypeptides.

US Patent:

20090142794, Jun 4, 2009

Filed:

Oct 20, 2008

Appl. No.:

12/288482

Inventors:

Stephen H. Leppla - Bethesda MD, US
Henning Birkedal-Hansen - Bethesda MD, US
Thomas Bugge - Bethesda MD, US

Assignee:

of Health and Human Services - Rockville MD

International Classification:

C12Q 1/02
C12N 5/06
C12N 5/08
C07K 7/00

US Classification:

435 29, 435375, 435366, 530328

Abstract:

The present invention provides methods of specifically targeting compounds to cells overexpressing matrix metalloproteinases, plasminogen activators, or plasminogen activator receptors, by administering a compound and a mutant protective antigen protein comprising a matrix metalloproteinase or a plasminogen activator-recognized cleavage site in place of the native protective antigen furin-recognized cleavage site, wherein the mutant protective antigen is cleaved by a matrix metalloproteinase or a plasminogen activator overexpressed by the cell, thereby translocating into the cell a compound comprising a lethal factor polypeptide comprising a protective antigen binding site.

US Patent:

20100168012, Jul 1, 2010

Filed:

Dec 14, 2007

Appl. No.:

12/519362

Inventors:

Stephen H. Leppla - Bethesda MD, US
Shihui Liu - Gaithersburg MD, US
Thomas H. Bugge - Bethesda MD, US
Brooke M. Curie - Washington DC, US

Assignee:

The Government of the United States of America as Represented by the Secretary of the Department of - Rockville MD

International Classification:

A61K 38/16
A61P 35/00

US Classification:

514 12

Abstract:

The present invention provides methods for inhibiting tumor associated angiogenesis by administering a mutant protective antigen protein comprising a matrix metalloproteinase-recognized cleavage site in place of the native protective antigen furin-recognized site in combination with a lethal factor polypeptide comprising a protective antigen binding site. Upon cleavage of the mutant protective antigen by a matrix metalloproteinase, the lethal factor polypeptide is translocated into cancer and endothelial cells and inhibits tumor associated angiogenesis.

US Patent:

7468352, Dec 23, 2008

Filed:

Sep 22, 2000

Appl. No.:

10/088952

Inventors:

Stephen H. Leppla - Bethesda MD, US
Henning Birkedal-Hansen - Bethesda MD, US
Thomas Bugge - Bethesda MD, US

Assignee:

The United States of America as represented by the Department of Health and Human Services - Washington DC

International Classification:

A61K 38/00

US Classification:

514 12

Abstract:

The present invention provides methods of specifically targeting compounds to cells overexpressing matrix metalloproteinases, plasminogen activators, or plasminogen activator receptors, by administering a compound and a mutant protective antigen protein comprising a matrix metalloproteinase or a plasminogen activator-recognized cleavage site in place of the native protective antigen furin-recognized cleavage site, wherein the mutant protective antigen is cleaved by a matrix metalloproteinase or a plasminogen activator overexpressed by the cell, thereby translocating into the cell a compound comprising a lethal factor polypeptide comprising a protective antigen binding site.

US Patent:

20180250376, Sep 6, 2018

Filed:

Aug 25, 2016

Appl. No.:

15/755341

Inventors:

- Bethesda MD, US
Stephen H. Leppla - Bethesda MD, US
Thomas H. Bugge - Bethesda MD, US
Alexander N. Wein - Decatur GA, US
Diane E. Peters - Grafton MA, US
Jie Liu - Gaithersburg MD, US
Kuang-Hua Chen - Gaithersburg MD, US

Assignee:

The United States of America as represented by the Secretary Department of Health and Human Services - Bethesda MD

International Classification:

A61K 39/07
A61K 39/00
A61P 35/00
A61K 45/06
C07K 14/325

Abstract:

Disclosed is a protective antigen (PA) comprising a PA amino acid sequence, wherein one or more of amino acid residues I207, I210, E654, I656, R659, M662, Y681, and L687, as defined by reference to SEQ ID NO: 1, are, independently, substituted, with the proviso that amino acid residue I207 is not substituted with alanine and amino acid residue I210 is not substituted with alanine. Related compositions, nucleic acids, recombinant expression vectors, host cells, populations of cells, methods of treating or preventing cancer in a mammal, and methods of inhibiting the growth of a target cell are also disclosed.