Jennifer J Harris

US Patent:

6680178, Jan 20, 2004

Filed:

May 25, 2001

Appl. No.:

09/866132

Inventors:

Jennifer L. Harris - San Diego CA
Bradley J. Backes - San Diego CA
Jonathan A. Ellman - Oakland CA
Charles S. Craik - San Francisco CA

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C12Q 137

US Classification:

435 23, 435 24, 435 34, 435 4, 530324, 530350, 530334, 530345, 525 50, 525 541, 549288, 702 22, 702 30

Abstract:

A method is presented for the preparation and use of fluorogenic peptide substrates that allows for the configuration of general substrate libraries to rapidly identify the primary and extended specificity of enzymes, such as proteases. The substrates contain a fluorogenic-leaving group, such as 7-amino-4-carbamoylmethyl-coumarin (ACC). Substrates incorporating the ACC leaving group show comparable kinetic profiles as those with the traditionally used 7-amino-4-methyl-coumarin (AMC) leaving group. The bifunctional nature of ACC allows for the efficient production of single substrates and substrate libraries using solid-phase synthesis techniques. The approximately 3-fold increased quantum yield of ACC over AMC permits reduction in enzyme and substrate concentrations. As a consequence, a greater number of substrates can be tolerated in a single assay, thus enabling an increase in the diversity space of the library. Soluble positional protease substrate libraries of 137,180 and 6,859 members, possessing amino acid diversity at the P4-P3-P2-P1 and P4-P3-P2 positions, respectively, were constructed.

US Patent:

6797461, Sep 28, 2004

Filed:

Sep 19, 2001

Appl. No.:

09/955639

Inventors:

Andrew L. Niles - Madison WI
Mary Haak-Frendscho - Newark CA
Jennifer L. Harris - San Diego CA
Charles S. Craik - San Francisco CA

Assignee:

Promega Corporation - Madison WI

International Classification:

C12Q 100

US Classification:

435 4, 435 23, 530324, 530330

Abstract:

The invention is directed to synthetic polypeptide substrates for tryptase enzymes and assays for tryptase activity that utilize the synthetic polypeptide substrates. The preferred synthetic polypeptide substrates are tetramers of the formula P4-P3-P2-P1, wherein the substrate is selected from the group consisting of P-R-N-K (SEQ. ID. NO: 2), P-K-N-K (SEQ. ID. NO: 3), P-R-N-R (SEQ. ID. NO: 4), P-K-N-R (SEQ. ID. NO: 5), P-A-N-K (SEQ. ID. NO: 6), and P-R-T-K (SEQ. ID. NO: 7).

US Patent:

7109243, Sep 19, 2006

Filed:

Mar 23, 2004

Appl. No.:

10/807612

Inventors:

Hong Liu - San Diego CA, US
David Tully - San Diego CA, US
Robert Epple - San Diego CA, US
Badry Bursulaya - San Diego CA, US
Jennifer Williams - La Jolla CA, US
Arnab Chatterjee - Encinitas CA, US
Jennifer Leslie Harris - San Diego CA, US
Jun Li - San Diego CA, US

Assignee:

IRM LLC - Hamilton

International Classification:

A01N 47/28

US Classification:

514595, 5142375, 514249, 514275, 514279, 51425501, 514330, 514355, 514364, 514359, 514406, 514394, 514422, 514416, 514448, 514459, 514471, 514472, 514602, 514603, 514604, 514522, 514596, 514598, 544165, 544231, 544332, 544312, 544391, 546226, 546316, 548131, 548255, 5482694, 5483044, 5483741, 548492, 548517, 548560

Abstract:

The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme (e. g. , cathespin K). The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.

US Patent:

7384970, Jun 10, 2008

Filed:

Mar 23, 2004

Appl. No.:

10/807613

Inventors:

Hong Liu - San Diego CA, US
Phil Alper - Poway CA, US
Arnab Chatterjee - Encinitas CA, US
David Tully - San Diego CA, US
Badry Bursulaya - San Diego CA, US
David Woodmansee - San Diego CA, US
Robert Epple - San Diego CA, US
Jennifer Leslie Harris - San Diego CA, US
Jun Li - San Diego CA, US

Assignee:

IRM LLC - Hamilton

International Classification:

A61K 31/4045
C07D 209/08

US Classification:

514415, 548491

Abstract:

The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme. The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.

US Patent:

7629437, Dec 8, 2009

Filed:

Oct 15, 2003

Appl. No.:

10/686884

Inventors:

Jennifer L. Harris - San Diego CA, US
Bradley J. Backes - San Diego CA, US
Jonathan A. Ellman - Oakland CA, US
Charles S. Craik - San Francisco CA, US

Assignee:

The Regents of the University of California - Oakland CA

International Classification:

C12Q 1/00
C12Q 1/37
C07K 5/00
C07K 7/00

US Classification:

530300, 530324, 530334, 530345, 530350, 435 4, 435 23, 435 24, 435 34, 525 50, 525 541, 549288

Abstract:

A method is presented for the preparation and use of fluorogenic peptide substrates that allows for the configuration of general substrate libraries to rapidly identify the primary and extended specificity of enzymes, such as proteases. The substrates contain a fluorogenic-leaving group, such as 7-amino-4-carbamoylmethyl-coumarin (ACC). Substrates incorporating the ACC leaving group show comparable kinetic profiles as those with the traditionally used 7-amino-4-methyl-coumarin (AMC) leaving group. The bifunctional nature of ACC allows for the efficient production of single substrates and substrate libraries using solid-phase synthesis techniques.

US Patent:

20030059847, Mar 27, 2003

Filed:

Aug 27, 2002

Appl. No.:

10/229950

Inventors:

Bradley Backes - Chicago IL, US
Jennifer Harris - San Diego CA, US

Assignee:

IRM, LLC - Hamilton

International Classification:

G01N033/53
C12Q001/37
C07K007/06
C07K007/08

US Classification:

435/007100, 435/023000, 530/324000

Abstract:

Non-peptide protease substrate libraries and high purity protease substrate libraries are constructed, e.g., using fluorogenic compounds. The libraries are useful in obtaining substrate profiles for a variety of proteases, such as methods for determining both prime and non-prime protease recognition sequences.

US Patent:

20040009911, Jan 15, 2004

Filed:

Jan 31, 2003

Appl. No.:

10/356656

Inventors:

Jennifer Harris - San Diego CA, US
Bradley Backes - Chicago IL, US
Jun Li - San Diego CA, US
David Tully - San Diego CA, US

Assignee:

IRM, LLC - Hamilton

International Classification:

A61K038/10
A61K038/08
C07K007/08
C07K007/06

US Classification:

514/012000, 514/013000, 514/014000, 514/015000, 514/016000, 514/017000, 530/324000, 530/325000, 530/326000, 530/327000, 530/328000, 530/329000, 530/330000

Abstract:

Substrate specificity profiles are used to determine optimal hepsin substrate sequences, both to the prime side and non-prime side of the hepsin recognition site. The hepsin substrate sequences are used in designing substrates, inhibitors, and prodrugs. For example, prodrugs are provided for use in the treatment of prostate cancer. Hepsin inhibitors based on substrate specificity are also provided.

US Patent:

20050054027, Mar 10, 2005

Filed:

Sep 3, 2004

Appl. No.:

10/933666

Inventors:

Jennifer Harris - San Diego CA, US
Aaron Shipway - Cardiff CA, US

Assignee:

IRM LLC - Hamilton

International Classification:

C12Q001/37
C12Q001/18

US Classification:

435023000, 435032000

Abstract:

This invention provides novel methods for identifying modulators of transmembrane protease serine 6 (TMPRSS6). The methods comprise screening test agents for ability to modulate proteolysis of a pathogenic toxin substrate or a synthetic peptide substrate of TMPRSS6. The methods can further comprise screening the identified modulating agents for ability to inhibit infections of pathogens. Also provided in the invention are methods and pharmaceutical compositions for treating infections of pathogens whose toxins are proteolytically activated by TMPRSS6.