The United States of America, As Represented by the Secretary, Department of Health and Human Services

Emory University

University of Georgia Research Foundation, Inc.

Jan Pohl

Conrad Padraig Quinn

Pavel Svoboda

Vera A Semenova

James Travis

William M Shafer

Neelesh Bangalore

Dennis C Liotta

Walid M Heneine

William M Switzer

Ngoc-Anh Le

John A Petros

Joseph M Kinkade, Jr

Chou-Pong Pau

Brian R Roberts

Jennifer L Gooch

W Virgil Brown

Ae Saekhou Youngpairoj

Raymond Shapira

Peter E Jensen

Shannon Dalton

Shiow-Jyi Wey

Jarad M Schiffer

Joan F Karr

Timothy Clyde Granade

HaoQiang Zheng

William Marshall Switzer

Disclosed are monoclonal antibodies that specifically bind emtricitabine (FTC). Methods are also disclosed for using these antibodies to detect FTC in samples. In some embodiments, these methods are of use for determining if a subject is complying with a therapeutic or prophylactic protocol. In other embodiments, methods are disclosed for determining the dose of FTC to administer to a subject.

Monoclonal antibody for the detection of the antiretroviral drug emtricitabine (FTC, 2',3&#x2032;-dideoxy-5-fluoro-3&#x2032;-thiacytidine)

Regions ofprotective antigen are provided representing epitopes recognized by antibodies in subjects that have acquired immunity toinfection. The recognition of these epitopes correlates with autoimmunity in a subject. Also provided are vaccines that include at least one of these epitopes that when administered to a subject provide improved acquired immunity.

[object Object]

Regions ofprotective antigen are provided representing sequences recognized by antibodies in subjects that have vaccine induced lethal toxin neutralizing anti-PA IgG responses. The recognition of these PA regions enhances the utility of anti-PA IgG reactivity as an immune correlate of protection against anthrax in a subject and increases predictive probability of survival. Also provided are vaccines that include at least one of these PA regions that when administered to a subject improve the predictive value of vaccine induced anti-PA IgG and TNA responses as immune correlates of protection against inhalation anthrax.

One aspect of the present disclosure encompasses methods for determining a protein kinase or phosphatase activity in a biological sample, comprising: contacting in a reaction mix a first test sample and a fluorescently-labeled peptide substrate capable of being modified by a protein phosphatase or a protein kinase, contacting the reaction mix with a TiOmatrix, thereby partitioning fluorescently-labeled phosphorylated peptide from fluorescently-labeled dephosphorylated peptide; and determining the fluorescence of the fluorescently-labeled dephosphorylated peptide, thereby determining a protein kinase or phosphatase activity.

Methods for determining calcineurin activity, and uses in predicting therapeutic outcomes

This invention related generally to methods of detecting and quantifying biomarkers of oxidative stress in proteins. The biomarker may be any amino acid that has undergone oxidation (or other modification, e.g. chloro-tyrosine, dityrosine). Emphasis is given herein on oxidized sulfur- or selenium-containing amino acids (SSAA). The biomarker of oxidative stress in proteins may be detected with an antibody that binds to oxidized amino acids, specifically oxidized sulfur- or selenium-containing amino acids. The antibody may be monoclonal or polyclonal. The presence of biomarker or amount of biomarker present in a sample may be used to aid in assessing the efficacy of environmental, nutritional and therapeutic interventions, among other uses.

Biomarkers for oxidative stress

The present invention relates to improved methods for introducing nucleic acid into cells by first complexing the nucleic acid with a selected polycationic oligomer which neutralizes the negative charge of the nucleic acid, and then contacting the cell with the complex facilitating uptake of the nucleic acid into the cells as a complex with the oligomer. The methods are preferably applied to introduction of nucleic acid into eukaryotic cells, and more preferably into human cells. The invention also relates to methods of introducing antisense and triplex-forming oligonucleotides into prostate cancer cells to inhibit expression of proteins associated with (or that promote) malignancy and to inhibit cell growth or proliferation. More particularly, the invention relates to a method for inhibiting the expression of the HER-2/NEU protein in prostate cancer cells and to a method for inhibiting prostate cancer cell growth or proliferation.

Polycationic oligomers

Peptides which exhibit antimicrobial activity comparable to certain known antibiotics are provided. These peptides are related in sequence to amino acid sequences within Cathepsin G. A broad spectrum bactericidal peptide disclosed herein is RPGTLCTVAGWGRVSMRRGT (SEQ ID NO:22). It is active against Pseudomonas aeruginosa, Neisseria gonorrhoeae and Staphylococcus aureus. RRENTQQHITARRAIRHPQY (SEQ ID NO:19) and GKSSGVPPEVFTRFVSSFLPWIRTTMR (SEQ ID NO:26) also exhibited potent activity against P. aeruginosa strains, including clinical isolates. IIGGR (SEQ ID NO:1) and IVGGR (SEQ ID NO:2) act against both gram-negative and gram-positive bacterial strains. HPQYNQR (SEQ ID NO:3) and certain related peptides are also active against both gram-negative and gram-positive bacteria, including, but not limited to, strains of Escherichia coli, Neisseria gonorrhoeae, Staphylococcus aureus, Capnocytophage sputigena and Pseudomonas aeruginosa. The peptides of the present invention will be useful in pharmaceutical compositions useful in the treatment of prophylaxis of infections.

Antimicrobial peptides

Peptides which exhibit antimicrobial activity comparable to certain known antibiotics are provided. These peptides are related in sequence to amino acid sequences within Cathepsin G. A broad spectrum bactericidal peptide disclosed herein is RPGTLCTVAGWGRVSMRRGT (SEQ ID NO:22). It is active against Pseudomonas aeruginosa, Neisseria gonorrhoeae and Staphylococcus aureus. RRENTQQHITARRAIRHPQY (SEQ ID NO:19) and GKSSGVPPEVFTRFVSSFLPWIRTTMR (SEQ ID NO:20) also exhibited potent activity against P, aeruginosa strains, including clinical isolates. IIGGR (SEQ ID NO:1) and IVGGR (SEQ ID NO:2) act against both gram-negative and gram-positive bacterial strains. HPQYNQR (SEQ ID NO:3) and certain related peptides are also active against both gram-negative and gram-positive bacteria, including, but not limited to, strains of Escherichia coli, Neisseria gonorrhoeae, Staphylococcus aureus, Capnocytophage sputigena and Pseudomonas aeruginosa. The peptides of the present invention will be useful in pharmaceutical compositions useful in the treatment of prophylaxis of infections.

Growing community of inventors

Tucker, GA, United States of America

Jan Pohl