Council of Scientific and Industrial Research

US Government as Represented by the Secretary of the Army

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

The United States of America as Represented by the Department of Health

Indian Council of Medical Research

University of Delhi

Yogendra Singh

Stephen H Leppla

Naveen Arora

Kurt R Klimpel

John B Robbins

Rachel Schneerson

Puranam Usha Sarma

Peter J Nicholls

Kurt Klimpel

Ramandeep Singh

Peter J Nichols

Preetida Jagdish Bhetariya

Anil Kumar Tyagi

Vivek Rao

Taruna Madan Gupta

Vadakkuppattu Devasenapathi Ramanathan

Chinnambedy Nainarappan Paramasivan

Anupam Varma

Paranji Ramaiyenger Narayanan

Hemant Khanna

Three important species ofandare known to contribute to the pathogenicity of allergic and invasive diseases in humans. They are also known to be plant pathogens. Several important ESTs/genes ofspecies are now identified and characterized. Efforts are still needed to explore 30% genes ofspecies for their valuable products which need to be explored. Polyketide biosynthetic pathway inspecies produce important secondary metabolites like polyketide toxins such as Aflatoxins, drugs such as Lovastatins and several other important pharmaceutically important polyketide compounds etc. With the availability ofgenome sequences it is possible today to characterize the structure and function of important genes ofspecies. Based on the gene sequence information on PKS enzymes in medically and agriculturally importantspecies such asandsequences of diagnostic use are identified and a multiplex PCR assay is developed using clinical and agricultural samples.

Diagnostic assays for the detection and identification of aspergilli

The invention relates to improved methods of producing and recoveringprotective antigen (PA), especially modified PA which is protease resistant, and to methods of using of these PAs or nucleic acids encoding these PAs for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of,bacterial infections and which are useful to prevent and/or treat illnesses caused by, such as inhalation anthrax, cutaneous anthrax and gastrointestinal anthrax.

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The present invention provides mutantstrains harboring a modified tyrosine phosphatase gene (mptpA or mptpB) wherein the mutantstrain is incapable of expressing the active tyrosine phosphatase. The invention provides a method for developing the said mutant strain from eitheror. The mptpA or mptpB gene may be modified by replacing the internal sequences with an antibiotic resistance marker gene, which disrupts the expression of the active gene. The invention further provides a recombinant vector comprising the modified mptpA or mptpB which may be used to develop the mutant strains of mycobacteria. The invention provides a method to assess the role of tyrosine phosphatases MptpA and MptpB in the virulence and pathogenesis ofwhich can be used as potential targets for developing anti-tubercular drug.

The present invention relates to a novel molecule useful for anthrax toxin inhibition in vivo and also provides a method for in vivo inhibition of anthrax toxin action using the new molecule.

Protein molecule useful for inhibition of anthrax toxin

The present invention provides a nucleic acid encoding a fusion protein comprising a nucleotide sequence encoding the anthrax protective antigen (PA) binding domain of the native anthrax lethal factor (LF) protein and a nucleotide sequence encoding an activity inducing domain of a second protein. Also provided is a nucleic acid encoding a fusion protein comprising a nucleotide sequence encoding the translocation domain and LF binding domain of the native anthrax PA protein and a nucleotide sequence encoding a ligand domain which specifically binds a cellular target. Proteins encoded by the nucleic acid of the invention, vectors comprising the nucleic acids and hosts capable of expressing the protein encoded by the nucleic acids are also provided. A composition comprising the PA binding domain of the native LF protein chemically attached to a non-LF activity inducing moiety is further provided. A method for delivering an activity to a cell is provided. The steps of the method include a) administering to the cell a protein comprising the translocation domain and the LF binding domain of the native PA protein and a ligand domain, and b) administering to the cell a product comprising the PA binding domain of the native LF protein and a non-LF activity inducing moiety, whereby the product administered in step b) is internalized into the cell and performs the activity within the cell. The invention also provides proteins including an anthrax protective antigen which has been mutated to replace the trypsin cleavage site with residues recognized specifically by the HIV-1 protease.

Anthrax toxin fusion proteins and related methods

The present invention provides a nucleic acid encoding a fusion protein, comprising a nucleotide sequence encoding the protective antigen (PA) binding domain of the native lethal factor (LF) protein and a nucleotide sequence encoding an activity inducing domain of a second protein. Also provided is a nucleic acid encoding a fusion protein, comprising a nucleotide sequence encoding the translocation domain and LF binding domain of the native PA protein and a nucleotide sequence encoding a ligand domain which specifically binds a cellular target. Proteins encoded by the nucleic acid of the invention, vectors comprising the nucleic acids and hosts capable of expressing the protein encoded by the nucleic acids are also provided. A composition comprising the PA binding domain of the native LF protein chemically attached to a non-LF activity inducing moiety is further provided. A method for delivering an activity to a cell is provided. The steps of the method include administering to the cell a protein comprising the translocation domain and the LF binding domain of the native PA protein and a ligand domain, and administering to the cell a product comprising the PA binding domain of the native LF protein and a non-LF activity inducing moiety, whereby the product administered is internalized into the cell and performs the activity within the cell.

Anthrax toxin fusion proteins, nucleic acid encoding same

Growing community of inventors

Delhi, India

Yogendra Singh