Cerus Corporation

Aduro Biotech Inc.

Miltenyi Biotec, Gmbh

Steritech, Inc.

Anza Therapeutics, Inc.

David N Cook

Thomas W Dubensky, Jr

Susan Wollowitz

Aileen Nerio

Adonis Stassinopoulos

Dirk G Brockstedt

John E Hearst

Justin Skoble

Peter M Lauer

William S Luckett, Jr

Henry Rapoport

Jan Matejovic

John E Merritt

William Alexander Denny

Daniel A Portnoy

Keith Sadoon Bahjat

Rodney L Monroy

Thomas W Dubensky

William S Luckett

The invention provides a bacterium containing a polynucleotide comprising a nucleic acid encoding a heterologous antigen, as well as fusion protein partners. Also provided are vectors for mediating site-specific recombination and vectors comprising removable antibiotic resistance genes.

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Engineered Listeria and methods of use thereof

The present invention providesthat are attenuated for entry into non-phagocytic cells as well as a variety of methods of inducing immune responses involving administering compositions comprising the attenuated. Some of the attenuatedare mutantthat comprise at least one mutation in a gene encoding an invasin, such as an internalin. Some of the attenuatedare further attenuated for cell-to-cell spread. Pharmaceutical compositions and vaccines useful in the methods of the invention are further provided. Methods of making and improving vaccines are also provided.

Free-living microbes are provided in which the nucleic acid has been modified so that the microbe is attenuated for proliferation and/or which comprise genetic mutations that attenuate the ability of the microbe to repair its nucleic acid. Methods of using the modified microbes for the loading, activation, and/or maturation of antigen-presenting cells are also provided. Vaccine compositions comprising the modified microbes and/or the antigen-presenting cells and methods of using the vaccines are also provided. The microbes may be further modified to include heterologous antigens, such as tumor antigens or infectious disease antigens, for use as a vaccine against cancer or infectious diseases.

Modified free-living microbes, vaccine compositions and methods of use thereof

The present invention provides recombinant nucleic acid molecules, expression cassettes, and vectors useful for expression of polypeptides, including heterologous polypeptides, such as antigens, in bacteria. Some of the recombinant nucleic acid molecules, expression cassettes and vectors comprise codon-optimized sequences encoding the polypeptides and/or signal peptides. Some of the recombinant nucleic acid molecules, expression cassettes, and expression vectors comprise sequences encoding non-Listerial and/or non-secA1 signal peptides for secretion of the polypeptides. The invention also provides bacteria comprising the nucleic acid molecules, expression cassettes, and expression vectors, as well as compositions such as vaccines comprising the bacteria. Methods of making and using the bacteria, recombinant nucleic acid molecules, and expression cassettes are also provided.

Recombinant nucleic acid molecules, expression cassettes, and bacteria, and methods of use thereof

Methods are provided for quenching undesired side reactions of pathogen inactivating compounds in biological materials comprising red blood cells. In a particular embodiment, methods are provided for quenching undesired side reactions of a pathogen inactivating compound that includes a functional group which is, or which is capable of forming, an electrophilic group. In this embodiment, the material is treated with the pathogen inactivating compound and a quencher, wherein the quencher comprises a nucleophilic functional group that is capable of covalently reacting with the electrophilic group. The electrophilic group on the pathogen inactivating compound is preferably a non-radical cationic group. In one embodiment, the pathogen inactivating compound includes a nucleic acid binding ligand and a mustard group, wherein the mustard group is capable of reacting in situ to form the electrophilic group. Preferred quenchers are thiols, such as glutathione. The methods permit inhibition of the modification of red blood cells in red blood cell containing materials during pathogen inactivation.

Methods for quenching pathogen inactivators in biological materials

Methods of using high-density microparticles to bind and remove pathogens from biological fluids are disclosed. Pathogens include prions, viruses, bacteria and protozoa.

Use of high density microparticles for removal of pathogens

Methods are provided for quenching undesired side reactions of pathogen inactivating compounds in biological materials. In a particular embodiment, methods are provided for quenching undesired side reactions of a pathogen inactivating compound that includes a functional group which is, or which is capable of forming, an electrophilic group. In this embodiment, the material is treated with the pathogen inactivating compound and a quencher, wherein the quencher comprises a nucleophilic functional group that is capable of covalently reacting with the electrophilic group. The electrophilic group on the pathogen inactivating compound is preferably a non-radical cationic group. In one embodiment, the pathogen inactivating compound includes a nucleic acid binding ligand and a mustard group, wherein the mustard group is capable of reacting in situ to form the electrophilic group. Preferred quenchers are thiols, such as glutathione. Biological materials which may be treated include whole blood, red blood cells, blood plasma, and platelets. The methods permit inhibition of the modification of red blood cells in red blood cell containing materials during pathogen inactivation.

Compounds and methods for inactivating pathogens in materials are described, including compositions and methods for inactivating pathogens in biological materials such as red blood cell preparations and plasma. The compounds and methods may be used to treat materials intended for in vitro or in vivo use, such as clinical testing or transfusion. The compounds are designed to specifically bind to and react with nucleic acid, and then to degrade to form breakdown products. The degradation reaction is preferably slower than the reaction with nucleic acid.

Frangible compounds for pathogen inactivation

Methods and compositions for treating pathogens in material are described, including methods of decontaminating human fluids prior to processing in the clinical laboratory and methods for decontaminating blood products prior to in vivo use. The techniques handle large volumes of human serum without impairing the testing results. Novel compounds for photodecontaminating biological material are also contemplated which are compatible with clinical testing, in that they do not interfere with serum analytes.

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Lafayette, CA, United States of America

David N Cook