The United States of America As Represented by the Administrator of the

New Century Pharmaceuticals, Inc.

Other

United States of America As Represented by the Secretary of the Air Force

University of Kentucky Research Foundation

Binford Holdings, LLC

Daniel C Carter

William K Witherow

Chester Q Li

Vaughn H Yost

Rajesh R Naik

Lawrence James DeLucas

Florian Ruker

Robert S Snyder

Thomas G Burke

Lawrence L Brott

Marc L Pusey

Teresa Y Miller

Morley O Stone

Blair J Herren

Robbie E Smith

Timothy Edward Dowling

Charles E Bugg

Zhongmin Wang

Mary B Broom

Fred L Suddath

Joseph Ho

Diana L Hecht

Zhong Min Wang

Joseph X Ho

A fusion protein is provided which is based on a self-assembling gene-regulatory NSP10 protein and a protein or peptide capable of being fused to NSP10 without interfering with the assembly or aggregation of the resulting fusion protein. The disclosure also relates to any nanoparticle formed thereby whether complete or not, and methods for the use of the NSP10 fusion protein are also disclosed, including use as vaccines for any indication in humans or animals, therapeutic methods involving the use of the fusion proteins such as using the protein to targeted an antibody or receptor, such as for treating or diagnosing cancer, biosensors using the fusion protein, or the use of the fusion proteins in cell sorting or any imaging application.

NSP10 self-assembling fusion proteins for vaccines, therapeutics, diagnostics and other nanomaterial applications

A method and composition is provided that aids in the reduction of objectionable volatile odors when a few drops are placed in the toilet prior to use. In one embodiment, the composition contains a high molecular weight polypropylene glycol (PPG) together with a dispersing agent to create an instantaneous multifunctional surface barrier of the polypropylene glycol/isopropanol mixture across the water surface. The composition may also optionally include one or more essential oils, fragrances or colorants.

Composition for reducing toilet odor containing polypropylene glycol as a reactive gas barrier

A hypoallergenic cleansing, cosmetic, conditioning or dermatological composition for treating skin or hair is provided which contains serum albumin in an amount effective to achieve cleansing, conditioning, wound debrisment, or other beneficial cosmetic or dermatological purpose for skin or hair, along with a suitable cleansing, conditioning, cosmetic, antibacterial or dermatological agent, vehicle, carrier or excipient. The compositions may be in any suitable form for treating skin or hair, such as a soap, shampoo, cream, oil, lotion, gel, gel-based ointment, and the like. The serum albumin compositions are preferably prepared using human serum albumin produced by recombinant means, and such compositions are useful in that they allow the albumin to be absorbed in the surface of skin or hair so as to replenish the structure of these tissues when utilized as a cleansing, cosmetic or dermatological agent. The compositions of the present invention will provide cleansing, cosmetic or dermatological compositions that can be used safely and effectively with reduced likelihood of allergic reaction.

Serum albumin compositions for use in cleansing or dermatological products for skin or hair

The present invention provides methods and formulations for optimizing the anti-cancer and anti-HIV activities of a camptothecin drug, including camptothecin and its related analogs including 9-aminocamptothecin and 9-nitrocamptothecin. The invention involves methodologies and formulations that limit human serum albumin-mediated reduction of the anti-cancer and anti-HIV effects of the camptothecins, and the methods and formulations provide combination therapies in which binding of the camptothecin agent to human serum albumin can be modulated by the administration of a competing agent that also binds human serum albumin. Reduced camptothecin drug binding to human serum albumin can result in elevated camptothecin free drug levels and thus improve the effectiveness of treatment regimens involving these drugs. Further agents such as methotrexate and AZT can also be used in cancer and HIV-positive patients employing camptothecin drugs.

Methods and compositions for optimizing blood and tissue stability of camptothecin and other albumin-binding therapeutic compounds

A Chalaropsis lysozyme (Lysozyme Ch) is provided which has a corrected amino acid sequence and which can be utilized to prepare recombinant proteins having higher activity than those proteins using the incorrect sequence. Methods are also provided to reduce immunogenicity or increase half-life of the lysozyme. The lysozyme Ch of the present invention will be extremely useful in killing bacteria, particularly resistance strains such as MRSA and VISA, and the enzyme can be utilized in a variety of settings wherein bacterial infection has been a particular problem such as the hospital setting or in veterinary applications, and can also be used as an effective means of combating bioterror agents.

Chalaropsis lysozyme protein and its method of use in anti-bacterial applications

An isolated ferritin fusion protein is provided in which ferritin is fused with a protein or peptide capable of being fused to ferritin without interfering with the polymeric self-assembly of the resulting fusion protein, and the protein may be of the endocapsid form when fused at the C terminus or an exocapsid form when fused at the N terminus. These fusion proteins may self-assemble into a variety of useful higher polymeric forms, e.g., capsid or other polymeric aggregate, and they are advantageous in that they are useful in a variety of applications, including human and veterinary vaccines and therapeutics, blood substitutes, image contrast agents, metal chelating agents, gelling agents, protein purification platforms, and therapeutic receptor-binding proteins.

Ferritin fusion proteins for use in vaccines and other applications

The present invention relates to the albumin-guided development of coumarin analogs and the analogs developed thereby. The coumarin analogs of the present invention are identified and isolated by the fact that they have binding sites to albumin which are different than the binding sites of conventional coumarin analogs such as sodium warfarin, and as a result will be less prone to be displaced since the binding site of sodium warfarin is shared by numerous drugs such as aspirin. The coumarin analogs of the invention are advantageous because they can achieve the effects of the prior coumarin analogs with a minimum of metabolic complications and undesirable side effects.

Coumarin analog compounds for safer anticoagulant treatment

A modified serum albumin is provided which has been modified in the n-terminal region or binding region VI, such as through a truncation of at least three amino acids at the n-terminal end, so that it exhibits reduced or eliminated binding of trace metals such as nickel and/or copper. Other suitable modifications to this binding region include mutations such as an elongation or insertion which will be sufficient to disrupt the trace metal binding which is highest at this site. The modified albumin of the present invention is advantageous in that its binding to trace metals is reduced or eliminated, and it can thus be used more safely and effectively than unmodified albumin with a reduced or eliminated likelihood of causing an allergic reaction to the trace metal in the human being treated with the albumin composition.

Modified serum albumin with reduced affinity for nickel and copper

A high resolution structure of the hemalbumin binding complex is provided which includes the detailed atomic coordinates which reflect the binding site and the binding characteristics of the structure. This high resolution structure can be used in methods of determining the primary residues involved in gas binding, redox potential of iron, etc., and thus will be used to identify and optimize the gas binding characteristics of heme and albumin, so as to allow for the development of modified recombinant albumins containing heme and/or heme derivatives which have improved gas binding properties and which can be used for therapeutic purposes.

Atomic structure of the hemalbumin complex and its use in designing therapeutic compounds

An apparatus and method for detecting infrared radiation is provided which comprises a temperature-sensing helical coiled-coil protein such as TlpA, CC1, collagen or myosin, incorporated into an electrically conductive film or gel deposited onto an electrically conductive medium such as an electrode, means for recording changes in conductivity or resistance of the conductive film or gel caused by the presence of infrared radiation and the effect of the infrared radiation on the thermal-sensing protein, and means to analyze the changes in conductivity or resistance in the conductive film caused by the infrared radiation so as to determine if infrared radiation is present. By virtue of the present invention, a 'biomimetic' infrared sensor is provided which can integrate a recombinantly produced thermally sensitive protein in a conductive polymer matrix, such as a film or gel, so as to provide for the first time a low-cost, lightweight, conformable, and even possibly disposable, infrared detecting device having high sensitivity and excellent dynamic range.

Method and apparatus for use of thermally switching proteins in sensing and detecting devices

An animal model is provided which is genetically engineered to express human serum albumin, and such animals may be advantageously used in assessing drugs, vaccines or other therapeutic compounds that may be used in humans. In addition, an animal model is provided which does not manufacture its own albumin and which has been injected with human serum albumin. Through the use of these animal models, drugs and other chemicals can be more accurately assessed in physiological environments that reflect the conditions to be expected in humans, and such models will be useful in assessing new drugs and evaluating toxic substances for potential dangers as carcinogens, mutagens, etc. Other applications include evaluating immunological properties of various albumin-engineered proteins which might be administered to humans as therapeutics or vaccines, and research of disease states, such as genetic diseases, to provide further insight in treating these diseases.

Human albumin animal models for drug evaluation, toxicology and immunogenicity studies

A modified serum albumin is provided which has been modified in the n-terminal region or binding region VI, such as through a truncation of at least one amino acid at the n-terminal end, so that it exhibits reduced or eliminated binding of trace metals such as nickel and/or copper. Other suitable modifications to this binding region include mutations such as an elongation or insertion which will be sufficient to disrupt the trace metal binding which is highest at this site. The modified albumin of the present invention is advantageous in that it is binding to trace metals is reduced or eliminated, and it can thus be used more safely and effectively than unmodified albumin with a reduced or eliminated likelihood of causing an allergic reaction to the trace metal in the human being treated with the albumin composition.

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Huntsville, AL, United States of America

Daniel C Carter