<?xml version="1.0" encoding="us-ascii"?><rss version="2.0"><channel><title>NIH OTT RSS Feed - Infectious Diseases - Therapeutics</title><link>http://www.ott.nih.gov/rss/default.aspx</link><description>Office of Technology Transfer (OTT).</description><copyright>Copyright 2009 NIH Office of Technology Transfer (OTT). All rights reserved.</copyright><item><title>A Novel HIV-1 Entry Inhibitor</title><description><![CDATA[The subject invention describes a novel polypeptide comprising a single human CD4 domain (mD1.22) which is highly soluble and stable with significantly higher neutralizing activity and lower non-specific binding to human blood cell lines.  More specifically, mD1.22 is highly promising for several applications due to its biophysical properties:  1) for conjugating with cytotoxic molecules for eradication of HIV-infected cells; 2) for generating multi-specific multi-valent HIV inhibitors with high neutralization potency and breadth, and relatively small molecular size; 3) for generating nanobio-sensors for rapid HIV detection; and 4) for studying the biological functions of CD4 in immune responses and HIV entry.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2566</link><pubDate>2013-05-22</pubDate></item><item><title>Novel Fusion Proteins for HIV Vaccine</title><description><![CDATA[The subject invention describes novel fusion proteins (CD4i antibody-HIV-1 envelop glycoprotein (gp120)) which can be used as 1) potential vaccine immunogens that could be more efficient than gp120 alone; 2) candidate therapeutics; and 3) research reagents for exploration of HIV-1 gp120 conformational flexibility, elucidation of mechanisms of virus entry, and evasion of immune responses.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2567</link><pubDate>2013-05-22</pubDate></item><item><title>New Molecules for HIV Therapeutics: Fab, scFv, and Related Binding Molecules Specific for HIV-1 Rev</title><description><![CDATA[The invention offered for licensing and commercial development is in the field of HIV therapeutics. More specifically, the invention relates to methods and compositions for treating and/or inhibiting HIV infection or any other lentivirus. The invention describes the identification, though phage display, of a chimeric rabbit/human anti-Rev Fab (SJS-R1) that can inhibit polymerization of the HIV Rev protein and thus inhibit its normal function in virus replication. The Fab binds with very high affinity to a conformational epitope in the N-terminal half of HIV-1 Rev. The corresponding single chain antibody (scFv) was also prepared and characterized. Methods of making and using SJS-R1 Fab and SJS-R1 scFv, and antibodies and antibody fragments that share at least one CDR with SJS-R1 Fab, are provided. Specific described methods include methods of preventing or reversing polymerization of HIV Rev, methods of reducing infectivity of replication of a lentivirus, inhibiting Rev function in a cell infected with a lentivirus, and methods of treating a disease or symptom associated with Rev expression in an animal.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2242</link><pubDate>2013-04-17</pubDate></item><item><title>HIV-Neutralizing Polypeptides: A Novel Use for Platelet Factor 4 or Its Derivatives</title><description><![CDATA[The subject invention describes the method for using Platelet Factor 4 (PF4), also called CXCL4, to inhibit HIV viral entry by blocking GP120 independent of HIV receptor. It also demonstrates that the active polypeptide fragment(s) of PF-4 could be used to identify potential peptide mimics or small molecules that could be used to inhibit HIV infection. PF4 and/or its derivatives may be developed as a systemic therapy or preventive measure using topical applications, such as microbicides. In addition, CXCL4 serum/plasma testing could be used as a clinical marker of HIV disease status to predict/monitor the efficacy of treatment and determine the prognosis of a subject with HIV infection.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2547</link><pubDate>2013-04-04</pubDate></item><item><title>Human Antibodies and Fusion Proteins with Potent and Broad HIV-1 Neutralizing Activity</title><description><![CDATA[The inventions listed below provide multiple novel human anti-HIV-1 domain antibodies (m36 and its affinity- matured versions) and their fusion proteins with two-domain or single-domain human soluble CD4 (sCD4) that can potentially be used alone or synergistically with other anti-HIV-1 antibodies and antiretroviral drugs as therapeutics and/or preventatives for infection by different HIV-1 strains.

Some of the inventions listed below also describe some fusion proteins as vaccine immunogens that could elicit broadly neutralizing antibodies against HIV-isolates from different clades. One invention also describes the methods to prepare and use the immunogens in the vaccination for prevention of HIV-1 infections. More specifically, the later invention provides a vaccine composed of a primary immunogen and a secondary immunogen, and a method for making the vaccine which could be effective in eliciting desired broadly neutralizing antibodies. The primary immunogen could be effective in activating B cell receptors (BCRs) that are on the maturational pathways of the desired antibodies and have an intermediate degree of somatic mutational diversity. The secondary immunogen contains epitopes of the desired antibodies and could be effective in further diversifying the BCRs sufficiently to form mature BCRs that have the identical or substantially identical sequence as the desired antibodies.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2482</link><pubDate>2013-03-18</pubDate></item><item><title>Cross-Reactive Dengue Fully Human Monoclonal Antibodies</title><description><![CDATA[Among the arthropod-borne flaviviruses, the four dengue virus serotypes, dengue type 1 virus (DENV-1), dengue type 2 virus (DENV-2), dengue type 3 virus (DENV-3), and dengue type 4 virus (DENV-4) are most important in terms of human morbidity and geographic distribution. Dengue viruses cause dengue outbreaks and major epidemics in most tropical and subtropical areas where Aedes albopictus and Aedes aegypti mosquitoes are abundant.

A safe and effective vaccine against dengue is currently not available. Passive immunization with monoclonal antibodies from non-human primates or humans represents a possible alternative to vaccines for prevention of illness caused by dengue virus.  This invention claims fully human monoclonal antibodies that bind and neutralize dengue type 1, 2, 3 and 4 viruses.  It also claims fragments of such antibodies and nucleic acids encoding the antibodies of the invention as well as prophylactic, therapeutic and diagnostic methods employing the antibodies and nucleic acids of the invention.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2508</link><pubDate>2013-03-18</pubDate></item><item><title>Novel Host Target for Treatment of Hepatitis C Virus Infection</title><description><![CDATA[The subject technology is a newly discovered Interferon-lambda 4 (IFNL4) protein found through analysis of genomic data derived from primary human hepatocytes, molecular cloning and functional annotation. The IFNL4 protein is related to but distinct from other know IFNs and its expression is inducible in conditions that mimic viral infection. Preliminary studies indicate that this protein may play a role in impaired natural and treatment induced clearance of HCV. These findings suggest that the protein can potentially be a new target for treating HCV infection.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2539</link><pubDate>2013-03-18</pubDate></item><item><title>Small, Stable, Functional, Soluble, Monomeric IgG1 Fc Molecules Engineered Therapies</title><description><![CDATA[This technology relates to small (~27 kDa) antibody fragments that are potentially useful for therapeutic development.  These are monomeric IgG fragment crystalizable (mFc) compositions; they are long half-lived, functional (pH dependent binders of neonatal Fc receptor - FcRn); and they are soluble and express efficiently in E. coli.  These molecules may serve as a platform for development of engineered mFc-based antibodies and fusion proteins with therapeutic applications.  Efforts to engineer antibody-based therapeutics, to date, have encountered technical limitations due to the relatively large fragment size and short fragment half-life.  The IgG fragment crystalizable (Fc) is a dimer of two constant domains (CH2-CH3 chains).  Fc has a long half-life, which makes it promising as a candidate for engineering antibody therapeutics.  Fusion proteins based on Fc dimer molecules demonstrate extended half-life, due to the ability to bind FcRn at acidic pH.  However, the relatively large size of the Fc domains (~50 kD) is not optimal.  This technology uses smaller (~27 kDa) mFc compositions that retain efficient binding to human FcRn and demonstrate long half-life.  These mFc compositions are promising for the development of novel therapeutics because the smaller size may allow for superior access to targets and tissues compared to full sized mAbs and larger fragment-based therapeutics, while also retaining important function characteristics.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2512</link><pubDate>2013-02-19</pubDate></item><item><title>Murine Monoclonal Antibodies Effective To Treat Respiratory Syncytial Virus</title><description><![CDATA[Available for licensing through a Biological Materials License Agreement are the murine MAbs described in Beeler et al, "Neutralization epitopes of the F glycoprotein of respiratory syncytial virus: effect of mutation upon fusion function," J Virol. 1989 Jul;63(7):2941-2950 (PubMed abs).  The MAbs that are available for licensing are the following: 1129, 1153, 1142, 1200, 1214, 1237, 1112, 1269, and 1243.  One of these MAbs, 1129, is the basis for a humanized murine MAb (see U.S. Patent 5,824,307 to humanized 1129 owned by MedImmune, Inc.), recently approved for marketing in the United States.  MAbs in the panel reported by Beeler et al. have been shown to be effective therapeutically when administered into the lungs of cotton rats by small-particle aerosol.  Among these MAbs several exhibited a high affinity (approximately 109M-1) for the RSV F glycoprotein and are directed at epitopes encompassing amino acid 262, 272, 275, 276 or 389.  These epitopes are separate, nonoverlapping and distinct from the epitope recognized by the human Fab of U.S. Patent 5,762,905 owned by The Scripps Research Institute.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=352</link><pubDate>2013-02-14</pubDate></item><item><title>Enzymatically-Active RNA-Dependent RNA Polymerase From a Human Norovirus (Calicivirus)</title><description><![CDATA[The noroviruses (formerly known as ?Norwalk-like viruses?) are associated with gastroenteritis outbreaks, affecting large numbers of individuals each year.  Emerging data are supporting their increasing recognition as important agents of diarrhea-related morbidity and mortality.  The frequency with which noroviruses are associated with gastroenteritis as ?food and water-borne pathogens? has led to the inclusion of caliciviruses as Category B Bioterrorism Agents/Diseases.  Because the noroviruses cannot be propagated by any means in the laboratory, an important strategy in their study is to development of molecular biology-based tools and replication systems.  This invention reports the isolation of the first recombinant, enzymatically-active proteinase and RNA dependent RNA polymerase (RdRp) complex for a human norovirus.  This enzyme should facilitate studies aimed at developing therapeutic drugs for norovirus disease.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=908</link><pubDate>2013-02-14</pubDate></item><item><title>Construction of an Infectious Full-Length cDNA Clone of the Porcine Enteric Calicivirus RNA Genome</title><description><![CDATA[Porcine enteric calicivirus (PEC) is a member of the genus Sapovirus in the family Caliciviridae.  This virus causes diarrheal illness in pigs, and is presently the only enteric calicivirus that can be grown in cell culture.  In addition to its relevance to veterinary medicine as a diarrheal agent in pigs, PEC serves as an important model for the study of enteric caliciviruses that cause diarrhea and that cannot be grown in cell culture (including the noroviruses represented by Norwalk virus).  The development of an infectious cDNA clone is important because it enables the use of ?reverse genetics? to engineer mutations of interest into the genome of PEC and to study their effects.  In addition, it allows the introduction of foreign coding sequences into the genome of PEC that could be useful for vaccine development in swine and possibly humans.  This discovery has both basic research applications such as mapping mutations involved in tissue culture adaptation, tissue tropism, and virulence as well as practical applications such as providing a genetic backbone for the development of chimeric vaccine viruses.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=909</link><pubDate>2013-02-14</pubDate></item><item><title>Construction of Recombinant Baculoviruses Carrying the Gene Encoding the Major Capsid Protein, VP1, From Calicivirus Strains (Including Norovirus Strains Toronto, Hawaii, Desert Shield, Snow Mountain, and MD145-12)</title><description><![CDATA[The noroviruses (known as "Norwalk-like viruses") are associated with an estimated 23,000,000 cases of acute gastroenteritis in the United States each year.  Norovirus illness often occurs in outbreaks, affecting large numbers of individuals, illustrated recently by well-publicized reports of gastroenteritis outbreaks on several recreational cruise ships and in settings such as hospitals and schools.  Norovirus disease is clearly important in terms of medical costs and missed workdays, and accumulating data support its emerging recognition as important agents of diarrhea-related morbidity.

Because the noroviruses cannot be propagated by any means in the laboratory, an important strategy in their study is the development of molecular biology-based tools.  This invention reports the development of recombinant baculoviruses carrying the capsid gene from several caliciviruses associated with human disease.  Growth of these baculovirus recombinants in insect cells results in the expression of virus-like particles (VLPs) that are antigenically indistinguishable from the native calicivirus particle.  These VLPs can be purified in large quantities for use as diagnostic reagents and potential vaccine candidates.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=910</link><pubDate>2013-02-14</pubDate></item><item><title>HIV Therapeutics Utilizing Peptide Secreting Commensal Bacteria</title><description><![CDATA[A patent estate covering genetically engineered commensal bacteria compositions and their methods of use that secrete HIV infectivity interfering peptides with the aid of co-expressed translocation mediators, such as HylB, HylD or tolC gene products. The bacteria can be, for example, Escherichia coli, and are preferably those that colonize the gastrointestinal or genitourinary tracts. The secreted anti-HIV peptide can be a functional inhibitory fragment from the C-terminus of HIV, SHIV or SIV, or an inhibitory peptide derived from the N-terminus receptor-binding domain of SIV gp41, HIV-1 gp41, or HIV-2 gp41. The secreted anti-HIV peptide can also be a peptide from the allosteric domain of gp120, an extracellular loop of CCR5, an anti-CD4 immunoglobulin, a mimetic of CD4, an alpha-defensin or theta-defensin, a CD38 fragment homologous to the V3 loop of gp120, polphemusin II (a CXCR4 antagonist), or a RANTES peptide that binds to CCR5 or an HIV surface binding peptide, such as cyanovirin.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1000</link><pubDate>2013-02-13</pubDate></item><item><title>Human Cells and Nanoparticles to Enhance Immunotherapy</title><description><![CDATA[NIH scientists have developed human cells and nanoparticles to enhance immunotherapy. Specifically, researchers have identified that cells or nanoparticles expressing a high temperature requirement serine peptidase 1 (HtrA1) activator and/or a cytokine-induced Src homology 2 protein (CIS) inhibitor are capable of increasing T cell activity. These compositions can be used primarily in T cell immunotherapy against various cancers and infectious diseases where enhanced T cell activity is beneficial. Conversely, cells or nanoparticles that express a HtrA1 inhibitor and/or a CIS activator can suppress T cell activity. These compositions can be utilized to treat various auto- or alloimmune diseases and can be used to prevent transplant rejections.

HtrA1 (also known as L56, ARMD7, ORF480, and PRSS11) is a serine protease that is known to inhibit the TGF-beta family proteins. CIS (also known as G18, SOCS, CIS-1, and CISH) is a member of the suppression of cytokine signaling (SOCS) family of proteins and inhibit the JAK/STAT signaling pathways. CIS acts to inhibit HtrA1 and repress cell activation targets. Immunotherapy, although an effective treatment strategy, sometimes fails when cells lose activity. T cells adoptively transferred into patients where CIS is inhibited and/or HtrA1 is activated should maintain their activity and lead to more successful adoptive T cell transfers.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2301</link><pubDate>2013-02-13</pubDate></item><item><title>Therapeutic Hepatitis C Virus Antibodies</title><description><![CDATA[Therapeutic antibodies against Hepatitis C Virus (HCV) have not been very effective in the past and there is evidence that this may result in part from interfering antibodies generated during infection that block the action of neutralizing antibodies. These neutralizing antibodies prevent HCV infection of a host cell.

The subject technologies are monoclonal antibodies against HCV that can neutralize different genotypes of HCV. Both antibodies bind to the envelope (E2) protein of HCV found on the surface of the virus. One of the monoclonal antibodies neutralizes HCV genotype 1a, the most prevalent HCV strain in the U.S., infection and in vitro data show that it is not blocked by interfering antibodies. The second antibody binds a conserved region of E2 and can cross neutralize a number of genotypes including genotypes 1a and 2a. The monoclonal antibodies have the potential to be developed either alone or in combination into therapeutic antibodies that prevent or treat HCV infection. These antibodies may be particularly suited for preventing HCV re-infection in HCV patients who undergo liver transplants; a population of patients that is especially vulnerable to the side effects of current treatments for HCV infection.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2524</link><pubDate>2013-02-05</pubDate></item><item><title>Transmission-Blocking Malaria Vaccine</title><description><![CDATA[There is no vaccine for malaria, and there is growing resistance to existing anti-malarial drugs.  Sexual stage-specific antigens are of interest as vaccine candidates because disruption of these antigens would reduce the fertility and, thus, the infectivity of the parasite.

This invention claims methods and compositions for delivering a Plasmodium P47 vaccine or antibody to P47 to prevent Plasmodium falciparum or Plasmodium vivax malaria.  P47 and other antigens have been mentioned as potential transmission-blocking vaccines due to their surface location on gametes.  The gene for P47 antigens is also well characterized.  Recent discoveries have noted that P47 allows the parasite to suppress or evade the immune system, thereby ensuring the mosquitoes' survival.  Recent discoveries have also shown the mechanism by which P47 enables survival of the parasite by manipulation of the mosquito immune system.  Based on the critical role of P47 antigens in transmission, the disruption of the function of P47 by various means can be an innovative and forceful means to control and/or reduce the prevalence of malaria.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2506</link><pubDate>2013-01-11</pubDate></item><item><title>Exposing T cells to Fas Ligand (FasL)-Fas Receptor (FasR) Antagonists Withholds Differentiation and Increases Expansion Making T cells More Suitable for Use in Cancer Immunotherapy</title><description><![CDATA[NIH scientists have developed methods to make a better immunotherapy by exposing T cells to Fas ligand (FasL) or Fas receptor (FasR) antagonists and agonists. Researchers have found that FasL-FasR antagonists suppress T cell differentiation leaving them in a na?ve state. These T cells are a more ideal cell type for adoptive cell transfer therapies because they have not exhausted their effector functions and demonstrate greater proliferation, enhanced persistence and survival, and better activity against their target antigen when infused in vivo to treat cancer. Also, the prevention of T cell differentiation/effector function in vivo has implications for autoimmune diseases and syndromes. FasL-FasR agonists enhance T cell differentiation towards more effector-like cells. Enhancing the differentiation of T cells is expected to be useful in treating cell proliferation disorders, such as leukemias, lymphomas, or Wiskott-Aldrich syndrome.

FasL (or cluster of differentiation 95L) is a transmembrane protein in the tumor necrosis factor (TNF) family. FasR (or apoptosis antigen 1, CD95, or TNF receptor superfamily member 6) is a transmembrane protein belonging to the TNF receptor/nerve growth factor receptor superfamily. Normally, when FasL binds to FasR, a cell death signal is triggered in the cell.  Antagonists of FasL-FasR interaction may include caspase inhibitors, mutated FasL/FasR, RNAi, or FasL/FasR antibodies. Agonists may include FasL/FasR encoding nucleotides.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2456</link><pubDate>2012-12-04</pubDate></item><item><title>Topical Antibiotic with Immune Stimulating Oligodeoxynucleotide Molecules to Speed Wound Healing</title><description><![CDATA[The present technology provides a mean of improving the activity of topical antibiotics. Currently available topical antibiotic formulations effectively eliminate bacteria at a wound site.  But in eliminating bacteria in the wound, such antibiotics also eliminate the  molecular signals present in bacterial DNA that stimulate to immune system's wound healing processes.   Without these signals the rate of wound healing is diminished.  It would be desirable for topical antibiotics to remove infectious bacteria but also provide the immune stimulating signals needed to promote and accelerate healing.  The present formulation accomplishes these goals by supplementing the antibiotic formulation with immunostimulatory oligodeoxynucleotides (ODN).  These ODN express the CpG motifs present in bacterial DNA and safely mimic the immune stimulation induced by bacterial DNA.  The formulation may be applied directly to a wide variety of wounds to  skin (such as traumatic, burn, or surgical wound), or the eyes (such as corneal abrasions) to effectively eliminate infection and stimulate rapid healing of the wound.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2487</link><pubDate>2012-11-19</pubDate></item><item><title>Selective Treatment of Cancer, HIV, Other RNA Viruses and Genetically Related Diseases Using Therapeutic RNA Switches</title><description><![CDATA[Targeted therapy in cancer or viral infections is a challenge because the disease state manifests itself mainly through differences in the cell interior, for example in the form of the presence of a certain RNAs or proteins in the cytoplasm.

The technology consists of designed RNA switches that activate the RNA interference pathway only in the presence of a trigger RNA or DNA to which they bind, in order to knock down a chosen gene that is not necessarily related to the initial trigger.

This new approach can lead to a new type of drug that has the unique feature of selectively causing a biochemical effect (such as apoptosis) in cells that are infected by RNA viruses (such as HIV), as well as cancer cells. The RNA switch concept can be expanded to selectively treat other genetically related diseases.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2495</link><pubDate>2012-11-19</pubDate></item><item><title>Activation of Therapeutic Functionalities with Chimeric RNA/DNA Nanoparticles for Treatment of Cancer, Viruses and Other Diseases</title><description><![CDATA[A new strategy based on RNA/DNA hybrid nanoparticles, which can be generally used for triggering multiple functionalities inside diseased cells is presented. Individually, each of the hybrids is functionally inactive and functional representation can only be activated by the re-association of at least two cognate hybrids simultaneously present in the same cell. Overall, this novel approach allows (i) the triggered release of therapeutic siRNAs or miRNAs inside the diseased cells, (ii) activation of other split functionalities (e.g. FRET, different aptamers, rybozymes, split proteins) intracellularly, (iii) higher control over targeting specificity (e.g. if two hybrids are decorated with two different tissue specific recognition moieties), (iv) biosensing and tracking of the delivery and re-association of these hybrids in real-time inside cells, (v) increasing the number of functionalities by introducing a branched hybrid structure, (vi) introduction of additional functionalities without direct interference of siRNA processivity, (vii) increasing the retention time in biological fluids by fine-tuning chemical stability through substituting the DNA strands with chemical analogs (e.g. LNA, PNA, etc.), (viii) conditional release of all functionalities.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2496</link><pubDate>2012-11-19</pubDate></item><item><title>Treatment of Tuberculosis ? Adjuvant Therapies to Increase the Efficiency of Antibiotic Treatments</title><description><![CDATA[There is growing evidence that resistance to Mycobacterium tuberculosis infection is governed in large part by the regulation of host cell death.  Lipid mediators called eicosanoids are thought to play a central role in this process.  The subject invention is a novel method of enhancing the efficacy of antibiotic treatments for Mycobacterium tuberculosis infection by co-administering an inhibitor of 5-lipoxygenase and a COX-2 dependent prostaglandin.  Inhibition of 5-lipoxygenase and treatment with prostaglandin E2 results in alteration of the eicosanoid balance.   The synergistic effects of altering the eicosanoid balance and treatment with antibiotics is believed to result in more efficient reduction of the bacterial burden and thus, the period of antibiotic administration and antibiotic dosage could potentially be reduced.  In vivo data from mouse models can be provided upon request.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2337</link><pubDate>2012-11-16</pubDate></item><item><title>Cross-Reactive Neutralizing Human Domain Antibody Against HIV-1</title><description><![CDATA[The invention describes the first identified anti-HIV human domain antibody (m36), which can potentially be used alone or synergistically with other anti-HIV antibodies and antiretroviral drugs as a therapeutic and/or preventative for HIV infection.  It targets an epitope whose exposure is enhanced by binding of the HIV receptor CD4 to the HIV envelope glycoprotein (Env).  M36 was identified by sequential panning of a newly developed large human VH library against Envs from different HIV-1 isolates.  The antibody can neutralize HIV-1 primary isolates from different clades at low (nM) concentrations and due to its small size (14 kDa) is potentially able to efficiently penetrate lymphoid tissues where the virus replicates.  The antibody is fairly well characterized and the inventors are generating derivatives of this antibody to improve the half-life and increase its potency and cross-reactivity.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1809</link><pubDate>2012-09-28</pubDate></item><item><title>Method of Making a Vaccine</title><description><![CDATA[Current invention describes the methods to prepare vaccines, and to use such vaccines in the vaccination and treatment of human disease, e.g., the human immunodeficiency virus (HIV) infections and cancer. More specifically, the present invention provides a vaccine and method for making same which is effective to elicit a desired antibody against a target antigen comprising a primary immunogen and a secondary immunogen, wherein the primary immunogen is effective to elicit B cell receptors (BCRs) that are on the maturational pathway of the desired antibody and have an intermediate degree of somatic mutational diversity, and the secondary immunogen comprises an epitope of the desired target antibody and is effective to further diversify the BCRs sufficient to form mature BCRs having the identical or substantially identical sequence as the desired antibody.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1899</link><pubDate>2012-09-28</pubDate></item><item><title>Generation of Wild-Type Dengue Viruses for Use in Rhesus Monkey Infection Studies</title><description><![CDATA[Dengue virus is a positive-sense RNA virus belonging to the Flavivirus genus of the family Flaviviridae.  Dengue virus is widely distributed throughout the tropical and semitropical regions of the world and is transmitted to humans by mosquito vectors.  Dengue virus is a leading cause of hospitalization and death in children in at least eight tropical Asian countries.  There are four serotypes of dengue virus (DEN-1, DEN-2, DEN-3, and DEN-4) that annually cause an estimated 50-100 million cases of dengue fever and 500,000 cases of the more severe form of dengue virus infection known as dengue hemorrhagic fever/dengue shock syndrome (DHFIDSS).  This latter disease is seen predominately in children and adults experiencing a second dengue virus infection with a serotype different than that of their first dengue virus infection and in primary infection of infants who still have circulating dengue-specific maternal antibody.  A vaccine is needed to lessen the disease burden caused by dengue virus, but none is licensed.

Because of the association of more severe disease with secondary dengue virus infection, a successful vaccine must induce immunity to all four serotypes.  Immunity is primarily mediated by neutralizing antibody directed against the envelope (E) glycoprotein, a virion structural protein.  Infection with one serotype induces long-lived homotypic immunity and a short-lived heterotypic immunity.  Therefore, the goal of immunization is to induce a long-lived neutralizing antibody response against DEN-1, DEN-2, DEN-3, and DEN-4, which can best be achieved economically using live attenuated virus vaccines.  This is a reasonable goal since a live attenuated vaccine has already been developed for the related yellow fever virus, another mosquito-borne flavivirus present in tropical and semitropical regions of the world.

The evaluation of live attenuated dengue vaccine candidates in rhesus monkeys requires wild type control viruses for each of the four dengue serotypes.  These control viruses are used for comparison to the attenuated strains and post-vaccination challenge to assess vaccine efficacy. As such, these viruses need to be well characterized and sufficiently pure to ensure that they will replicate to consistent levels in rhesus monkeys.  Characterization generally includes sequence analysis, titration, and evaluation in monkeys.  The following viruses have been characterized: (1) DEN1 WP (2) DEN1 Puerto Rico/94 (3) DEN2 NGC prototype (4) DEN2 Tonga/74 (5) DEN3 Sleman/78 and (6) DEN4 Dominica/81.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1736</link><pubDate>2012-09-12</pubDate></item><item><title>Methods of Treating Giardiasis Using FDA-Approved Compounds</title><description><![CDATA[This technology includes a group of at least twenty-nine, diverse, commercially available compounds that are newly identified for activity against Giardia lamblia parasites.  At least six of the candidate compounds, Bortezomib, Decitabine, Hydroxocobalamin, Amlexanox, Idarubicin, and Auranofin have preexisting FDA approval for human use for other (non-Giardia) conditions.  Another three compounds, Fumagillin, Nitarsone and Carbadox have preexisting approval for veterinary use for non-Giardia conditions.  Additional active compounds identified include:  Acivicin, Riboflavin butyrate, BTO-1, GW9662, Dinitroph-dfgp, Deserpidine, Tetramethylthiuram disulsulfide, Disulfiram, Mitoxantrone,  Ecteinascidin 743, 17-allyaminogeldanamycin, Carboquone and Nocodazole. The anti-Giardial activity of these compounds presents a cost saving opportunity for the rapid development of new, better tolerated treatments for the most prevalent human intestinal parasite infection in the United States and the world.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2307</link><pubDate>2012-08-17</pubDate></item><item><title>Salen-Manganese Compounds for Therapy of Viral Infections</title><description><![CDATA[Salen-manganese compounds are synthetic, stable, low toxicity, low cost agents that may provide protection from immune reaction-related oxidative cell damage associated with many illnesses. In particular, oxidative cell damage has been associated with many viral infections including influenza. This invention demonstrates that treating mice with salen-manganese compounds, after lethal pandemic influenza virus infection, significantly enhances survival. Salen-manganese treatment also reduces lung pathology and also improved cellular recovery and repair. Because oxidative damage is observed in many viral infections, administration of salen-manganese compounds may have therapeutic relevance to a wide range of viral infections, in addition influenza. Existing viral therapeutics merely target the infectious viral agent and not the damage caused by the immune system reaction related to infection. Because, salen-manganese treatments target the untapped therapeutic space of infection-induced, immune system-related pathology and have favorable safety and cost profiles, such therapies are ideal candidates for development.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2464</link><pubDate>2012-07-20</pubDate></item><item><title>Linked Purine Pterin HPPK Inhibitors Useful as Antibacterial Agents</title><description><![CDATA[The invention offered for licensing describes and claims novel inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), a key enzyme in the folate biosynthetic pathway which is essential for microorganisms but absent in mammals. These novel inhibitors are based on linked purine pterin compounds. They can disrupt the folate biosynthesis of bacteria and thus can find utility as potential antimicrobials. Antibiotics based on these lead molecules can be specifically designed and synthesized to serve as broad-spectrum or narrow-spectrum antibiotics. None of the currently established antibiotics target HPPK.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2169</link><pubDate>2012-07-10</pubDate></item><item><title>New Ammunition to Fight Cancer: The Rapid Isolation of Central Memory T Cells for Adoptive Immunotherapy</title><description><![CDATA[This technology is a new technique to rapidly isolate tumor-reactive central memory T cells in a highly enriched, non-invasive manner from the peripheral blood of cancer patients for cancer adoptive cell immunotherapy.  Cells are drawn from a patient's blood, divided into subsets, and contacted with the tumor antigen of interest to identify T cells whose T cell receptor (TCR) recognizes the tumor antigen. Such T cells are identified by measuring the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) produced by the cells (i.e., the IL-2 index) using high-throughput quantitative PCR (HT-qPCR). NIH scientists have identified that cells with a specific IL-2 index consistently contain central memory T cells for the tumor antigen of interest.

Preclinical animal studies have suggested that central memory T cells can proliferate, persist, and survive better after adoptive transfer compared to other T cell types. They also show increased anti-cancer activity. Clinical trials using central memory T cells represent an important extension of these studies. Adoptive immunotherapy is showing promise as a cancer treatment, but one drawback to this method, prior to this invention, was the laborious and time consuming nature of the cell isolation process and the unpredictable and sometimes ineffective nature of the cells infused into patients.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2454</link><pubDate>2012-07-10</pubDate></item><item><title>Treatment of Viral Infection by Blocking Interleukin-21</title><description><![CDATA[Blocking interleukin (IL-21) may be an effective method to treat or prevent various viral infections.  In the course of an immune response to a virus, IL-21, produced primarily by CD4+ T cells, can inhibit or stimulate (regulate), immune cell function (B cells, T cells, natural killer cells, dendritic cells).  IL-21 regulation may be either protective or pathological; autoimmune disease pathology has been associated with IL-21 promoted inflammation (in: type 1 diabetes, lupus, and multiple sclerosis).  This technology describes methods of blocking IL-21 that may reduce damaging inflammatory responses during certain viral infections.  Specifically, the absence of IL-21 during respiratory viral infection such as pneumonia virus infection actually prevents some of the pathogenic effects that may be promoted by IL-21.  Methods for controlling IL-21 signaling may be used to treat to prevent many pathological effects of pneumonia viruses, and other viral infections.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2448</link><pubDate>2012-06-06</pubDate></item><item><title>Novel Reduced Toxicity Tropolone Derivative Compounds That Have Anti-Viral Activity Through Inhibiting RNase H Activity</title><description><![CDATA[Several novel tropolone derivatives have been identified that inhibit HIV-1 RNase H function and have potential for anti-viral activity due to reduced cellular toxicity.  Inhibiting RNase H function is a potential treatment for many viral infections, since RNase H function is essential for viral replication for many pathogenic retroviruses such as HIV-1 and HIV-2.  Although many hydroxytropolone compounds are potent RNase H inhibitors biding at the enzymatic active site, they are limited as therapeutic candidates by their toxicity in mammalian cells.  The toxicity thought to be a result of inhibition of multiple essential mammalian metalloenzymes.  We reasoned that the potential beneficial application of tropolone RNase H inhibition might be of therapeutic use if the toxic effects in mammalian cell were eliminated.  By selectively adding steric bulk to add new drug-enzyme contacts for the RNase H active site, a number of novel compounds, that have initially demonstrated reduced cytotoxicity, have been produced.  Importantly, these novel compounds appear to retain antiviral activity essential for use as therapeutics.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2429</link><pubDate>2012-05-08</pubDate></item><item><title>Induced Internalization of Surface Receptors to Disrupt Cell Surface Signaling</title><description><![CDATA[Cell-surface receptors are responsible for the biological activities of many molecules.  Specific ligands bind to them, causing the cell-surface receptors to internalize or bring the receptor and ligand inside the cell.  A number of diseases, including cancer, metabolic disorders, and viral infections are known to require the expression of cell-surface receptors for critical pathogenetic steps. This has prompted significant research efforts towards the development of pharmaceutical agents that block the signals from cell-surface receptors. While this current research shows great promise, there is a strong need for new therapeutic strategies that utilize the mechanistic properties of cell-surface receptors.

This technology describes a strategy for artificially inducing the internalization of surface receptors, and thereby blocking the effects of the ligands associated with that receptor.  This method employs bifunctional ligands that bind to both a scavenger receptor and a target receptor.  As proof of concept, the inventors Drs. Narazaki and Tosato have shown that a ligand capable of binding to the scavenger receptor SREC-1 and the neuropilin-1 receptor NRP1 induces the internalization of NRP1 and inhibits NRP1 signaling.  The inventors propose that this strategy can be used to inhibit signaling from any target receptor if an appropriate bifunctional ligand is used.  For example, the concept could be expanded to other receptors, such as HDL and LDL receptors.  Likewise the bifunctional ligand could include specific antibodies or modified ligands that recognize cell surface receptors of biological importance.  Accordingly, this approach could be used to limit tumor angiogenesis, limit tumor growth, block metastasis formation, block inflammation, block viral infection, and treat just about any disease where we identify a cell surface receptor an the molecular basis for disease.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1843</link><pubDate>2012-05-01</pubDate></item><item><title>A Broadly Neutralizing Human Anti-HIV Monoclonal Antibody (10E8) Capable of Neutralizing Most HIV-1 Strains</title><description><![CDATA[This Human Anti-HIV Monoclonal Antibody (10E8) has great potential to provide passive protection from infection, as a therapeutic vaccine, or as a tool for the development of vaccine immunogens. 10E8 is one of the most potent HIV-neutralizing antibodies isolated thus far and it can potently neutralize up to 98% of genetically diverse HIV-1 strains. 10E8 is specific to the membrane-proximal external region (MPER) of the HIV envelope protein, GP41. It is anticipated that 10E8 could be used in combination with another human anti-HIV-1 monoclonal antibody to provide an antibody response that neutralizes nearly all strains of HIV-1.  Additionally, 10E8 is a useful tool for the design of vaccine immunogens that can elicit an adaptive immune response to produces 10E8 like antibodies.  This technology also includes monoclonal antibodies from the same germ line as 10E8.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2428</link><pubDate>2012-05-01</pubDate></item><item><title>Nonpathogenic Bacteria, Paenibacillus alvei, Useful as a Natural Biocontrol Agent for Elimination of Food-borne Pathogenic Bacteria</title><description><![CDATA[This newly isolated non-pathogenic bacterial strain (TS-15) has shown the ability to kill or inhibit a wide variety of harmful bacteria including many of the most common food-borne pathogens such as Salmonella, Escherichia, Listeria, Shigella, Enterobacter and Staphylococcus.  The TS-15 stain may provide a natural low cost means to help protect the food supply. The strain may be used as a biocontrol agent in the form of a pesticide or pretreatment to soils in which fruits and vegetable are grown.  Preventative use of the TS-15 strain in biocontrol measures may prevent many of the millions of illnesses in the U.S. that are caused by food-borne pathogens each year. Such prevention may also reduce the associated costs of treatment for such illnesses. Furthermore, isolation and development of the antibiotic compounds produced by the TS-15 strain may yield useful new compositions to help treat bacterial illness, including infections by some pathogens resistant to standard antibiotics.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2396</link><pubDate>2012-04-23</pubDate></item><item><title>Method of Treating Hepatitis C Virus Infection With a Small Molecule CHK2 Inhibitor</title><description><![CDATA[DNA damage sensors such as Checkpoint Kinase 2 (Chk2) are key regulators of the cellular DNA damage response that limits cell-cycle progression in response to DNA damage.  It has been reported that these DNA damage sensors also play a key role in Hepatitis C virus (HCV) replication.  The subject technology are small molecule CHK2 kinase inhibitors that have been shown to have promising activity against HCV replication.  The compounds were discovered by high throughput screening of chemical libraries with more than 150,000 compounds.  These novel compounds can potentially be used in combination with other anti-HCV drugs or interferon and represent a novel target for treating HCV.  In vitro antiviral assay data, as well as preliminary in vitro and in vivo pharmokinetic data are available upon request.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2388</link><pubDate>2012-03-23</pubDate></item><item><title>A Novel Treatment for Malarial Infections</title><description><![CDATA[The inventions described herein are antimalarial small molecule inhibitors of the plasmodial surface anion channel (PSAC), an essential nutrient acquisition ion channel expressed on human erythrocytes infected with malaria parasites.  These inhibitors were discovered by high-throughput screening of chemical libraries and analysis of their ability to kill malaria parasites in culture.  Two separate classes of inhibitors were found to work synergistically in combination against PSAC and killed malaria cultures at markedly lower concentrations than separately.  These inhibitors have high affinity and specificity for PSAC and have acceptable cytotoxicity profiles.  Preliminary in vivo testing of these compounds in a mouse malaria model is currently ongoing.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1827</link><pubDate>2012-02-13</pubDate></item><item><title>Clones Encoding Mammalian ADP-Ribosylarginine Hydrolases</title><description><![CDATA[ADP-ribosylation of arginine residues in proteins may be involved in cell adhesion and is crucial for the action of cholera toxin and E. coli heat-labile enterotoxin, agents involved in the pathogenesis of cholera and traveller's diarrhoea, respectively. ADP-ribosylation is reversed by ADP-ribosylarginine hydrolases, which cleave the ADP-ribose-arginine bond. ADP-ribosylarginine hydrolases from a variety of mammalian species and tissues were isolated, and the coding regions for the hydrolases were cloned and expressed. The availability of this new hydrolase cDNA and expression system provides a novel molecular approach for studying the role of ADP-ribosylation in cell function. The gene products may be useful in treating or preventing a variety of bacterial diseases, including cholera, that appear to be mediated via ADP-ribosylation.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=399</link><pubDate>2012-01-11</pubDate></item><item><title>Gas Permeable Flasks to Grow Tumor Infiltrating Lymphocytes (TIL) for More Effective Anti-Cancer Immunotherapy</title><description><![CDATA[Scientists at NIH have developed a strategy to obtain large quantities of highly reactive tumor infiltrating lymphocytes (TIL) from patient tumor samples for anti-cancer immunotherapy by making use of gas permeable (GP) flasks. This advancement in personalized anti-cancer immunotherapy involves culturing a tumor sample in a series of GP containers to isolate and rapidly expand TIL. The process provides suitable quantities of TIL for adoptive transfer into the cancer patient more reliably than previous approaches.

Culturing and growing TIL in the GP containers permits efficient gas exchange between TIL cells and the air to promote optimal respiration, growth, and viability of the patient's TIL throughout the process. Using GP flasks in the TIL expansion process provides for better circulation of the growth media and larger surface area so more TIL can grow per unit volume. Therefore, less reagents and fewer numbers of culture containers are need to generate the required number of TIL for adoptive immunotherapy protocols to treat cancer patients.  NIH researchers have demonstrated the advantages of this GP TIL growth process in comparison to their more established TIL expansion protocols using human patient tumor samples.  This new TIL production method should enable TIL therapy to become more GMP compliant and allow it to become more standardized for widespread utilization as a cancer treatment option outside of NIH.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2312</link><pubDate>2011-10-28</pubDate></item><item><title>Protease Deficient Bacillus anthracis with Improved Recombinant Protein Yield Capabilities</title><description><![CDATA[Species of Bacillus, such as Bacillus anthracis, Bacillus cereus, and Bacillus subtilis, are attractive microorganisms for recombinant protein production in view of their fast growth rate, high yield, and ability to secrete produced products directly into the medium. Bacillus anthracis is also attractive in view of its ability to produce anthrax toxin and ability to fold proteins correctly.  This application claims a B. anthracis strain in which more than one secreted protease is inactivated by genetic modification.  Such a protease-deficient B. anthracis has an improved ability to produce recombinant secreted proteins compared to other bacteria, particularly other Bacillus.  Improvements include production of intact (i.e., mature full-length) proteins, often at high yield.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2330</link><pubDate>2011-10-21</pubDate></item><item><title>Humanized Monoclonal Antibodies Efficient for Neutralization of Tick-Borne Encephalitis Virus (TBEV)</title><description><![CDATA[TBEV causes serious illnesses from meningitis to meningo-encephalitis, totaling 3,000 cases of hospitalization in Europe and between 5,000-10,000 cases in Russia reported every year. The Far Eastern hemorrhagic TBEV strains are associated with a mortality rate (between 1-2%), higher than other strains isolated in the Siberia or Western Europe. There is a high proportion (up to 46%) of TBEV patients with temporary or permanent neurological sequelae. The number of TBEV infections has increased steadily and TBEV cases have been reported in new areas, probably reflecting an increased spread of vector tick species.  Prevention of TBEV infections has been carried out in a few countries in Europe by immunization using an inactivated TBEV vaccine. The vaccine carries a high manufacturing cost and requires a regimen of multiple doses, and for this reason, vaccination is not generally carried out. The materials disclosed are humanized monoclonal antibodies derived from TBEV-neutralizing Fab antibodies isolated from infected chimpanzees by repertoire cloning. One antibody in particular, MAb 2E6, has been demonstrated to bind to and neutralize a TBEV/dengue type 4 virus chimera (via interaction with the TBEV antigenic determinants) as well as the related Langat virus.  Protection against TBEV/DEN-4 infection and Langat infection has been demonstrated using animal models of infection. The antibodies disclosed, in particular MAb 2E6, have the potential for use as prophylactic and therapeutic agents against TBEV and Langat virus. Additionally, these antibodies may be suitable as diagnostic reagents for the detection of TBEV and/or Langat virus.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2319</link><pubDate>2011-09-29</pubDate></item><item><title>PSM Peptides as Vaccine Targets Against Methicillin-Resistant Staphylococcus aureus</title><description><![CDATA[Available for licensing and commercial development are compositions and methods for the treatment and inhibition of Methicillin-resistant Staphylococcus aureus (MRSA), a dangerous human pathogen. The invention concerns immunogenic peptides that can be used to induce protective immunity against MRSA, including phenol-soluble modulin (PSM) peptides.

In addition to the MRSA infections that occur in immunocompromised patients in hospitals, new MRSA strains have recently emerged that can cause severe infections (such as necrotizing fasciitis) or death in otherwise healthy adults.  These strains are increasingly involved in community-associated (CA)-MRSA infections, and can be contracted outside of the health care settings.  The incidence of CA-MRSA infections is increasing and the majority of infections in patients reporting to emergency departments in the US is now due to CA-MRSA.

The invention describes a class of secreted staphylococcal peptides with an extraordinary ability to recruit, activate, and subsequently lyse human neutrophils, thus eliminating the main cellular defense against S. aureus infection.  The peptides are encoded by the PSM gene cluster and include PSMalpha1, PSMalpha2, PSMalpha3, and PSMalpha4, all of which activate and subsequently lyse neutrophils.  These peptides are produced at especially high levels in CA-MRSA and to a large extent determine their aggressive behavior and ability to cause disease in animal models of infection.  Thus, the peptides represent a set of virulence factors of S. aureus that account for the enhanced virulence of CA-MRSA.  The identification of these peptides enables the production of vaccines and other preventative and/or therapeutic agents for use in subjects infected with MRSA.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1717</link><pubDate>2011-09-01</pubDate></item><item><title>Monoclonal Antibodies Against Poliovirus</title><description><![CDATA[Early work by Hammond at al. showed gamma globulin to be effective for the prevention of poliomyelitis. Therefore, passive immunotherapy could be another way to treat chronic excretors. Even though prior attempts to use intravenous immunoglobulin (IVIG) and breast milk were unsuccessful, there is reason to think that higher doses of antipoliovirus antibodies could result in complete clearance of poliovirus from chronically infected individuals.  Six poliovirus-neutralizing MAbs were recovered from a combinatorial Fab phage display library constructed from bone marrow-derived lymphocytes of immunized chimpanzees.  The six MAbs neutralized vaccine strains and virulent strains of poliovirus. Five MAbs were serotype specific, while one MAb cross-neutralized serotypes 1 and 2.   Both serotype 2-specific antibodies recognized antigenic site 1. No escape mutants to serotype 3-specific MAbs could be generated. The administration of a serotype 1-specific MAb to transgenic mice susceptible to poliovirus at a dose of 5 ?g/mouse completely protected them from paralysis after challenge with a lethal dose of wild-type poliovirus. Moreover, MAb injection 6 or 12 h after virus infection provided significant protection.  This application claims the antibodies described above and methods for their use.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2306</link><pubDate>2011-08-12</pubDate></item><item><title>Method to Create Vaccines for the Prevention of Flavivirus Infections by Targeting Micro-RNA</title><description><![CDATA[There are more than seventy (70) single-stranded, positive-sense RNA viruses in the arthropod-borne flavivirus genus of the Flaviviridae family, many of which are important human pathogens that cause a devastating and often fatal neuroinfection. Flaviviruses are transmitted in nature to various mammals and birds through the bite of an infected mosquito or tick; they are endemic in many regions of the world and include mosquito-borne yellow fever (YFV), Japanese encephalitis (JEV), West Nile (WNV), St. Louis encephalitis (SLEV), dengue viruses (DEN) and the tick-borne encephalitis viruses (TBEV). During the past two decades, both mosquito-borne and tick-borne flaviviruses have emerged in new geographic areas of the world where previously they were not endemic and have caused outbreaks of diseases in humans and domestic animals.

Long-term experience with the only two successful live attenuated flavivirus vaccines has demonstrated that live attenuated virus vaccines are an efficient approach to prevent diseases caused by virulent flaviviruses because, in most cases, just a single dose of the vaccine provides a long-lasting protective immunity in humans that mimics the immune response following natural infection.

This application claims recombinant attenuated neurotropic flaviviruses comprising nucleic acid sequences complementary to the target sequences of microRNAs. The application also claims live attenuated chimeric flaviviruses, where the first flavivirus is a different flavivirus from the second flavivirus.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2220</link><pubDate>2011-08-02</pubDate></item><item><title>A New Class of Antibiotics: Naturally-occurring Chrysophaetins and Their Analogues</title><description><![CDATA[This invention, offered for licensing and commercial development, relates to a new class of naturally occurring antimicrobial compounds called Chrysophaetins, and to their synthetic analogues. Isolated from an alga species, the mechanism of action of these compounds is through the inhibition of bacterial cytoskeletal protein FtsZ, an enzyme necessary for the replication of bacteria. FtsZ is responsible for Z-ring assembly in bacteria, which leads to bacterial cell division.  Highly conserved among all bacteria, FtsZ is a very attractive antimicrobial target.

The chrysophaetin exhibits antimicrobial activity against drug resistant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE), as well as other drug susceptible strains. The general structure of the natural compound is shown below:



The inventors are working on a synthetic route for the compound and analogs.  They have made progress and now have two halves of the molecule.  These will be further dimerized to produce a synthetic chrysophaentin.  It is expected that the analogues will show similar antimicrobial activity to the natural products and will utilize the same mechanism of action.

The market potential for the disclosed compounds is huge ($24 billion in 2008) due to the very limited number of new antibiotics developed in recent decades and the increased epidemic of infectious diseases. In fact, infectious diseases are the leading cause of death worldwide. In the United States alone, more people die from MRSA than from HIV (Journal of the American Medical Association, 2007) and more than 90,000 people die each year from hospital acquired bacterial infections (Centers for Disease Control).  A development of new drugs with distinct mechanism of action and efficacy against resistant bacterial strains may therefore be commercially attractive.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2123</link><pubDate>2011-03-29</pubDate></item><item><title>Anti-Plasmodium Compositions and Methods of Use</title><description><![CDATA[This invention describes methods and compositions of peptides that inhibit the binding of Plasmodium falciparum (P. falciparum) to erythrocytes.  Malarial parasites enter the red blood cell through several erythrocyte receptors, each being specific for a given species of Plasmodia.  For P. falciparum, the erythrocyte binding antigen (EBA-175) is the ligand of the plasmodia merozoites that interacts with the receptor glycophorin A on the surface of red blood cells.  Inhibiting this ligand/receptor interaction is one method of preventing further malarial attacks and is an active area of vaccine research.

This invention describes another specific peptide and antibodies that inhibit this ligand/receptor binding, thus is a potential source for vaccine development.  The peptide described herein is a paralogue of EBA-175, identified as EBP2.  Further, the invention includes antibodies and peptides that are specific for the claimed paralogue.  Claims include the development of vaccines to the EBA-175 and EBP2.  In addition, these antibodies and peptides can be developed as diagnostic and analytical reagents as well. Methods include the use of the peptides and the antibodies for the diagnosis, prevention and potential treatment of malaria.  Further claims include their use in detection of P. falciparum in biological samples and culture methods.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1181</link><pubDate>2011-02-28</pubDate></item><item><title>Aspartic Protease Inhibitors, Compositions, and Associated Therapeutic Methods</title><description><![CDATA[The human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS).  Drug-resistance is a critical factor contributing to the gradual loss of clinical benefit to treatments for HIV infection.  Accordingly, combination therapies have further evolved to address the mutating resistance of HIV.  However, there has been great concern regarding the apparent growing resistance of HIV strains to current therapies. 

The subject invention provides compounds which may serve as therapeutic candidates for inhibition of HIV-1 PR (protease) and thus serve in controlling AIDS, as well as having anti-malarial properties.  These compounds may be used in combination with other protease inhibitors or inhibitors of HIV-1 reverse transcriptase, especially in patients who have developed resistance to other HIV protease inhibitors.  These inhibitors have high potency, lower molecular weight, and lower lipophilicity than previous compounds, as well as a better profile towards drug resistant mutant strains of HIV.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1221</link><pubDate>2011-02-28</pubDate></item><item><title>Monoclonal Antibodies Against Dengue and Other Viruses With Deletion in Fc Region</title><description><![CDATA[The four dengue virus (DENV) serotypes (DENV-1 to DENV-4) are the most important arthropod-borne flaviviruses in terms of morbidity and geographic distribution.  Up to 100 million DENV infections occur every year, mostly in tropical and subtropical areas where vector mosquitoes are abundant.  Infection with any of the DENV serotypes may be asymptomatic or may lead to classic dengue fever or more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which are increasingly common in the dengue endemic areas.  Immunity to the same virus serotype (homotypic immunity) is life-long, whereas immunity to different serotypes (heterotypic immunity) lasts 2?3 months so that infection with a different serotype virus is possible.  DHF/DSS often occurs in patients with second, heterotypic DENV infections or in infants with maternally transferred dengue immunity.  Severe dengue is a major cause of hospitalization, and fatality rates vary from 

Antibody-dependent enhancement (ADE) has been proposed as an underlying pathogenic mechanism of DHF/DSS.  ADE occurs because preexisting subneutralizing antibodies and the infecting DENV form complexes that bind to Fc receptor-bearing cells, leading to increased virus uptake and replication.  ADE has been repeatedly demonstrated in vitro using dengue immune sera or monoclonal antibodies and cells of monocytic and recently, B lymphocytic lineages bearing Fc receptors.  ADE of DENV-2 infection has also been demonstrated in monkeys infused with a human dengue immune serum. 

We have identified chimpanzee?human chimeric IgG1 mAbs capable of neutralizing or binding to one or more DENV serotypes.  Cross-reactive IgG 1A5 neutralizes DENV-1 and DENV-2 more efficiently than DENV-3 and DENV-4, and type-specific IgG 5H2 neutralizes DENV-4 at a high titer.  Analysis of antigenic variants has localized the IgG 1A5 binding site to the conserved fusion peptide in E.  Thus, IgG 1A5 shares many characteristics with the cross-reactive antibodies detected in flavivirus infections. 

This application claims a variant of an antibody comprising a polypeptide in the Fc region, which binds an Fc gamma receptor (FcgammaR) with lower affinity than the parent antibody.  The variant polypeptide comprises a deletion of nine amino acids at the N-terminus of the CH2 domain in the Fc region.  Introduction of the Fc variant abrogates the antibody-mediated dengue virus replication enhancing activity.  This invention has important implications for the antibody-mediated prevention of dengue virus infection.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1608</link><pubDate>2011-02-28</pubDate></item><item><title>Monoclonal Antibodies That Bind or Neutralize Dengue Virus</title><description><![CDATA[Among the arthropod-borne flaviviruses, the four dengue virus serotypes, dengue type 1 virus (DENV-1), dengue type 2 virus (DENV-2), dengue type 3 virus (DENV-3), and dengue type 4 virus (DENV-4 are most important in terms of human morbidity and geographic distribution.  Dengue viruses cause dengue outbreaks and major epidemics in most tropical and subtropical areas where Aedes albopictus and Aedes aegypti mosquitoes are abundant.  Dengue infection produces fever, rash, and joint pain in humans.  A more severe and life-threatening form of dengue, characterized by hemorrhagic fever and hemorrhagic shock, has occurred with increasing frequency in Southeast Asia and Central and South America, where all four dengue virus serotypes circulate.  A safe and effective vaccine against dengue is currently not available.  Passive immunization with monoclonal antibodies from non-human primates or humans represents a possible alternative to vaccines for prevention of illness caused by dengue virus. 

The application claims monoclonal antibodies that bind or neutralize dengue type 1, 2, 3, and/or 4 viruses.  The application also claims fragments of such antibodies retaining dengue virus-binding ability, fully human or humanized antibodies retaining dengue virus-binding ability, and pharmaceutical compositions including such antibodies.  The application also claims isolated nucleic acids encoding the antibodies of the invention.  Additionally, application claims prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1684</link><pubDate>2011-02-28</pubDate></item><item><title>Method of Treating and Preventing Infections in Immunocompromised Subjects with Immunostimulatory CpG Oligonucleotides</title><description><![CDATA[Primary disorders of the immune system can be divided into four categories, (1) disorders of the humoral immunity, (2) disorders of cellular immunity, (3) disorders of phagocytes, and (4) disorders of complement. In addition, there are many causes of secondary immunodeficiency such as treatment with immunosuppressive or chemotherapeutic agents, protein-losing enteropathy, and infection with a human immunodeficiency virus (HIV). Generally, immunocompromised patients are unable to mount an immune response to a vaccine or an infection in the same manner as non-immunocompromised individuals. 

Opportunistic infections to which individuals infected with HIV are susceptible include bacterial infections such as salmonellosis, syphilis and neurosyphilis, tuberculosis (TB), a typical mycobacterial infection, and bacillary angiomatosis (cat scratch disease), fungal infections such as aspergillosis, candidiasis (thrush, yeast infection), coccidioidomycosis, cryptococcal meningitis, and histoplasmosis, protozoal infections such as cryptosporidiosis, isosporiasis, microsporidiosis, Pneumocystis Carinii pneumonia (PCP), and toxoplasmosis, viral infections such as Cytomegalovirus (CMV), hepatitis, herpes simplex (HSV, genital herpes), herpes zoster (HZV, shingles), human papilloma virus (HPV, genital warts, cervical cancer), Molluscum Contagiosum, oral hairy leukoplakia (OHL), and progressive multifocal leukoencephalopathy (PML), and neoplasms such as Kaposi's sarcoma, systemic non-Hodgkin's lymphoma (NHL), and primary CNS lymphoma, among others. These opportunistic infections remain principally responsible for the morbidity and mortality associated with HIV disease. 

This application claims use of immunostimulatory D-type CpG oligonucleotides for the treatment of immunocompromised individuals.  More specifically, the application claims use of immunostimulatory D-type CpG oligonucleotides for the treatment of individuals infected with HIV.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1752</link><pubDate>2011-02-28</pubDate></item><item><title>Anti-Plasmodium Compositions and Methods of Use</title><description><![CDATA[The present invention comprises peptides/antibodies specific for the binding proteins of Plasmodium, a parasite responsible for malaria, hence in effect blocking the parasite?s binding to the erythrocytes. Also included are methods for their use in preventing, diagnosing or treating the related infections. 

Although malaria is virtually eradicated in the United States, it continues to be one of the most serious infectious diseases in the world, killing millions of people each year in the countries throughout Africa, Asia and Latin America.  In fact, over 41% of the world population lives in the regions affected by malaria.  In vitro studies using the antibodies described in the current technology showed ~80% reduction in the number of blood cells infected with Plasmodium parasite.  Infectivity studies using peptides demonstrated that they are also specifically able to prevent binding of parasites to blood cells.  The claimed antibodies and peptides can also be used for immunization of humans and animals, or for development of diagnostic kits capable of detecting the presence, localization and quantity of the Plasmodium parasites in tissues and cells.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1863</link><pubDate>2011-02-28</pubDate></item><item><title>Compounds That Treat Malaria and Prevent Malaria Transmission</title><description><![CDATA[The invention offered for licensing relates to therapeutic compounds and related pharmaceutical compositions that can be used in the prevention and treatment of malaria infection. More specifically, the invention is drawn to compounds that can kill malaria gametocytes to block malaria transmission and treat malaria infection in the non-erthtrocytic stages, as well as therapeutic uses of these molecules to prevent or slow the transmission of plasmodium organisms between mammals and eliminate or prevent infection in mammal. Furthermore, the compounds of the invention are tricyclic compounds where the side rings may be 5-7 membered rings (preferably 6-membered), and the center ring may be 6-8 membered ring (preferably 7-membered). Also, preferable structures are ones in which the side rings are aryl rings while the center ring is cycloalkyl ring. The compounds of the invention have been identified by integrating quantitative high-throughput screening (qHTS) with genetic mapping and in vivo oocyst formation assay.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2201</link><pubDate>2011-02-28</pubDate></item></channel></rss>