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Government-Owned Inventions; Availability for Licensing

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AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

SUMMARY:

The inventions listed below are owned by an agency of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected inventions to extend market coverage for companies and may also be available for licensing.

ADDRESSES:

Licensing information and copies of the U.S. patent applications listed below may be obtained by writing to the indicated licensing contact at the Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

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)

Description of Technology: 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.

Inventors: Kim Y. Green, Judy F. Lew, Adriene D. King, Stanislav V. Sosnovtsev, Gael M. Belliot (NIAID).

Publication: An example of the application of these materials is further described in KY Green et al., “A predominant role for Norwalk-like viruses as agents of epidemic gastroenteritis in Maryland nursing homes for the elderly,” J. Infect. Dis. 2002 Jan. 15;185(2):133-146.

Patent Status: HHS Reference No. E-198-2003/0—Research Material.

Licensing Status: The materials embodied in this invention are available Start Printed Page 34763nonexclusively through a biological materials license.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

Collaborative Research Opportunity: The Laboratory of Infectious Diseases, NIAID, NIH, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize norovirus VLP antigens. Please contact Kim Y. Green at kgreen@niaid.nih.gov for more information.

Full-Length cDNA Clone Representing the Consensus Sequence of the RNA Genome of a Human Norovirus (Strain MD145-12) That Encodes Biologically Active Proteins

Description of Technology: The invention provides for a full-length cloned cDNA copy of the RNA genome of a predominant norovirus strain (Genogroup II.4) designated MD145-12 that was associated with human gastrointestinal illness. The noroviruses, which were formerly known as “Norwalk-like” viruses are estimated to cause 23 million cases of acute gastroenteritis in the USA each year. The virus has been designated into category B of the CDC biodefense-related priority pathogens because it can be used as an agent of bioterrorism. The subject cDNA clone of the virus encodes proteins of the MD145-12 strain that, when expressed in vitro, exhibit properties that would be expected from those produced by the original infectious virus. This cDNA clone is presently the only source to obtain norovirus proteins to facilitate studies aimed at developing control strategies such as vaccines and therapeutic drugs.

Inventors: Gael M. Belliot, Kim Y. Green, Stanislav V. Sosnovtsev (NIAID).

Patent Status: HHS Reference No. E-212-2003/0—Research Material.

Licensing Status: The cDNA clone for norovirus strain MD145-12 is available for licensing via a biological material license (BML).

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

Collaborative Research Opportunity: The Laboratory of Infectious Diseases, NIAID, NIH, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize reagents derived from a cDNA clone of the genome of a predominant human norovirus strain, Genogroup II.4. Please contact Kim Y. Green at kgreen@niaid.nih.gov for more information.

Construction of an Infectious Full-Length cDNA Clone of the Porcine Enteric Calicivirus RNA Genome

Description of Technology: Porcine enteric calicivirus (PEC) is a member of the genus Sapovirus in the family Caliciviridae. This virus causes diarrheal illness in pigs. In addition, 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 and the sapoviruses represented by Sapporo 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.

Inventors: Kyeong-Ok Chang (NIAID), Stanislav V. Sosnovtsev (NIAID), Gael M. Belliot (NIAID), Kim Y. Green (NIAID), et al.

Publication: The materials are further described in KO Chang et al., “Cell-culture propagation of porcine enteric calicivirus mediated by intestinal contents is dependent on the cyclic AMP signaling pathway,” Virology. 2002 Dec 20;304(2):302-310.

Patent Status: HHS Reference No. E-214-2003/0—Research Material.

Licensing Status: The materials embodied in this invention are available nonexclusively through a biological materials license.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

Collaborative Research Opportunity: The Laboratory of Infectious Diseases, NIAID, NIH, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize reagents derived from an infectious cDNA copy of the genome of porcine enteric calicivirus. Please contact Kim Y. Green at kgreen@niaid.nih.gov for more information.

Enzymatically-Active RNA-Dependent RNA Polymerase From a Human Norovirus (Calicivirus)

Description of Technology: 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 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.

Inventors: Gael M. Belliot, Stanislav V. Sosnovtsev, Kyeong-Ok Chang, Kim Y. Green (NIAID).

Publication: The materials are further described in L Wei et al., “Proteinase-polymerase precursor as the active form of feline calicivirus RNA-dependent RNA polymerase,” J. Virol. 2001 Feb;75(3):1211-1219.

Patent Status: HHS Reference No. E-283-2003/0—Research Material.

Licensing Status: The materials embodied in this invention are available nonexclusively through a biological materials license.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

Collaborative Research Opportunity: The Laboratory of Infectious Diseases, NIAID, NIH, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize an active human norovirus proteinase-polymerase enzyme. Please contact Kim Y. Green at kgreen@niaid.nih.gov for more information.

A Sensitive, High Throughput Pseudovirus-Based Papillomavirus Neutralization Assay for HPV 16 and HPV 18

Description of Technology: This invention is a research tool for measuring protective antibody responses against Human Papilloma Viruses (HPV). Sensitive high-throughput neutralization assays, based upon pseudoviruses carrying a secreted alkaline phosphatase (SEAP) reporter gene, were developed and validated by the inventors for HPV 16, HPV 18, and bovine papillomavirus 1 (BPV1). In a Start Printed Page 3476496-well plate format, the assay was reproducible and appears to be as sensitive as, but more type-specific than, a standard papillomavirus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA). The SEAP pseudovirus-based neutralization assay should be a practical method for quantifying potentially protective antibody responses in HPV natural history and prophylactic vaccine studies.

Inventors: John T. Schiller (NCI), Douglas R. Lowy (NCI), Christopher Buck (NCI), Diana V. Pastrana (NCI), et al.

Publication: The assay is further described in Pastrana et al., “Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18,” Virology. 2004 Apr 10;321(2):205-216.

Patent Status: HHS Reference No. E-137-2004/0—Research Material.

Licensing Status: This assay is available nonexclusively through a biological materials license.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

Methods for Preparing Complex Multivalent Immunogenic Conjugates

Description of Invention: Claimed in this application are novel methods for preparing complex multivalent immunogenic conjugates and conjugate vaccines. The multivalent conjugates and conjugate vaccines are synthesized by conjugating mixtures of more than one polysaccharide at a desired ratio of the component polysaccharides to at least one carrier protein using hydrazide chemistry. Because of the high efficiency of hydrazide chemistry in conjugation, the polysaccharides are effectively conjugated to the carrier protein(s) so that the resulting complex synthesized vaccine conjugate products, without requiring tedious and complicated purification procedures such as chromatography and/or ammonium sulfate precipitation, are efficacious in inducing antibodies in mice against each component polysaccharide. The methods claimed in this application simplify the preparation of multivalent conjugate vaccines by utilizing simultaneous conjugation reactions in a single reaction mixture or batch that includes at least two immunogenic-distinct polysaccharides. This single-batch simultaneous reaction eliminates the need for multiple parallel synthesis processes for each polysaccharide vaccine conjugate component as employed in conventional methods for making multivalent conjugate vaccines.

Application: Cost effective and efficient manufacturing of conjugate vaccines.

Inventors: Che-Hung Robert Lee (CBER/FDA).

Patent Status: PCT Application No. PCT/US2007/006627 filed 16 Mar 2007 (HHS Reference No. E-085-2005/0-PCT-02).

Licensing Status: Available for exclusive or non-exclusive licensing. The technology is not available for licensing in the field of use of multivalent meningitis vaccines.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

Human Neutralizing Monoclonal Antibodies to Respiratory Syncytial Virus and Human Neutralizing Antibodies to Respiratory Syncytial Virus

Description of Technology: This invention is a human monoclonal antibody fragment (Fab) discovered utilizing phage display technology. It is described in Crowe et al., Proc Natl Acad Sci USA. 1994 Feb 15;91(4):1386-1390 and Barbas et al., Proc Natl Acad Sci USA. 1992 Nov 1;89(21):10164-10168. This MAb binds an epitope on the RSV F glycoprotein at amino acid 266 with an affinity of approximately 109 M-1. This MAb neutralized each of 10 subgroup A and 9 subgroup B RSV strains with high efficiency. It was effective in reducing the amount of RSV in lungs of RSV-infected cotton rats 24 hours after treatment, and successive treatments caused an even greater reduction in the amount of RSV detected.

Applications: Research and drug development for treatment of respiratory syncytial virus.

Inventors: Robert M. Chanock (NIAID), Brian R. Murphy (NIAID), James E. Crowe Jr. (NIAID), et al.

Patent Status: U.S. Patent 5,762,905 issued 09 Jun 1998 (HHS Reference No. E-032-1993/1-US-01); U.S. Patent 6,685,942 issued 03 Feb 2004 (HHS Reference No. E-032-1993/1-US-02); U.S. Patent Application No. 10/768,952 filed 29 Jan 2004 (HHS Reference No. E-032-1993/1-US-03).

Licensing Status: Available for non-exclusive licensing.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

Neutralizing Monoclonal Antibodies to Respiratory Syncytial Virus

Description of Technology: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia among infants and children under 1 year of age. Illness begins most frequently with fever, runny nose, cough, and sometimes wheezing. During their first RSV infection, between 25% and 40% of infants and young children have signs or symptoms of bronchiolitis or pneumonia, and 0.5% to 2% require hospitalization. Most children recover from illness in 8 to 15 days. The majority of children hospitalized for RSV infection are under 6 months of age. RSV also causes repeated infections throughout life, usually associated with moderate-to-severe cold-like symptoms; however, severe lower respiratory tract disease may occur at any age, especially among the elderly or among those with compromised cardiac, pulmonary, or immune systems.

This invention is a human monoclonal antibody fragment (Fab) discovered utilizing phage display technology. The neutralizing monoclonal antibody was isolated and its binding site was identified. Fab F2-5 is a broadly reactive fusion (F) protein-specific recombinant Fab generated by antigen selection from a random combinatorial library displayed on the surface of filamentous phage. In an in vitro plaque-reduction test, the Fab RSVF2-5 neutralized the infectivity of a variety of field isolates representing viruses of both RSV subgroups A and B. The Fab recognized an antigenic determinant that differed from the only other human anti-F monoclonal antibody (RSV Fab 19) described thus far. A single dose of 4.0 mg of Fab RSVF2-5/kg of body weight administered by inhalation was sufficient to achieve a 2000-fold reduction in pulmonary virus titer in RSV-infected mice. The antigen-binding domain of Fab RSVF2-5 offers promise as part of a prophylactic regimen for RSV infection in humans.

Application: Respiratory Syncytial Virus prophylaxis/therapeutic.

Development Stage: The antibodies have been synthesized and preclinical studies have been performed.

Inventors: Brian Murphy (NIAID), Robert Chanock (NIAID), James Crowe (NIAID), et al.

Publication: JE Crowe et al. Isolation of a second recombinant human respiratory syncytial virus monoclonal antibody fragment (Fab RSVF2-5) that exhibits therapeutic efficacy in vivo. J Infect Dis. 1998 Apr;177(4):1073-1076.

Patent Status: HHS Reference No. E-001-1996/0—U.S. and Foreign Rights Available.

Licensing Status: Available for exclusive or non-exclusive licensing.Start Printed Page 34765

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

Murine Monoclonal Antibodies Effective To Treat Respiratory Syncytial Virus

Description of Technology: 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. 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 109 M-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.

Applications: Research and drug development for treatment of respiratory syncytial virus.

Inventors: Robert M. Chanock, Brian R. Murphy, Judith A. Beeler, and Kathleen L. van Wyke Coelingh (NIAID).

Patent Status: HHS Reference No. B-056-1994/1—Research Tool.

Licensing Status: Available for non-exclusive licensing under a Biological Materials License Agreement.

Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; soukasp@mail.nih.gov.

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Dated: June 10, 2008.

Richard U. Rodriguez,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.

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[FR Doc. E8-13672 Filed 6-17-08; 8:45 am]

BILLING CODE 4140-01-P