Notices. Notice
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/register/2008/01/25/08-275A research copy — for the controlling text, always check the official state or federal source. Not legal advice.
BILLING CODE 4165-16-M DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Submission for OMB Review; Comment Request; NIH-American Association for Retired Persons
(AARP)Short Follow-Up Questionnaire 2008
(NCI)SUMMARY: Under the provisions of Section 3507(a)(1)(D) of the Paperwork Reduction Act of 1995, the National Cancer Institute (NCI), the National Institutes of Health (NIH), has submitted to the Office of Management and Budget
(OMB)a request to review and approve the information collection listed below. This proposed information collection was previously published in the **Federal Register** on November 6, 2007 (Vol. 72, No. 214, p. 62660) and allowed 60-days for public comment. One public comment was received on November 6, 2007 which questioned why AARP was not funding this study as opposed to using NIH funds. An e-mail response was sent on January 14, 2008 stating, “We received your comment. We will take your comments into consideration”. The purpose of this notice is to allow an additional 30 days for public comment. The National Institutes of Health may not conduct or sponsor, and the respondent is not required to respond to, an information collection that has been extended, revised, or implemented on or after October 1, 1995, unless it displays a currently valid OMB control number. *Proposed Collection:* *Title:* NIH-American Association for Retired Persons
(AARP)Short Follow-Up Questionnaire 2008 (NCI). *Type of Information Collection Request:* New. *Need and Use of Information Collection:* The purpose of this short 2-page questionnaire is to obtain information on 18 different medical conditions, several medical procedures, and lifestyle characteristics from 513,225 participants of the NIH-AARP Diet and Health Study. The questionnaire will support the ongoing examination between cancer and nutritional exposures. This questionnaire adheres to The Public Health Service Act, Section 412 (42 U.S.C. 285a-1) and Section 413 (42 U.S.C. 285a-2), which authorizes the Division of Cancer Epidemiology and Genetics of the National Cancer Institute
(NCI)to establish and support programs for the detection, diagnosis, prevention and treatment of cancer; and to collect, identify, analyze and disseminate information on cancer research, diagnosis, prevention and treatment. *Frequency of Response:* Once. *Affected Public:* Individuals. *Type of Respondents:* U.S. adults (persons aged 50-85). The annual reporting burden is as follows: *Estimated Number of Respondents:* 513,225; *Estimated Number of Responses per Respondent:* 1; *Average Burden Hours Per Response:* .0668; and *Estimated Total Annual Burden Hours Requested:* 34,283. The annualized cost to respondents is estimated at: $302,158. There are no Capital Costs, Operating Costs, and/or Maintenance Costs to report. Type of respondents Number of respondents Frequency of response Average burden hours per response Annual hour burden Hourly wage rate Cost to respond Senior Adults 513,225 1 .0668 (4 minutes) 34,283 $17.68 $302,158 *Request for Comments:* Written comments and/or suggestions from the public and affected agencies are invited on one or more of the following points:
(1)Whether the proposed collection of information is necessary for the proper performance of the function of the agency, including whether the information will have practical utility;
(2)The accuracy of the agency's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used;
(3)Ways to enhance the quality, utility, and clarity of the information to be collected; and
(4)Ways to minimize the burden of the collection of information on those who are to respond, including the use of appropriate automated, electronic, mechanical, or other technological collection techniques or other forms of information technology. FOR FURTHER INFORMATION CONTACT: To request more information on the proposed project or to obtain a copy of the data collection plans and instruments, contact Arthur Schatzkin, M.D., Dr.P.H, Chief, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Executive Plaza South, Room 3040, 6120 Executive Blvd., EPS-MSC 7242, Bethesda, MD 20892-7335 or call non-toll-free number 301-594-2931 or e-mail your request, including your address to: *schatzka@mail.nih.gov.* *Comments Due Date:* Comments regarding this information collection are best assured of having their full effect if received within 30 days of the date of this publication. Dated: January 14, 2008. Vivian Horovitch-Kelley, NCI Project Clearance Liaison, National Institutes of Health. [FR Doc. E8-1249 Filed 1-24-08; 8:45 am] BILLING CODE 4140-01-P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Human Monoclonal Antibodies, Their Fragments and Derivatives as Biotherapeutics for the Treatment of HIV Infections AGENCY: National Institutes of Health, Public Health Service, HHS. ACTION: Notice. SUMMARY: This is notice, in accordance with 35 U.S.C. 209(c)(1) and 37 CFR 404.7(a)(1)(i), that the National Institutes of Health (NIH), Department of Health and Human Services, is contemplating the grant of an exclusive license to practice the inventions embodied in: 1. U.S. Provisional Patent Application S/N 60/329,709 (E-130-2001/0-US-01). PCT/US02/33165 was filed on October 16, 2002 (E-130-2001/0-PCT-01) and converted into 02773789.9 (E-130-2001/0-EP-03) filed in Europe on May 12, 2004, 2002337885 (E-130-2001/0-AU-02) filed in Australia on March 29, 2004, 10/492,729 (E-130-2001/0-US-05) filed in the U.S. on April 15, 2004, divisional application 11/748,992 (E-130-2001/0-US-07) filed in the U.S. on May 15, 2007, and 2,463,931(E-130-2001/0-CA-04) filed in Canada on April 15, 2004; entitled “Broadly Cross-Reactive Neutralizing Antibodies Against Human Immunodeficiency Virus Selected By Env-CD4-Co-Receptor Complex.” Inventor(s): Dimiter S. Dimitrov (NCI), Maxime Moulard (EM), Xiadong Xiao (NCI), Yuuei Shu (NCI), Sanjay K. Phogat (IAVI), Mei-Yun Zhang (NCI), and Dennis Burton (Scripps Inst.) 2. U.S. Provisional Patent Application S/N 60/623,394 (E-251-2004/0-US-01). PCT/US2005/39175 (E-251-2004/0-PCT-02) filed on October 28, 2005 and converted into 2,585,574 (E-251-2004/0-CA-04) filed in Canada on October 28, 2005, 05819487.9 (E-251-2004/0-EP-05) filed in Europe on April 27, 2007, 2005302416 (E-251-2004/0-AU-06) filed in Australia on October 28, 2005, and 11/718,202 (E-251-2004/0-US-03) filed in the U.S. on August 10, 2007; entitled “Novel Broadly Cross-Reactive HIV Neutralizing Human Monoclonal Antibodies Selected From Phage Display Libraries Using Novel Strategy Based On Competitive Antigen Panning.” Inventor(s): Dimiter S. Dimitrov
(NCI)and Mei-Yun Zhang
(SAIC)to Profectus Biosciences, Inc. (hereafter Profectus) having a place of business in Baltimore, Maryland. The patent rights in these inventions have been assigned to the United States of America. DATES: Only written comments and/or application for a license, which are received by the NIH Office of Technology Transfer on or before March 25, 2008 will be considered. ADDRESSES: Requests for a copy of the patent application, inquiries, comments and other materials relating to the contemplated license should be directed to: Sally Hu, Ph.D., M.B.A., Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, MD 20852-3804; E-mail: *hus@od.nih.gov;* Telephone:
(301)435-5606; Facsimile:
(301)402-0220. SUPPLEMENTARY INFORMATION: The first invention (E-130-2001/0) provides a novel anti-HIV human monoclonal antibody named X5. This antibody demonstrates promise over conventional anti-HIV antibodies because the X5 antibody exhibits a unique binding activity compared to its counterparts. It has been established that the initial stage of HIV-1 entry into cells is mediated by a complex between the viral envelope glycoprotein
(Env)such as gp120-gp41, a receptor CD4 and a co-receptor CCR5. The X5 antibody binds to an epitope on gp120 that is induced by interaction between gp120 and the receptor CD4 and enhanced by the co-receptor CCR5. The X5 antibody also shows strong activity at very low levels (in the range from 0.0001—0.1 Mg/ml concentration based on the particular isolate). Because it is a human antibody, it can be administered directly into patients so that it is an ideal candidate for clinical trials. It also can be easily produced because it was obtained by screening of phage display libraries and its sequence is known. Finally, since it has neutralized all virus envelope glycoproteins, including those from primary isolates of different clades, the epitope is highly conserved and resistance is unlikely to develop. Therefore, this antibody and/or its derivatives including fusion proteins with CD4 are good candidates for clinical development. The second invention (E-251-2004/0) provides for pharmaceutical compositions of, and methods of using potent cross-reactive human monoclonal antibodies to HIV. Specifically, the invention describes a competitive antigen panning
(CAP)method of isolating antibodies that bind to the gp41 subunit of the HIV-1 envelope glycoprotein. Additionally, the invention includes compositions of the aforementioned antibodies and the epitopes recognized by the antibodies. Methods of using the invention in the development of vaccine immunogens for the treatment and prevention of HIV, as well as the detection of HIV in a mammal are also described. The invention has significant implications in the development of HIV inhibitors, vaccines, and research tools for understanding mechanisms of HIV entry. Further development of the disclosed invention may yield novel therapies and methods in the prevention of mother-to-child transmission of HIV, treatment of accidental exposure to HIV, and chronic infection in patients with resistance to current therapies. The prospective exclusive license will be royalty bearing and will comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR 404.7. The prospective exclusive license may be granted unless, within 60 days from the date of this published Notice, NIH receives written evidence and argument that establishes that the grant of the license would not be consistent with the requirements of 35 U.S.C. 209 and 37 CFR 404.7. The field of use may be limited to the development of human monoclonal antibodies for use as a therapeutic or preventative in HIV infection either alone or in combination with other compounds. Properly filed competing applications for a license filed in response to this notice will be treated as objections to the contemplated license. Comments and objections submitted in response to this notice will not be made available for public inspection, and, to the extent permitted by law, will not be released under the Freedom of Information Act, 5 U.S.C. 552. Dated: January 16, 2008. Steven M. Ferguson, Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health. [FR Doc. E8-1258 Filed 1-24-08; 8:45 am] BILLING CODE 4140-01-P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Government-Owned Inventions; Availability for Licensing: Flavivirus Technologies 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. Development of Antigenic Chimeric St. Louis Encephalitis Virus/Dengue Virus Type Four Recombinant Viruses (SLEV/DEN4) as Vaccine Candidates for the Prevention of Disease Caused by SLEV *Description of Invention:* St. Louis Encephalitis Virus
(SLEV)is a mosquito-borne flavivirus that is endemic in the Americas and causes sporadic outbreaks of disease in humans. SLEV is a member of the Japanese encephalitis virus serocomplex and is closely related to West Nile Virus (WNV). St. Louis encephalitis is found throughout North, Central, and South America, and the Caribbean, but is a major public health problem mainly in the United States. Prior to the outbreak of West Nile virus in 1999, St. Louis encephalitis was the most common human disease caused by mosquitoes in the United States. Since 1964, there have been about 4,440 confirmed cases of St. Louis encephalitis, with an average of 130 cases per year. Up to 3,000 cases have been reported during epidemics in some years. Many more infections occur without symptoms and go undiagnosed. At present, a vaccine or FDA approved antiviral therapy is not available. The inventors have previously developed a WNV/Dengue4Delta30 antigenic chimeric virus as a live attenuated virus vaccine candidate that contains the WNV premembrane and envelope (prM and E) proteins on a dengue virus type 4
(DEN4)genetic background with a thirty nucleotide deletion (Delta30) in the DEN4 3'-UTR. Using a similar strategy, the inventors have generated an antigenic chimeric virus, SLE/DEN4Delta30. Preclinical testing results indicate that chimerization of SLE with DEN4Delta30 decreased neuroinvasiveness in mice, did not affect neurovirulence in mice, and appeared to overattenuate the virus for non-human primates. Modifications of the SLE/DEN4Delta30 vaccine candidate are underway to improve its immunogenicity. This application claims live attenuated chimeric SLE/DEN4Delta30 vaccine compositions and bivalent WNV/SLE/DEN4Delta30 vaccine compositions. Also claimed are methods of treating or preventing SLEV infection in a mammalian host, methods of producing a subunit vaccine composition, isolated polynucleotides comprising a nucleotide sequence encoding a SLEV immunogen, methods for detecting SLEV infection in a biological sample and infectious chimeric SLEV. *Application:* Immunization against SLEV or SLEV and WNV. *Development Status:* Live attenuated vaccine candidates are currently being developed and preclinical studies in mice and monkeys are in progress. Suitable vaccine candidates will then be evaluated in clinical studies. *Inventors:* Stephen S. Whitehead, Joseph Blaney, Alexander Pletnev, Brian R. Murphy (NIAID). *Patent Status:* U.S. Provisional Application No. 60/934,730 filed 14 Jun 2007 (HHS Reference No. E-240-2007/0-US-01). *Licensing Status:* Available for exclusive or non-exclusive licensing. *Collaborative Research Opportunity:* The NIAID Laboratory of Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize live attenuated virus vaccine candidates for St. Louis encephalitis virus. Please contact Dr. Whitehead at 301-496-7692 for more information. Live Attenuated Virus Vaccines for La Crosse Virus and Other Bunyaviridae *Description of Invention:* La Crosse virus (LACV), family Bunyaviridae, is a mosquito-borne pathogen endemic in the United States. LACV infection results in 70-130 clinical cases a year and is the major cause of pediatric arboviral encephalitis in North America. LACV was first identified as human pathogen in 1960 after its isolation from a 4 year-old girl from Minnesota who suffered meningoencephalitis and later died in La Crosse, Wisconsin. The majority of LACV infections are mild and never reported, however serologic studies estimate annual infection rates of 10-30/100,000 in endemic areas. LACV is a member of the California serogroup of viruses in the genus *Orthobunyavirus.* The serogroup contains members found on five continents that include human pathogens such as La Crosse, Snowshoe hare, and Jamestown Canyon viruses in North America; Guaroa virus in North and South America; Inkoo and Tahyna viruses in Europe; and Lumbo virus in Africa. Children who recover from severe La Crosse encephalitis may have significantly lower IQ scores than expected and a high prevalence (60% of those tested) of attention-deficit-hyperactivity disorder. Seizure disorders are also common in survivors. LACV can also cause encephalitis in immunosuppressed adults. Projected lifelong economic costs associated with neurologic sequelae range from $48,775-3,090,398 per case. At present, a vaccine or FDA approved antiviral therapy is not available. This application principally claims live attenuated LACV vaccine compositions, but also includes subunit vaccine compositions including California encephalitis virus
(CEV)serogroup immunogens, attenuated and inactivated CEV serogroup and chimeric *Bunyaviridae.* Also claimed are methods of treating or preventing CEV serogroup infection in a mammalian host, methods of producing a subunit vaccine composition, isolated polynucleotides comprising a nucleotide sequence encoding a CEV serogroup immunogen, methods for detecting LACV infection in a biological sample and infectious chimeric *Bunyaviridae.* *Application:* Immunization against *Bunyaviridae.* *Developmental Status:* Live attenuated vaccine candidates are currently being developed and preclinical studies in mice and monkeys are in progress. Suitable vaccine candidates will then be evaluated in clinical studies. *Inventors:* Stephen S. Whitehead, Richard S. Bennett, Brian R. Murphy (NIAID). *Publication:* RS Bennett *et al.* Genome sequence analysis of La Crosse virus and in vitro and in vivo phenotypes. Virol J. 2007 May 8;4:41. *Patent Status:* U.S. Provisional Application No. 60/920,691 filed 29 Mar 2007 (HHS Reference No. E-158-2007/0-US-01); U.S. Provisional Application No. 60/928,406 filed 08 May 2007 (HHS Reference No. E-158-2007/1-US-01); U.S. Provisional Application filed 29 Jun 2007 (HHS Reference No. E-158-2007/2-US-01). *Licensing Status:* Available for exclusive or non-exclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov.* *Collaborative Research Opportunity:* The NIAID Laboratory of Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize live attenuated virus vaccine candidates for La Crosse virus and other *Bunyaviridae.* Please contact Dr. Whitehead at 301-496-7692 for more information. Development of Dengue Virus Type 3 Vaccine Candidates Containing Either
(1)Nucleotide Deletions in the 3′-UTR of the Genome Consisting of More Than 30 Contiguous Nucleotides in One or Multiple Regions, or
(2)a 3′-UTR Derived From DEN4 and Containing the A30 Nucleotide Deletion *Description of Technology:* The disease burden associated with dengue virus infection has increased over the past several decades in the tropical and semi-tropical regions of the world, where over 2 billion people live at risk of dengue infection. Annually, there are an estimated fifty
(50)to one hundred
(100)million cases of dengue fever, making development of an effective vaccine a priority. In addition, there is a need for a “travelers vaccine” to protect those visiting dengue virus endemic areas, similar in scope to other currently available “travelers vaccines”, such as hepatitis A vaccine. The previously identified Δ30 attenuating mutation, created in each dengue virus serotype by the removal of 30 homologous nucleotides from the 3′-UTR, is capable of attenuating wild-type strains of dengue virus type 1 (DEN1), type 4
(DEN4)and to a limited extent type 2 (DEN2). These DEN1Δ30 and DEN4Δ30 viruses have been shown to be both safe and immunogenic in humans. However, the Δ30 mutation failed to have an attenuating effect on dengue virus type 3 (DEN3). To generate DEN3 vaccine candidates with a clearly attenuated phenotype, viruses were produced containing 3′-UTR deletions consisting of extensions of the original Δ30 mutation or additional mutations which remove stem-loop structures similar to those removed by Δ30. In addition, the entire 3′-UTR of DEN3 was replaced with the 3′-UTR derived from DEN4 and containing the Δ30 mutation. Studies in monkeys demonstrated that these newly developed viruses are highly attenuated, yet sufficiently immunogenic to warrant their further development for use as live attenuated vaccine candidates. Such viruses are anticipated to become the DEN3 component of a tetravalent vaccine formulation designed to immunize against all four dengue virus serotypes. *Application:* Immunization against all four serotypes of dengue virus. *Developmental Status:* Vaccine candidates have been synthesized and preclinical studies have been performed. The vaccine candidates of this invention are slated to enter Phase I clinical trials in the next year. *Inventors:* Stephen S. Whitehead, Joseph E. Blaney, Brian R. Murphy (NIAID). *Patent Status:* PCT Application No. PCT/US2007/076004 filed 15 Aug 2007, claiming priority to 15 Aug 2006 (HHS Reference No. E-139-2006/0-PCT-02). *Licensing Status:* Available for exclusive or non-exclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov.* *Collaborative Research Opportunity:* The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or *bm25f@nih.gov* for more information. Dengue Tetravalent Vaccine Containing a Common 30-Nucleotide Deletion in the 3′-UTR of Dengue Types 1, 2, 3, and 4 *Description of Technology:* The invention relates to a dengue virus tetravalent vaccine containing a common 30-nucleotide deletion (Δ30) in the 3′-untranslated region
(UTR)of the genome of dengue virus serotypes 1, 2, 3, and 4. The previously identified Δ30 attenuating mutation, created in dengue virus type 4
(DEN4)by the removal of 30 nucleotides from the 3′-UTR, is also capable of attenuating a wild-type strain of dengue virus type 1 (DEN1). Removal of 30 nucleotides from the DEN1 3′-UTR in a highly conserved region homologous to the DEN4 region encompassing the Δ30 mutation yielded a recombinant virus attenuated in rhesus monkeys to a level similar to recombinant virus DEN4Δ30. This established the transportability of the Δ30 mutation and its attenuation phenotype to a dengue virus type other than DEN4. The effective transferability of the Δ30 mutation establishes the usefulness of the Δ30 mutation to attenuate and improve the safety of commercializable dengue virus vaccines of any serotype. A tetravalent dengue virus vaccine containing dengue virus types 1, 2, 3, and 4 each attenuated by the Δ30 mutation is being developed. The presence of the Δ30 attenuating mutation in each virus component precludes the reversion to a wild-type virus by intertypic recombination. In addition, because of the inherent genetic stability of deletion mutations, the Δ30 mutation represents an excellent alternative for use as a common mutation shared among each component of a tetravalent vaccine. *Inventors:* Stephen S. Whitehead (NIAID), Brian R. Murphy (NIAID), Lewis Markoff (FDA), Barry Falgout (FDA), Kathryn A. Hanley (NIAID), Joseph E. Blaney (NIAID). *Patent Status:* U.S. Patent Application No. 10/970,640 filed 21 Oct 2004, claiming priority to 03 May 2002 (HHS Reference No. E-089-2002/1-US-02). *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov.* *Collaborative Research Opportunity:* The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or *bm25f@nih.gov* for more information. Development of Mutations Useful for Attenuating Dengue Viruses and Chimeric Dengue Viruses *Description of Technology:* Although flaviviruses cause a great deal of human suffering and economic loss, there is a shortage of effective vaccines. This invention relates to dengue virus mutations that may contribute to the development of improved dengue vaccines. Site directed and random mutagenesis techniques were used to introduce mutations into the dengue virus genome and to assemble a collection of useful mutations for incorporation in recombinant live attenuated dengue virus vaccines. The resulting mutant viruses were screened for several valuable phenotypes, including temperature sensitivity in Vero cells or human liver cells, host cell restriction in mosquito cells or human liver cells, host cell adaptation for improved replication in Vero cells, and attenuation in mice or in mosquitoes. The genetic basis for each observed phenotype was determined by direct sequence analysis of the genome of the mutant virus. Mutations identified through these sequencing efforts have been further evaluated by re-introduction of the identified mutations, singly, or in combination, into recombinant dengue virus and characterization of the resulting recombinant virus for phenotypes. In this manner, a menu of attenuating and growth promoting mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccine candidates. The mutations promoting growth in Vero cells have usefulness for the production of live or inactivated dengue virus vaccines. *Inventors:* Stephen S. Whitehead, Brian R. Murphy, Kathryn A. Hanley, Joseph E. Blaney (NIAID). *Patent Status:* U.S. Patent No. 7,226,602 issued 05 Jun 2007 (HHS Reference No. E-120-2001/0-US-04); U.S. Patent Application No. 11/446,050 filed 02 Jun 2006 (HHS Reference No. E-120-2001/0-US-10). *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov.* *Collaborative Research Opportunity:* The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or *bm25f@nih.gov* for more information. Date: January 10, 2008. Steven M. Ferguson, Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health. [FR Doc. E8-1234 Filed 1-24-08; 8:45 am] BILLING CODE 4140-01-P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Government-Owned Inventions; Availability for Licensing 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. Monoclonal Antibodies Against Dengue and Other Viruses With Deletion in Fc Region *Description of Invention:* 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 <1% to 5% in children. 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 C <sup>H</sup> 2 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. *Application:* Immunization against Dengue and/or flaviviruses. *Developmental Status:* Antibody candidates have been synthesized and preclinical studies have been performed. *Inventors:* Ana Goncalvez, Robert Purcell, C.J. Lai (NIAID). *Publication:* AP Goncalvez, *et al.* Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention Proc Natl Acad Sci USA. 2007 May 29;104(22):9422-9427. *Patent Status:* U.S. Provisional Application No. 60/922,282 filed 04 Apr 2007 (HHS Reference No. E-159-2007/0-US-01); U.S. Provisional Application No. 60/927,755 filed 04 May 2007 (HHS Reference No. E-159-2007/1-US-01); U.S. Provisional Application No. 60/928,405 filed 08 May 2007 (HHS Reference No. E-159-2007/2-US-01). *Licensing Status:* Available for exclusive or non-exclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . Monoclonal Antibodies that Neutralize B. anthracis Protective Antigen (PA), Lethal Factor
(LF)and Edema Factor
(EF)*Description of Invention:* Anthrax, whether resulting from natural or bioterrorist-associated exposure, is a constant threat to human health. The lethality of anthrax is primarily the result of the effects of anthrax toxin, which has 3 components: a receptor-binding protein known as “protective antigen”
(PA)and 2 catalytic proteins known as “lethal factor”
(LF)and “edema factor” (EF). Although production of an efficient anthrax vaccine is an ultimate goal, the benefits of vaccination can be expected only if a large proportion of the population at risk is immunized. The low incidence of anthrax suggests that large-scale vaccination may not be the most efficient means of controlling this disease. In contrast, passive administration of neutralizing human or chimpanzee monoclonal antibody to a subject at risk for anthrax or exposed to anthrax could provide immediate efficacy for emergency prophylaxis against or treatment of anthrax. Four monoclonal antibodies
(mAbs)against PA, three mAbs against LF and four mAbs specific for EF of anthrax were isolated from a phage display library generated from immunized chimpanzees. Two mAbs recognizing PA (W1 and W2), two anti-LF mAbs efficiently neutralized the cytotoxicity of lethal toxin in a macrophage lysis assay. One anti-EF mAb efficiently neutralized edema toxin in cell culture. All five neutralizing mAbs protected animals from anthrax toxin challenge. *Application:* Prophylactics or therapeutics against *B. anthracis.* *Developmental Status:* Preclinical studies have been performed. *Inventors:* Zhaochun Chen, Robert Purcell, Suzanne Emerson, Stephen Leppla, Mahtab Moyeri (NIAID). *Publication:* Z Chen, *et al.* Efficient neutralization of anthrax toxin by chimpanzee monoclonal antibodies against protective antigen. J Infect Dis. 2006 Mar 1;193(5):625-633. *Patent Status:* U.S. Provisional Application No. 60/903,022 filed 23 Feb 2007 (HHS Reference No. E-123-2007/0-US-01); U.S. Patent Application No. 11/793,735 filed 22 Jun 2007 (HHS Reference No. E-146-2004/0-US-03). *Licensing Status:* Available for exclusive or non-exclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . *Collaborative Research Opportunity:* The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Chimpanzee/human neutralizing monoclonal antibodies against anthrax toxins. Please contact Dr. Robert Purcell at 301-496-5090 for more information. Cell-Nanofiber Composite and Cell-Nanofiber Composite Amalgam Based Engineered Intervertebral Disc *Description of Invention:* Diseased or damaged musculoskeletal tissues are often replaced by an artificial material, cadaver tissue or donated, allogenic tissue. Tissue engineering offers an attractive alternative whereby a live, natural tissue is generated from a construct made up of a patient's own cells or an acceptable/compatible cell source in combination with a biodegradable scaffold for replacement of defective tissue. Degeneration of the intervertebral disc
(IVD)is a common and significant source of morbidity in our society. Approximately 8 of 10 adults at some point in their life will experience an episode of significant low back pain, with the majority improving without any formal treatment. However, for the subject requiring surgical management current interventions focus on fusion of the involved IVD levels, which eliminates pain but does not attempt to restore disc function. Approximately 200,000 spinal fusions were performed in the United States in 2002 to treat pain associated with lumbar disc degeneration. Spinal fusion however is thought to significantly alter the biomechanics of the disc and lead to further degeneration, or adjacent segment disease. Therefore, in the past decade there has been mounting interest in the concept of IVD replacement. The replacement of the IVD holds tremendous potential as an alternative to spinal fusion for the treatment of degenerative disc disease by offering a safer alternative to current spinal fusion practices. At the present time, several disc replacement implants are at different stages of preclinical and clinical testing. These disc replacement technologies are designed to address flexion, extension, and lateral bending motions; however, they do little to address compressive forces and their longevity is limited due to their inability to biointegrate. Therefore, a cell-based tissue engineering approach offers the most promising alternative to replace the degenerated IVD. Current treatment for injuries that penetrate subchondral bone include subchondral drilling, periosteal tissue grafting, osteochondral allografting, chondrogenic cell and transplantation; but are limited due to suboptimal integration with host tissues. The present invention claims tissue engineered intervertebral discs comprising a nanofibrous polymer hydrogel amalgam having cells dispersed therein, methods of fabricating tissue engineered intervertebral discs by culturing a mixture of stem cells or intervertebral disc cells and a electrospun nanofibrous polymer hydrogel amalgam in a suitable bioreactor, and methods of treatment comprising implantation of tissue engineered intervertebral disc into a subject. *Application:* Intervertebral disc bio-constructs and electrospinning methods for fabrication of the discs. *Developmental Status:* Prototype devices have been fabricated and preclinical studies have been performed. *Inventors:* Wan-Ju Li, Leon Nesti, Rocky Tuan (NIAMS) *Patent Status:* U.S. Provisional Application No. 60/847,839 filed 27 Sep 2006 (HHS Reference No. E-309-2006/0-US-01); U.S. Provisional Application No. 60/848,284 filed 28 Sep 2006 (HHS Reference No. E-309-2006/1-US-01) *Licensing Status:* Available for exclusive or non-exclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . Cell-Nanofiber Composite Based Engineered Cartilage *Description of Invention:* Available for licensing and commercial development is a tissue-engineered cartilage derived from a cellular composite made from a biodegradable, biocompatible polymeric nanofibrous matrix having dispersed chondrocytes or adult mesenchymal stem cells. More particularly, tissue-engineered cartilage can be prepared where the cartilage has a biodegradable and biocompatible nanofibrous polymer matrix prepared by electrospinning and a plurality of chondrocytes or mesenchymal stem cells dispersed in the pores of the matrix. The tissue-engineered cartilage possesses compressive strength properties similar to natural cartilage. The electrospinning process is a simple, economical means to produce biomaterial matrices or scaffolds of ultra-fine fibers derived from a variety of biodegradable polymers (Li WJ, *et al.* *J. Biomed. Mater. Res.* 2002; 60:613-21). Nanofibrous scaffolds
(NFSs)formed by electrospinning, by virtue of structural similarity to natural extracellular matrix (ECM), may represent promising structures for tissue engineering applications. Electrospun three-dimensional NFSs are characterized by high porosity with a wide distribution of pore diameter, high-surface area to volume ratio and morphological similarities to natural collagen fibrils (Li WJ, *et al. J. Biomed. Mater. Res.* 2002; 60:613-21). These physical characteristics promote favorable biological responses of seeded cells in vitro and in vivo, including enhanced cell attachment, proliferation, maintenance of the chondrocytic phenotype (Li WJ, *et al. J. Biomed. Mater. Res.* 2003; 67A: 1105-14), and support of chondrogenic differentiation (Li WJ, *et al. Biomaterials* 2005; 26:599-609) as well as other connective tissue linage differentiation (Li WJ, *et al. Biomaterials* 2005; 26:5158-5166). The invention based on cell-nanofiber composite represents a candidate engineered tissue for cell-based approaches to cartilage repair. *Application:* Cartilage repair and methods for making tissue-engineered cartilage. *Developmental Status:* Electrospinning method is fully developed and cartilage has been synthesized. *Inventors:* Wan-Ju Li and Rocky Tuan (NIAMS). *Publications:* The invention is further described in: 1. W-J Li, *et al.* Engineering controllable anisotropy in electrospun biodegradable nanofibrous scaffolds for musculoskeletal tissue engineering. J Biomech. 2007;40(8):1686-1693. 2. W-J Li, *et al.* Fabrication and characterization of six electrospun poly(alpha-hydroxy ester)-based fibrous scaffolds for tissue engineering applications. Acta Biomater. 2006 Jul;2(4):377-385. 3. CK Kuo, *et al.* Cartilage tissue engineering: its potential and uses. Curr Opin Rheumatol. 2006 Jan;18(1):64-73. Review. 4. W-J Li, *et al.* Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. Biomaterials. 2005 Sep;26(25):5158-5166. *Patent Status:* U.S. Provisional Application No. 60/690,998 filed 15 Jun 2005 (HHS Reference No. E-116-2005/0-US-01); PCT Application No. PCT/US2006/0237477 filed 15 Jun 2006 (HHS Reference No. E-116-2005/0-PCT-02) *Licensing Status:* Available for exclusive or non-exclusive licensing. *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* . Bioreactor Device and Method and System for Fabricating Tissue *Description of Invention:* Available for licensing and commercial development is a millifluidic bioreactor system for culturing, testing, and fabricating natural or engineered cells and tissues. The system consists of a millifluidic bioreactor device and methods for sample culture. Biologic samples that can be utilized include cells, scaffolds, tissue explants, and organoids. The system is microchip controlled and can be operated in closed-loop, providing controlled delivery of medium and biofactors in a sterile temperature regulated environment under tabletop or incubator use. Sample perfusion can be applied periodically or continuously, in a bidirectional or unidirectional manner, and medium re-circulated. *Advantages:* The device is small in size, and of conventional culture plate format. Provides the ability to grow larger biologic samples than microfluidic systems, while utilizing smaller medium volumes than conventional bioreactors. The bioreactor culture chamber is adapted to contain sample volumes on a milliliter scale (10 [mu]L to 1 mL, with a preferred size of 100 [mu]L), significantly larger than chamber volumes in microfluidic systems (on the order of 1 [mu]L). Typical microfluidic systems are designed to culture cells and not larger tissue samples. The integrated medium reservoirs and bioreactor chamber design provide for,
(1)concentration of biofactors produced by the biologic sample, and
(2)the use of smaller amounts of exogenous biofactor supplements in the culture medium. The local medium volume (within the vicinity of the sample) is less than twice the sample volume. The total medium volume utilized is small, preferably 2 ml, significantly smaller than conventional bioreactors (typically using 500-1,000 mL). Provides for real-time monitoring of sample growth and function in response to stimuli via an optical port and embedded sensors. The optical port provides for microscopy and spectroscopy measurements using transmitted, reflected, or emitted (e.g., fluorescent, chemiluminescent) light. The embedded sensors provide for measurement of culture fluid pressure and sample pH, oxygen tension, and temperature. Capable of providing external stimulation to the biologic sample, including mechanical forces (e.g. fluid shear, hydrostatic pressure, matrix compression, microgravity via clinorotation), electrical fields (e.g., AC currents), and biofactors (e.g., growth factors, cytokines) while monitoring their effect in real-time via the embedded sensors, optical port, and medium sampling port. Monitoring of biologic sample response to external stimulation can be performed non-invasively and non-destructively through the embedded sensors, optical port, and medium sampling port. Testing of tissue mechanical and electrical properties (e.g., stiffness, permeability, loss modulus via stress or creep test, electrical impedance) can be performed over time without removing the sample from the bioreactor device. The bioreactor sample chamber can be constructed with multiple levels fed via separate perfusion circuits, facilitating the growth and production of multiphasic tissues. *Application:* Cartilage repair and methods for making tissue-engineered cartilage. *Development Stage:* Electrospinning method is fully developed and cartilage has been synthesized. *Inventors:* Juan M. Taboas (NIAMS), Rocky S. Tuan (NIAMS), *et al.* *Patent Status:* U.S. Provisional Application No. 60/701,186 filed 20 Jul 2005 (HHS Reference No. E-042-2005/0-US-01); PCT Application No. PCT/US2006/028417 filed 20 Jul 2006, which published as WO 2007/012071 on 25 Jan 2007 (HHS Reference No. E-042-2005/0-PCT-02) *Licensing Status:* Available for exclusive or non-exclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . Monoclonal Antibodies Against Orthopoxviruses *Description of Invention:* Concerns that variola (smallpox) virus might be used as a biological weapon have led to the recommendation of widespread vaccination with vaccinia virus. While vaccination is generally safe and effective for prevention of smallpox, it is well documented that various adverse reactions in individuals have been caused by vaccination with existing licensed vaccines. Vaccinia immune globulin
(VIG)prepared from vaccinated humans has historically been used to treat adverse reactions arising from vaccinia immunization. However, VIG lots may have different potencies and carry the potential to transmit other viral agents. Chimpanzee Fabs against the B5 and A33 outer extracellular membrane proteins of vaccinia virus were isolated and converted into complete mAbs with human gamma1 heavy chain constant regions. The two mAbs displayed high binding affinities to B5 and A33. The mAbs inhibited the spread of vaccinia virus as well as variola virus (the causative agent of smallpox) *in vitro* , protected mice from subsequent intranasal challenge with virulent vaccinia virus, protected mice when administered 2 days after challenge, and provided significantly greater protection than that afforded by VIG. *Application:* Prophylactics or therapeutics against orthopoxviruses. *Developmental Status:* Preclinical studies have been performed. *Inventors:* Zhaochun Chen, Robert Purcell, Suzanne Emerson, Patricia Earl, Bernard Moss (NIAID). *Publications:* 1. Z Chen, *et al.* Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and smallpox viruses and protect mice against vaccinia virus. Proc Natl Acad Sci USA. 2006 Feb 7;103(6):1882-1887. Epub 2006 Jan 25. 2. Z Chen, *et al.* Characterization of chimpanzee/human monoclonal antibodies to the vaccinia A33 glycoprotein and its variola virus homolog in vitro and in a vaccinia mouse protection model. J Virol. 2007 Jun 20; Epub ahead of print, doi 10.1128/JVI.00906-07. *Patent Status:* PCT Patent Application No. PCT/US2006/048832 filed 22 Dec 2006 (HHS Reference No. E-145-2004/3-PCT-01); PCT Patent Application No. PCT/US2006/048833 filed 22 Dec 2006 (HHS Reference No. E-145-2004/4-PCT-01) *Licensing Status:* Available for exclusive or non-exclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . *Collaborative Research Opportunity:* The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Chimpanzee/human neutralizing monoclonal antibodies against orthopoxviruses. Please contact Dr. Robert Purcell at 301-496 5090 for more information. A Method With Increased Yield for Production of Polysaccharide-Protein Conjugate Vaccines Using Hydrazide Chemistry *Description of Invention:* Current methods for synthesis and manufacturing of polysaccharide-protein conjugate vaccines employ conjugation reactions with low efficiency (about twenty percent). This means that up to eighty percent of the added activated polysaccharide
(PS)is lost. In addition, inclusion of a chromatographic process for purification of the conjugates from unconjugated PS is required. The present invention utilizes the characteristic chemical property of hydrazide groups on one reactant to react with aldehyde groups or cyanate esters on the other reactant with an improved conjugate yield of at least sixty percent. With this conjugation efficiency the leftover unconjugated protein and polysaccharide would not need to be removed and thus the purification process of the conjugate product can be limited to diafiltration to remove the by-products of small molecules. The new conjugation reaction can be carried out within one or two days with reactant concentrations between 1 and 25 mg/mL at PS/protein ratios from 1:2 to 3:1, at temperatures between 4 and 40 degrees Centigrade, and in a pH range of 5.5 to 7.4, optimal conditions varying from PS to PS. *Application:* Cost effective and efficient manufacturing of conjugate vaccines. *Inventors:* Che-Hung Robert Lee and Carl E. Frasch (CBER/FDA) *Patent Status:* U.S. Patent Application No. 10/566,899 filed 01 Feb 2006, claiming priority to 06 Aug 2003 (HHS Reference No. E-301-2003/0-US-10); U.S. Patent Application No. 10/566,898 filed 01 Feb 2006, claiming priority to 06 Aug 2003 (HHS Reference No. E-301-2003/1-US-02); International rights available. *Licensing Status:* Available for non-exclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . γPGA Conjugates for Eliciting Immune Responses Directed Against Bacillus anthracis and Other Bacilli *Description of Invention:* This invention claims immunogenic conjugates of a poly-γ-glutamic acid (γPGA) of *B. anthracis* , or of another bacillus that expresses a γPGA that elicit a serum antibody response against *B. anthracis* , in mammalian hosts to which the conjugates are administered. The invention also relates methods which are useful for eliciting an immunogenic response in mammals, particularly humans, including responses which provide protection against, or reduce the severity of, infections caused by *B. anthracis* . The vaccines claimed in this application are intended for active immunization for prevention of *B. anthracis* infection, and for preparation of immune antibodies. The vaccines of this invention are designed to confer specific immunity against infection with *B. anthracis* , and to induce antibodies specific to *B. anthracis* γPGA. The *B. anthracis* vaccine is composed of non-toxic bacterial components, suitable for infants, children of all ages, and adults. *Inventors:* Rachel Schneerson (NICHD), Stephen Leppla (NIAID), John Robbins (NICHD), Joseph Shiloach (NIDDK), Joanna Kubler-Kielb (NICHD), Darrell Liu (NIDCR), Fathy Majadly (NICHD). *Publication:* R Schneerson, *et al.* Poly (gamma-D-glutamic acid) protein conjugates induce IgG antibodies in mice to the capsule of *Bacillus anthracis* : a potential addition to the anthrax vaccine. Proc Natl Acad Sci USA. 2003 Jul 22;100(15):8945-50. *Patent Status:* U.S. Patent Application No. 10/559,825 filed 02 Dec 2005, claiming priority to 05 Jun 2003 (HHS Reference No. E-343-2002/0-US-04). *Licensing Status:* Available for licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . Oligodeoxynucleotide and its Use To Induce an Immune Response *Description of Invention:* This invention comprises oligodeoxynucleotides
(ODNs)having at least 10 nucleotides with an unmethylated central CpG motif that are immunostimulatory in humans. The inventors have shown that the various ODNs of this invention (having different CpG motifs and backbones) induce immune responses from human non-B and B cells. The motif that stimulates non-B cells induces production and release of multiple T cell cytokines and chemokines; specifically, the Th1 cytokine IFN-gamma, which facilitates the development of a cytotoxic T cell response. In contrast, the motif that stimulates B cells induces production and release of various cytokines, including, but not limited to IL-6, which supports a Th2 antibody response. The inventors have generated in vitro and ex vivo data showing the ODNs of this invention have utility in precisely regulating the type and magnitude of the immune response in human cells. The present invention has multiple therapeutic uses, including but not limited to cancer, vaccine adjuvants, treating autoimmune disorders and immune system deficiencies, as well as an anti-infective agent and in combination with any antisense therapy. *Inventors:* Dennis Klinman (FDA), Daniela Verthelyi (FDA), Kenji Ishii (NINDS). *Patent Status:* U.S. Patent Application No. 11/595,211 filed 09 Nov 2006, claiming priority to 12 Apr 1999 (HHS Reference No. E-147-1999/0-US-05). *Licensing Status:* Available for licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . A Method of Immunizing Humans Against Salmonella Typhi Using a Vi-rEPA Conjugate Vaccine *Description of Invention:* This invention is a method of immunization against typhoid fever using a conjugate vaccine comprising the capsular polysaccharide of *Salmonella typhi* , Vi, conjugated through an adipic dihydrazide linker to nontoxic recombinant exoprotein A
(rEPA)from *Pseudomonas aeruginosa* . The three licensed vaccines against typhoid fever, attenuated *S. typhi* Ty21a, killed whole cell vaccines and Vi polysaccharide, have limited efficacy, in particular for children under 5 years of age, which make an improved vaccine desirable. It is generally recognized that an effective vaccine against *Salmonella typhi* is one that increases serum anti-Vi IgG eight-fold six weeks after immunization. The conjugate vaccine of the invention increases anti-Vi IgG, 48-fold, 252-fold and 400-fold in adults, in 5-14 years-old and 2-4 years-old children, respectively. Thus this is a highly effective vaccine suitable for children and should find utility in endemic regions and as a traveler's vaccine. The route of administration can also be combined with routine immunization. In 2-5 years old, the protection against typhoid fever is 90% for 4 years. In school age children and in adults the protection could mount to completer protection according to the immunogenicity data. *Application:* Immunization against *Salmonella typhi* for long term prevention of typhoid fever in all ages. *Developmental Status:* Conjugates have been synthesized and clinical studies have been performed. The synthesis of the conjugates is described by Kossaczka, *et al.* in Infect Immun. 1997 June;65(7):2088-2093. Phase III clinical studies are described by Mai, *et al.* in N Engl J Med. 2003 October 2; 349(14):1390-1391. Dosage studies are described by Canh, *et al.* in Infect Immun. 2004 Nov; 72(11):6586-6588. A safety and immunogenicity study in infants are under way. The aim is to administer the conjugate vaccine with routine infant immunization. Preliminary results shows the vaccine is safe in 2 months old infants. *Inventors:* Zuzana Kossaczka, Shousun C. Szu, and John B. Robbins (NICHD). *Patent Status:* U.S. Patent 6,797,275 issued 28 Sep 2004 (HHS Reference No. E-020-1999/0-US-02); U.S. Patent Application No. 10/866,343 filed 10 Jun 2004 (HHS Reference No. E-020-1999/0-US-03); U.S. Patent Application No. 11/726,304 filed 20 Mar 2007 (HHS Reference No. E-020-1999/0-US-04). *Licensing Status:* Available for non-exclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . *Collaborative Research Opportunity:* The National Institute of Child Health and Human Development, Laboratory of Developmental and Molecular Immunity, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize A Method of Immunizing Humans Against Salmonella Typhi Using a Vi-rEPA Conjugate Vaccine. Please contact John D. Hewes, Ph.D., at 301-435-3121 or *hewesj@mail.nih.gov* for more information. Dated: January 10, 2008. Steven M. Ferguson, Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health. [FR Doc. E8-1232 Filed 1-24-08; 8:45 am] BILLING CODE 4140-01-P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Government-Owned Inventions; Availability for Licensing 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. Diagnosis and Treatment of Barrett's Esophagus and Associated Esophageal Adenocarcinoma *Description of Invention:* Barrett's esophagus is a condition in which the normal esophageal tissue lining has been replaced by an abnormal lining of gastric and intestinal tissue resulting from chronic gastroesophageal reflux disease. Patients have an increased risk of developing esophageal adenocarcinoma, which is often detected at later stages and is associated with poor prognosis. Survival rates are very low ranging from 10% in Europe to 16% in the United States. Available for licensing are microRNA (miRNA) biomarkers that show differential expression in the adenocarcinoma diagnosis and Barrett's esophagus status, and they can predict diagnosis and Barrett's esophagus with accuracies of 71.4% and 74.7%, respectively. Thus, these miRNA biomarkers that may predispose individuals to Barrett's esophagus and/or esophageal adenocarcinoma could provide a means for earlier detection and help in better identifying treatment options. *Applications:* Method to diagnose and treat Barrett's esophagus and esophageal adenocarcinoma. miRNA pharmaceutical compositions to treat Barrett's esophagus. *Advantages:* Early diagnostic that can more accurately stratify patients for increased survival rates and appropriate treatments. *Development Status:* The technology is currently in the pre-clinical stage of development. *Market:* Esophageal cancer is the 8th most common cancer and 6th most common cause of cancer worldwide. Survival rate of esophageal cancer is 10% to 16% in Europe and United States respectively. miRNA technologies have an emerging market, and in 2007, it was worth an estimated 23 million dollars in the U.S. and it has a projected annual growth rate of 100%. *Inventors:* Ewy Mathe (NCI), Curtis C. Harris (NCI), *et al.* *Patent Status:* U.S. Provisional Application No. 60/979,300 filed 11 Oct 2007 (HHS Reference No. E-008-2008/0-US-01). *Licensing Status:* Available for non-exclusive licensing. *Licensing Contact:* Jennifer Wong; 301-435-4633; *wongje@mail.nih.gov.* *Collaborative Research Opportunity:* The Laboratory of Human Carcinogenesis at the National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods to diagnose and treat Barrett's esophagus and esophageal carcinoma. Please contact John D. Hewes, Ph.D. at 301-435-3121 or *hewesj@mail.nih.gov* for more information. Mouse Model for Obesity and Type 2 Diabetes Due to Inactivation of ANKRD26 Gene *Description of Invention:* Obesity and type II diabetes are major health hazards both in the United States and internationally. The incidence of obesity has been steadily increasing, underscoring the need to identify and develop effective treatments. As a result, there has been a strong effort to create animal models to help study these diseases. NIH inventors have created a new mouse model for obesity and type II diabetes. In this model, both copies of the ANKRD26 gene are inactivated by the insertion of a marker gene (beta-galactosidase) into the open reading frame of the gene. The resulting knockout mouse exhibits extreme obesity, increased organ and body size, and acquired insulin resistance. The mouse also expresses the marker gene, thereby allowing the monitoring of ANKRD26 expression patterns. *Applications:* Study and identify treatments for obesity and type II diabetes. Examine ANKRD26 expression under various conditions. Study the progression of obesity and type II diabetes in a specific genetic background. *Advantages:* Distinct phenotype from other mouse models for obesity and type II diabetes allows broader study of the diseases when used in combination with other mouse models. Distinct phenotype allows the study of obesity in a previously unidentified genetic background. *Benefits:* Obesity can increase the susceptibility to other health conditions such as cardiovascular disease. It has been reported that billions of tax dollars a year are spent in the treatment of obesity-attributable conditions. The use of this animal model could result in social benefit, in terms of both health and financial concerns, by leading to the development of new methods of treating obesity. Furthermore, the incidence of obesity has more than doubled over the past 10 years, suggesting that the discovery of new treatments would result in strong financial returns. *Inventor:* Ira Pastan (NCI). *Publication:* TK Bera *et al.* A model for obesity and gigantism due to disruption of the Ankrd26 gene. Proc Natl Acad Sci USA. 2008 Jan 8;105(1):270-275. *Patent Status:* HHS Reference No. E-156-2007/0—Research Tool. Patent protection is not being sought for this technology. *Licensing Status:* Available for licensing. *Licensing Contact:* David A. Lambertson, PhD; 301-435-4632; *lambertsond@mail.nih.gov.* Photosensitization by Nuclear Receptor-Ligand Complexes and Cell Ablation Uses Thereof *Description of Invention:* Androgen receptors
(AR)mediate the effects of male steroid hormones and contribute to a wide variety of physiological and pathophysiological conditions. Prostate cancer development and progression are mediated through AR, a ligand-dependent transcription factor, and it is present in all stages of prostate carcinoma. Increased levels of PSA, an AR-induced prostate tumor-specific protein, are indicative of prostate cancer. Benign, non-cancerous conditions are also AR-dependent and can be therapeutic targets as well. This technology is a method to cause AR-induced cell death (apoptosis) through photoactivation of a non-steroidal androgen receptor antagonist 1,2,3,4-tetrahydro-2,2-dimethyl-6-(trifluoromethyl)-8-pyridono[5,6-g] quinoline (TDPQ). Upon TDPQ binding to AR, a highly potent photocytoxic reaction induced once the TDPQ-AR complex is exposed to visible light irradiation of a specific wavelength. The inventors have cell-culture results demonstrating that cell death is a function of TDPQ, AR and light irradiation. This treatment method can potentially target AR-containing cancerous cells, while sparing nearby cells that lack AR. The process has been extended to other nuclear receptors by choice of other photoactivatable ligands for these receptors. Certain suitable ligands are marketed drugs. *Applications:* Therapeutic compounds to treat AR related conditions such as prostate cancer, baldness, hirsutism, and acne. Potential therapeutics for progesterone and glucorticoid receptor ligand related conditions such as breast and brain cancers, lymphoma, leukemia and arthritis. Method to treat androgen, progesterone, and glucorticoid receptor related conditions. *Market:* Prostate cancer is the second most common type of cancer among men, wherein one in six men will be diagnosed with prostate cancer. An estimated 218,890 new cases of prostate cancer and 27,050 deaths due to prostate cancer in the U.S. in 2007. Hirsutism affects approximately 5% of adult women in the United States. Hair loss and acne industries are worth several billions of dollars. *Development Status:* The technology is currently in the pre-clinical stage of development. *Inventors:* William T. Schrader *et al.* (NIEHS). *Publications:* 1. B Risek *et al.* Androgen Receptor-Mediated Apoptosis is Regulated by Photoactivatable AR Ligands. Presented at the Annual Meeting of the Endocrine Society in Toronto, Canada in June 2007. 2. B Risek *et al.* Photocytotoxic Properties of the Non-Steroidal Androgen Receptor Antagonist TDPQ. Presented at the Annual Meeting of the Endocrine Society in Boston, MA in June 2006. *Patent Status:* U.S. Provisional Application No. 60/926,218 filed 24 Apr 2007 (HHS Reference No. E-108-2007/0-US-01). *Licensing Status:* Available for exclusive or non-exclusive licensing. *Licensing Contact:* Jennifer Wong; 301-435-4633; *wongje@mail.nih.gov.* Antibodies and Polypeptides Specific to AAMP-1: Diagnostic and Therapeutic Uses Thereof *Description of Invention:* Angio-associated migratory cell protein (AAMP-1) was first isolated from a human melanoma cell line as a motility-associated cell protein. AAMP-1 contains two immunoglobin domains, six WD40 repeats, and a heparin-binding domain. In vitro, over expression of AAMP-1 promotes tumor cell invasion and metastasis as well as angiogenesis. AAMP-1 was later found to be over expressed in endothelial cells, cytotrophoblasts, and poorly differentiated colon adenocarcinoma cells found in lymphatics. In addition, gene expression studies have shown that AAMP-1 is over expressed in breast and gastrointestinal tumors. The issued patents claim proteins, polypeptides, and recombinant polyclonal antibodies specific to AAMP-1 and their use in diagnostic and therapeutic applications. *Applications:* The antibodies specific to AAMP-1 can detect formalin-fixed antigen and SDS-denatured antigen. These antibodies can be used for detailed expression studies of AAMP-1 in different cancer cell lines. The antibodies could also be used to detect AAMP-1 in patient's sera as a useful diagnostic marker for multiple carcinomas including high nuclear grade ductal carcinoma in situ (Clinical Cancer Research Dec 2002 8:3788-95). Claimed proteins and polypeptides could also be used to promote cell adhesion to a substrate, promote tissue acceptance of prostheses, and promote wound healing. *Development Status:* This technology is currently in the pre-clinical stage of development. *Market:* Estimated new cases and deaths from breast cancer in the United States in 2007: New cases: 178,480 (female); 2,030 (male); Deaths: 40,460 (female); 450 (male). *Inventors:* Marie Beckner, Henry Krutzsch and Lance Liotta (NCI). *Publications:* 1. ME Beckner *et al.* AAMP, a newly identified protein, shares a common epitope with alpha-actinin and a fast skeletal muscle fiber protein. Exp Cell Res. 1996 Jun 15;225(2):306-314. 2. A Adeyinka *et al.* Analysis of gene expression in ductal carcinoma in situ of the breast. Clin Can Res. 2002 Dec;8(12):3788-3795. *Patent Status:* U.S. Patent No. 6,274,134 issued 14 Aug 2001 (HHS Reference No. E-084-1991/1-US-01); Australian Patent No. 684,806 issued 23 Apr 1998 (HHS Reference No. E-084-1991/1-AU-05); Australian Patent No. 668,134 issued 26 Apr 1996 (HHS Reference No. E-084-1991/0-AU-03) and Japanese Patent No. 3,715,313 issued 9 November 2005 (HHS Reference No. E-084-1991/1-JP-04). *Licensing Status:* Available for exclusive or non-exclusive licensing. *Licensing Contact:* Surekha Vathyam, PhD; 301-435-4076; *vathyams@mail.nih.gov.* Dated: January 16, 2008. Steven M. Ferguson, Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health. [FR Doc. E8-1244 Filed 1-24-08; 8:45 am] BILLING CODE 4140-01-P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Government-Owned Inventions; Availability for Licensing 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. Human Papillomavirus microRNA Diagnostics and Therapeutics *Description of Technology:* Available for licensing and commercial development are patent rights that cover the uses of a p53 specific microRNA (miRNA). It has been reported that the tumor suppressive mRNA miR-34a is downregulated in HPV-infected primary keratinocytes. miR-34a arrests the cell cycle at G2 phase and promotes apoptosis. Therapeutic restoration of normal miR-34a expression levels and/or simultaneous stabilization of p53 (inhibited by HPV E6) may induce miR-34a accumulation in G0/G1 phase and potentially arrest tumor growth. *Applications:* Cervical cancer; Human papillomavirus; Therapeutics. *Inventors:* Zhi-Ming Zheng, Xiaohong Wang (NCI). *Relevant Publications:* 1. WO Lui *et al.* Patterns of known and novel small RNAs in human cervical cancer. Cancer Res. 2007 Jul 1;67(13):6031-6043. 2. I Martinez *et al.* Human papillomavirus type 16 reduces the expression of microRNA-218 in cervical carcinoma cells. Oncogene 2007 Nov 12; Advance online publication, doi:10.1038/sj.onc.1210919. *Patent Status:* U.S. Provisional Application No. 60/983,368 filed 29 Oct 2007 (HHS Reference No. E-029-2008/0-US-01). *Licensing Status:* Available for licensing. *Licensing Contact:* Michael A. Shmilovich, Esq.; 301/435-5019; *shmilovm@mail.nih.gov.* *Collaborative Research Opportunity:* The National Cancer Institute HIV and AIDS Malignancy Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize HPV-induced aberrant expression of microRNAs for cervical cancer diagnostics and therapeutics. Please contact John D. Hewes, PhD at 301-435-3121 or *hewesj@mail.nih.gov* for more information. Nitroxide Radical as a Treatment for Neurodegeneration *Description of Technology:* This invention describes the use of a nitroxide radical to treat or prevent the progression of neurodegeneration characterized by a deficiency in iron regulatory protein 2 (IRP 2) function. The inventors discovered that IRP 2 null mice with adult-onset neurodegeneration and microcytic anemia regain activity of iron regulatory protein 1 (IRP 1) after eating food formulations containing specific nitroxide radicals. The inventors also discovered the nitroxide agent prevents the progression of neurodegeneration by attacking inhibitory iron-sulfur clusters found on IRP 1 thereby allowing IRP 1 to bind to iron responsive elements found on transcripts that encode iron metabolism proteins that regulate cellular iron homeostasis in the brain. *Applications:* Treatment for neurological disorders resulting from a deficiency in the amount of bioavailable iron in the central nervous system, including Alzheimer's and Parkinson's disease, erythropoietic protoporphyria or adult-onset neurodegeneration. *Market:* Over 22 million people suffer from neurodegenerative diseases worldwide, and in 2050, this number could triple due to increased life expectancy and an increased aging population. *Development Status:* Early-stage. *Inventors:* Tracey Rouault *et al.* (NICHD). *Patent Status:* U.S. Provisional Application No. 60/894,134 filed 09 Mar 2007 (HHS Reference No. E-153-2007/0-US-01). *Licensing Status:* Available for licensing. *Licensing Contact:* Charlene A. Sydnor, PhD; 301/435-4689; *sydnorc@mail.nih.gov.* 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 96-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.* Molecular Motors Powered by Proteins Description of Technology: The technology available for licensing and commercial development relates to molecular motors powered by proteins. Some implementations describe a molecular motor in which multiple concentric cylinders or nested cones rotate around a common longitudinal axis. Opposing complementary surfaces of the cylinders or cones are coated with complementary motor protein pairs, such as actin and myosin. The actin and myosin interact with one another in the presence of ATP to rotate the cylinders or cones relative to one another, and this rotational energy is harnessed to produce work. Speed of movement is controlled by the concentration of ATP and the number of nested cylinders or cones. The length of the cylinders or cones can also be used to control the power generated by the motor. Another configuration forms the motor out of a set of stacked disks, much like CDs on a spindle. The advantage of this form is extreme simplicity of construction compared to the nested cylinders or cones. In yet another configuration, which has aspects of both of the previous forms, the surfaces are broken into annular rings in order to overcome that the inner surfaces rotate at a different rate than the outer surfaces. This belt form may ultimately be used in molecular manufacturing. *Applications:* Supplying power to prosthetic implants and other medical devices without external power sources. Many other applications that could use a motor in other biotechnological areas, in addition to the medical applications. The inventions can be implemented on either a microscopic or macroscopic scale. *Development Status:* Very early stage of development. *Inventors:* Thomas D. Schneider and Ilya G. Lyakhov (NCI). *Relevant Publications:* “Molecular motor”, Patent Publication Nos. WO 2001/009181 A1, published 02/08/2001; CA 2380611A1, published 02/08/2001; AU 6616600A, published 02/19/2001; EP 1204680A1, published 05/15/2002; and U.S. 20020083710, published 07/04/2002. *Patent Status:* HHS Reference No. E-018-1999/0—International Application Number PCT/US 2000/20925 filed 07/31/2000; granted Application AU 2002/18688 B2, and the corresponding European and Canadian applications being prosecuted, all entitled “Molecular Motor.” HHS Reference No. E-018-1999/1—allowed U.S. Application No. 10/061,377 filed 02/01/2002, entitled “Molecular Motor.” *Licensing Status:* Available for non-exclusive or exclusive licensing. Licensing Contact: Cristina Thalhammer-Reyero, PhD, MBA; 301-435-4507; *thalhamc@mail.nih.gov.* *Collaborative Research Opportunity:* The National Cancer Institute, Center for Cancer Research Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the Molecular Rotation Engine. Please contact John D. Hewes, PhD at 301-435-3121 or *hewesj@mail.nih.gov* for more information. Dated: January 16, 2008. Steven M. Ferguson, Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health. [FR Doc. E8-1247 Filed 1-24-08; 8:45 am] BILLING CODE 4140-01-P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Government-Owned Inventions; Availability for Licensing 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. ADDRESS: 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. 3D Imaging of Mammalian Cells Using Focused Ion Beam-Secondary Ion Mass Spectrometry (FIB-SIMS) *Description of Technology:* Available for licensing and commercial development is a new automated approach to cellular imaging that allows 3D visualization of cellular organelles and protein expression at nanometer
(nm)resolution using ion abrasion scanning electron microscopy (IA-SEM). The approach uses established technologies for 3D imaging [1, 2] by iterative use of a focused ion beam and scanning electron beam combined with established technologies for mass spectrometry. Strategies to explore the 3D distribution of cellular components are being developed with the goal of establishing rapid methods for determining protein, metabolite and drug localization in the subcellular space. *Applications:* Cytology; Oncology; Cell biology; Drug development; Drug targeting. *Development Status:* Pilot experiments are ongoing for the development and optimization of the technology using commercially available components. Clinical applications for the diagnosis of tissue specimens are also being explored. *Inventor:* Sriram Subramaniam (NCI). *Publications:* 1. J Heymann, M Hayles, I Gestmann, L Giannuzzi, L Lich, S Subramaniam. Site-specific 3D imaging of cells and tissues with a dual beam microscope. J. Struct. Biol. 2006 Jul;155(1):63-73. 2. J Heymann, D Shi, S Kim, D Bliss, J Milne, S Subramaniam. 3D imaging of melanoma cells using automated “ion abrasion scanning electron microscopy”. Microsc Microanal. 2007 Aug;13(Suppl 2):360-361, doi 10.1017/S1431927607079287. *Patent Status:* U.S. Provisional Application No. 60/970,070 filed 05 Sep 2007 (HHS Reference No. E-313-2007/0-US-01); U.S. Provisional Application No. 60/974,686 filed 24 Sep 2007 (HHS Reference No. E-313-2007/1-US-01). *Licensing Status:* Available for exclusive or non-exclusive licensing. *Licensing Contact:* Michael A. Shmilovich, Esq.; 301/435-5019; *shmilovm@mail.nih.gov* . *Collaborative Research Opportunity:* The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research and/or partnership agreements to further develop and commercialize tools for 3D mapping cells and tissues at nanometer resolution. Please contact John D. Hewes, Ph.D. at 301-435-3121 or *hewesj@mail.nih.gov* for more information. A Drug Index to Quantify Harmful Drug Exposure in Older Adults *Description of Technology:* Polypharmacy is the simultaneous use of multiple drugs. It is prevalent in individuals ages 65 and older who carry a high burden of illness and take various medications for treatment. Reducing the incidence of polypharmacy in older people presents a major challenge for healthcare professionals. NIH scientists have discovered a novel method to assess polypharmacy for which physicians can use to evaluate drug response of patients more effectively and determine better therapeutic regimens for the patient. This method calculates the total drug burden
(TDB)index associated with anticholinergic and sedative drugs, using the equation, TDB = B <sup>AC</sup> + B <sup>S</sup> . Further, this invention could be implemented into a portable computing device, such as personal digital assistant (PDA). *Applications:* Useful for physicians to help reduce prescribing errors, lower the incidence of adverse drug reactions and improve medical outcomes in older patients. *Market:* Seven percent (7%) of the elderly are under polypharmacy and purchase over 30% of prescription drugs and 40% of over-the-counter
(OTC)drugs. Medication misuse costs the health care system over $177 billion dollars and results in more than 200,000 deaths each year. *Development Status:* Early stage. *Inventors:* Darrell R. Abernethy (NIA), *et al.* *Patent Status:* International Application No. PCT/US06/44718 filed 17 Nov 2006 (HHS Reference No. E-241-2006/0-PCT-01) *Licensing Status:* Available for licensing. *Licensing Contact:* Rung C. Tang, J.D.; 301/435-5031; *tangrc@mail.nih.gov* . Recombinant Modified Bacillus anthracis Protective Antigen for Use in Vaccines *Description of Invention:* This invention relates to improved methods of preparing Bacillus anthracis protective antigen
(PA)for use in vaccines. PA is a secreted, non-toxic protein with a molecular weight of 83 KDa. PA is a major component of the currently licensed human vaccine (Anthrax Vaccine Adsorbed, AVA). Although the licensed human vaccine has been shown to be effective against cutaneous anthrax infection in animals and humans and against inhalation anthrax in rhesus monkeys, the licensed vaccine has several limitations:
(1)AVA elicits a relatively high degree of local and systemic adverse reactions, probably mediated by variable amounts of undefined bacterial products, making standardization difficult;
(2)the immunization schedule requires administration of six doses within an eighteen
(18)month period, followed by annual boosters;
(3)there is no defined vaccine-induced protective level of antibody to PA by which to evaluate new lots of vaccines; and
(4)AVA is comprised of a wild-type PA. It has been suggested that a vaccine comprising a modified purified recombinant PA would be effective, safe, allow precise standardization, and require fewer injections. This invention claims methods of producing and recovering PA from a cell or organism, particularly a recombinant cell or microorganism. The invention claims production and purification of modified PA from a non-sporogenic strain of *Bacillus anthracis* . In contrast to other previously described methods, greater quantities of PA are obtainable from these cells or microorganisms. Specifically, a scalable fermentation and purification process is claimed that is suitable for vaccine development, and that produces almost three times more product than earlier-reported processes. This is accomplished using a biologically inactive protease-resistant PA variant in a protease-deficient non-sporogenic avirulent strain of *B. anthracis* (BH445). One of the PA variants described in the patent application lacks the furin and chymotrypsin cleavage sites. The invention relates to improved methods of producing and recovering sporulation-deficient *B. anthracis* mutant stains, and for producing and recovering recombinant *B. anthracis* protective antigen (PA), especially modified PA which is protease resistant, and to methods of using of these PAs or nucleic acids encoding these PAs for eliciting an immunogenic response in humans, including responses which provide protection against, or reduce the severity of, *B. anthracis* bacterial infections and which are useful to prevent and/or treat illnesses caused by *B. anthracis* , such as inhalation anthrax, cutaneous anthrax and gastrointestinal anthrax. *Application:* *Improved B. anthracis vaccines* . *Developmental Status:* Phase I clinical studies are being performed. *Inventors:* Stephen Leppla (NIDCR), M. J. Rosovitz (NIDCR), John Robbins (NICHD), Rachel Schneerson (NICHD) *Patent Status:* U.S. Provisional Application No. 60/402,285 filed 09 Aug 2002 (HHS Reference No. E-268-2002/0-US-01). U.S. Patent Application No. 10/638,006 filed 08 Aug 2003, now U.S. Patent 7,261,900 (HHS Reference No. E-268-2002/0-US-02). U.S. Patent Application No. 11/831,860 filed 31 Jul 2007 (HHS Reference No. E-268-2002/0-US-03). *Licensing Status:* Available for exclusive or nonexclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . Methods for Preparing Bacillus anthracis Protective Antigen for Use in Vaccines *Description of Invention:* This invention relates to improved methods of preparing *Bacillus anthracis* protective antigen
(PA)from a cell or organism, particularly a recombinant cell or microorganism, for use in vaccines. Production and purification methods of modified PA from a non-sporogenic strain of *Bacillus anthracis* are described. Specifically, a scalable fermentation and purification process is claimed that is suitable for vaccine development, and that produces almost three times more product than earlier-reported processes. This is accomplished using a biologically inactive protease-resistant PA variant in a protease-deficient non-sporogenic avirulent strain of *B. anthracis* (BH445). One of the PA variants described in the patent application lacks the furin and chymotrypsin cleavage sites. *Advantages: Bacillus anthracis* protective antigen is a major component of the currently licensed human vaccine (Anthrax Vaccine Adsorbed, AVA). Although the current human vaccine has been shown to be effective against cutaneous anthrax infection in animals and humans and against inhalation anthrax in rhesus monkeys, the licensed vaccine has several limitations:
(1)AVA elicits a relatively high degree of local and systemic adverse reactions, probably mediated by variable amounts of undefined bacterial products, making standardization difficult;
(2)the immunization schedule requires administration of six doses within an eighteen
(18)month period, followed by annual boosters;
(3)there is no defined vaccine-induced protective level of antibody to PA by which to evaluate new lots of vaccines; and
(4)AVA is comprised of a wild-type PA. Thus a vaccine comprising a modified purified recombinant PA would be effective, safe, allow precise standardization, and require fewer injections. The invention also relates to PA variants, and/or compositions thereof, which are useful for eliciting an immunogenic response in mammals, particularly humans, including responses that provide protection against, or reduce the severity of, infections caused by *B. anthracis* . The vaccines claimed in this application are intended for active immunization for prevention of *B. anthracis* infection, and for preparation of immune antibodies. *Application:* Improved *B. anthracis* vaccines. *Developmental Status:* Phase I clinical studies are being performed. *Inventors:* Joseph Shiloach (NIDDK), Stephen Leppla (NIDCR), Delia Ramirez (NIDDK), Rachel Schneerson (NICHD), John Robbins (NICHD). *Publication:* DM Ramirez, *et al.* Production, recovery and immunogenicity of the protective antigen from a recombinant strain of *Bacillus anthracis* . J Ind Microbiol Biotechnol. 2002 Apr;28(4):232-238. *Patent Status:* U.S. Provisional Application No. 60/344,505 filed 09 Nov 2001 (HHS Reference No. E-023-2002/0-US-01); U.S. Patent Application No. 10/290,712 filed 08 Nov 2002 (HHS Reference No. E-023-2002/0-US-02). *Licensing Status:* Available for exclusive or nonexclusive licensing. *Licensing Contact:* Peter A. Soukas, J.D.; 301/435-4646; *soukasp@mail.nih.gov* . *Collaborative Research Opportunity:* The National Institutes of Health is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods of preparing *Bacillus anthracis* protective antigen
(PA)from a cell or organism, particularly a recombinant cell or microorganism, for use in vaccines. Please contact Rochelle S. Blaustein, J.D., at 301/451-3636 or *Rochelle.Blaustein@nih.gov* for additional information. Chimeric Gag Pseudovirions *Description of Technology:* The human immunodeficiency virus
(HIV)is the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV virion basically consists of a viral core and envelope. The core consists predominantly of gag- and pol-encoded proteins and the viral RNA. Expression of recombinant Gag precursor proteins can lead to assembly and budding of virus-like particles (pseudovirions). The production of Gag-based pseudovirions in mammalian and insect cell systems using recombinant virus vectors provides a novel technology for engineering recombinant protein-based particulate vaccines for HIV and other viruses. The incorporation of additional viral or cellular, peptides and polypeptides may be advantageous in vaccine preparations, since they may contain antigenic epitopes that may play a role in inducing protection from infection or disease. The subject invention provides chimeric nucleic acids comprising a retroviral gag sequence, a target nucleic acid sequence derived from a nucleic acid encoding a fusion partner, and a frame shift site. Expression of the chimeric gene cassette results in packaging the fusion partner into the Gag pseudovirion. Suitable fusion partners can be derived from any protein of interest which has a biological activity or which elicits a cellular or humoral immune response. *Applications:* HIV vaccines and/or therapeutics. *Development Status:* Early stage. *Inventors:* Gregory J. Tobin (NCI/SAIC), *et al.* *Patent Status:* U.S. Patent No. 6,099,847 issued 08 Aug 2000 (HHS Reference No. E-105-1996/1-US-01). *Licensing Status:* Available for non-exclusive or exclusive licensing. *Licensing Contact:* Susan Ano, PhD; 301/435-5515; *anos@mail.nih.gov* . Dated: January 14, 2008. Steven M. Ferguson, Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health. [FR Doc. E8-1259 Filed 1-24-08; 8:45 am] BILLING CODE 4140-01-P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Center for Scientific Review; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2), notice is hereby given of the following meetings. The meetings will be closed to the public in accordance with the provisions set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended. The grant applications and the discussions could disclose confidential trade secrets or commercial property such as patentable material, and personal information concerning individuals associated with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of personal privacy. *Name of Committee:* Oncological Sciences Integrated Review Group; Basic Mechanisms of Cancer Therapeutics Study Section. *Date:* January 28-29, 2008. *Time:* 8 a.m. to 5 p.m. *Agenda:* To review and evaluate grant applications. *Place:* Embassy Suites at the Chevy Chase Pavilion, 4300 Military Road, NW., Washington, DC 20015. *Contact Person:* Lambratu Rahman, PhD, Scientific Review Officer, Center for Scientific Review; National Institutes of Health, 6701 Rockledge Drive, Room 6214, MSC 7804, Bethesda, MD 20892, 301-451-3493, *rahmanl@csr.nih.gov.* This notice is being published less than 15 days prior to the meeting due to the timing limitations imposed by the review and funding cycle. (Catalogue of Federal Domestic Assistance Program Nos. 93.306, Comparative Medicine; 93.333, Clinical Research, 93.306, 93.333, 93.337, 93.393-93.396, 93.837-93.844, 93.846-93.878, 93.892, 93.893, National Institutes of Health,
(HHS)Dated: January 16, 2008. Jennifer Spaeth, Director, Office of Federal Advisory Committee Policy. [FR Doc. 08-275 Filed 1-24-08; 8:45 am]
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