Notices. Notice
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BILLING CODE 4165-16-M DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; NCCAM Office of Communications and Public Liaison Communications Program Planning and Evaluation Research *Summary:* In compliance with the requirement of Section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995, for opportunity for public comment on proposed data collection projects, the National Center for Complementary and Alternative Medicine (NCCAM), at the National Institutes of Health (NIH), will publish periodic summaries of proposed projects to be submitted to the Office of Management and Budget
(OMB)for review and approval. Proposed Collection *Title:* NCCAM Office of Communications and Public Liaison Communications Program Planning and Evaluation Research. *Type of Information Collection Request:* Renewal. *Need and Use of Information Collection:* To carry out NCCAM's legislative mandate to educate and disseminate information about complementary and alternative medicine
(CAM)to a wide variety of audiences and organizations, the NCCAM Office of Communications and Public Liaison
(OCPL)requests clearance to carry out
(1)formative and
(2)evaluative research of a variety of print and online materials, outreach activities, and messages to maximize their impact and usefulness. OCPL wishes to continue to carry out formative research to further understand the knowledge, attitudes, and behaviors of its core constituent groups: members of the general public, researchers, and providers of both conventional and CAM health care. In addition, it seeks to test newly formulated messages and identify barriers and impediments to the effective communication of those messages. With this audience research, OCPL will carry out pretesting of audience responses to NCCAM's fact sheets, Web content, and other materials and messages. Clearance is also requested to continue to carry out evaluative research on existing materials and messages, as part of OCPL's ongoing effort to develop a comprehensive program of testing and evaluation of all of its communications strategies. This evaluative research will include pilot testing of recently developed messages and information products such as fact sheets and brochures. It will also address the need to evaluate the processes by which new materials and messages were developed, the effectiveness of an outreach or the extent to which behaviors were changed by the message, and the impact of a message on health knowledge and behaviors. The tools to collect this information have been selected to minimize burden on NCCAM's audiences, produce or refine messages that have the greatest potential to influence target audience attitudes and behavior in a positive manner, and to use Government resources efficiently. They may include individual in-depth interviews, focus group interviews, intercept interviews, self-administered questionnaires, gatekeeper reviews, and omnibus surveys. The data will enhance OCPL's understanding of
(1)the unique information needs and distinct health-information-seeking behaviors of its core constituencies, and
(2)the segments within these constituencies with special information needs (for example, among the general public these segments include cancer patients, the chronically ill, minority and ethnic populations, the elderly, users of dietary supplements, and patients integrating complementary therapies with conventional medical treatments). *Frequency of Response:* On occasion. *Affected Public:* Individuals and households; non-profit institutions; Federal Government; State, Local, or Tribal Government. *Type of Respondents:* Adult patients; members of the public; health care professionals; organizational representations. The annual reporting burden is as follows. *Estimated Number of Respondents:* 2,440; *Estimated Number of Responses per Respondent:* 1; *Average Burden Hours per Response:* 0.29; and *Estimated Total Burden Hours Requested:* 2,137.5 for the 3-year clearance period (approximately 712.5 hours annually). The annualized cost to respondents is estimated at $21,333. There are no Capital Costs, Operating Costs, or Maintenance Costs to report. *Request for Comments:* Written comments and/or suggestions from the public and affected agencies are invited on 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 assumption 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 Christy Thomsen, Director, Office of Communications and Public Liaison, NCCAM, 31 Center Drive, Room 2B11, Bethesda, MD 20892, or fax your request to 301-402-4741, or e-mail *thomsenc@mail.nih.gov.* Ms. Thomsen can be contacted by telephone at 301-451-8876. *Comments Due Date:* Comments regarding this information collection are best assured of having their full effect if received within 60 days of the date of this publication. Dated: March 20, 2007. Christy Thomsen, Director, Office of Communications and Public Liaison, National Center for Complementary and Alternative Medicine, National Institutes of Health. [FR Doc. E7-5671 Filed 3-27-07; 8:45 am] BILLING CODE 4140-01-P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health List of Drugs for Which Pediatric Studies Are Needed ACTION: Notice. SUMMARY: The National Institutes of Health
(NIH)is providing notice of the “Priority List of Drugs for Which Pediatric Studies Are Needed.” The NIH develops the list in consultation with the Food and Drug Administration
(FDA)and pediatric experts, as mandated by the Best Pharmaceuticals for Children Act. This list prioritizes certain drugs that are most in need of study for use by children to ensure their safety and efficacy. The NIH will update the list at least annually until the Act expires on October 1, 2007. DATES: The list is effective upon publication. FOR FURTHER INFORMATION CONTACT: Dr. Perdita Taylor-Zapata, National Institute of Child Health and Human Development (NICHD), 6100 Executive Boulevard, Suite 4A-01, Bethesda, MD 20892-7510, e-mail *taylorpe@mail.nih.gov* or *BestPharmaceuticals@mail.nih.gov,* telephone 301-496-9584 (not a toll-free number). SUPPLEMENTARY INFORMATION: The NIH is providing notice of the “List of Drugs for Which Pediatric Studies Are Needed,” as authorized under Section 3, Public Law 107-109 (42 U.S.C. 409I). On January 4, 2002, President Bush signed into law the Best Pharmaceuticals for Children Act (BPCA). The BPCA mandates that not later than one year after the date of enactment, the NIH in consultation with the FDA and experts in pediatric research shall develop, prioritize, and publish an annual list of certain approved drugs for which pediatric studies are needed. For inclusion on the list, an approved drug must meet the following criteria:
(1)There is an approved application under section 505(j) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j));
(2)there is a submitted application that could be approved under the criteria of section 505(j) of the Federal Food, Drug, and Cosmetic Act;
(3)there is no patent protection or market exclusivity protection under the Federal Food, Drug, and Cosmetic Act; or
(4)there is a referral for inclusion on the list under section 505A(d)(4)(c); and additional studies are needed to assess the safety and effectiveness of the use of the drug in the pediatric population. The BPCA further stipulates that in developing and prioritizing the list, the NIH shall consider for each drug on the list:
(1)The availability of information concerning the safe and effective use of the drug in the pediatric population;
(2)whether additional information is needed;
(3)whether new pediatric studies concerning the drug may produce health benefits in the pediatric population; and
(4)whether reformulation of the drug is necessary. For this year, we are providing an update and a summary of the progress made by the prioritization working group from last year's notice until now, as well as a summary of the annual scientific prioritization meeting held with pediatric experts on December 5-6, 2006. We have updated the complete list of drugs, listed previously in the April 2006 **Federal Register** notice, and post it on the BPCA Web site *http://bpca.nichd.nih.gov/index.cfm.* We will continue to reevaluate this list throughout the year and will provide updates as required, based upon the reauthorization of the BPCA. In 2005, and with the suggestion of pediatric experts, NIH changed the listing system from a focus on individual off-patent drugs to a therapeutic class-based approach. Pediatric experts indicated that this approach will allow us to compare drugs within a therapeutic class (on and off patent) and give a broader description of the use of these drugs in children. This approach will also allow us to obtain focused expertise in therapeutic areas that will subsequently give us more insight into scientific gaps in treatments of the proposed conditions, as well as feasibility and study designs. Based on expert opinion obtained throughout the year as part of our regular outreach program, a preliminary list of conditions and suggested drugs was drafted and categorized for the 2007 prioritization based on this approach. The following are the conditions and the drugs discussed in our December 5-6, 2006 scientific meeting with experts in pediatric research: Infectious Diseases, with a focus on Methicillin-resistant Staphylococcus aureus
(MRSA)infections; Pediatric Cancer, specifically Neuroblastoma; Neonatal Pain; and Asthma. The gaps in scientific knowledge as well as specific drugs thought to be effective for treatment in each of these conditions were then discussed based on off-patent status, gaps in pediatric labeling, and the potential for providing a health benefit in the general pediatric population. We also provided updates on our current work in the areas of Pediatric Hypertension, Sickle Cell Anemia, and Attention Deficit Hyperactivity Disorder during this meeting. There was also a brief discussion on future areas of consideration, pending the reauthorization of the BPCA, that include topics such as childhood obesity, counter-terrorism research, and Fragile X Syndrome. Following below are the conditions and drugs we discussed in the December 5-6, 2006, scientific meeting with experts in pediatric research. We will add these conditions and drugs, and their indications for use, to the Priority List for 2007 for which pediatric studies are most urgently needed. Treatment of Pediatric Cancers: 13-Cis-Retinoic Acid There is a need for information regarding the pharmacokinetics, safety, and efficacy of 13-Cis-Retinoic Acid in the treatment of neuroblastoma. Treatment of Pediatric MRSA: Clindamycin, Tetracycline, Doxycycline and Trimethoprim-Sulfamethoxazole There is a need for further pharmacokinetic and safety data in the use of these drugs to treat children with MRSA infections. In addition to the above conditions and their associated drugs for consideration, the following are conditions that have been identified as needing improvements in the treatment strategies and/or assessments in pediatrics. Pediatric Hypertension Data from the medical literature, clinical trials, and experience were presented and discussed by experts in the field of Pediatric Hypertension. Gaps in knowledge in this field include standardization of blood pressure measurements in children as well as the sequence of drugs for hypertension treatment in children. Asthma Data from the medical literature, clinical trials, and experience were presented and discussed by experts in the field of Pediatric Asthma. Gaps in knowledge in this field include gaps in measuring efficacy and safety of treatments and drug delivery systems, especially in young children. There is also a need for the development of new tools to identify symptom measures, pulmonary function tests, biomarkers, and genetics. Neonatal Research There are many areas in the field of neonatal medicine that can benefit from advances in neonatal research. Such gaps in research include areas such as determining feasibility of studying specific drugs in low-birth-weight infants based on current use; the development of novel study designs that take into account the small number of patients available due to either ethical limitations and/or feasibility issues; and the performance of clinical studies in areas such as the treatment of pain, neonatal seizures, and bronchopulmonary dysplasia, based on templates that are being developed by experts in research such as the working groups of the Newborn Drug Development Initiative. For the coming year, NICHD is planning a series of discussions with experts in the fields listed above and plans to identify and work with experts in these respective fields along with our continuing discussions with the other NIH Institutes and Centers. The goal of all of these discussions will be to specifically identify current gaps in scientific knowledge regarding research and treatment of these various pediatric conditions with the ultimate goal of determining future approved drugs for which pediatric studies are needed. Dated: March 15, 2007. Raynard S. Kington, Deputy Director, National Institutes of Health. [FR Doc. E7-5673 Filed 3-27-07; 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. Microarray for Detection and Subtyping of Human Influenza Viruses *Description of Technology:* Available for licensing and commercial development are a novel influenza virus microarray and methods for using the microarray for the identification of existing and new types and subtypes of human influenza viruses. There are three types of influenza viruses, type A, B and C. Influenza types A or B viruses cause epidemics of disease almost every winter, with type A causes major pandemic periodically. Influenza type A viruses are further divided into subtypes based on two proteins on the surface of the virus. These proteins are called hemagglutinin
(H)and neuraminidase (N). There are 16 known HA subtypes and 9 known NA subtypes of influenza A viruses. Each subtype may have different combination of H and N proteins. Although there are only three known A subtypes of influenza viruses (H1N1, H1N2, and H3N2) currently circulating among humans, many other different strains are circulating among birds and other animals and these viruses do spread to humans occasionally. There is a requirement for sensitive and rapid diagnostic techniques in order to improve both the diagnosis of infections and the quality of surveillance systems. This microarray platform tiles the genomes of all types/subtypes of influenza viruses, and is capable of correctly identifying all 3 types/subtypes of influenza viruses from an influenza vaccine sample. More specifically, the invention consists of:
(1)Microarrays comprising a solid support with a plurality of n-mer influenza viral nucleotide segments of influenza Types A, B and C, including each respective subtypes, and
(2)methods of detecting and identifying known and unknown influenza viral types and subtypes by:
(a)Using hybridization microarrays to known influenza viral nucleotide sequences,
(b)sequencing the nucleotides which hybridize to the microarrays and
(c)analyzing the hybridized sequences using existing databases, thus identifying existing or new subtypes of influenza viruses. *Applications:* Detection and identification of human influenza viruses; Efficient discovery of new subtypes of influenza viruses; Diagnosis of influenza outbreaks. *Development Status:* This microarray platform was capable of correctly identifying all 3 types/subtypes of influenza viruses from an influenza vaccine sample. *Inventors:* Xiaolin Wu, Cassio S. Baptista, Elizabeth Shannon, and David J. Munroe (NCI). *Patent Status:* U.S. Provisional Application No. 60/857,695 filed 07 Nov 2006 (HHS Reference No. E-208-2006/0-US-01). *Licensing Status:* Available for non-exclusive or exclusive licensing. *Licensing Contact:* Cristina Thalhammer-Reyero, PhD, MBA; 301/435-4507; *thalhamc@mail.nih.gov.* Improved Interleukin Expression for Immunogenic Compositions and Vaccine Adjuvant *Description of Technology:* The NIH is pleased to announce as available for licensing a technology that provides for optimized nucleic acids for improved expression of interleukin-15 (IL-15) and IL-15 receptor alpha (IL-15Ralpha) in mammalian cells. IL-15 is a cytokine important for both the innate and adaptive immune systems. Based on its many functions and relative safety in animal models, IL-15 finds use in vaccines, cancer immunotherapeutics, and autoimmune disease and as a vaccine adjuvant. The present technology enhances the production and bioavailability of IL-15 through use of optimized nucleic acid sequences. Native IL-15 coding sequences do not express IL-15 optimally for several reasons, and the optimized sequences of the subject technology overcome these deficiencies. The nucleic acids can be part of expression vectors, which could be utilized either in vitro or in vivo. The expression vectors express IL-15 alone, IL-15Ralpha alone, or both molecules together from a single vector. Further enhanced expression of IL-15 and/or IL-15Ralpha can be achieved through the use of signal peptides or propeptides from heterologous proteins. These nucleic acids can be administered to enhance the immune response of an individual against one or more antigens. Primate studies have shown that co-administration of IL-15 and IL-15Ralpha increased antigen specific cells, cells expressing IL-2, and/or cells expressing IL-2 and IFN-gamma (i.e. multifunctional cells). The present compositions are useful for the increased bioavailability and therefore biological effects of IL-15 after its administration to humans or other mammals. *Applications:* Vaccines; Improved protein expression; Cancer immunotherapeutics; Autoimmune disease; Vaccine adjuvant. *Inventors:* Barbara K. Felber and George N. Pavlakis (NCI). *Related Publication:* MA Kutzler *et al.* Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol. 2005 Jul 1;175(1):112-123. *Patent Status:* U.S. Provisional Application No. 60/758,819 filed 13 Jan 2006 (HHS Reference No. E-254-2005/0-US-01); U.S. Provisional Application No. 60/812,566 filed 09 Jun 2006 (HHS Reference No. E-254-2005/1-US-01); PCT Application filed 13 Jan 2007 (HHS Reference No. E-254-2005/2-PCT-01). *Licensing Status:* Available for non-exclusive or exclusive licensing. *Licensing Contact:* Susan Ano, PhD; 301/435-5515; *anos@mail.nih.gov.* Potent Activation of Antigen Presenting Cells by the Hepatitis A Virus Cellular Receptor 1 and Its Role in the Regulation of Immune Responses *Description of Technology:* Available for licensing and commercial development are compositions and methods to regulate various immune responses through the hepatitis A virus cellular receptor 1 (HAVCR1). HAVCR1 (also known as TIM-1) is a member of the TIM family of receptors that is usurped by the hepatitis A virus
(HAV)to infect cells. The gene encoding HAVCR1 has been shown to be an important asthma and allergy susceptibility gene. HAVCR1 plays a critical role in regulating T cell differentiation and the development of atopy. HAVCR1 is over-expressed in kidney ischemic cells and malignant renal tumors. The invention describes a ligand of HAVCR1 in antigen presenting cells
(APCs)that is unrelated to murine Tim-4, a TIM family member reported as the ligand of murine Tim-1. The ligand was identified using an expression cloning strategy. The specific binding of HAVCR1 to this ligand on APCs causes activation and induces the expression of co-stimulatory receptors at the cell surface of the APCs and the secretion of cytokines such as IL-6, IL-10, and TNF-a. Furthermore, treatment of APCs with soluble forms of HAVCR1 induced T cell proliferation. The invention describes a novel mechanism by which HAVCR1 regulates immune responses, in which the activation of APCs is mediated by HAVCR1 binding to ligands on APCs. The association of HAVCR1 with the ligand identified in APCs also enhances the interaction of HAVCR1 with HAV. Aspects of the technology are further described in Tami *et al.* , 2007. J. Virol., in press. *Applications:* Therapies that target the interaction of HAVCR1 with the ligand on APCs, such as small molecules or monoclonal antibodies, can control immune responses, the development of asthma, allergies and other atopic diseases, hepatitis A, kidney regeneration, and cancer. *Development Status:* The technology is in early stages of development. *Inventors:* Gerardo Kaplan (CBER/FDA), *et al.* *Patent Status:* U.S. Provisional Application No. 60/865,631 filed 13 Nov 2006 (HHS Reference No. E-035-2005/0-US-01). *Licensing Status:* Available for non-exclusive or exclusive licensing. *Licensing Contact:* Cristina Thalhammer-Reyero, PhD, M.B.A.; 301/435-4507; *thalhamc@mail.nih.gov.* *Collaborative Research Opportunity:* The Food and Drug Administration, Center of Biologics Research and Evaluation, Laboratory of Hepatitis and Related Emerging Agents, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the hepatitis A virus cellular receptor as a potent activator of antigen presenting cells. Please contact Beatrice Droke, 301/872-7008 or *beatrice.droke@fda.hhs.gov,* for more information. Cyanovirins and Related Conjugates, Compositions, Nucleic Acids, Vectors, Host Cells, Methods of Production and Methods of Use for Microbicide Development *Description of Technology:* The development of an effective anti-HIV topical microbicide, especially a female-controlled, vaginal microbicide, has been deemed an urgent global priority by numerous international agencies, including the World Health Organization, the U.S. Department of Health and Human Services, the National Institute of Allergy and Infectious Diseases, and others. The present invention provides antiviral proteins (collectively referred to as cyanovirins), conjugates thereof, DNA sequences encoding such agents, host cells containing such DNA sequences, antibodies directed to such agents, compositions comprising such agents, and methods of obtaining and using such agents for the production of microbicides. Cyanovirin-N (CV-N) potently and irreversibly inactivates diverse primary strains of HIV-1, including M-tropic forms involved in sexual transmission of HIV, as well as T-tropic and dual-tropic forms; CV-N also blocks cell-to-cell transmission of HIV infection. CV-N is directly virucidal, interacting in an unusual manner with the viral envelope, apparently binding with extremely high affinity to poorly immunogenic epitopes on gp120. Further, cyanovirin-N (CV-N) and homologous proteins and peptides potently inhibit diverse isolates of influenza viruses A and B, the two major types of influenza virus that infect humans. The described technology includes glycosylation-resistant mutants of CV-N, which code sequences to enable ultra large-scale recombinant production of functional cyanovirins in non-bacterial (yeast or insect) host cells or in transgenic animals or plants. Therefore, these glycosylation-resistant mutants may allow industry to produce CV-Ns on a large scale and make CV-Ns cheap enough for developing countries to benefit from this invention. CV-N was benign in vivo when tested in the rabbit vaginal toxicity/irritancy model, and was not cytotoxic in vitro against human immune cells and lactobacilli (unpublished). CV-N is readily soluble in aqueous media, is remarkably resistant to physicochemical degradation and is amenable to very large-scale production by a variety of genetic engineering approaches. *Applications:* Development of microbicides against HIV and influenza. *Development Status:* Preclinical data is available at this time. *Inventors:* Michael Boyd (NCI), Robert Shoemaker (NCI), Barry O'Keefe (NCI), Toshiyuki Mori (NCI), Angela Gronenborn (NIDDK). *Related Publications:* 1. B Giomarelli, R Provvedi, F Meacci, T Maggi, D Medaglini, G Pozzi, T Mori, JB McMahon, R Gardella, MR Boyd. The microbicide cyanovirin-N expressed on the surface of commensal bacterium Streptococcus gordonii captures HIV-1. AIDS. 2002 Jul 5;16(10):1351-1356. 2. CC Tsai, P Emau, Y Jiang, MB Agy, RJ Shattock, A Schmidt, WR Morton, KR Gustafson, MR Boyd. Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models. AIDS Res Hum Retroviruses. 2004 Jan;20(1):11-18. *Patent Status:* 1. Patent Cooperation Treaty Serial No. PCT/US00/06247 filed 10 Mar 2000; National Stage Filing in United States, Japan, Australia, Europe, Germany, France, China, United Kingdom, and Belgium (HHS Reference No. E-074-1999/2). 2. Patent Cooperation Treaty Serial No. PCT/US99/18975 filed 19 Aug 1999; National Stage Filing in United States, Japan, Australia, Europe, Germany, France, China, United Kingdom, and Belgium (HHS Reference No. E-117-1995/3). *Licensing Status:* Available for licensing and commercial development. *Licensing Contact:* Sally Hu, PhD; 301/435-5606; *HuS@mail.nih.gov.* *Collaborative Research Opportunity:* The National Cancer Institute's Molecular Targets Development Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize microbicides for HIV and influenza. Please contact John D. Hewes at
(301)435-3121 or *hewesj@mail.nih.gov* for more information. Dated: March 16, 2007. Steven M. Ferguson, Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health. [FR Doc. E7-5670 Filed 3-27-07; 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. Enhanced Function of Gene Modified T-Cells: Identification of T-Cell Receptors
(TCR)with Altered Amino Acid Sequence *Description of Technology:* A major limitation of the current chemotherapy-based therapeutics is the cytotoxic side-effects associated with them. Thus there is a dire need to develop new therapeutic strategies with fewer side-effects. Immunotherapy has taken a lead among the new cancer therapeutic approaches. Adoptive immunotherapy is one of the most promising new therapeutic approaches that enhance the innate immunity of an individual to fight against a certain disease. T cell receptors
(TCR)are the proteins responsible for the T cell's ability to recognize infected or transformed cells. TCR consists of two domains, one variable domain that recognizes the antigen and one constant region that helps the TCR anchor to the membrane and transmit the recognition signal by interacting with other proteins. This invention is directed to substitutions in gene sequences that code for T cell receptors, specifically the inventors found that one to two amino acid substitutions in the TCRs that recognize 1G4 XY-ESO-1 and MART-1 resulted in a marked increase of these modified TCRs to recognize tumor cell targets. These mutated sequences are currently being evaluated as candidates for clinical development. The inventors also consider the invention as providing a “general paradigm” that will allow the generation of TCR directed against a variety of antigens that can enhance the function of gene modified T cells. *Applications:* 1. Improved ability of modified TCRs to recognize tumor cell targets. 2. High affinity TR can be generated that recognizes a variety of antigens that can be potentially used for the diagnosis and treatment of patients with a variety of conditions that include cancer, infectious diseases and autoimmunity. 3. Mutant high affinity TR can also be used to transduce T cells in order to generate cells reactive with tumor antigens as well as viral antigens. *Development Status:* Pre-clinical work has been completed and clinical work is undergoing. *Inventors:* Paul F. Robbins (NCI), Steven A. Rosenberg (NCI), Richard A. Morgan (NCI), *et al.* *Relevant Publication:* A manuscript relating to this invention is under preparation and will be available once accepted. *Patent Status:* U.S. Provisional Application No. 60/847,447 filed 26 Sep 2006 (HHS Reference No. E-304-2006/0-US-01). *Licensing Status:* This technology is available for licensing under an exclusive or non-exclusive patent license. *Licensing Contact:* Michelle Booden, PhD; 301/451-7337; *boodenm@mail.nih.gov.* *Collaborative Research Opportunity:* The NIH Surgery Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize adoptive immunotherapy. Please contact John D. Hewes, PhD at 301-435-3121 or *hewesj@mail.nih.gov* for more information. Novel Benzindole Based Compounds for HIV Therapy *Description of Technology:* The HIV/AIDS epidemic continues despite efforts from scientists, drug companies, and non-profit organizations. Although the existing therapy, is effective in the treatment of many infected individuals in developed nations, the infected individual is not cured and therapy must be life-long. There are problems with drug toxicity, the development of resistant viral strains, and with the cost of therapy. New anti-viral agents are needed for a more effective, and a more cost-effective, treatment of HIV. The invention describes compounds based on a benzindole moiety, which alkylates DNA. The compounds comprise a benzindole moiety, a bifunctional linker, and a fatty acid residue or dendrimer residue comprising at least one fatty acid. Several benzindole derivatives are synthesized. The compounds bind to the minor groove of DNA and can be useful in the inhibition of gene expression. The advantage of the compounds is that they remain inactive until conformational change induced by DNA binding makes them active. The fatty acid moiety immobilizes them on the cytoplasmic side of the plasma membrane. These anchored compounds are specifically designed to inhibit retroviral DNA before it translocates to the host nucleus and integrates with the host genome. *Applications and Modality:* 1. Novel benzindole-based compounds for HIV therapy. 2. Compounds are specifically designed to inhibit retroviral DNA before it can integrate with the host genome. 3. Additionally, compounds might have potential anti-cancer activities. *Market:* 1. More than 45 million people are living with HIV/AIDS worldwide. 2. More than 3 million estimated deaths due to HIV/AIDS occurred worldwide in 2003. 3. HIV/AIDS epidemic has caused more than 30 million deaths. *Development Status:* The technology is currently in the pre-clinical stage of development. *Inventors:* Christopher J. Michejda (NCI), Stephen H. Hughes (NCI), *et al.* *Relevant Publication:* A manuscript directly related to the above technology will be available as soon as it is accepted for publication. *Patent Status:* U.S. Provisional Application No. 60/850,437 filed 10 Oct 2006 (HHS Reference No. E-126-2006/0-US-01). *Licensing Availability:* Available for exclusive and non-exclusive licensing. *Licensing Contact:* Adaku Nwachukwu, J.D.; 301/435-5560; *madua@mail.nih.gov* *Collaborative Research Opportunity:* The National Cancer Institute's Structural Biophysics Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize novel benzindole based compounds for HIV therapy. Please contact John D. Hewes, PhD at 301-435-3121 or *hewesj@mail.nih.gov* for more information. Cloning and Characterization of an Avian Adeno-Associated Virus and Uses Thereof *Description of Technology:* Currently, adeno-associated virus
(AAV)represents the gene therapy vehicle of choice because it has many advantages over current strategies for therapeutic gene insertion. AAV is less pathogenic than other virus types; stably integrates into dividing and non-dividing cells; integrates at a consistent site in the host genome; and shows good specificity towards various cell types for targeted gene delivery. To date, 11 AAV isolates have been isolated and characterized. New serotypes derived from non-human animal species have added to the specificity and repertoire of current AAV gene therapy techniques by avoiding the immunologic complications associated with human isolates. This invention describes vectors derived from an avian AAV. These vectors have innate properties related to their origin that may confer them with a unique cellular specificity in targeted human gene therapy and a unique immunologic profile that would avoid neutralization by pre-existing antibodies. Therefore, vectors derived from this avian AAV are likely to find novel applications for gene therapy in humans. Furthermore because of their species of origin, this vector would also be useful in the engineering of avian cells. *Inventors:* Ioannis Bossis and John A. Chiorini (NIDCR). *Publication:* I Bossis, JA Chiorini. Cloning of an avian adeno-associated virus
(AAAV)and generation of recombinant AAAV particles. J Virol. 2003 Jun;77(12):6799-6810. *Patent Status:* U.S. Patent Application No. 10/557,662 filed 21 Dec 2006 (HHS Reference No. E-105-2003/0-US-03). *Licensing Status:* Available for non-exclusive or exclusive licensing. *Licensing Contact:* Jesse S. Kindra, J.D.; 301/435-5559; *kindraj@mail.nih.gov* *Collaborative Research Opportunity:* The National Institute of Dental and Craniofacial Research, Laboratory of Dr. John Chiorini, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize gene therapy methods using AAV vectors. Please contact David W. Bradley, PhD at *bradleyda@nidcr.nih.gov* for more information. Serotonin-Deficient Knock-Out Mouse *Description of Technology:* Serotonin is an important modulator of many developmental, behavioral, and physiological processes, and it has been implicated in depression, anxiety, schizophrenia, obsessive compulsive disorders, and substance abuse. Serotonin's pharmacology is extremely complex and it is mediated by seven of serotonin receptor subtypes and it is present in several tissues. Although it has been a subject of a number of studies, its role has been difficult to ascertain. To investigate the role of serotonin in these disorders, the murine gene was disrupted by homologous recombination. Results indicate that serotonin binding sites were absent in different brain regions (brain stem, frontal cortex, hippocampus, and striatum), and its concentrations were reduced by 60-80%. These mice represent a powerful tool for the investigation of behavioral and neuropsychiatric disorders, and development of drug treatments for these disorders. *Applications:* A model to study serotonin's role in behavioral and neuropsychiatric disorders. *Market:* 1. Serotonin inhibitors are most widely used treatment in neuropsychological disorders. Examples include Zoloft, Paxil, and Prozac. 2. Depression effects approximately 18.8 million U.S. citizens and over 121 million people worldwide. 3. Antidepressant market was worth $16.2 billion in 2005, and it has annual growth of 2% year on year. 4. Anxiety disorders affect 40 million (18.1%) of the adult U.S. population. 5. Global anxiety disorder market was $4.5 billion in 2006. *Inventors:* Dennis L. Murphy
(NIMH)*et al.* *Publications:* 1. RF Ren-Patterson, LW Cochran, A Holmes, S Sherrill, SJ Huang, T Tolliver, K-P Lesch. Loss of brain-derived neurotrophic factor gene allele exacerbates brain monoamine deficiencies and increases stress abnormalities of serotonin transporter knockout mice. J Neurosci Res. 2005 Mar 15:79(6):756-771. 2. DL Murphy, A Lerner, G Rudnick, K-P Lesch. Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv. 2004 April:4(2):109-123. 3. RF Ren-Patterson, D-K Kim, X Zheng, S Sherrill, S-J Huang, T Tolliver, DL Murphy. Serotonergic-like progenitor cells propagated from neural stem cells in vitro: survival with SERT protein expression following implantation into brains of mice lacking SERT. FASEB J. 2005 Sep:19(11):1537-1539. 4. Q Li, A Holmes, L Ma, LD Van de Kar, F Garcia, DL Murphy. Medical hypothalamic 5-hydroxytryptamine (5HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity application of recombinant adenovirus containing 5-HT1A sequences. J Neurosci. 2004 Dec 1:24(48):10868-10877. 5. F Kilic, DL Murphy, G Rudnick. A human serotonin transporter mutation causes constitutive activation of transport activity. Mol Pharmacol. 2003 Aug:64(2):440-446. 6. DL Murphy, GR Uhl, A Holmes, R Ren-Patterson, FS Hall, I Sora, S Detera-Wadleigh, K-P Lesch. Experimental gene interaction studies with SERT mutant mice as models for human polygenic and epistatic traits and disorders. Genes Brain Behav. 2003 Dec:2(6):350-364. 7. N Ozaki, D Goldman, WH Kaye, K Plotnicov, BD Greenberg, J Lappalainen, G Rudnick, DL Murphy. Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol Psychiatry. 2003 Nov:8(11):933-936. *Patent Status:* HHS Reference No. B-019-1999/0—Research Tool. *Licensing Status:* This technology is available as a research tool under a Biological Materials License. *Licensing Contact:* Jennifer Wong; 301/435-4633; *wongje@mail.nih.gov.* Dated: March 15, 2007. Steven M. Ferguson, Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health. [FR Doc. E7-5675 Filed 3-27-07; 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. Microdialysis Probe for Accessing Tissue in-vivo *Description of Technology:* Available for licensing and commercial development is a microdialysis probe. This device permits *in-vivo* measurement of bioavailable substances ( *e.g.* , cytokines, growth factors, neuropeptides, inflammatory mediators, etc.) at picogram levels of concentration directly from soft tissue and organ systems. The probe may also serve as an *in-situ* drug delivery vehicle of micro doses of medication to specific anatomical sites by slow diffusion. It also permits measurement of efficacy of drug delivery, whether given orally, systemically or topically, at the local tissue level. It can be utilized in a variety of patient populations and conditions. For example, the probe can be used to monitor the local biochemical milieu in soft tissue and organ systems to provide insights into the pathophysiology of musculoskeletal, neuromuscular, rheumatic, gastrointestinal, renal, cardiovascular and endocrinologic diseases, cancers, dermatological conditions, and pediatric disorders, especially in premature newborns. The probe is made from a small-bore (32 gauge) needle, whose probe surface has been fashioned to permit near trauma-less entry, containing both a fluid delivery and recovery tube within the bore. A molecular exchange membrane is positioned about 200 microns from the tip. Fluid flows across the membrane removing diffused molecules to a collection device. The rounded tip of the needle is designed to cause minimal tissue damage while allowing investigations to be performed on local tissue fluids. Additionally, this device allows simultaneous delivery of small concentrations of drug. In summary, this unique apparatus provides a minimally invasive means for sampling biological fluids in any human or animal organ or tissue and for *in-situ* drug-delivery, in continuous or incremental dosing, of extremely small doses. *Applications:* Measurement of bioavailable substances in organs and soft tissues; Localized drug delivery vehicle; Measurement of tissue drug levels. *Market:* Drug discovery; Tissue/fluid sampling; Pain management. *Inventors:* Jay Shah (NIHCC), Terence Martyn Phillips (ORS), Jerome V. Danoff (NIHCC), Lynn Gerber (NIHCC). *Publication:* JP Shah, TM Phillips, JV Danoff, LH Gerber. An *in vivo* microanalytical technique for measuring the local biochemical milieu of human skeletal muscle. J Appl Physiol. 2005 Nov; 99(5):1977-1984. Epub 2005 Jul 21. *Patent Status:* U.S. Provisional Application No. 60/795,176 filed 27 Apr 2006 (HHS Reference No. E-024-2006/0-US-01). *Licensing Contact:* Michael A. Shmilovich, Esq.; 301/435-5019; *shmilovm@mail.nih.gov.* Fluorescent Intracellular Calcium Indicators *Description of Technology:* Calcium is a key element in the regulation of many cellular processes, including muscle contraction, hormone excretion from gland cells, neurotransmitter release from nerve synapses, and the regulation of cellular metabolism. Elevated calcium levels are found in a number of diseases. The present invention relates to chromophoric or fluorescent dye calcium indicators that are superior for measurement of high concentrations of calcium ions due to their high dissociation constants. As a result of the high calcium ion dissociation constants, the perturbation resulting from introducing the indicator into the cell is greatly reduced. These calcium ion indicators can be measured by various techniques including 19F NMR spectroscopy, flow cytometry, and quantitative fluorescence techniques, and are useful for measuring calcium levels within the cytosol or within cellular organelles. *Application:* Research tool for quantifying intracellular calcium concentrations. *Inventors:* Robert E. London, Louis A. Levy, and Elizabeth Murphy (NIEHS). *Patent Status:* U.S. Patent Application No. 08/175,590 filed 30 Dec 1993, which issued as U.S. Patent No. 5,516,911 on 14 May 1996 (HHS Reference No. E-015-1993/0-US-01). *Licensing Status:* Available for nonexclusive licensing. *Licensing Contact:* Tara Kirby, PhD; 301/435-4426; *tarak@mail.nih.gov.* *Collaborative Research Opportunity:* The NIEHS Laboratory of Structural Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact Dr. Robert London at 919/541-4879 or *london@niehs.nih.gov* for more information. Dated: March 19, 2007. Steven M. Ferguson, Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health. [FR Doc. E7-5676 Filed 3-27-07; 8:45 am] BILLING CODE 4140-01-P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Center on Minority Health and Health Disparities; Notice of Closed Meetings 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:* National Center on Minority Health and Health Disparities Special Emphasis Panel, LRP for Health Disparities and Clinical Research-Panel B. *Date:* April 29, 2007. *Time:* 9 a.m. to 5 p.m. *Agenda:* To review and evaluate grant applications. *Place:* National Institutes of Health, 6707 Democracy Blvd./Suite 800, Bethesda, MD 20892, (Virtual Meeting). *Contact Person:* Lorrita Watson, PhD, National Center on Minority Health, and Health Disparities, National Institutes of Health, 6707 Democracy Blvd., Suite 800, Bethesda, MD 20892-5465,
(301)402-1366, *watsonl@ncmhd.nih.gov.* *Name of Committee:* National Center on Minority Health and Health Disparities Special Emphasis Panel, NCMHD Conference Grant Application
(R13)Review. *Date:* May 1, 2007. *Time:* 8 a.m. to 5 p.m. *Agenda:* To review and evaluate grant applications. *Place:* National Institutes of Health, Two Democracy Plaza, 6707 Democracy Boulevard, Bethesda, MD 20892, (Virtual Meeting). *Contact Person:* Robert Nettey, MD, Scientific Review Administrator, National Institute on Minority Health, and Health Disparities, 6707 Democracy Blvd., Suite 800, Bethesda, MD 20892, 301-496-3996. Dated: March 21, 2007. Jennifer Spaeth, Director, Office of Federal Advisory Committee Policy. [FR Doc. 07-1516 Filed 3-27-07; 8:45 am]
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- Pub. L. 107-109
- 42 USC 409I
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