Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices 14589 

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 Methicillinresistant 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-CisRetinoic 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 


sroberts on PROD1PC70 with NOTICES
14590 Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices 

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 nonexclusive 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 IL15Ralpha 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 coadministration 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 IL15 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 nonexclusive 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 TNFa. 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 


sroberts on PROD1PC70 with NOTICES
Federal Register / Vol. 72, No. 59 / Wednesday, March 28, 2007 / Notices 14591 

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 nonexclusive 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 femalecontrolled, 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 dualtropic forms; CV-N also blocks cell-tocell transmission of HIV infection. CVN 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. 


sroberts on PROD1PC70 with NOTICES