[Federal Register Volume 64, Number 152 (Monday, August 9, 1999)]
[Notices]
[Pages 43201-43203]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-20456]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by agencies 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

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be required to receive copies of the patent applications.

Direct C-14 Oxidation of Opioids

A Coop and KC Rice (NIDDK)

Serial No. 60/132,628 filed 05 May 1999, Licensing Specialist: Leopold 
J. Luberecki, Jr.; 301/496-7735 ext. 223; e-mail: 
[email protected].
    This application describes a simple one-step method for the direct 
oxidation of 14-H opioids into the desired 14-hydroxy opioid 
derivatives, providing a quicker and less expensive means for the 
manufacture of these compounds. For example, this process converts 
codeinone into 14-hydroxycodeinone, eliminating the need for using 
thebaine, the currently used common starting material, whose price is 
increasing at 10% annually. The invention claims a process of employing 
certain oxidizing agents, using much less reagent volume than the 
present standard. The invention also circumvents diene intermediate 
formation, thus eliminating the need for expensive chromatographic 
isolation. The process takes much less time than the industry standard 
and produces high yields between 50% and 80% at higher cost-
effectiveness than current methods. The 14-hydroxyl substituted opioid 
antagonists are useful in a number of medicinal applications. For 
instance, the antagonists naltrexone and naloxone are drugs used in the 
treatment of opiate abuse, opiate overdose, and alcohol addiction. In 
addition, certain derivatives of these compounds have been found useful 
in the prevention of tolerance to morphine and as immunosuppressants.

Methods for Detecting Cancer Cells

Thomas Ried, Evelin Schrock, Bijan M. Ghadimi (NHGRI)

DHHS Reference No. E-211-98/0 filed 01 Apr 1999, Licensing Contact: 
John Fahner-Vihtelic; 301/496-7735 ext. 270; e-mail: [email protected]
    The present application describes a highly sensitive assay for 
distinguishing between cancer and non-cancer epithelial cells in the 
blood. It provides an improved diagnostic technique for detecting 
cancer and determining the organ-origin of the cancer. This assay can 
be used to prove the neoplastic nature of cells and predict when shed 
tumor cells have or will become metastatic. A major advantage of the 
present invention is that tumor cells can also be recovered as viable 
cells. Thus, the tumor cells can be kept alive in vitro for a 
sufficient period of time to determine the effect of particular anti-
tumor pharmaceuticals on the cells. Furthermore, the assay provides an 
early detector of treatment success or failure and thereby allows a 
treatment regimen to be customized for an individual patient with 
advanced primary cancer.

Replication-Defective Dengue Viruses that are Replication-Defective 
in Mosquitoes for Use as Vaccines

L Zeng, L Markoff (FDA)

Serial No. 60/098,981 filed 01 Sep 1998, Licensing Contact: Carol 
Salata; 301/496-7735 ext. 232; e-mail [email protected]
    Although flaviviruses cause a great deal of human suffering and 
economic loss, there is a shortage of effective vaccines. The present 
invention is directed toward vector stage replication-defective 
flaviviruses that are replication-defective in mosquito vectors that 
transmit them to humans. The replication-defective flaviviruses of the 
present invention demonstrate a limited ability to replicate in the 
vector organisms that transmit flaviviruses from one host to another. 
More specifically, the present invention is directed toward the 
construction and propagation of flaviviruses that possess 3'-noncoding 
regions altered in such a way as to prevent or severely limit viral 
reproduction in a vector organism. Such mutant flaviviruses may be 
useful as vaccines.

Vaccine Against Eschericha coli 0157 Infection, Composed of 
Detoxified LPS Conjugated to Proteins

Shousun C. Szu, Edward Konadu, and John B. Robbins (NICHD) DHHS 
Reference No. E-158-98/0 filed 20 July 1998 (PCT/US98/14976)

Licensing Contact: Robert Benson; 301/496-7056 ext. 267; e-mail: 
[email protected]

    This invention is a conjugate vaccine to prevent infection, in 
particular in young children under 5 years of age, by E. coli 0157:H7, 
an emerging human pathogen which causes a spectrum of illnesses with 
high morbidity and mortality, ranging from diarrhea to hemorrhagic 
colitis and hemolytic-uremic syndrome (HUS). Infection is due to the 
consumption of water or meat contaminated by feces from infected 
animals, such as cattle. The conjugate is composed of the O-specific 
polysaccharide isolated from E. coli 0157, or other Shiga-toxin 
producing bacteria, conjugated to carrier proteins, such as non-toxic 
P. aeruginosa exotoxin A or Shiga toxin 1. A Phase I clinical trial, 
involving adult humans, showed the vaccine is safe and highly 
immunogenic. Adults, after one injection containing 25 (g of antigen, 
responded with high titers of bactericidal antibodies. Thus the 
conjugates of the invention are promising vaccines, especially for 
children and the elderly, who are most likely to suffer serious 
consequences from infection. The clinical study is described in J. 
Infectious Diseases 177, 383-387, 1998.

Applicator System and Method of Use

Michael J. Lenardo, Galen Fisher (NIAID)

Serial No. 09/005,475 filed 12 Jan 1998, Licensing Contact: John 
Fahner-Vihtelic, 301/496-7735 ext. 270
    The present application describes a novel microcentrifuge tube and 
tube cap and research method, which allows for dispensing the contents 
of a microcentrifuge tube without pipetting. The design eliminates 
pipetting volume error and prevents the cross-contamination which can 
be experienced in conventional pipetting. This invention is 
particularly useful for such applications as loading tube contents into 
an electrophoresis gel after a reaction such as PCR. Using the 
disclosed apparatus and methods increases the speed of a variety of 
routine procedures and prevents contamination of samples due to soiled 
lab apparatus.

Method To Reduce the Bias in the Mean and Variance of Indices of 
Water Diffusion Anisotropy as Measured by Diffusion Tensor MRI

Carlo Pierpaoli (NINDS/NICHD), Peter J. Basser (NICHD)

Serial No. 08/824,706 filed 14 Apr 1997; Licensing Contact: John 
Fahner-Vihtelic; 301/496-7735, ext. 270; e-mail: [email protected].
    This invention describes several novel MRI ``stains'' to measure 
and display water diffusion anisotropy data obtained by diffusion 
tensor MRI (DT-MRI). One problem that this invention overcomes is that 
it significantly reduces the statistical bias in the mean and variance 
of the measured anisotropy of water diffusion caused by background 
noise in the MR images. These benefits are achieved by exploiting the 
idea that fiber tracts exhibiting diffusion anisotropy vary 
continuously in most regions. Thus, the principal axes of the diffusion 
tensor (or eigenvectors) can be used to improve the estimate of the 
principal diffusivities (or eigenvalues) within a local region of 
interest. These eigenvalues, in turn, are used to

[[Page 43203]]

compute our improved local measures of diffusion anisotropy. Images or 
maps of water diffusion anisotropy are increasingly being used to 
gather structural information about fibrous tissue, such as white 
matter fibers as well as cardiac and skeletal muscle fibers in vivo, in 
health, disease, development, and aging. This invention results not 
only in a more accurate measurement of diffusion anisotropy, but it 
improves image quality and reduces scanning time in clinical and 
biological applications of DT-MRI. Since the reduction in diffusion 
anisotropy has been shown to be sensitive to nerve fiber degeneration, 
this new data should be useful in studies to screen for and determine 
the efficacy of neuroprotective agents, as well as streamline multi-
site and longitudinal clinical trials designed to assess their safety 
and efficacy.

A New Class of Anti-Tumor Agents

Christopher J. Michejda (NCI), Richard H. Smith, Jr.

Serial No. 07/179,622 filed 29 Mar 1988; U.S. Patent 4,9023,970 issued 
08 May 1990; Licensing Contact: Girish Barua; 301/496-7056, ext. 263; 
e-mail: [email protected]
    Substituted triazenes are potentially useful anti-tumor agents. 
Examples of substituted triazenes in clinical use include 5-
(dimethyltriazeno)imidazole-4-carboxamide (DTIC), which is used in the 
treatment of metastatic melanoma and some soft tissue sarcomas, and the 
recently approved temozolomide, which is used in brain cancer. The 
National Institutes of Health has developed compounds which have many 
advantages over known triazene anti-cancer compounds. Advantages 
include a novel mechanism of action for at least one of them, namely, 
1-(2-chloroethyl)-3-(N-methylcarbamoyl)-methyltriazene, which is a 
highly selective, non-toxic anti-tumor compound, their well understood 
chemistry, and ease of synthesis of new analogs.
    The technology covers compounds of the series of 1-(2-chloroethyl)-
3-acyl-3-alkyltriazenes and a method for their synthesis. Some of the 
subject acyl triazenes generate 2-chloroethyldiazonium ions at very 
easily controlled rates, while others require metabolic activation to 
release the electrophilic agent.
    Several of the acyltriazenes have shown excellent in vivo activity 
against human tumor xenografts in nude mice and low toxicity. These 
compounds are good candidates for development as anti-tumor drugs.

    Dated: August 3, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 99-20456 Filed 8-6-99; 8:45 am]
BILLING CODE 4140-01-P