[Federal Register Volume 73, Number 180 (Tuesday, September 16, 2008)]
[Notices]
[Pages 53433-53437]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-21519]


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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, HHS.

ACTION: Notice.

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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

[[Page 53434]]

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.

Cyclized NGR Peptide for Tumor Targeting

    Description of Technology: Available for licensing and commercial 
development are patent rights and materials related to NGR peptides for 
targeting therapeutic and diagnostic agents to cancer cells. 
Specifically targeted are tumors that express aminopeptidase N isoform 
CD13. NGR peptides include the Asn-Gly-Arg peptide motif, a ligand for 
APN/CD13. NGR-containing peptides have been proven useful for 
delivering cytotoxic drugs, apoptotic peptides, and cytokines (such as 
tumor necrosis factor (TNF)) to tumor vasculature. In some embodiments 
of the invention, the NGR peptide is conjugated with a diagnostic 
moiety such as a fluorophore, nonmetallic isotope, an optical reporter, 
a boron neutron absorber, a paramagnetic metal ion, a ferromagnetic 
metal, a gamma-emitting radioisotope, a positron-emitting radioisotope, 
or an x-ray absorber. In another embodiment, the peptide can be 
conjugated with a therapeutic such as daunorubicin, doxorubicin, 
epirubicin, idarubicin, mitoxantrone, or a combination of these. The 
therapeutic agent, such as an anti-tumor or anti-neoplastic agent of 
choice, can be entrapped within a liposome; the liposomes are 
formulated to be of a size known to penetrate the endothelial and 
basement membrane barriers. The resulting liposomal formulation can be 
administered parenterally to a subject in need of such treatment, 
preferably by intravenous administration. Tumors characterized by an 
acute increase in permeability of the vasculature in the region of 
tumor growth are particularly suited for treatment by the present 
invention.
[GRAPHIC] [TIFF OMITTED] TN16SE08.029

    Applications:

 Cancer diagnostics
 Cancer therapeutics
 Anti-angiogenesis
 Imaging

    Inventors: Bradford Wood, Matthew Dreher, Ayele Negussie (CC).
    Relevant Publications:
    1. W Arap et al. Cancer treatment by targeted drug delivery to 
tumor vasculature in a mouse model. Science. 1998 Jan 16;279(5349):377-
380.
    2. H Ellerby et al. Anti-cancer activity of targeted pro-apoptotic 
peptides. Nat Med. 1999 Sep;5(9):1032-1038.
    3. F Curnis et al. Enhancement of tumor necrosis factor alpha 
antitumor immunotherapeutic properties by targeted delivery to 
aminopeptidase N (CD13). Nat Biotechnol. 2000 Nov;18(11):1185-1190.
    4. G Colombo et al. Structure-activity relationships of linear and 
cyclic peptides containing the NGR tumor-homing motif. J Biol Chem. 
2002 Dec 6;277(49):47891-47897.
    5. F Pastorino et al. Vascular damage and anti-angiogenic effects 
of tumor vessel-targeted liposomal chemotherapy. Cancer Res. 2003 Nov 
1;63(21):7400-7409.

[[Page 53435]]

    6. F Pastorino et al. Targeting liposomal chemotherapy via both 
tumor cell-specific and tumor vasculature-specific ligands potentiates 
therapeutic efficacy. Cancer Res. 2006 Oct 15;66(20):10073-10082.
    7. SV Garde et al. Binding and internalization of NGR-peptide-
targeted liposomal doxorubicin (TVT-DOX) in CD13-expressing cells and 
its antitumor effects. Anti-Cancer Drugs. 2007 Nov;18(10):1189-1200.
    Patent Status: U.S. Provisional Application No. 61/074,864 filed 23 
Jun 2008 (HHS Reference No. E-147-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].

Microfabricated Particles Useful as MRI Contrast Agents

    Description of Technology: MRI contrast agents are versatile yet 
lack the sensitivity and multiplexing capabilities of optical agents. 
Available for licensing is an invention pertaining to microfabricated 
structures that can be used as MRI contrast agents with enhanced 
functionality or as micro-RFID (radio-frequency identification) tags. 
The microstructures can be engineered to appear as different effective 
colors when resolved using MRI as opposed to strictly grey-scale 
contrast of existing MRI agents. In this way they can be thought as 
radio-frequency analogs to quantum dots. A set of agents could be 
produced that would enable in vivo labeling and tracking of multiple 
different types of cells simultaneously. The agents can also act as 
radio-frequency probes of various physiological conditions. The 
invention can include a plurality of microstructures dispersed a 
liquid. The structures can have magnetic portions that vary in size, 
thickness and shape that are arranged to provide a substantially 
uniform Larmor precession frequency or a characteristic substantially 
uniform shift in Larmor precession frequency experienced by nuclear 
magnetic moments of a material when it is located in the substantially 
uniform field region created by the magnetic portions. In some 
embodiments, each of the nuclear magnetic resonance microstructures has 
a maximum dimension less than about 1 mm. The magnetic portions of the 
microstructure can be arranged proximate to each other, in contact with 
each other or be partially, substantially or totally coincident.
    Applications:

 Magnetic Resonance Imaging
 Cancer
 Cardiovascular diseases imaging
 Drug development
 Drug candidate distribution tracking
 Diagnostics
 Microfluidics

    Inventors: Gary Zabow, Stephen Dodd (NINDS), Alan Koretsky (NINDS), 
John Moreland (NIST).
    Publications:
    1. G Zabow et al. Micro-engineered local field control for high-
sensitivity multispectral MRI. Nature 2008 Jun 19;453(7198):1058-1063.
    2. KA Hinds et al. Highly efficient endosomal labeling of 
progenitor and stem cells with large magnetic particles allows magnetic 
resonance imaging of single cells. Blood 2003 Aug 1;102(3):867-872.
    Patent Status: U.S. Provisional Application No. 61/071,263 filed 18 
Apr 2008 (HHS Reference No. E-081-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: NINDS Laboratory of Functional 
and Molecular Imaging is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize the use of microfabricated devices as MRI 
contrast agents. Please contact Dr. Melissa Maderia at 301-451-3943 or 
[email protected] for more information.

Active Guidewire Visualization Device and System for MRI Guided 
Interventions

    Description of Technology: Available for licensing and commercial 
development is a guidewire device and system for MRI guidance of 
vascular interventions. The guidewire design, and its coupled system, 
enables interventionalists to visualize the location of the tip and 
distal shaft of an MRI compatible guidewire relative to the vascular 
system and surrounding anatomy. Visualization of both the shaft and tip 
enables interventionalists to advance the guidewire through tortuous 
vessels reducing the risk of puncturing vessel walls and also steering 
it through labyrinthine vasculature. The guidewire provided by the 
present invention includes distal and proximal ends with a space 
therein, a dipole antenna disposed in the space reserved within the 
guidewire body, the dipole antenna being adapted to be electrically 
connected to a signal processing system through a first signal channel 
through the proximal end of the guidewire body, and a loop antenna 
disposed in the space reserved within the guidewire body toward the 
distal end of the guidewire body, the loop antenna being adapted to be 
electrically connected to the signal processing system through a second 
signal channel through the proximal end of the guidewire body. The 
dipole antenna and the loop antenna are each constructed to receive 
magnetic resonance imaging signals independently of each other and to 
transmit received signals through the first and second signal channels, 
respectively, to be received by the signal processing system. More 
specifically, both loop and dipole antenna are tuned to resonate at the 
same Larmour frequency as produced by the magnet.
    Applications:

 Interventional cardiology
 MRI guided surgery

    Inventors: Ozgur Kocaturk (NHLBI).
    Publications:
    1. McKinnon GC, et al. Towards active guidewire visualization in 
interventional magnetic resonance imaging. MAGMA. 1996 Mar;4(1):13-18.
    2. Ladd ME, et al. Active MR visualization of a vascular guidewire 
in vivo. J Magn Reson Imaging. 1998 Jan-Feb;8(1):220-225.
    Patent Status: U.S. Provisional Application No. 61/006,265 filed 03 
Jan 2008 (HHS Reference No. E-209-2007/0-US-01)
    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The National Institutes of 
Health / Cardiac Catheter Core Lab is seeking statements of capability 
or interest from parties interested in collaborative research to 
further develop, evaluate, or commercialize Active two channel 0.035'' 
guidewire. Please contact Ozgur Kocaturk at 301-402-9430 or 
[email protected].

Respiratory Syncytial Virus (RSV) Vaccines Based on Promoter-Proximate 
Attenuation

    Description of Technology: Available for licensing and commercial 
development is a patent estate and related biological materials for 
producing therapeutic or prophylactic vaccines against Respiratory 
Syncytial Virus (RSV). The claimed vaccine strategy relates to the 
engineering and creation of live-attenuated RSV vaccine candidates by 
shifting the position of one or more viral genes relative to the viral 
promoter (aka promoter-proximal

[[Page 53436]]

attenuation). The gene shifts can be constructed by insertion, deletion 
or rearrangement of genes or genome segments within the recombinant 
genome or antigenome. Viral replication can increase or decrease 
depending on the position of expressed viral gene and depending on the 
nature and degree of the positional shift. Viral gene rearrangements 
are selected to maintain sufficient non-infectious replication of RSV 
while eliciting host anti-RSV immune responses. Viral genes targeted 
for such rearrangement include any of the NS1, NS2, N, P, M, SH, 
M2(ORF1), M2(ORF2), L, F or G genes or genome segment.
    One modification of particular interest is the placement of the G 
and F protective antigen genes in a promoter-proximal position for 
increased expression. The gene position-shifted RSV can be further 
manipulated by the addition of specific nucleotide and amino acid point 
mutations or host range restriction determinants to yield desired 
phenotypic and structural effects.
    Applications:

 Infectious Disease--Respiratory Syncytial Virus
 Vaccines
 Therapeutics
 Prophylactics
 Childhood Vaccines

    Inventors: Christine D. Krempl, Peter L. Collins, Brian R. Murphy, 
Ursula Buchholz, Stephen S. Whitehead (NIAID)
    Publications:
    1. C Krempl et al. Recombinant respiratory syncytial virus with the 
G and F genes shifted to the promoter-proximal positions. J Virol. 2002 
Dec;76(23):11931-11942.
    2. Y Aloni, N Hay. Attenuation may regulate gene expression in 
animal viruses and cells. CRC Crit Rev Biochem. 1985;18(4):327-383.
    Patent Status:

HHS Reference No. E-225-2000/0--
     U.S. Patent No. 6,923,971 issued 02 Aug 2005
     U.S. Patent Application No. 11/033,055 filed 10 Jan 2005
     U.S. Patent Application No. 11/054,343 filed 08 Feb 2005
     International Patent Application PCT/US2001/20107, which 
published as WO 2002/00693 on 03 Jan 2002 (expired)
     Australian Patent 2001268709
     Brazilian Patent Application PI0112276-2
     Canadian Patent Application 2413786
     Chinese Patent Application 01814362.8
     European Patent Application 01946696.0
     Israeli Patent Application 153530
     Japanese Patent Application 10-2002-505815
     Korean Patent Application 10-2002-7017577 and
     Mexican Patent Application 2002-012818.

    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The NIAID Office of Technology 
Development is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize live attenuated vaccines. Please contact 
Michael Piziali at 301-451-3527 for more information.

Quantitative Assessment of Changes in Tissue Status in Disease, 
Development, Aging, or Degeneration Using Diffusion Tensor Magnetic 
Resonance Imaging

    Description of Technology: This invention significantly enhances 
the quality and utility of diffusion tensor magnetic resonance imaging 
(DT-MRI) data. The patent application for the invention describes 
quantitative statistical methodology to extract novel clinical and 
biological information from DT-MRI data. These parametric and non-
parametric statistical methods help distinguish changes in tissue state 
from background noise inherent in all MRI measurements. The invention 
also includes hypothesis tests to determine the statistical 
significance of changes observed in MRI ``stains'' (e.g., the Trace of 
the diffusion tensor, Trace(D), and the mean apparent diffusion 
coefficient, ADC), which are widely used in the diagnosis of stroke. 
Further, this invention describes how to detect systematic artifacts in 
each pixel of a diffusion weighted image (e.g., artifacts caused by 
patient motion). Indeed, this new statistical methodology for analyzing 
and interpreting diffusion tensor MRI data should improve the efficacy 
of drug screening studies, as well as streamline multi-site and 
longitudinal studies designed to assess the safety and efficacy of 
drugs undergoing clinical evaluation.
    Inventors: Peter J. Basser (NICHD), Sinisa Pajevic (CIT).
    Patent Status: U.S. Patent No. 6,845,324 issued 15 Jan 2005 (HHS 
Reference No. E-192-1999/0-US-07)
    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].

Human-Bovine Chimeric Respiratory Syncytial Virus (RSV) Vaccines

    Description of Technology: Available for licensing and commercial 
development is a patent estate and related biological materials for 
making human-bovine chimeric virus particles for formulating live 
attenuated vaccines against human respiratory syncytial virus (RSV). 
Chimeric human-bovine RSVs are recombinantly engineered to incorporate 
nucleotide sequences from both human and bovine RSV strains and produce 
infectious, chimeric viruses that elicit anti-RSV immunological 
responses in humans and non-human primates. The chimeras incorporate 
partial or complete human or bovine RSV background genomes with one or 
more recombinantly integrated heterologous genes or genome segments of 
a different RSV strain.
    Heterologous genes of interest for making chimeric recombinants 
include NS1, NS2, N, P, M, SH glycoprotein (or an immunogenic domain or 
epitope thereof), M2(ORF1), M2(ORF2), L, F or G genes or a genome 
segment including a protein or portion thereof or alternatively a 
leader, trailer or intergenic region of the RSV genome, or a segment 
thereof. A variety of additional mutations and nucleotide modifications 
are provided within the human-bovine chimeric RSV of the invention to 
yield desired phenotypic and structural effects. Exemplary human-bovine 
chimeric RSV of the invention incorporate a chimeric RSV genome or 
antigenome comprising both human and bovine polynucleotide sequences, 
as well as a major nucleocapsid (N) protein, a nucleocapsid 
phosphoprotein (P), a large polymerase protein (L), and an RNA 
polymerase elongation factor. Additional RSV proteins may be included 
in various combinations to provide a range of infectious subviral 
particles up to a complete viral particle or a viral particle 
containing supernumerary proteins, antigenic determinants or other 
additional components.
    Applications:

 Infectious Disease--Respiratory Syncytial Virus
 Vaccines
 Therapeutics
 Prophylactics
 Childhood Vaccines

    Inventors: Ursula Buchholz, Peter L. Collins, Brian R. Murphy, 
Stephen S. Whitehead, Christine D. Krempl (NIAID).

[[Page 53437]]

    Publications:
    1. UJ Buchholz et al. Chimeric bovine respiratory syncytial virus 
with glycoprotein gene substitutions from human respiratory syncytial 
virus (HRSV): effects on host range and evaluation as a live-attenuated 
HRSV vaccine. J Virol. 2000 Feb;74(3):1187-1199.
    2. A Karger et al. Recombinant bovine respiratory syncytial virus 
with deletions of the G or SH genes: G and F proteins bind heparin. J 
Gen Virol. 2001 Mar;82(Pt 3):631-640.
    3. UJ Buchholz et al. Generation of bovine respiratory syncytial 
virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication 
in tissue culture, and the human RSV leader region acts as a functional 
BRSV genome promoter. J Virol. 1999 Jan;73(1):251-259.
    Patent Status:

HHS Reference No. E-178-1999/0--
     International Patent Application PCT/US00/17755, which 
published as WO 2001/04335 on 09 Jan 2001 (expired)
     Australian Patent 784216
     Chinese Patent 00810119.1
     Canadian Patent Application 2378552
     European Patent Application 00941756.9
     Israeli Patent Application 147447
     Japanese Patent Application 2001-509539
     Korean Patent Application 10-2002-7000318
     Mexican Patent Application 2002-000220
     Brazilian Patent Application PI0013195-4 and
     Chinese Patent Application 200710167112.6
HHS Reference No. E-178-1999/1--
     U.S. Patent Application No. 11/097,946 filed 31 Mar 2005
HHS Reference No. E-178-1999/2--
     U.S. Patent Application No. 10/704,116 filed 07 Nov 2003

    Licensing Status: Available for licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301-435-5019; 
[email protected].
    Collaborative Research Opportunity: The NIAID Office of Technology 
Development is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize attenuated live vaccines against respiratory 
syncytial virus (RSV). Please contact Barry Buchbinder at 301-594-1696 
for more information.

    Dated: September 9, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-21519 Filed 9-15-08; 8:45 am]
BILLING CODE 4140-01-P