[Federal Register Volume 73, Number 17 (Friday, January 25, 2008)]
[Notices]
[Pages 4606-4608]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-1259]


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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.

ADDRESS: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by writing to the indicated 
licensing contact at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

3D Imaging of Mammalian Cells Using Focused Ion Beam-Secondary Ion Mass 
Spectrometry (FIB-SIMS)

    Description of Technology: Available for licensing and commercial 
development is a new automated approach to cellular imaging that allows 
3D visualization of cellular organelles and protein expression at 
nanometer (nm) resolution using ion abrasion scanning electron 
microscopy (IA-SEM). The approach uses established technologies for 3D 
imaging [1, 2] by iterative use of a focused ion beam and scanning 
electron beam combined with established technologies for mass 
spectrometry. Strategies to explore the 3D distribution of cellular 
components are being developed with the goal of establishing rapid 
methods for determining protein, metabolite and drug localization in 
the subcellular space.
    Applications: Cytology; Oncology; Cell biology; Drug development; 
Drug targeting.
    Development Status: Pilot experiments are ongoing for the 
development and optimization of the technology using commercially 
available components. Clinical applications for the diagnosis of tissue 
specimens are also being explored.
    Inventor: Sriram Subramaniam (NCI).
    Publications:
    1. J Heymann, M Hayles, I Gestmann, L Giannuzzi, L Lich, S 
Subramaniam. Site-specific 3D imaging of cells and tissues with a dual 
beam microscope. J. Struct. Biol. 2006 Jul;155(1):63-73.
    2. J Heymann, D Shi, S Kim, D Bliss, J Milne, S Subramaniam. 3D 
imaging of melanoma cells using automated ``ion abrasion scanning 
electron microscopy''. Microsc Microanal. 2007 Aug;13(Suppl 2):360-361, 
doi 10.1017/S1431927607079287.
    Patent Status: U.S. Provisional Application No. 60/970,070 filed 05 
Sep 2007 (HHS Reference No. E-313-2007/0-US-01); U.S. Provisional 
Application No. 60/974,686 filed 24 Sep 2007 (HHS Reference No. E-313-
2007/1-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Michael A. Shmilovich, Esq.; 301/435-5019; 
[email protected].
    Collaborative Research Opportunity: The National Cancer Institute 
is seeking statements of capability or interest from parties interested 
in collaborative research and/or partnership agreements to further 
develop and commercialize tools for 3D mapping cells and tissues at 
nanometer resolution. Please contact

[[Page 4607]]

John D. Hewes, Ph.D. at 301-435-3121 or [email protected] for more 
information.

A Drug Index to Quantify Harmful Drug Exposure in Older Adults

    Description of Technology: Polypharmacy is the simultaneous use of 
multiple drugs. It is prevalent in individuals ages 65 and older who 
carry a high burden of illness and take various medications for 
treatment. Reducing the incidence of polypharmacy in older people 
presents a major challenge for healthcare professionals. NIH scientists 
have discovered a novel method to assess polypharmacy for which 
physicians can use to evaluate drug response of patients more 
effectively and determine better therapeutic regimens for the patient. 
This method calculates the total drug burden (TDB) index associated 
with anticholinergic and sedative drugs, using the equation, TDB = 
BAC + BS. Further, this invention could be 
implemented into a portable computing device, such as personal digital 
assistant (PDA).
    Applications: Useful for physicians to help reduce prescribing 
errors, lower the incidence of adverse drug reactions and improve 
medical outcomes in older patients.
    Market:
    Seven percent (7%) of the elderly are under polypharmacy and 
purchase over 30% of prescription drugs and 40% of over-the-counter 
(OTC) drugs.
    Medication misuse costs the health care system over $177 billion 
dollars and results in more than 200,000 deaths each year.
    Development Status: Early stage.
    Inventors: Darrell R. Abernethy (NIA), et al.
    Patent Status: International Application No. PCT/US06/44718 filed 
17 Nov 2006 (HHS Reference No. E-241-2006/0-PCT-01)
    Licensing Status: Available for licensing.
    Licensing Contact: Rung C. Tang, J.D.; 301/435-5031; 
[email protected].

Recombinant Modified Bacillus anthracis Protective Antigen for Use in 
Vaccines

    Description of Invention: This invention relates to improved 
methods of preparing Bacillus anthracis protective antigen (PA) for use 
in vaccines. PA is a secreted, non-toxic protein with a molecular 
weight of 83 KDa. PA is a major component of the currently licensed 
human vaccine (Anthrax Vaccine Adsorbed, AVA). Although the licensed 
human vaccine has been shown to be effective against cutaneous anthrax 
infection in animals and humans and against inhalation anthrax in 
rhesus monkeys, the licensed vaccine has several limitations: (1) AVA 
elicits a relatively high degree of local and systemic adverse 
reactions, probably mediated by variable amounts of undefined bacterial 
products, making standardization difficult; (2) the immunization 
schedule requires administration of six doses within an eighteen (18) 
month period, followed by annual boosters; (3) there is no defined 
vaccine-induced protective level of antibody to PA by which to evaluate 
new lots of vaccines; and (4) AVA is comprised of a wild-type PA. It 
has been suggested that a vaccine comprising a modified purified 
recombinant PA would be effective, safe, allow precise standardization, 
and require fewer injections.
    This invention claims methods of producing and recovering PA from a 
cell or organism, particularly a recombinant cell or microorganism. The 
invention claims production and purification of modified PA from a non-
sporogenic strain of Bacillus anthracis. In contrast to other 
previously described methods, greater quantities of PA are obtainable 
from these cells or microorganisms. Specifically, a scalable 
fermentation and purification process is claimed that is suitable for 
vaccine development, and that produces almost three times more product 
than earlier-reported processes. This is accomplished using a 
biologically inactive protease-resistant PA variant in a protease-
deficient non-sporogenic avirulent strain of B. anthracis (BH445). One 
of the PA variants described in the patent application lacks the furin 
and chymotrypsin cleavage sites.
    The invention relates to improved methods of producing and 
recovering sporulation-deficient B. anthracis mutant stains, and for 
producing and recovering recombinant B. anthracis protective antigen 
(PA), especially modified PA which is protease resistant, and to 
methods of using of these PAs or nucleic acids encoding these PAs for 
eliciting an immunogenic response in humans, including responses which 
provide protection against, or reduce the severity of, B. anthracis 
bacterial infections and which are useful to prevent and/or treat 
illnesses caused by B. anthracis, such as inhalation anthrax, cutaneous 
anthrax and gastrointestinal anthrax.
    Application: Improved B. anthracis vaccines.
    Developmental Status: Phase I clinical studies are being performed.
    Inventors: Stephen Leppla (NIDCR), M. J. Rosovitz (NIDCR), John 
Robbins (NICHD), Rachel Schneerson (NICHD)
    Patent Status:
    U.S. Provisional Application No. 60/402,285 filed 09 Aug 2002 (HHS 
Reference No. E-268-2002/0-US-01).
    U.S. Patent Application No. 10/638,006 filed 08 Aug 2003, now U.S. 
Patent 7,261,900 (HHS Reference No. E-268-2002/0-US-02).
    U.S. Patent Application No. 11/831,860 filed 31 Jul 2007 (HHS 
Reference No. E-268-2002/0-US-03).
    Licensing Status: Available for exclusive or nonexclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Methods for Preparing Bacillus anthracis Protective Antigen for Use in 
Vaccines

    Description of Invention: This invention relates to improved 
methods of preparing Bacillus anthracis protective antigen (PA) from a 
cell or organism, particularly a recombinant cell or microorganism, for 
use in vaccines. Production and purification methods of modified PA 
from a non-sporogenic strain of Bacillus anthracis are described. 
Specifically, a scalable fermentation and purification process is 
claimed that is suitable for vaccine development, and that produces 
almost three times more product than earlier-reported processes. This 
is accomplished using a biologically inactive protease-resistant PA 
variant in a protease-deficient non-sporogenic avirulent strain of B. 
anthracis (BH445). One of the PA variants described in the patent 
application lacks the furin and chymotrypsin cleavage sites.
    Advantages: Bacillus anthracis protective antigen is a major 
component of the currently licensed human vaccine (Anthrax Vaccine 
Adsorbed, AVA). Although the current human vaccine has been shown to be 
effective against cutaneous anthrax infection in animals and humans and 
against inhalation anthrax in rhesus monkeys, the licensed vaccine has 
several limitations: (1) AVA elicits a relatively high degree of local 
and systemic adverse reactions, probably mediated by variable amounts 
of undefined bacterial products, making standardization difficult; (2) 
the immunization schedule requires administration of six doses within 
an eighteen (18) month period, followed by annual boosters; (3) there 
is no defined vaccine-induced protective level of antibody to PA by 
which to evaluate new lots of vaccines; and (4) AVA is comprised of a 
wild-type PA. Thus a vaccine comprising a modified purified recombinant 
PA would be effective, safe, allow precise standardization, and require 
fewer injections.

[[Page 4608]]

    The invention also relates to PA variants, and/or compositions 
thereof, which are useful for eliciting an immunogenic response in 
mammals, particularly humans, including responses that provide 
protection against, or reduce the severity of, infections caused by B. 
anthracis. The vaccines claimed in this application are intended for 
active immunization for prevention of B. anthracis infection, and for 
preparation of immune antibodies.
    Application: Improved B. anthracis vaccines.
    Developmental Status: Phase I clinical studies are being performed.
    Inventors: Joseph Shiloach (NIDDK), Stephen Leppla (NIDCR), Delia 
Ramirez (NIDDK), Rachel Schneerson (NICHD), John Robbins (NICHD).
    Publication: DM Ramirez, et al. Production, recovery and 
immunogenicity of the protective antigen from a recombinant strain of 
Bacillus anthracis. J Ind Microbiol Biotechnol. 2002 Apr;28(4):232-238.
    Patent Status: U.S. Provisional Application No. 60/344,505 filed 09 
Nov 2001 (HHS Reference No. E-023-2002/0-US-01); U.S. Patent 
Application No. 10/290,712 filed 08 Nov 2002 (HHS Reference No. E-023-
2002/0-US-02).
    Licensing Status: Available for exclusive or nonexclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The National Institutes of 
Health is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize methods of preparing Bacillus anthracis protective 
antigen (PA) from a cell or organism, particularly a recombinant cell 
or microorganism, for use in vaccines. Please contact Rochelle S. 
Blaustein, J.D., at 301/451-3636 or [email protected] for 
additional information.

Chimeric Gag Pseudovirions

    Description of Technology: The human immunodeficiency virus (HIV) 
is the causative agent of acquired immunodeficiency syndrome (AIDS). 
The HIV virion basically consists of a viral core and envelope. The 
core consists predominantly of gag- and pol-encoded proteins and the 
viral RNA. Expression of recombinant Gag precursor proteins can lead to 
assembly and budding of virus-like particles (pseudovirions). The 
production of Gag-based pseudovirions in mammalian and insect cell 
systems using recombinant virus vectors provides a novel technology for 
engineering recombinant protein-based particulate vaccines for HIV and 
other viruses. The incorporation of additional viral or cellular, 
peptides and polypeptides may be advantageous in vaccine preparations, 
since they may contain antigenic epitopes that may play a role in 
inducing protection from infection or disease.
    The subject invention provides chimeric nucleic acids comprising a 
retroviral gag sequence, a target nucleic acid sequence derived from a 
nucleic acid encoding a fusion partner, and a frame shift site. 
Expression of the chimeric gene cassette results in packaging the 
fusion partner into the Gag pseudovirion. Suitable fusion partners can 
be derived from any protein of interest which has a biological activity 
or which elicits a cellular or humoral immune response.
    Applications: HIV vaccines and/or therapeutics.
    Development Status: Early stage.
    Inventors: Gregory J. Tobin (NCI/SAIC), et al.
    Patent Status: U.S. Patent No. 6,099,847 issued 08 Aug 2000 (HHS 
Reference No. E-105-1996/1-US-01).
    Licensing Status: Available for non-exclusive or exclusive 
licensing.
    Licensing Contact: Susan Ano, PhD; 301/435-5515; [email protected].

    Dated: January 14, 2008.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-1259 Filed 1-24-08; 8:45 am]
BILLING CODE 4140-01-P