[Federal Register Volume 73, Number 17 (Friday, January 25, 2008)]
[Notices]
[Pages 4598-4603]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-1232]


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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 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.

Monoclonal Antibodies Against Dengue and Other Viruses With Deletion in 
Fc Region

    Description of Invention: The four dengue virus (DENV) serotypes 
(DENV-1 to DENV-4) are the most important arthropod-borne flaviviruses 
in terms of morbidity and geographic distribution. Up to 100 million 
DENV infections occur every year, mostly in tropical and subtropical 
areas where vector mosquitoes are abundant. Infection with

[[Page 4599]]

any of the DENV serotypes may be asymptomatic or may lead to classic 
dengue fever or more severe dengue hemorrhagic fever (DHF) and dengue 
shock syndrome (DSS), which are increasingly common in the dengue 
endemic areas. Immunity to the same virus serotype (homotypic immunity) 
is life-long, whereas immunity to different serotypes (heterotypic 
immunity) lasts 2-3 months so that infection with a different serotype 
virus is possible. DHF/DSS often occurs in patients with second, 
heterotypic DENV infections or in infants with maternally transferred 
dengue immunity. Severe dengue is a major cause of hospitalization, and 
fatality rates vary from <1% to 5% in children.
    Antibody-dependent enhancement (ADE) has been proposed as an 
underlying pathogenic mechanism of DHF/DSS. ADE occurs because 
preexisting subneutralizing antibodies and the infecting DENV form 
complexes that bind to Fc receptor-bearing cells, leading to increased 
virus uptake and replication. ADE has been repeatedly demonstrated in 
vitro using dengue immune sera or monoclonal antibodies and cells of 
monocytic and recently, B lymphocytic lineages bearing Fc receptors. 
ADE of DENV-2 infection has also been demonstrated in monkeys infused 
with a human dengue immune serum.
    We have identified chimpanzee-human chimeric IgG1 mAbs capable of 
neutralizing or binding to one or more DENV serotypes. Cross-reactive 
IgG 1A5 neutralizes DENV-1 and DENV-2 more efficiently than DENV-3 and 
DENV-4, and type-specific IgG 5H2 neutralizes DENV-4 at a high titer. 
Analysis of antigenic variants has localized the IgG 1A5 binding site 
to the conserved fusion peptide in E. Thus, IgG 1A5 shares many 
characteristics with the cross-reactive antibodies detected in 
flavivirus infections.
    This application claims a variant of an antibody comprising a 
polypeptide in the Fc region, which binds an Fc gamma receptor 
(FcgammaR) with lower affinity than the parent antibody. The variant 
polypeptide comprises a deletion of nine amino acids at the N-terminus 
of the CH2 domain in the Fc region. Introduction of the Fc 
variant abrogates the antibody-mediated dengue virus replication 
enhancing activity. This invention has important implications for the 
antibody-mediated prevention of dengue virus infection.
    Application: Immunization against Dengue and/or flaviviruses.
    Developmental Status: Antibody candidates have been synthesized and 
preclinical studies have been performed.
    Inventors: Ana Goncalvez, Robert Purcell, C.J. Lai (NIAID).
    Publication: AP Goncalvez, et al. Monoclonal antibody-mediated 
enhancement of dengue virus infection in vitro and in vivo and 
strategies for prevention Proc Natl Acad Sci USA. 2007 May 
29;104(22):9422-9427.
    Patent Status: U.S. Provisional Application No. 60/922,282 filed 04 
Apr 2007 (HHS Reference No. E-159-2007/0-US-01); U.S. Provisional 
Application No. 60/927,755 filed 04 May 2007 (HHS Reference No. E-159-
2007/1-US-01); U.S. Provisional Application No. 60/928,405 filed 08 May 
2007 (HHS Reference No. E-159-2007/2-US-01).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Monoclonal Antibodies that Neutralize B. anthracis Protective Antigen 
(PA), Lethal Factor (LF) and Edema Factor (EF)

    Description of Invention: Anthrax, whether resulting from natural 
or bioterrorist-associated exposure, is a constant threat to human 
health. The lethality of anthrax is primarily the result of the effects 
of anthrax toxin, which has 3 components: a receptor-binding protein 
known as ``protective antigen'' (PA) and 2 catalytic proteins known as 
``lethal factor'' (LF) and ``edema factor'' (EF). Although production 
of an efficient anthrax vaccine is an ultimate goal, the benefits of 
vaccination can be expected only if a large proportion of the 
population at risk is immunized. The low incidence of anthrax suggests 
that large-scale vaccination may not be the most efficient means of 
controlling this disease. In contrast, passive administration of 
neutralizing human or chimpanzee monoclonal antibody to a subject at 
risk for anthrax or exposed to anthrax could provide immediate efficacy 
for emergency prophylaxis against or treatment of anthrax.
    Four monoclonal antibodies (mAbs) against PA, three mAbs against LF 
and four mAbs specific for EF of anthrax were isolated from a phage 
display library generated from immunized chimpanzees. Two mAbs 
recognizing PA (W1 and W2), two anti-LF mAbs efficiently neutralized 
the cytotoxicity of lethal toxin in a macrophage lysis assay. One anti-
EF mAb efficiently neutralized edema toxin in cell culture. All five 
neutralizing mAbs protected animals from anthrax toxin challenge.
    Application: Prophylactics or therapeutics against B. anthracis.
    Developmental Status: Preclinical studies have been performed.
    Inventors: Zhaochun Chen, Robert Purcell, Suzanne Emerson, Stephen 
Leppla, Mahtab Moyeri (NIAID).
    Publication: Z Chen, et al. Efficient neutralization of anthrax 
toxin by chimpanzee monoclonal antibodies against protective antigen. J 
Infect Dis. 2006 Mar 1;193(5):625-633.
    Patent Status: U.S. Provisional Application No. 60/903,022 filed 23 
Feb 2007 (HHS Reference No. E-123-2007/0-US-01); U.S. Patent 
Application No. 11/793,735 filed 22 Jun 2007 (HHS Reference No. E-146-
2004/0-US-03).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases, Laboratory of Infectious Diseases is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
Chimpanzee/human neutralizing monoclonal antibodies against anthrax 
toxins. Please contact Dr. Robert Purcell at 301-496-5090 for more 
information.

Cell-Nanofiber Composite and Cell-Nanofiber Composite Amalgam Based 
Engineered Intervertebral Disc

    Description of Invention: Diseased or damaged musculoskeletal 
tissues are often replaced by an artificial material, cadaver tissue or 
donated, allogenic tissue. Tissue engineering offers an attractive 
alternative whereby a live, natural tissue is generated from a 
construct made up of a patient's own cells or an acceptable/compatible 
cell source in combination with a biodegradable scaffold for 
replacement of defective tissue.
    Degeneration of the intervertebral disc (IVD) is a common and 
significant source of morbidity in our society. Approximately 8 of 10 
adults at some point in their life will experience an episode of 
significant low back pain, with the majority improving without any 
formal treatment. However, for the subject requiring surgical 
management current interventions focus on fusion of the involved IVD 
levels, which eliminates pain but does not attempt to restore disc 
function. Approximately 200,000 spinal fusions were performed in the 
United States in 2002 to treat pain associated with lumbar disc 
degeneration. Spinal fusion however is thought to significantly alter 
the

[[Page 4600]]

biomechanics of the disc and lead to further degeneration, or adjacent 
segment disease. Therefore, in the past decade there has been mounting 
interest in the concept of IVD replacement. The replacement of the IVD 
holds tremendous potential as an alternative to spinal fusion for the 
treatment of degenerative disc disease by offering a safer alternative 
to current spinal fusion practices.
    At the present time, several disc replacement implants are at 
different stages of preclinical and clinical testing. These disc 
replacement technologies are designed to address flexion, extension, 
and lateral bending motions; however, they do little to address 
compressive forces and their longevity is limited due to their 
inability to biointegrate. Therefore, a cell-based tissue engineering 
approach offers the most promising alternative to replace the 
degenerated IVD. Current treatment for injuries that penetrate 
subchondral bone include subchondral drilling, periosteal tissue 
grafting, osteochondral allografting, chondrogenic cell and 
transplantation; but are limited due to suboptimal integration with 
host tissues.
    The present invention claims tissue engineered intervertebral discs 
comprising a nanofibrous polymer hydrogel amalgam having cells 
dispersed therein, methods of fabricating tissue engineered 
intervertebral discs by culturing a mixture of stem cells or 
intervertebral disc cells and a electrospun nanofibrous polymer 
hydrogel amalgam in a suitable bioreactor, and methods of treatment 
comprising implantation of tissue engineered intervertebral disc into a 
subject.
    Application: Intervertebral disc bio-constructs and electrospinning 
methods for fabrication of the discs.
    Developmental Status: Prototype devices have been fabricated and 
preclinical studies have been performed.
    Inventors: Wan-Ju Li, Leon Nesti, Rocky Tuan (NIAMS)
    Patent Status: U.S. Provisional Application No. 60/847,839 filed 27 
Sep 2006 (HHS Reference No. E-309-2006/0-US-01); U.S. Provisional 
Application No. 60/848,284 filed 28 Sep 2006 (HHS Reference No. E-309-
2006/1-US-01)
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Cell-Nanofiber Composite Based Engineered Cartilage

    Description of Invention: Available for licensing and commercial 
development is a tissue-engineered cartilage derived from a cellular 
composite made from a biodegradable, biocompatible polymeric 
nanofibrous matrix having dispersed chondrocytes or adult mesenchymal 
stem cells. More particularly, tissue-engineered cartilage can be 
prepared where the cartilage has a biodegradable and biocompatible 
nanofibrous polymer matrix prepared by electrospinning and a plurality 
of chondrocytes or mesenchymal stem cells dispersed in the pores of the 
matrix. The tissue-engineered cartilage possesses compressive strength 
properties similar to natural cartilage.
    The electrospinning process is a simple, economical means to 
produce biomaterial matrices or scaffolds of ultra-fine fibers derived 
from a variety of biodegradable polymers (Li WJ, et al. J. Biomed. 
Mater. Res. 2002; 60:613-21). Nanofibrous scaffolds (NFSs) formed by 
electrospinning, by virtue of structural similarity to natural 
extracellular matrix (ECM), may represent promising structures for 
tissue engineering applications. Electrospun three-dimensional NFSs are 
characterized by high porosity with a wide distribution of pore 
diameter, high-surface area to volume ratio and morphological 
similarities to natural collagen fibrils (Li WJ, et al. J. Biomed. 
Mater. Res. 2002; 60:613-21). These physical characteristics promote 
favorable biological responses of seeded cells in vitro and in vivo, 
including enhanced cell attachment, proliferation, maintenance of the 
chondrocytic phenotype (Li WJ, et al. J. Biomed. Mater. Res. 2003; 67A: 
1105-14), and support of chondrogenic differentiation (Li WJ, et al. 
Biomaterials 2005; 26:599-609) as well as other connective tissue 
linage differentiation (Li WJ, et al. Biomaterials 2005; 26:5158-5166). 
The invention based on cell-nanofiber composite represents a candidate 
engineered tissue for cell-based approaches to cartilage repair.
    Application: Cartilage repair and methods for making tissue-
engineered cartilage.
    Developmental Status: Electrospinning method is fully developed and 
cartilage has been synthesized.
    Inventors: Wan-Ju Li and Rocky Tuan (NIAMS).
    Publications: The invention is further described in:
    1. W-J Li, et al. Engineering controllable anisotropy in 
electrospun biodegradable nanofibrous scaffolds for musculoskeletal 
tissue engineering. J Biomech. 2007;40(8):1686-1693.
    2. W-J Li, et al. Fabrication and characterization of six 
electrospun poly(alpha-hydroxy ester)-based fibrous scaffolds for 
tissue engineering applications. Acta Biomater. 2006 Jul;2(4):377-385.
    3. CK Kuo, et al. Cartilage tissue engineering: its potential and 
uses. Curr Opin Rheumatol. 2006 Jan;18(1):64-73. Review.
    4. W-J Li, et al. Multilineage differentiation of human mesenchymal 
stem cells in a three-dimensional nanofibrous scaffold. Biomaterials. 
2005 Sep;26(25):5158-5166.
    Patent Status: U.S. Provisional Application No. 60/690,998 filed 15 
Jun 2005 (HHS Reference No. E-116-2005/0-US-01); PCT Application No. 
PCT/US2006/0237477 filed 15 Jun 2006 (HHS Reference No. E-116-2005/0-
PCT-02)
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Methods for Preparing Complex Multivalent Immunogenic Conjugates

    Description of Invention: Claimed in this application are novel 
methods for preparing complex multivalent immunogenic conjugates and 
conjugate vaccines. The multivalent conjugates and conjugate vaccines 
are synthesized by conjugating mixtures of more than one polysaccharide 
at a desired ratio of the component polysaccharides to at least one 
carrier protein using hydrazide chemistry. Because of the high 
efficiency of hydrazide chemistry in conjugation, the polysaccharides 
are effectively conjugated to the carrier protein(s) so that the 
resulting complex synthesized vaccine conjugate products, without 
requiring tedious and complicated purification procedures such as 
chromatography and/or ammonium sulfate precipitation, are efficacious 
in inducing antibodies in mice against each component polysaccharide. 
The methods claimed in this application simplify the preparation of 
multivalent conjugate vaccines by utilizing simultaneous conjugation 
reactions in a single reaction mixture or batch that includes at least 
two immunogenic-distinct polysaccharides. This single-batch 
simultaneous reaction eliminates the need for multiple parallel 
synthesis processes for each polysaccharide vaccine conjugate component 
as employed in conventional methods for making multivalent conjugate 
vaccines.

[[Page 4601]]

    Application: Cost effective and efficient manufacturing of 
conjugate vaccines.
    Inventors: Che-Hung Robert Lee (CBER/FDA)
    Patent Status: PCT Application No. PCT/US2007/006627 filed 16 Mar 
2007 (HHS Reference No. E-085-2005/0-PCT-02).
    Licensing Status: Available for exclusive or non-exclusive 
licensing. The technology is not available for licensing in the field 
of use of multivalent meningitis vaccines.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Bioreactor Device and Method and System for Fabricating Tissue

    Description of Invention: Available for licensing and commercial 
development is a millifluidic bioreactor system for culturing, testing, 
and fabricating natural or engineered cells and tissues. The system 
consists of a millifluidic bioreactor device and methods for sample 
culture. Biologic samples that can be utilized include cells, 
scaffolds, tissue explants, and organoids. The system is microchip 
controlled and can be operated in closed-loop, providing controlled 
delivery of medium and biofactors in a sterile temperature regulated 
environment under tabletop or incubator use. Sample perfusion can be 
applied periodically or continuously, in a bidirectional or 
unidirectional manner, and medium re-circulated.
    Advantages: The device is small in size, and of conventional 
culture plate format.
    Provides the ability to grow larger biologic samples than 
microfluidic systems, while utilizing smaller medium volumes than 
conventional bioreactors. The bioreactor culture chamber is adapted to 
contain sample volumes on a milliliter scale (10 [mu]L to 1 mL, with a 
preferred size of 100 [mu]L), significantly larger than chamber volumes 
in microfluidic systems (on the order of 1 [mu]L). Typical microfluidic 
systems are designed to culture cells and not larger tissue samples.
    The integrated medium reservoirs and bioreactor chamber design 
provide for, (1) concentration of biofactors produced by the biologic 
sample, and (2) the use of smaller amounts of exogenous biofactor 
supplements in the culture medium. The local medium volume (within the 
vicinity of the sample) is less than twice the sample volume. The total 
medium volume utilized is small, preferably 2 ml, significantly smaller 
than conventional bioreactors (typically using 500-1,000 mL).
    Provides for real-time monitoring of sample growth and function in 
response to stimuli via an optical port and embedded sensors. The 
optical port provides for microscopy and spectroscopy measurements 
using transmitted, reflected, or emitted (e.g., fluorescent, 
chemiluminescent) light. The embedded sensors provide for measurement 
of culture fluid pressure and sample pH, oxygen tension, and 
temperature.
    Capable of providing external stimulation to the biologic sample, 
including mechanical forces (e.g. fluid shear, hydrostatic pressure, 
matrix compression, microgravity via clinorotation), electrical fields 
(e.g., AC currents), and biofactors (e.g., growth factors, cytokines) 
while monitoring their effect in real-time via the embedded sensors, 
optical port, and medium sampling port.
    Monitoring of biologic sample response to external stimulation can 
be performed non-invasively and non-destructively through the embedded 
sensors, optical port, and medium sampling port. Testing of tissue 
mechanical and electrical properties (e.g., stiffness, permeability, 
loss modulus via stress or creep test, electrical impedance) can be 
performed over time without removing the sample from the bioreactor 
device.
    The bioreactor sample chamber can be constructed with multiple 
levels fed via separate perfusion circuits, facilitating the growth and 
production of multiphasic tissues.
    Application: Cartilage repair and methods for making tissue-
engineered cartilage.
    Development Stage: Electrospinning method is fully developed and 
cartilage has been synthesized.
    Inventors: Juan M. Taboas (NIAMS), Rocky S. Tuan (NIAMS), et al.
    Patent Status: U.S. Provisional Application No. 60/701,186 filed 20 
Jul 2005 (HHS Reference No. E-042-2005/0-US-01); PCT Application No. 
PCT/US2006/028417 filed 20 Jul 2006, which published as WO 2007/012071 
on 25 Jan 2007 (HHS Reference No. E-042-2005/0-PCT-02)
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Monoclonal Antibodies Against Orthopoxviruses

    Description of Invention: Concerns that variola (smallpox) virus 
might be used as a biological weapon have led to the recommendation of 
widespread vaccination with vaccinia virus. While vaccination is 
generally safe and effective for prevention of smallpox, it is well 
documented that various adverse reactions in individuals have been 
caused by vaccination with existing licensed vaccines. Vaccinia immune 
globulin (VIG) prepared from vaccinated humans has historically been 
used to treat adverse reactions arising from vaccinia immunization. 
However, VIG lots may have different potencies and carry the potential 
to transmit other viral agents.
    Chimpanzee Fabs against the B5 and A33 outer extracellular membrane 
proteins of vaccinia virus were isolated and converted into complete 
mAbs with human gamma1 heavy chain constant regions. The two mAbs 
displayed high binding affinities to B5 and A33. The mAbs inhibited the 
spread of vaccinia virus as well as variola virus (the causative agent 
of smallpox) in vitro, protected mice from subsequent intranasal 
challenge with virulent vaccinia virus, protected mice when 
administered 2 days after challenge, and provided significantly greater 
protection than that afforded by VIG.
    Application: Prophylactics or therapeutics against orthopoxviruses.
    Developmental Status: Preclinical studies have been performed.
    Inventors: Zhaochun Chen, Robert Purcell, Suzanne Emerson, Patricia 
Earl, Bernard Moss (NIAID).
    Publications:
    1. Z Chen, et al. Chimpanzee/human mAbs to vaccinia virus B5 
protein neutralize vaccinia and smallpox viruses and protect mice 
against vaccinia virus. Proc Natl Acad Sci USA. 2006 Feb 7;103(6):1882-
1887. Epub 2006 Jan 25.
    2. Z Chen, et al. Characterization of chimpanzee/human monoclonal 
antibodies to the vaccinia A33 glycoprotein and its variola virus 
homolog in vitro and in a vaccinia mouse protection model. J Virol. 
2007 Jun 20; Epub ahead of print, doi 10.1128/JVI.00906-07.
    Patent Status: PCT Patent Application No. PCT/US2006/048832 filed 
22 Dec 2006 (HHS Reference No. E-145-2004/3-PCT-01); PCT Patent 
Application No. PCT/US2006/048833 filed 22 Dec 2006 (HHS Reference No. 
E-145-2004/4-PCT-01)
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The National Institute of 
Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is 
seeking statements of capability or interest from

[[Page 4602]]

parties interested in collaborative research to further develop, 
evaluate, or commercialize Chimpanzee/human neutralizing monoclonal 
antibodies against orthopoxviruses. Please contact Dr. Robert Purcell 
at 301-496 5090 for more information.

A Method With Increased Yield for Production of Polysaccharide-Protein 
Conjugate Vaccines Using Hydrazide Chemistry

    Description of Invention: Current methods for synthesis and 
manufacturing of polysaccharide-protein conjugate vaccines employ 
conjugation reactions with low efficiency (about twenty percent). This 
means that up to eighty percent of the added activated polysaccharide 
(PS) is lost. In addition, inclusion of a chromatographic process for 
purification of the conjugates from unconjugated PS is required.
    The present invention utilizes the characteristic chemical property 
of hydrazide groups on one reactant to react with aldehyde groups or 
cyanate esters on the other reactant with an improved conjugate yield 
of at least sixty percent. With this conjugation efficiency the 
leftover unconjugated protein and polysaccharide would not need to be 
removed and thus the purification process of the conjugate product can 
be limited to diafiltration to remove the by-products of small 
molecules. The new conjugation reaction can be carried out within one 
or two days with reactant concentrations between 1 and 25 mg/mL at PS/
protein ratios from 1:2 to 3:1, at temperatures between 4 and 40 
degrees Centigrade, and in a pH range of 5.5 to 7.4, optimal conditions 
varying from PS to PS.
    Application: Cost effective and efficient manufacturing of 
conjugate vaccines.
    Inventors: Che-Hung Robert Lee and Carl E. Frasch (CBER/FDA)
    Patent Status: U.S. Patent Application No. 10/566,899 filed 01 Feb 
2006, claiming priority to 06 Aug 2003 (HHS Reference No. E-301-2003/0-
US-10); U.S. Patent Application No. 10/566,898 filed 01 Feb 2006, 
claiming priority to 06 Aug 2003 (HHS Reference No. E-301-2003/1-US-
02); International rights available.
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

[gamma]PGA Conjugates for Eliciting Immune Responses Directed Against 
Bacillus anthracis and Other Bacilli

    Description of Invention: This invention claims immunogenic 
conjugates of a poly-[gamma]-glutamic acid ([gamma]PGA) of B. 
anthracis, or of another bacillus that expresses a [gamma]PGA that 
elicit a serum antibody response against B. anthracis, in mammalian 
hosts to which the conjugates are administered. The invention also 
relates methods which are useful for eliciting an immunogenic response 
in mammals, particularly humans, including responses which 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. The vaccines of this invention are 
designed to confer specific immunity against infection with B. 
anthracis, and to induce antibodies specific to B. anthracis 
[gamma]PGA. The B. anthracis vaccine is composed of non-toxic bacterial 
components, suitable for infants, children of all ages, and adults.
    Inventors: Rachel Schneerson (NICHD), Stephen Leppla (NIAID), John 
Robbins (NICHD), Joseph Shiloach (NIDDK), Joanna Kubler-Kielb (NICHD), 
Darrell Liu (NIDCR), Fathy Majadly (NICHD).
    Publication: R Schneerson, et al. Poly (gamma-D-glutamic acid) 
protein conjugates induce IgG antibodies in mice to the capsule of 
Bacillus anthracis: a potential addition to the anthrax vaccine. Proc 
Natl Acad Sci USA. 2003 Jul 22;100(15):8945-50.
    Patent Status: U.S. Patent Application No. 10/559,825 filed 02 Dec 
2005, claiming priority to 05 Jun 2003 (HHS Reference No. E-343-2002/0-
US-04).
    Licensing Status: Available for licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

Oligodeoxynucleotide and its Use To Induce an Immune Response

    Description of Invention: This invention comprises 
oligodeoxynucleotides (ODNs) having at least 10 nucleotides with an 
unmethylated central CpG motif that are immunostimulatory in humans. 
The inventors have shown that the various ODNs of this invention 
(having different CpG motifs and backbones) induce immune responses 
from human non-B and B cells. The motif that stimulates non-B cells 
induces production and release of multiple T cell cytokines and 
chemokines; specifically, the Th1 cytokine IFN-gamma, which facilitates 
the development of a cytotoxic T cell response. In contrast, the motif 
that stimulates B cells induces production and release of various 
cytokines, including, but not limited to IL-6, which supports a Th2 
antibody response. The inventors have generated in vitro and ex vivo 
data showing the ODNs of this invention have utility in precisely 
regulating the type and magnitude of the immune response in human 
cells. The present invention has multiple therapeutic uses, including 
but not limited to cancer, vaccine adjuvants, treating autoimmune 
disorders and immune system deficiencies, as well as an anti-infective 
agent and in combination with any antisense therapy.
    Inventors: Dennis Klinman (FDA), Daniela Verthelyi (FDA), Kenji 
Ishii (NINDS).
    Patent Status: U.S. Patent Application No. 11/595,211 filed 09 Nov 
2006, claiming priority to 12 Apr 1999 (HHS Reference No. E-147-1999/0-
US-05).
    Licensing Status: Available for licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

A Method of Immunizing Humans Against Salmonella Typhi Using a Vi-rEPA 
Conjugate Vaccine

    Description of Invention: This invention is a method of 
immunization against typhoid fever using a conjugate vaccine comprising 
the capsular polysaccharide of Salmonella typhi, Vi, conjugated through 
an adipic dihydrazide linker to nontoxic recombinant exoprotein A 
(rEPA) from Pseudomonas aeruginosa. The three licensed vaccines against 
typhoid fever, attenuated S. typhi Ty21a, killed whole cell vaccines 
and Vi polysaccharide, have limited efficacy, in particular for 
children under 5 years of age, which make an improved vaccine 
desirable.
    It is generally recognized that an effective vaccine against 
Salmonella typhi is one that increases serum anti-Vi IgG eight-fold six 
weeks after immunization. The conjugate vaccine of the invention 
increases anti-Vi IgG, 48-fold, 252-fold and 400-fold in adults, in 5-
14 years-old and 2-4 years-old children, respectively. Thus this is a 
highly effective vaccine suitable for children and should find utility 
in endemic regions and as a traveler's vaccine. The route of 
administration can also be combined with routine immunization. In 2-5 
years old, the protection against typhoid fever is 90% for 4 years. In 
school age children and in adults the protection could mount to

[[Page 4603]]

completer protection according to the immunogenicity data.
    Application: Immunization against Salmonella typhi for long term 
prevention of typhoid fever in all ages.
    Developmental Status: Conjugates have been synthesized and clinical 
studies have been performed. The synthesis of the conjugates is 
described by Kossaczka, et al. in Infect Immun. 1997 June;65(7):2088-
2093. Phase III clinical studies are described by Mai, et al. in N Engl 
J Med. 2003 October 2; 349(14):1390-1391. Dosage studies are described 
by Canh, et al. in Infect Immun. 2004 Nov; 72(11):6586-6588.
    A safety and immunogenicity study in infants are under way. The aim 
is to administer the conjugate vaccine with routine infant 
immunization. Preliminary results shows the vaccine is safe in 2 months 
old infants.
    Inventors: Zuzana Kossaczka, Shousun C. Szu, and John B. Robbins 
(NICHD).
    Patent Status: U.S. Patent 6,797,275 issued 28 Sep 2004 (HHS 
Reference No. E-020-1999/0-US-02); U.S. Patent Application No. 10/
866,343 filed 10 Jun 2004 (HHS Reference No. E-020-1999/0-US-03); U.S. 
Patent Application No. 11/726,304 filed 20 Mar 2007 (HHS Reference No. 
E-020-1999/0-US-04).
    Licensing Status: Available for non-exclusive licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].
    Collaborative Research Opportunity: The National Institute of Child 
Health and Human Development, Laboratory of Developmental and Molecular 
Immunity, is seeking statements of capability or interest from parties 
interested in collaborative research to further develop, evaluate, or 
commercialize A Method of Immunizing Humans Against Salmonella Typhi 
Using a Vi-rEPA Conjugate Vaccine. Please contact John D. Hewes, Ph.D., 
at 301-435-3121 or [email protected] for more information.

    Dated: January 10, 2008.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
 [FR Doc. E8-1232 Filed 1-24-08; 8:45 am]
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