[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
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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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