[Federal Register Volume 73, Number 118 (Wednesday, June 18, 2008)]
[Notices]
[Pages 34756-34762]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-13669]


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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.

[[Page 34757]]

Use of Amyloid Proteins as Vaccine Scaffolds

    Description of Technology: Amyloid proteins are composed of 
peptides whose chemical properties are such that they spontaneously 
aggregate in vitro or in vivo, assuming parallel or antiparallel beta 
sheet configurations. Amyloid proteins can arise from peptides which, 
though differing in primary amino acid sequences, assume the same 
tertiary and quaternary structures. The amyloid structure presents a 
regular array of accessible N-termini of the peptide molecules.
    Claimed in this application are compositions and methods for use of 
amyloid proteins as vaccine scaffolds, on which peptide determinants 
from microorganisms or tumors may be presented to more efficiently 
generate and produce a sustained neutralizing antibody response to 
prevent infectious diseases or treat tumors. The inventors have arrayed 
peptides to be optimally immunogenic on the amyloid protein scaffold by 
presenting antigen using three different approaches. First, the N-
terminal ends of the amyloid forming peptides can be directly modified 
with the peptide antigen of interest; second, the N-termini of the 
amyloid forming peptides are modified with a linker to which the 
peptide antigens of interest are linked; and third, the scaffold 
amyloid may be modified to create a chimeric molecule.
    Aside from stability and enhanced immunogenicity, the major 
advantages of this approach are the synthetic nature of the vaccine and 
its low cost. Thus, concerns regarding contamination of vaccines 
produced from cellular substrates, as are currently employed for some 
vaccines, are eliminated; the robust stability allows the amyloid based 
vaccine to be stored at room temperature for prolonged periods of time; 
and the inexpensive synthetic amino acid starting materials, and their 
rapid spontaneous aggregation in vitro should provide substantial cost 
savings over the resource and labor-intensive current vaccine 
production platforms.
    Application: Immunization to prevent infectious diseases or treat 
chronic conditions or cancer.
    Development Status: Vaccine candidates have been synthesized and 
preclinical studies have been performed.
    Inventors: Amy Rosenberg (CDER/FDA), James E. Keller (CBER/FDA), 
Robert Tycko (NIDDK).
    Patent Status: PCT Application No. PCT/US2008/059499 filed 04 Apr 
2008, claiming priority to 06 Apr 2007 (HHS Reference No. E-106-2007/0-
PCT-02).
    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 FDA, Division of 
Therapeutic Proteins (CDER) and Office of Vaccines, Division of 
Bacterial Products (CBER) is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize amyloid based vaccines for 
prevention of infectious disease or treatment of malignant states. 
Please contact Amy Rosenberg at [email protected] or (301) 827-
1794 for more information.

Immunostimulatory Combinations of TLR Ligands and Methods of Use

    Description of Technology: New drugs or therapies that act by 
stimulating the immune system, or alternatively inhibiting certain 
aspects of the immune system, may be useful for treating various 
diseases or disorders, for example viral diseases, neoplasias, and/ or 
allergies, and may also have use as vaccine adjuvants. However, 
although adjuvants have been suggested for use in vaccine compositions, 
there is an unmet need for adjuvants that can effectively enhance 
immune response.
    Development of innate and adaptive immunity critically depends on 
the engagement of pattern recognition receptors (PRRs), which 
specifically detect microbial components named pathogen-or microbe-
associated molecular patterns (PAMPs or MAMPs) (1-4). Toll-like 
receptors (TLRs) represent an important group of PRRs that can sense 
PAMPs or MAMPs once in the body. TLRs are widely expressed by many 
types of cells, for example cells in the blood, spleen, lung, muscle 
and intestines.
    The present invention claims immunostimulatory combinations of TLR 
ligands and therapeutic and/or prophylactic methods that include 
administering an immunostimulatory combination to a subject. In 
general, the immunostimulatory combinations can provide an increased 
immune response compared to other immunostimulatory combinations and/or 
compositions. More specifically, combinations of TLR 2, 3 and 9 are 
claimed. The application also describes a novel mechanism for TLR 
synergy in terms of both signaling pathways and cytokine combinations.
    Application: Development of improved adjuvants and/or synergistic 
combinations of adjuvants for vaccines.
    Development Status: Compositions have been synthesized and 
preclinical studies have been performed.
    Inventors: Jay Berzofsky and Qing Zhu (NCI).
    Patent Status: U.S. Provisional Application No. 60/995,212 filed 24 
Sep 2007 (HHS Reference No. E-298-2007/0-US-01).
    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 Cancer Institute's 
Vaccine Branch is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize this invention of synergistic combinations 
of TLR ligands. Please contact John D. Hewes, PhD at 301-435-3121 or 
[email protected] for more information.

Catalytic Domains of [beta](1,4)-galactosyltransferase I Having Altered 
Donor and Acceptor Specificities, Domains That Promote In Vitro Protein 
Folding, and Methods for Their Use

    Description of Technology: [beta](1,4)-galactosyltransferase I 
catalyzes the transfer of galactose from the donor, UDP-galactose, to 
an acceptor, N-acetylglucosamine, to form a galactose-[beta](1,4)-N-
acetylglucosamine bond. This reaction allows galactose to be linked to 
an N-acetylglucosamine that may itself be linked to a variety of other 
molecules. The reaction can be used to make many types of molecules 
having great biological significance. For example, galactose-
[beta](1,4)-N-acetylglucosamine linkages are very important for 
cellular recognition and binding events as well as cellular 
interactions with pathogens, such as viruses. Therefore, methods to 
synthesize these types of bonds have many applications in research and 
medicine to develop pharmaceutical agents and improved vaccines that 
can be used to treat disease.
    The present invention is based on the surprising discovery that the 
enzymatic activity of [beta](1,4)-galactosyltransferase can be altered 
such that the enzyme can make chemical bonds that are very difficult to 
make by other methods. These alterations involve mutating the enzyme 
such that the mutated enzyme can transfer many different types of 
sugars from sugar nucleotide donors to many different types of 
acceptors. Therefore, the mutated [beta](1,4)-galactosyltransferases of 
the invention

[[Page 34758]]

can be used to synthesize a variety of products that, until now, have 
been very difficult and expensive to produce.
    The invention also provides amino acid segments that promote the 
proper folding of a galactosyltransferase catalytic domain and 
mutations in the catalytic domain that enhance folding efficiency and 
make the enzyme stable at room temperature. The amino acid segments may 
be used to properly fold the galactosyltransferase catalytic domains of 
the invention and thereby increase their activity. The amino acid 
segments may also be used to increase the activity of 
galactosyltransferases that are produced recombinantly. Accordingly, 
use of the amino acid segments according to the invention allows for 
production of [beta](1,4)-galactosyltransferases having increased 
enzymatic activity relative to [beta](1,4)-galactosyltransferases 
produced in the absence of the amino acid segments.
    Applications: Synthesis of polysaccharide antigens for conjugate 
vaccines, glycosylation of monoclonal antibodies, and as research 
tools.
    Development Status: The enzymes have been synthesized and 
preclinical studies have been performed.
    Inventors: Pradman K. Qasba, Boopathy Ramakrishnan, Elizabeth 
Boeggeman (NCI).
    Patent Status: U.S. and Foreign Rights Available (HHS Reference No. 
E-230-2002/2).
    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 Cancer Institute's 
Nanobiology Program is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize the use of galactose and modified galactose 
to be linked to an N-acetylglucosamine that may itself be linked to a 
variety of other molecules. Please contact John D. Hewes, Ph.D. at 301-
435-3121 or [email protected] for more information.

Methods of Glycosylation and Bioconjugation

    Description of Technology: Eukaryotic cells express several classes 
of oligosaccharides attached to proteins or lipids. Animal glycans can 
be N-linked via beta-GlcNAc to Asn (N-glycans), O-linked via -GalNAc to 
Ser/Thr (O-glycans), or can connect the carboxyl end of a protein to a 
phosphatidylinositol unit (GPI-anchors) via a common core glycan 
structure. Beta (1,4)-galactosyltransferase I catalyzes the transfer of 
galactose from the donor, UDP-galactose, to an acceptor, N-
acetylglucosamine, to form a galactose-beta (1,4)-N-acetylglucosamine 
bond, and allows galactose to be linked to an N-acetylglucosamine that 
may itself be linked to a variety of other molecules. Examples of these 
molecules include other sugars and proteins. The reaction can be used 
to make many types of molecules having great biological significance. 
For example, galactose-beta (1,4)-N-acetylglucosamine linkages are 
important for many recognition events that control how cells interact 
with each other in the body, and how cells interact with pathogens. In 
addition, numerous other linkages of this type are also very important 
for cellular recognition and binding events as well as cellular 
interactions with pathogens, such as viruses. Therefore, methods to 
synthesize these types of bonds have many applications in research and 
medicine to develop pharmaceutical agents and improved vaccines that 
can be used to treat disease.
    The invention provides in vitro folding methods for a polypeptidyl-
alpha-N-acetylgalactosaminyltransferase (pp-GalNAc-T) that transfers 
GalNAc to Ser/Thr residue on a protein. The application claims that 
this in vitro-folded recombinant ppGalNAc-T enzyme transfers modified 
sugar with a chemical handle to a specific site in the designed C-
terminal polypeptide tag fused to a protein. The invention provides 
methods for engineering a glycoprotein from a biological substrate, and 
methods for glycosylating a biological substrate for use in 
glycoconjugation. Also included in the invention are diagnostic and 
therapeutic uses.
    Application: Enzymes and methods are provided that can be used to 
promote the chemical linkage of biologically important molecules that 
have previously been difficult to link.
    Development Status: Enzymes have been synthesized and 
characterization studies have been performed.
    Inventors: Pradman Qasba and Boopathy Ramakrishnan (NCI).
    Patent Status: U.S. Provisional Application No. 60/930,294 filed 14 
May 2007 (HHS Reference No. E-204-2007/0-US-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 Cancer Institute 
is seeking statements of capability or interest from parties interested 
in collaborative research to further develop, evaluate, or 
commercialize this technology. Please contact John D. Hewes, Ph.D. at 
301-435-3121 or [email protected] for more information.

Alpha 1-3 N-Acetylgalactosaminyltransferases With Altered Donor and 
Acceptor Specificities, Compositions, and Methods of Use

    Description of Technology: The present invention relates to the 
field of glycobiology, specifically to glycosyltransferases. The 
present invention provides structure-based design of novel 
glycosyltransferases and their biological applications.
    The structural information of glycosyltransferases has revealed 
that the specificity of the sugar donor in these enzymes is determined 
by a few residues in the sugar-nucleotide binding pocket of the enzyme, 
which is conserved among the family members from different species. 
This conservation has made it possible to reengineer the existing 
glycosyltransferases with broader sugar donor specificities. Mutation 
of these residues generates novel glycosyltransferases that can 
transfer a sugar residue with a chemically reactive functional group to 
N-acetylglucosarnine (GlcNAc), galactose (Gal) and xylose residues of 
glycoproteins, glycolipids and proteoglycans (glycoconjugates). Thus, 
there is potential to develop mutant glycosyltransferases to produce 
glycoconjugates carrying sugar moieties with reactive groups that can 
be used in the assembly of bio-nanoparticles to develop targeted-drug 
delivery systems or contrast agents for medical uses.
    Accordingly, methods to synthesize N-acetylglucosamine linkages 
have many applications in research and medicine, including in the 
development of pharmaceutical agents and improved vaccines that can be 
used to treat disease.
    This application claims compositions and methods based on the 
structure-based design of alpha 1-3 N-Acetylgalactosaminyltransferase 
(alpha 3 GalNAc-T) mutants from alpha l-3galactosyltransferase (a3Gal-
T) that can transfer 2'-modified galactose from the corresponding UDP-
derivatives due to mutations that broaden the alpha 3Gal-T donor 
specificity and make the enzyme alpha3 GalNAc-T.
    Application: Development of pharmaceutical agents and improved 
vaccines.

[[Page 34759]]

    Development Status: Enzymes have been synthesized and preclinical 
studies have been performed.
    Inventors: Pradman Qasba, Boopathy Ramakrishnan, Elizabeth 
Boeggman, Marta Pasek (NCI).
    Patent Status: PCT Patent Application filed 22 Aug 2007 (HHS 
Reference No. E-279-2007/0-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 Cancer Institute's 
Nanobiology Program is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize structure-based design of novel 
glycosyltransferases. Please contact John D. Hewes, PhD at 301-435-3121 
or [email protected] for more information.

Beta 1,4-Galactosyltransferases With Altered Donor and Acceptor 
Specificities, Compositions and Methods of Use

    Description of Technology: The present invention relates to the 
field of glycobiology, specifically to glycosyltransferases. The 
present invention provides structure-based design of novel 
glycosyltransferases and their biological applications.
    The structural information of glycosyltransferases has revealed 
that the specificity of the sugar donor in these enzymes is determined 
by a few residues in the sugar-nucleotide binding pocket of the enzyme, 
which is conserved among the family members from different species. 
This conservation has made it possible to reengineer the existing 
glycosyltransferases with broader sugar donor specificities. Mutation 
of these residues generates novel glycosyltransferases that can 
transfer a sugar residue with a chemically reactive functional group to 
N-acetylglucosarnine (GlcNAc), galactose (Gal) and xylose residues of 
glycoproteins, glycolipids and proteoglycans (glycoconjugates). Thus, 
there is potential to develop mutant glycosyltransferases to produce 
glycoconjugates carrying sugar moieties with reactive groups that can 
be used in the assembly of bio-nanoparticles to develop targeted-drug 
delivery systems or contrast agents for medical uses.
    Accordingly, methods to synthesize N-acetylglucosamine linkages 
have many applications in research and medicine, including in the 
development of pharmaceutical agents and improved vaccines that can be 
used to treat disease.
    The invention claims beta (1,4)-galactosyltransferase I mutants 
having altered donor and acceptor and metal ion specificities, and 
methods of use thereof. In addition, the invention claims methods for 
synthesizing oligosaccharides using the beta (1,4)-
galactosyltransferase I mutants and to using the beta (1,4)-
galactosyltransferase I mutants to conjugate agents, such as 
therapeutic agents or diagnostic agents, to acceptor molecules. More 
specifically, the invention claims a double mutant beta 1,4 
galactosyltransferase, human beta-1,4-Tyr289Leu-Met344His-Gal-T1, 
constructed from the individual mutants, Tyr289Leu-Gal-T1 and 
Met344His-Gal-T1, that transfers modified galactose in the presence of 
magnesium ion, in contrast to the wild-type enzyme which requires 
manganese ion.
    Application: Development of pharmaceutical agents and improved 
vaccines.
    Development Status: Enzymes have been synthesized and preclinical 
studies have been performed.
    Inventors: Pradman Qasba, Boopathy Ramakrishnan, Elizabeth Boeggman 
(NCI).
    Patent Status: PCT Patent Application filed 22 Aug 2007 (HHS 
Reference No. E-280-2007/0-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 Cancer Institute's 
Nanobiology Program is seeking statements of capability or interest 
from parties interested in collaborative research to further develop, 
evaluate, or commercialize glycosyltransferases. Please contact John D. 
Hewes, Ph.D., Technology Transfer Specialist, NCI, at (301) 435-3121 or 
[email protected].

Bioreactor Device and Method and System for Fabricating Tissue

    Description of Technology: 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 500-1000 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

[[Page 34760]]

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 Status: Electrospinning method is fully developed and 
cartilage has been synthesized.
    Inventors: Juan M. Taboas (NIAMS), Rocky S. Tuan (NIAMS), et al.
    Patent Status: PCT Application No. PCT/US2006/028417 filed 20 Jul 
2006, which published as WO 2007/012071 on 25 Jan 2007; claiming 
priority to 20 Jul 2005 (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].

Cell-Nanofiber Composite Based Engineered Cartilage

    Description of Technology: 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 
lineage 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.
    Development 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: PCT Application No. PCT/US2006/0237477 filed 15 Jun 
2006, claiming priority to 15 Jun 2005 (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].

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

    Description of Technology: 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 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.
    Development Status: Prototype devices have been fabricated and

[[Page 34761]]

preclinical studies have been performed.
    Inventors: Wan-Ju Li, Leon Nesti, Rocky Tuan (NIAMS).
    Patent Status: PCT Application No. PCT/US07/020974 filed 27 Sep 
2007, claiming priority to 27 Sep 2006 (HHS Reference No. E-309-2006/2-
PCT-01).
    Licensing Status: Available for exclusive or non-exclusive 
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 Technology: 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.
    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.
    Development 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. 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.

Recombinant Modified Bacillus anthracis Protective Antigen for Use in 
Vaccines

    Description of Technology: 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 strains, 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.
    Development 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. Patent No. 7,261,900 issued 28 Aug 2007 (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.

[[Page 34762]]

    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 Technology: 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):8945-8950.
    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].

Methods for Conjugation of Oligosaccharides or Polysaccharides to 
Protein Carriers Through Oxime Linkages Via 3-Deoxy-D-Manno-Octulsonic 
Acid

    Description of Technology: This technology comprises new methods 
for the conjugation of O-specific polysaccharides/oligosaccharides (O-
SP/OS) derived from bacterial lipooligosaccharides/ lipopolysaccharides 
(LOS/LPS), after their cleavage from Lipid A, to carrier proteins, to 
serve as potential vaccines. Conjugation is performed between the 
carbonyl group on the terminal reducing end of the saccharide and the 
aminooxy group of a bifunctional linker bound further to the protein.
    The inventors have carried out the reaction under mild conditions 
and in a short time resulting in binding 3-deoxy-D-manno-octulosonic 
acid (KDO) on the sacchride to the protein. These conjugates preserve 
the external non-reducing end of the sacchride, are recognized by 
antisera, and induce immune responses in mice to both conjugate 
components (i.e., the OS and the associated carrier protein).
    Application: Cost effective and efficient manufacturing of 
conjugate vaccines.
    Inventors: Joanna Kubler-Kielb (NICHD), Vince Pozsgay (NICHD), Gil 
Ben-Menachem (NICHD), Rachel Schneerson (NICHD), et al.
    Patent Status: PCT Application No. PCT/US2007/016373 filed 18 Jul 
2007, which published as WO 2008/013735 on 31 Jan 2008; claiming 
priority to 21 Jul 2006 (HHS Reference No. E-183-2005/0-PCT-02).
    Licensing Status: Available for exclusive or non-exclusive 
licensing.
    Licensing Contact: Peter A. Soukas, J.D.; 301/435-4646; 
[email protected].

    Dated: June 10, 2008.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-13669 Filed 6-17-08; 8:45 am]
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