BIO2009 Federal Science and Opportunities Track

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BIO2009 Federal Science and Opportunities Track
Hot Federal Biotechnologies Available for
Collaboration and Licensing Tuesday, May 19,
2009 1000AM 1130AM You will hear about the
innovative, cutting-edge research being conducted
at Federal laboratories in the field of
Biotechnology
Session Chair Vio Conley (National Cancer
Institute, NIH) Presenters Melissa Maderia
(National Cancer Institute, NIH) Rosemary Walsh
(National Institute of Allergy and Infectious
Diseases, NIH) John Hewes (National Cancer
Institute, NIH) Suzanne Seavello Shope (Centers
for Disease Control and Prevention)
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Technology Transfer at National Institutes of
Health (NIH) Food and Drug Administration (FDA)
Centers for Disease Control (CDC)

• Work with Investigators on IP issues
• Employee Invention Reports (EIR)
• Transactional Agreements (CDA, MTA, CTA, CRADA)
• Patent prosecution
• Licensing/Enforcement
• Policy
• Marketing

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Research Tools Available from the Public Health
Service
Many technologies are not patented, but are
instead classified as Research Tools

• Research Tools may include
• Not usually advertised or marketed
• Described in investigators publication
• Freely available to non-profits and academia
• Available via license to for-profit entities
• NIH Research Tools Policy

Peptides/Proteins
Animal Models
Peptides/Proteins
Animal Models
Peptides/Proteins
Animal Models
Antibodies
Antibodies
Antibodies
Nucleic Acids/Vectors
Nucleic Acids/Vectors
Nucleic Acids/Vectors
Assays
Cell Lines
Assays
Cell Lines
Assays
Cell Lines
Small Molecules
Libraries
Small Molecules
Libraries
Small Molecules
Libraries

and more!

and more!
http//ott.od.nih.gov/policy/research_tool.html
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In Stock Cell Lines
Genotoxin-Detecting Cell Lines Myung (NHGRI),
HHS Ref. No. E-108-2008/0 Cell lines expressing
fluorescent ELG1, involved in DNA repair useful
as a screening tool to detect genotoxic agents.
BRCA2 Cell Lines Sharan et al. (NCI), HHS
Ref. No. E-261-2007/0 Eleven murine cell lines
expressing wild-type or mutant BRCA2 PAM212
Epidermal Keratinocyte Cell line - Yuspa (NCI),
HHS Ref. No. B-003-1999/0 For studies of
inflammation and cancer TNF-Sensitive Leukemia
Cell Lines - Chan et al. (NIAID), HHS Ref. No.
E-289 2003 For screening of drugs that inhibit
TNF-induced cell death
There are many more available cell lines!
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In Stock Nucleic Acids and Vectors
Recombineering Shuttle Vector Casellas et al.
(NIAMS), HHS. Ref. No. E-026-2009/0 Highly
efficient vector for modifying Bacterial
Artificial Chromosomes (BACs) Bitter Taste
Receptor Haplotypes Drayna (NIDCD), HHS Ref.
Nos. E-222-2003/2 and E-169-2001/0 22 receptors
and gt100 different haplotypes High-Throughput E.
coli Expression Vectors Waugh (NCI), HHS
Ref. No. E-041-2006/0 Vectors for producing
maltose binding protein and hexahistidine-double
tagged fusion proteins, to facilitate protein
stability and purification Thermostable Y-Family
Polymerases Woodgate et al. (NICHD), HHS
Ref. No. E-166-2004/2 For amplification of
damaged DNA
There are many more available nucleic acids and
vectors!
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In Stock Mouse Models

• Interferon-alpha Mouse Model - Kottilil et al.
  (NIAID/NCI/NIHCC),
• HHS Ref. No. E-106-2009/0
• Overexpresses Interferon-Alpha Receptor 2 model
  for hepatitis, as well as other diseases where
  type-1 interferon plays a role
• T Cell Receptor Mouse Model Restifo et al.
  (NCI), HHS Ref. No. E-187-2008/0
• Expresses a class II-restricted T cell receptor
  (TCR) recognizing TRP-1 (Tyrosinase Related
  Protein-1) useful for the development of new
  tumor immunotherapies
• Proadrenomedullin Mouse Model - Cuttitta (NCI),
  HHS Ref. No. E-099-2004/0
• Floxed (conditional knockout) mouse model for
  cancer, hypertension, and diabetes
• ARNT Mouse Model Gonzalez (NCI), HHS Ref. No.
  E-047-2007/0
• Floxed (conditional knockout) mouse model for
  cancer, diabetes, and inflammation
• Conditional LRRK2 transgenic Mouse Model Cai
  (NIA), HHS Ref. No. E-015-2009/0
• Tet-responsive model for Parkinsons disease and
  other inherited diseases caused by LRRK2
  mutations.

There are more mouse models for a variety of
diseases and conditions!
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In Stock Antibodies
Tuberculosis Monoclonal Antibody Parra et al.
(FDA), HHS Ref. No. E-103-2008/0  Recognizes
PE-PGRS proteins from M. tuberculosis useful for
research, or as a diagnostic tool. Monoclonal
Antibodies for Chromosomal Segregation Monitoring
Jeang (NIAID), HHS Ref. No. E-119-2003/0 Recogn
ize MAD1,a human spindle assembly checkpoint
protein involved in chromosomal segregation
Natural Killer Cell Monoclonal Antibodies
Ortaldo et al. (NCI), HHS Ref. No.
B-015-1997/0 Useful for studies of Natural
Killer cell activation and signal transduction
clones 12A8 (Ly49A/D), 4D11(Ly49G2),and 4E5
(Ly49D) Tetanus Toxin Monoclonal Antibodies
Shapiro et al. (FDA), HHS Ref. No.
E-061-2009/0 Recognize Tetanus Toxin Heavy Chain
Fragment C Arf GAP Polyclonal Antibodies
Randazzo et al. (NCI), HHS Ref. No. E-220-2008/0
(and others) Arf GAP proteins are involved in
cancer cell invasion into normal tissues
antisera against several family members
available. Kidney Transporter Polyclonal
Antibodies Knepper (NHLBI), HHS Ref. No.
E-253-2008/0, E-254-2008/0, E-255-2008/0 and
E-268-2008/0 Polyclonal antisera against kidney
proteins NHE3, NCC, NKCC2, UTA1, involved in
water homeostasis
There are many more available antibodies!
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Generation and validation of a highly selective
and versatile rabbit monoclonal antibody against
the receptor tyrosine kinase ErbB4 Detlef
Vullhorst and Andres Buonanno Section of
Molecular Neurobiology, National Institute of
Child Health and Human Development
Technology

• A monoclonal antibody (Ab-10) was derived from
• rabbits immunized with a fragment of the
  intracellular
• domain of ErbB4 of mouse origin fused to GST
• Ab-10 selectively reacts with ErbB4 of human,
  rat and
• mouse origin in Western blots,
  immunoprecipitation,
• immunofluorescence, immunohistology and
  ELISA

Value Proposition
Figure Ab-10 in Western blotting (A) and
immuno-histology (B,C).Adult mouse hippocampal
sections isolated from wildtype (WT) and ErbB4
knockout (KO) mice.

• ErbB4 is of broad interest to scientists in the
  fields of
• cancer biology and neuroscience, and is
  emerging as a risk
• gene for psychiatric disorders
  (schizophrenia and BiP disorder)

• There is a scarcity of commercially available
  and well-characterized antibodies selective for
  ErbB4
• that perform in a variety of different
  immunological applications

RD Status completed available for
licensing/collaboration
Reference E-171-2009/0 Collaboration Contact
Information Andres.Buonanno_at_nih.gov Licensing
Contact Information Mojdeh.Bahar_at_nih.gov
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To obtain copies of these slides, please visit
http//ttc.nci.nih.gov Or http//www.ott.nih.gov
/BIO2009 Or http//www.cdc.gov/tto keyword BIO
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BIO2009 Federal Science and Opportunities Track
Hot Federal Biotechnologies Available for
Collaboration and Licensing
Melissa Maderia, Ph.D. Technology Transfer
Specialist Technology Transfer Center National
Cancer Institute Competitive Service Center in
support of National Institute of Neurological
Disorders and Stroke maderiam_at_mail.nih.gov http
//ttc.nci.nih.gov/ http//tto.ninds.nih.gov/
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A Splice Isoform of Carboxypeptidase E (CPE)
Promotes and Predicts Metastasis in Human
Cancers Y Peng Loh et al. SCN, National Institute
of Child Health and Human Development
CPE splice variant CPE-?N predicts metastasis in
various human cancers

• Easy detection by RT-PCR or immunostaining
• Specific for cancer tissues of different origin
• Prediction with higher prognostic significance
  than other biomarkers for metastasis

Value Proposition

• Biomarker for metastasis in various cancers
  Liver, colon, prostate breast, head and neck
• High CPE-?N levels in primary tumors able to
  predict future metastasis/recurrence in liver and
  
• colon cancer patients
• Suppression of CPE-?N expression inhibits tumor
  growth and metastasis

• RD Status
• Detection of CPE-?N by RT-PCR in patient blood
  underway for early diagnosis of cancer
• Prediction of metastasis in patients with various
  other cancers underway
• Available for licensing/collaboration.

IP Status U.S. provisional patent application
No.61/080,508 filed 2008
Reference E-234-2008 Collaboration Contact
Information Y. Peng Loh, PhD. lohp_at_mail.nih.gov L
icensing Contact Information Jennifer Wong. B.A.
wongje_at_mail.nih.gov
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Novel thermostable Y-family DNA polymerases
applications for the PCR amplification of
damaged or ancient DNAs R. Woodgate, J.P.
McDonald and W. Yang Laboratory of
Genomic Integrity, National Institute of Child
Health and Human Development

• Thermostable lesion-bypassing
• DNA polymerases
• Easily expressed and purified
• Augment recovery of forensic
• and ancient DNAs
• Optimized chimeric enzymes

Enhanced PCR recovery of Alu sequences from UV
lesion-containing human genomic DNA samples
utilizing a blend of Taq and Y-family DNA
polymerases
PCR amplification by Y-family DNA Polymerases
Value Proposition

• Y-family DNA polymerases synthesize DNA through
  a variety of replication-blocking DNA lesions
• Thermostable Y-family DNA polymerases substitute
  for Taq DNA polymerase in PCR DNA amplification
  reaction
• Inclusion of Y-family DNA polymerases in
  standard PCR reactions augments recovery of
  lesion-containing DNA
• samples, such as those commonly found in
  forensic or ancient DNA molecular applications
• Y-family DNA polymerases can incorporate labeled
  dNTPs including fluorescent labels
• Y-family DNA polymerases can be used in
  mutagenic PCR applications

RD Status Expression and purification of
enzymes and amplification of lesion-containing
DNA demonstrated. Available for
licensing/collaboration.
IP Status PTC application filed May 2005
United States Patent Application 20080193925,
Reference E- Collaboration Contact
Information Dr. Roger Woodgate,
woodgate_at_nih.gov Licensing Contact Information
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MRI Techniques Providing Solutions in NeuroImaging
Jeff Duyn, Alan Koretsky, and Afonso Silva
Lab of Functional and Molecular Imaging,
National Institute of Neurological Disorders and
Stroke
Technology
Multi-channel and birdcage coils arrays can be
used to obtain improved homogeneity.

• Passive circuitry control to improve homogeneity
• Novel RF coil designs provide improve signal to
  noise
• Motion Detection for improved MR Imaging

RD Status

• Improvement of neuroimaging through basic
  development
• New techniques for the acquisition and analysis
• of MRI images
• Improved MRI images that provide anatomical and
  functional contrast
• Improved signal to noise and shorter acquisition
  times

before
after
Inductively matched approach for decoupling MRI
coil arrays.
Reference E-020-2007 E-099-2006
E-144-2008 For Collaboration, please contact
Melissa Maderia, Ph.D 301-451-3943 or
maderiam_at_mail.nih.gov For Licensing, please
contact John Stansberry, Ph.D. 301-435-5236 or
stansbej_at_mail.nih.gov
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Microfabricated Magnetic Nanostructures
Alan Koretsky, John Moreland, Steve Dodd, and
Gary Zabow National Institute of Neurological
Disorders and Stroke National Institute of
Standards and Technology
Technology

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

• New imaging modality based on magnetic geometry
  rather than chemical structure
• Engineered to appear as different effective
  colors when resolved using MRI as opposed to
  strictly grey-scale contrast of existing MRI
  agents
• Enable in vivo labeling and tracking of multiple
  different types of cells simultaneously
• Act as radio-frequency probes of various
  physiological conditions

RD Status

• Several geometries have been microfabricated with
  varying materials of different properties
• Biological compatibility and uptake in cells in
  progress

IP Status PCT application claiming priority to
provisional application filed 17
April 2008 Reference E-081-2008 For
Collaboration, please contact Melissa Maderia,
Ph.D 301-451-3943 or maderiam_at_mail.nih.gov For
Licensing, please contact John Stansberry,
Ph.D. 301-435-5236 or stansbej_at_mail.nih.gov
Chemical shift imaging (CSI) of demonstration
1.25 mm-diameter particles magnetized by B0.
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The current invention describes a simulation
procedure in which several parameters can be used
to model microarray image formation.

• The model can be used to measure the
• performance of imaging procedures designed to
  
• measure the true intensity of spots on
  microarrays.
• The simulation procedure can be incorporated
  into
• hardware/software for ease of use.

Value Proposition

• Efficient and accurate microarray signal
  analysis
• Improved detection of weak targets and improved
• local background estimation for microarray
  spots

Classification error surfaces from simulated
intensity and ratio data plotted to demonstrate
the domains where expression ratio or expression
intensity data performs better than the other
(Attoor, S., et al, Bioinformatics, 20(16)
p.2513-2520, 2004).
RD Status Late stage microarray imaging and
evaluation of gene expression. Available for
exclusive or non-exclusive licensing. Publication
Y Balagurunathan, ER Dougherty, Y Chen, ML
Bittner, JM Trent. Simulation of cDNA microarrays
via a parameterized random signal model. J Biomed
Opt. 2002 Jul7(3)507523. IP Status U.S.
Patent No. 7,363,169 issued April 22,
2008 Reference E-089-2003/0 Contact Jeffrey
A. James, Ph.D. 301-435-5474 jeffreyja_at_mail.nih.
gov
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CYCLIZED NGR PEPTIDE B.J. Wood et al.
Clinical Center Radiology and Imaging Sciences,
Interventional Radiology Research Laboratory
Design and synthesis of novel cyclic NGR (cNGR)
ligands for targeting angiogenic tumor vasculature
cNGR

• Advantages
• Easily attached to nano drug
• delivery vehicles such as liposomes
• Permanently cyclized
• Avoid disulfide bridge
• Greater affinity than linear versions
• Molecular imaging applications

Targeted liposome

• Value Proposition
• Able to be attached to nano
• delivery systems without disulfide
• bridge formation on surface
• Greater affinity as a monomer
• and on the surface of liposome
• than common linear forms of NGR

Improved avidity
RD Status Synthesis and characterization
demonstrated. Animal studies are underway. IP
Status U.S. Provisional Application filed June
2008 Reference E-147-2008 Contact Michael
Shmilovich shmilovm_at_mail.nih.gov, 301-435-5019

• Retains drug release properties from temperature
  
• sensitive liposomes (TSL)
• Opens a local-regional therapy (TSL) to a more
  whole
• body treatment with metastasis targeting

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Encapsulated Nanoparticles for Computed
Tomography Imaging Ronald M. Summers et al.
Clinical Center Virtual Endoscopy and
Computer-Aided Diagnosis Laboratory, Radiology
and Imaging Sciences
Technology

• Characterize polyps mucinous layer using UEA-1
  lectin.
• Fabricate polymerized liposomes with
• conjugated UEA-1 targeting moiety.
• Utilize polymerized liposomes to detect
• polyps in APCMin/ mouse tissue with
• optical and CT imaging.

Normal Cells
Polyp
Polyp
Value Proposition
Optical Imaging of UEA-1 conjugated polymerized
liposomes (targeted) binding the surface of a
polyp found in APCMin/ tissue.

• Potential to improve detection of polyps at
• optical and virtual colonoscopy.
• Potential to enable noninvasive histopathologic
  assessment of polyps to determine
• which need to be removed. Majority of polyps
  do not need to be removed but
• currently no way to tell which do.

RD Status Discovery.
IP Status US Application 61/064,086 filed 15
February 2008
Reference E-254-2007
Contact Michael Shmilovich shmilovm_at_mail.nih.gov
301-435-5019
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Automated Identification of Ileocecal
Valve Ronald M. Summers et al.
Clinical Center Virtual Endoscopy and
Computer-Aided Diagnosis Laboratory, Radiology
and Imaging Sciences
A method for automated identification of
ileocecal valve in CT colonography images
Value Proposition

• Improve specificity of computer-
• aided detection of polyps by including
  this technique as
• part of a CAD system for
• analyzing virtual colons.

Ileocecal valve of a 51 y.o. male detected by
this method. Average Attenuation -131 HU Volume
2.7 cc. (Left) Transaxial CTC images. (Middle)
Lung window settings showing the ICV. (Right)
Marked CTC image showing computer generated
boundary of ICV.

• Increase physician attention to
• polyp candidates in the cecum.

RD Status Licensed.
IP Status US Applications 60/510,640
(10/10/2003) 7,440,601 (10/21/2008)
Reference E-174-2003
Contact Jeffrey James jeffreyja_at_mail.nih.gov,
301-594-7219
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Virtual Colonoscopy via Wavelets Ronald M.
Summers et al. Clinical
Center Virtual Endoscopy and Computer-Aided
Diagnosis Laboratory, Radiology and Imaging
Sciences
Wavelet-based technologies that reduce false
positive detections in computer-aided detection
(CAD) of polyps in CT colonography (CTC).
Value Proposition

• Significantly reduce false positives by 41.5
• in a CTC CAD system for detecting 6-9 mm
• polyps.

• Potential to improve specificity of CTC and
• reduce unnecessary colonoscopies.

The search path to efficiently locate a good
viewpoint. The dotted line represents the colon
centerline, C is the polyp centroid, D is the
nearest centerline point to C, and PN is the
average normal of the polyp surface.
RD Status Ready for Implementation in CAD
Software.
IP Status US Application 11/685,127 (3/12/2007)
Reference E-314-2006
Contact Jeffrey James jeffreyja_at_mail.nih.gov,
301-594-7219
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Nanoparticles for Imaging and Treatment of Brain
Tumors H. Sarin National Institute of Biomedical
Imaging and Bioengineering, Clinical Center
Nanoparticles selectively cross the blood-brain
tumor barrier (BBTB) of brain tumors but not the
normal brain-brain barrier (BBB)

• Advantages
• Particle Size Adjustable to achieve
• the desired particle blood half-life
• Particle size Only increases
• 1 to 2 nanometers per generation (G)
• Particle Exterior Wide variety of
• small agents can be attached to the
• functional groups on the nanoparticle
• exterior
• Multifunctional Same particle can be
• used for both imaging and drug
• delivery
• RD Status
• Discovery
• Animal brain tumor regression studies
• underway

IP Status U.S. Provisional Application No.
61/055,328 filed 22 May 2008 Reference
E-063-2008 Contact Surekha Vathyam, Ph.D.
vathyams_at_mail.nih.gov, 301-435-4076
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Non-Invasive Device and Methods for Swallowing
Recovery Treatment and Training for Volitional
Swallowing
Christy Ludlow Laryngeal and Speech Section,
National Institute of Neurological Disorders and
Stroke

• Advantages of Technology
• button press to initiate sensory stimulation and
  coordinate
• muscular movement to permit volitional
  swallowing
• sensor for monitoring pressure on the patients
  larynx and a
• swallowing motion detector
• methods to produce vibratory stimulation,
  pressure stimulation,
• auditory stimulation, temperature stimulation,
  visual stimulation,
• olfactory stimulation, taste stimulation, or a
  combination of these

• Indications and Uses
• initiation and retraining of swallowing
• for these indications
• post-stroke
• post-extubation
• neurologically impaired
• throat cancer
• prevention of aspiration pneumonia

Prototype of device currently being tested in
patients

• Current State of Development
• Two on-going clinical trials at the NIH to test
  device in
• dysphagic patients
• Future Development Needed
• Manufacture, market, and distribute device
• Technological improvements based on current
  clinical trial results

Patents PCT/US2007/007993 (device) filed 30
March 2007
PCT/US2006/025535 (method) filed 30 June 2006
Reference E-194-2006 E-251-2005 For
Licensing and Collaborative Opportunities contact
Heather Gunas 301-451-3944
guansh_at_mail.nih.gov
Device consists of -- Device controller
(including circuit and battery) Motor
(vibrator) Adjustable, flexible
keel Patient-controlled switch
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Selective Killing of Cancer Cells Wenge Zhu
Melvin L. DePamphilis Program on Genomics of
Differentiation National Institute of Child
Health and Human Development

• Technology
• Small interfering RNA (siRNA) targeted against
  Geminin, a key regulator of DNA replication
• Induces unscheduled DNA re-replication in human
  cancer cells
• DNA re-replication spontaneously triggers
  apoptosis (cell death)
• NO effect on normal cells

• Value Proposition
• Simple, target specific designer drug
• Effective against wide range of
• cancer cells

• RD Status
• Animal study in progress
• Available for licensing
• IP Status U.S. Provisional Application No
  61/106,465
• Collaboration Contact Information
  depamphm_at_mail.nih.gov
• Licensing Contact Information Betty Tong
  (tongb_at_mail.nih.gov)

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Therapeutic Use of E-selectin For Treatment of
Multiple Sclerosis and Prevention of Secondary
Stroke Hallenbeck, Shukaliak and Takeda National
Institute of Neurological Disorders and Stroke
Intranasal delivery of E-selectin
E-selectin over-expression is a necessary
component of many inflammation-associated
autoimmune disorders, and suppression of this
pro-inflammatory signal has shown beneficial
effects in mouse models for Multiple Sclerosis
(MS) and Secondary Stroke.
Value Proposition

• Multi market therapeutic platform based on nasal
  delivery with a tolerization dosing regimen.
• Safety and efficacy trials may be conducted in
  collaboration with NINDS

• RD Status
• In vivo and in vitro data are available
• Collaborative opportunity NINDS is actively
  seeking partners for further research,
• development, and commercialization

IP Status National stage, with three issued
patents in Secondary Stroke
Reference E-153-2005 (MS) and E-237-1999
(secondary stroke) Collaboration Contact
Information Laurie Arrants, arrantsL_at_ninds.nih.g
ov, 301-435-3112 Licensing Contact Information
Dr. Norbert Pontzer,pontzern_at_mail.nih.gov ,
301-435-5502.
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Drug Treatment for Neurological Disorders
Jill Heemskerka, Jacquie Shukaliakb, and Gene
Majorc National Institute of Neurological
Disorders and Stroke

• Compounds for the Treatment of Stop
  Codon Diseasesa
• A library of compounds for the treatment of
  various neurological disorders, such as Spinal
• Muscular Atrophy Muscular Dystrophy, and
  Cystic Fibrosis.
• Operate via translational read-through of
  non-sense stop codons to produce full length
  protein
• Pass through the blood-brain barrier

Tempol
Analogs based on Indoprofen Template

• Method of Treating Disease Involving
  Myelin and/or Axonal Lossb
• Use of Tempol for treatment of Multiple Sclerosis
  (MS), and other neurodegenerative diseases
• Use of Tempol to modulate the generation and
  limit the damage caused by autoimmune T cells

• Tranilast as an Effective Inhibitor of
  JC Virus and BK Virus Infectionc
• Use in treatment and prevention of polyomavirus
  infection in immunocompromised patients
• Used for prevention of PML in treatment therapies
  for MS patients

Reference E-133-2006 E-187-2007 E-290-2007
E-179-2007 For Collaboration or Licensing,
please contact Melissa Maderia 301-451-3943
maderiam_at_mail.nih.gov
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Use of Razoxane for the Treatment of Alzheimer's
DiseaseNigel H. GreigDrug Design and
Development Section, Laboratory of Neurosciences
NATIONAL INSTITUTE ON AGING
Technology Razoxane and other bisdioxopiperazines
reduce amyloid-beta peptide levels, reduce
aggregation of alpha-synuclein and tau protein,
and reduce abnormal protein folding or
aggregation for the treatment of Alzheimers
Disease (AD) and related diseases with protein
aggregation pathology. Value Proposition
Razoxane has been approved for human use and
could be more quickly developed as a treatment
for Alzheimers Disease, Parkinsons Disease and
other diseases. RD Status Clinical safety
data and pre-clinical efficacy data for treatment
of AD. Available for licensing. IP Status PCT
Application No. PCT/US2007/013607 filed 08 Jun
2007. Reference E-216-2007/0 Licensing
Contact Norbert J. Pontzer, Ph.D., J.D.
pontzern_at_mail.nih.gov
26
Method of Treating or Preventing Oxidative
Stress-related Diseases Nigel H. Greig et
al.Drug Design and Development
Section Laboratory of Neurosciences, NATIONAL
INSTITUTE ON AGING
Technology Uric acid analogs with improved
anti-oxidative and solubility properties for use
as free radical scavengers or antioxidants.
Novel uric acid analogs for use as antioxidants
to help reduce the risk of stroke, neurological
diseases and assisting with wound repair.
Value Proposition A number of diseases are
associated with oxidative stress including
Alzheimer's disease, ischemic stroke, heart
disease, cancer, hepatitis, and autoimmune
disease. (stroke and neurodegenerative diseases,
wound healing and cardiovascular diseases) RD
Status Pre-clinical IP Status PCT Application
No. PCT/US2007/076597 filed 23 Aug 2007 Reference
No. E-059-2006/0 Collaboration Contact John
Hewes, Ph.D. , hewesj_at_mail.nih.gov Licensing
Contact Norbert J. Pontzer, Ph.D., J.D.,
pontzern_at_mail.nih.gov
27
Novel Inhibitors of p53 for Treatment of
Neurodegenerative Disorders, Myocardial
Infarction and Other Tissue InsultsNigel H.
Greig et al.
Drug Design and Development Section, Laboratory
of Neurosciences, NATIONAL INSTITUTE ON AGING
Technology Novel inhibitors of p53 and methods
of using these inhibitors for the prevention or
treatment of the stress related tissue
degeneration observed in Alzheimer's disease,
myocardial infarction and stroke. Value
Proposition In vitro and ex vivo studies
demonstrated that p53 inhibition protected nerve
cells from toxic insults that otherwise induced
programmed cell death. In a rat model of stroke,
p53 inhibition produced a 50 reduction in stroke
volume. RD Status Pre-clinical IP Status
PCT/US01/21504 filed 06 Jul 2001 Reference
No. E-222-2000/0 Contact Norbert Pontzer,
Ph.D., J.D. Email pontzern_at_mail.nih.gov
28
Novel Benztropine Analogs for Treatment of
Cocaine Abuse and Other Mental Disorders Amy H.
Newman, Mu-fa Zou, Jonathan L. Katz The
Medicinal Chemistry and Psychobiology Sections,
National Institute on Drug Abuse
Technology Novel benztropine analogs and methods
of using these analogs for treatment of mental
and conduct disorders such as cocaine abuse,
narcolepsy, ADHD, obesity and nicotine abuse.
Value Proposition Drug leads for treatment of
cocaine abuse, ADHD, nicotine abuse, obesity, and
other dopamine-related disorders RD Status
Pre-clinical IP Status U.S. Patent Application
No. 12/063,072 filed 06 Feb 2008 Reference
E-234-2005/1 Licensing Contact Charlene A.
Sydnor, Ph.D. for licensing. Email
sydnorc_at_mail.nih.gov
29
Inhibitors of CD25 to Treat Autoimmune Diseases
and Tumors Bibiana Bielekova National Institute
of Neurological Disorders and Stroke

• Description of Technology
• Therapeutics treatment of Multiple Sclerosis,
  uveitis, and certain cancers
• Provides methods and compositions for selectively
  blocking CD25 on T cells or dendritic cells
• Ability to exhibit superior specificity and
  minimal side-effects
• Applications
• Therapeutics for autoimmune diseases
• Therapeutics for tumors
• Development Status
• Early stage

• Scientific Findings
• Mature dendritic cells (mDC) use CD25 for
  trans-presentation of IL-2
• Blockade of CD25 on the surface of mDCs abrogates
  T cell proliferation
• CD25 expression on T cells is dispensable for
  their proliferation
• CD 25 expression limits effector T cell survival

Patent Status U.S. Provisional Application No.
61/201,589 filed 12 Dec 2008 Reference
E-007-2009 For Collaboration, please contact
Martha Lubet, Ph.D, 301-4435-3120
lubetm_at_mail.nih.gov For Licensing, please
contact Suryanarayana (Sury) Vepa, Ph.D., J.D.
301-435-5020 vepas_at_mail.nih.gov
30
A Novel Efficient Technology for Targeted
Delivery of siRNA Arya Biragyn, Ph.D, et
al. National Institute on Aging (NIA), Laboratory
of Immunology
Novel compositions and methods for delivering
inhibitory oligonucleotides to cells in a
targeted and efficient manner

• Cell surface receptor targeting ligand, such as
  a chemokine or
• cytokine, fused to a domain that binds an
  inhibitory oligonucleotide
• Inhibitory oligonucleotide is efficiently
  delivered to the cell
• expressing the cell surface receptor
  targeting ligand

Value Proposition
Figure caption

• In vivo targeted delivery of inhibitory RNAs
  instead of
• systemic delivery
• Long term repression of target gene expression
• Treatment of cancers and autoimmune diseases

Eradication of CEM tumors established in NOD-SCID
mice using novel siRNA delivery method. A and B,
Macroscopic appearance of tumors treated with
control (A) or TARC-PE38 (B) at day 27 posttumor
challenge. C and D, Microscopic appearance
(HE-stained slides, original magnification,
x200) of tumors treated with control (C) and
TARC-PE38 (D, margin of necrotic area) at day 27
posttumor challenge.. Representative data from
two independent experiments with comparable data
with eight mice per group.
RD Status Animal studies in progress. The NIA
is currently seeking licensing partners and/or
collaborative partners for further development.
IP Status PCT application claiming priority to
provisional application filed 15
April 2008
Reference E-051-2008 Collaboration Contact
Information Nicole Darack Guyton, Ph.D.,
darackn_at_mail.nih.gov Licensing Contact
Information Surekha Vathyam, Ph.D.
vathyams_at_mail.nih.gov
31
Treatment of Cocaine-Induced Fetal Brain Injury
Chun-Ting Lee and William J. Freed Cellular
Neurobiology Research Branch National Institute
on Drug Abuse
Technology Methods of using cytochrome P450
inhibitors to treat or prevent cocaine-induced
fetal brain injury, as well as methods for
screening for inhibitory drugs to treat or
prevent cocaine-induced fetal brain injury.
Value Proposition Useful in diagnosing and
treating fetal brain injury caused by cocaine
exposure. It is estimated that one percent of
pregnant women use cocaine at some point in their
pregnancies. RD Status Pre-clinical IP
Status PCT Application No. PCT/US2008/055998
filed 06 Mar 2008 Reference No. E-025-2007/0
Licensing Contact Charlene A. Sydnor, Ph.D.
Email sydnorc_at_mail.nih.gov
32
Targets for Treatment of Neurological Disorders
Stem Cell Proliferation and Survival
Ron McKay Laboratory of Molecular Biology,
National Institute of Neurological Disorders and
Stroke
Stem cell survival and proliferation has been
demonstrated in vitro and in neuronal precursor
cells in vivo via several targets, including the
Notch ligand, growth factors (FGF-2 or insulin),
as well as a population of stem cells expressing
STAT3 phosphorylated at serine 727.

• Applications
• Increased generation of stem cells in vitro for
  treatment of neurological disorders
• Treatment of neurodegenerative disorders, such as
  Parkinsons disease, stroke, and
• spinal cord injury

• Development Status
• In vitro method described in Nature 2006 Aug
  17442(7104)823-826.
• In vivo method validated in rodent models of
  Parkinsons disease and stroke.

Reference E-001-2003 E-182-2007
E-239-2005 For Collaboration, please contact
Martha Lubet, Ph.D, 301-4435-3120
lubetm_at_mail.nih.gov For Licensing, please
contact Fatima Sayyid, M.H.P.M., 301-435-4521
sayyidf_at_od.nih.gov
33
Zscan4 A Gene Critical for Early Embryonic
Development Minoru S.H. Ko, M.D., Ph.D., et
al. National Institute on Aging (NIA), Laboratory
of Genetics
Zscan4 plays an essential role in early embryonic
development, with potential applications for the
development of stem cell therapeutics and
assisted reproduction technologies.

• Inhibition of Zscan4 expression
• using siRNA delays progression
• from the 2-cell to the 4-cell
• stage of embryogenesis and
• produces blastocysts that fail to
• implant in the mouse embryo.
• Invention discloses methods of
• promoting blastocyst
• outgrowth of ES cells and
• methods of identifying ES cells
• expressing Zscan4.

Insert figure here
Figure caption
A schematic illustration of Zscan4 expression
patterns.
RD Status Early stage development. Technology
is available for licensing.
Value Proposition

• Development of stem cell therapeutics
• Assisted reproduction technologies and
• studies of early embryonic development

IP Status PCT application claiming priority to
provisional application filed 26 March
2007 Reference E-088-2007
Contact Tara Kirby, Ph.D. tarak_at_mail.nih.gov
34
The Neuregulin/ErbB Signaling Pathway as a Novel
Drug Target to Treat Schizophrenia and Bipolar
Disorder Andres Buonanno Section of
Molecular Neurobiology, National Institute of
Child Health and Human Development
Technology

• Identification of novel drug targets in the
  NRG-ErbB signaling
• pathway to treat cognitive deficits
  associated with schizophrenia
• (Scz) and bipolar (BiP) disorder, such as
  working memory.
• Develop novel markers to diagnose and classify
  distinct types and
• phases Scz and BiP disorder.
• Use of novel knockout mice and
  lentivirus-targeted shRNAs to
• identify and test novel drugs.

Value Proposition

• Neuregulin, and its receptor ErbB4, are the most
  reproducibly
• known at risk genes for Scz and BiP
  disorder.

• All drugs presently used are D2-type dopamine
  receptor antagonist that
• treat positive symptoms (i.e.,
  hallucinations) but fail to treat the most
• debilitating aspects of the disease, such
  as deficits in executive functions.

RD Status in progress, searching collaborations
Figure Effects of Neuregulin (NRG) and a small
molecule antagonist on dopamine release (A) and
long-term potentiation(LTP), a form of memory
(B,C). A) NRG causes dramatic dopamine release
?, which is blocked by antagonist ?. B) NRG
reverses LTP (?,blue), as compared to control
(?,black). C) LTP reversal by NRG is prevented by
small molecule inhibitor (?,blue).
IP Status PCT/US2007/75724
Reference E-304-2005/0-PCT-02 Collaboration
Contact Information Andres.Buonanno_at_nih.gov Licen
sing Contact Information Norbert.Pontzer_at_nih.gov
35
The various pharmaceutical compositions and
methods for the treatment of Schistosomiasis in
mammals are based on a number of compounds
derived from 1,2,5-oxadiazole that are potent
inhibitors of thioredoxin glutathione reductase
(TGR), a critical parasite redox protein.
Technology

• TGR as an appropriate molecular target for
• pharmacological intervention
• TGR potential chemotherapy for schistosomiasis

Value Proposition

• selected oxidiazole-2-oxides are being evaluated
  in advanced ADME/T assays and are being
  formulated for oral dosing experiments.

RD Status To date, the general
oxidiazole-2-oxide chemotype described here has
shown efficacy in animal models. Available for
licensing. Publications Sayed, A. A. Simeonov,
A. Thomas, C. J. Inglese, J. Austin, C. P.
Williams, D. L. Identification of oxadiazoles as
new drug leads for the control of
schistosomiasis. (2008) Nature Med. 14,
407-412. IP Status U.S. Provisional Application
No. 61/088,970 filed August 14, 2008 Reference
E-162-2008/0 Contact Cristina
Thalhammer-Reyero, Ph.D., MBA 301-435-4507
thalhamc_at_mail.nih.gov
36
Design and synthesis of novel Triazolothiadiazines
and Triazolopyridazines as PDE4 Inhibitors

• Low nM inhibition of PDE4 Isozymes.
• Low nM inhibition in cells.
• High selectivity for PDE4.
• Extensive SAR investigations.
• Known DMPK data.

• Value Proposition
• Easily scalable synthesis for gram
• scale production.
• Excellent SAR understanding will
• provide room for modulation of
• bioavailability properties.
• Physiologically proven target for
• drug discovery programs including
• from asthma, chronic obstructive pulmonary
  disease (COPD) and memory enhancement.
• RD Status Synthesis, SAR, biochemical and
  cell based activity demonstrated. Animal studies
  are underway.
• Publication AP Skoumbourdis et al.
  Identification of a potent new chemotype for the
  selective inhibition of PDE4.
• Bioorg Med Chem Lett. 2008 Feb
  1518(4)12971303.
• IP Status U.S. Patent Application filed
  January 8, 2009. Application No.
  PCT/US/2009/000105
• Contact Fatima Sayyid, M.H.P.M.
  301-435-4521 fatima.Sayyid_at_nih.hhs.gov

37
Parasitic protozoa are responsible for a wide
variety of infections in both humans and animals.

• novel triazine and purine compounds for the
• treatment and prevention of

• mammalian protozoal diseases
• (including African trypanosomiasis)
• Chagas disease
• opportunistic infections

notable inhibitors of cruzain
Value Proposition

• Novel compounds against the cysteine proteases,
  cruzain and rhodesain
• Compounds possess low nanomolar inhibitory
  potential against cruzain and rhodesain

RD Status In vitro and in vivo data are
available upon request and upon execution of an
appropriate confidentiality agreement. IP Status
U.S. Provisional Application No. 61/199,763 filed
Nov 19, 2008 Reference E-267-2008 Contact
Kevin W. Chang, Ph.D. 301-435-5018
changke_at_mail.nih.gov
38
Contact Info
Melissa Maderia, Ph.D. maderiam_at_mail.nih.gov 301-
451-3943 To obtain copies of these slides,
please visit http//ttc.nci.nih.gov
or http//ott.od.nih.gov or http//www.cdc.gov/t
to keyword BIO
39
BIO2009 Federal Science and Opportunities Track
Hot Federal Biotechnologies Available for
Collaboration and Licensing
Rosemary C. Walsh, Ph.D. Technology Development
Associate Office of Technology Development Natio
nal Institute of Allergy and Infectious
Diseases rcwalsh_at_niaid.nih.gov
40
Novel Approach to Vaccine Design
Peter D. Kwong, et al. National Institute of
Allergy and Infectious Diseases

• Epitope-Transplant Scaffolds and Their Use
• Epitopes are removed from whole antigen
• and placed on a protein scaffold
• Epitopes retain their 3-D structure even when
  missing
• some of the surrounding original antigen sequence
  
• Model system utilizes one or more
• gp120 epitopes from HIV-1
• Value Proposition
• Novel, structure-based approach for vaccine
  design
• may succeed in maximizing generation of
  neutralizing antibodies
• Method can be generalized to non-HIV vaccines
• RD Status Pre-clinical
• IP Status Filed US EP WO 2008/025015
• Reference E-302-2006/1
• Collaboration Contact Marguerite Miller
  millermarg_at_niaid.nih.gov
• Licensing Contact Cristina Thalhammer-Reyero
  thalhamc_at_mail.nih.gov

Conserved neutralization epitope on HIV-1 gp120
41
Potential HIV Vaccine Immunogens
Peter D. Kwong, et al. National Institute of
Allergy and Infectious Diseases

• HIV Vaccine Immunogens and Immunization
  Strategies to Elicit Broadly Neutralizing
  Anti-HIV-1 Against the Membrane-Proximal
  Ectodomain of HIV gp41
• Generate an immune response against HIV-1 gp41.
• Binds to the broadly neutralizing antibodies 2F5,
  4E10, and Z13.
• IP Status Filed US, WO 2005/111079
  Reference E-218-2004/0
• Conformationally Stabilized HIV Envelope
  Immunogens, and Triggering HIV-1 to Reveal
  Cryptic V3-Loop Epitopes
• Stabilizing HIV envelope gp120 improves its
  immunogenicity
• Stabilization is accomplished by non-naturally
  occurring disulfide bonds
• IP Status Filed US, WO 2007/030518
  Reference E-324-2005/3
• HIV gp120 Crystal Structure and its Use to
  Identify Immunogens
• Immunogens present HIV-1 epitopes that bind
  neutralizing antibodies
• Do not induce other antibodies that might
  interfere with epitope binding
• IP Status Filed US EP, WO 2007/030637
  Reference E-280-2006/1
• RD Status Pre-clinical
• Collaboration Contact Marguerite Miller, MBA
  millermarg_at_niaid.nih.gov
• Licensing Contact Cristina Thalhammer-Reyero
  thalhamc_at_mail.nih.gov

42
Chikungunya Vaccine
G. Nable National Institute of Allergy and
Infectious Diseases

• Use of Virus-Like Particles (VLPs) as Vaccine
  against Chikungunya Virus
• Structural Proteins (core, E1 and E2) were
  expressed in 293 producer cells as VLPs
• Immunization of mice with VLPs
• Generates neutralizing antibodies against both
  homologous and heterologous virus strains
• Ab titer is 2 orders of magnitude greater than
  that achieved with DNA vaccines
• Value Proposition
• Efficient method of developing vaccines against
  Chikungunya virus
• Strategy amenable to developing vaccines against
  other pathogens
• RD Status Animal (mouse and non-human primate)
  data available
• IP Status Filed US Provisional Pat. Application
  61/201,118 on12/5/2008
• Reference E-004-2009
• Collaboration Contact Marguerite Miller
  millermarg_at_niaid.nih.gov
• Licensing Contact Cristina Thalhammer-Reyero
  thalhamc_at_mail.nih.gov

43
Chlamydial Vaccine
H. D. Caldwell National Institute of Allergy and
Infectious Diseases

• Polymorphic Membrane Protein D (PmpD) as vaccine
  candidate
• gt99 Sequence identity between serovariants
• Surface located antigen
• Antibodies neutralize all 15 serotypes in vitro
• Can be expressed in E.coli and Modified
• Vaccinia Ankara (MVA)
• Value Proposition
• Antigen common to all serotypes
• Vaccination preferable to antibiotic intervention
  which can compromise development of immunity
• RD Status preclinical
• IP Status Filed PCT application (WO 2008/048348)
  on1/9/07, priority date1/9/06
• Reference E031-2006
• Collaboration Contact Anna Amar
  aamar_at_niaid.nih.gov
• Licensing Contact Peter Soukas
  soukasp_at_mail.nih.gov

44
Anti-tick Vaccine
M. Kotsyfakis, J.M.C Ribeiro, J.G. Valenzuela, J.
Anderson, J. Andersen National Institute of
Allergy and Infectious Diseases S. Karim, T.N.
Mather at the University of Rhode Island

• Sialostatin L2 Mediation Controls Blood Feeding
  Success
• of Ixodes scapularis
• I. scapularis main vector of Lymes Disease
• Salivary secretions crucial for pathogen
  transmission
• Use of Sialostatin 2 as vaccine in guinea pigs
• Decrease in feeding ability of tick nymphs
• Increase in rejection rate of nymphs
• Increase in inflammation of guinea pigs
• Value Proposition
• Use of Sialostatin L2 as anti-tick vaccine will
  confer protection from tick nymphs and pathogens
  transmitted by tick bites
• Potential as part of a multi-component vaccine
• Environmentally friendly alternative to
  acaricides(pesticides)
• RD Status Animal (Guinea Pig) data available
• IP Status Filed PCT (WO 2009/017689) on
  7/25/2008, priority date 8/2/2007
• Reference E-289-2007
• Collaboration Contact S. Dana Hsu
  dhsu_at_niaid.nih.gov
• Licensing Contact RC Tang tangrc_at_mail.nih.gov

45
Novel Targets Against Staphlycocci Bacterial
Infections
M. Otto National Institute of Allergy and
Infectious Diseases

• Phenol-soluble modulin (PSM) polypeptides
• Secreted peptides that recruit, activate and
  lyse human neutrophils
• Eliminate main cellular defense against S. aureus
  infection
• High PSM expression gives methicillin resistant
  S. aureus infections contracted in community
  settings greater virulence that MRSA found in
  health care settings
• Deletion of encoding gene cluster (psm?) in
  Staphlycocci is associated with reduced capacity
  to form lesions and kill mice
• Application
• Target for development of new classes of
  antibiotics and vaccines against MRSA
• RD Status Animal data available
• IP Status Filed International application on
  5/8/2008 priority date6/6/2007
• Reference E-239-2007/2-PCT-01
• Collaboration Contact Johanna Schneider
  schneiderjs_at_niaid.nih.gov
• Licensing Contact Cristina Thalhammer-Reyero
  thalhamc_at_mail.nih.gov

46
Platelet Aggregation Inhibitor
E. Calvos, et al. National Institute of Allergy
and Infectious Diseases

• Aegyptin, a collagen binding protein
• Selectively inhibits collagen platelet
  aggregation
• Blocks interaction of collagen with its major
  ligands
• Willebrand factor
• Glycoprotein VI (GPVI)
• Integrin a2ß1
• Applications
• Adjuvant to clot busting therapeutics
• Prevention/treatment of cardiovascular/thrombotic
  disease
• Treatment for patients undergoing invasive cardio
  procedures
• May play role in treatment of pancreatic
  carcinoma
• RD Status Pre-clinical development
• IP Status Filed US Provisional Applications
  60/198,629 on 7/9/2007 and
• 60/982,241 on 10/24/2007
• Reference E-1722007/1
• Collaboration Contact S. Dana Hsu
  dhsu_at_niaid.nih.gov
• Licensing Contact Jennifer Wong
  wongje_at_mail.nih.gov

47
Mono-amine oxidase inhibitors (MAOi) for
treatment of herpes simplex infection
T. Kristie, et al. National Institute of Allergy
and Infectious Diseases

• MAOi(s) prevent HSV infection and may prevent
  periodic reactivation from latency
• Herpes viruses are repressed by host chromatin
  structures that wrap the viral genome
• Enzymes (LSD1) are recruited to halt repression
• LSD1 is inhibited by MAOi(s) expression of viral
  genes is inhibited
• Application
• May also prevent significant lytic replication of
  other herpes viruses
• May reduce viral infection during transplant
• Other more specific drugs targeted to LSD1 may
  prevent other viral infections
• RD Status Pre-clinical
• IP Status Filed US Provisional 61/111,109 on
  11/4/2008
• Reference E275-2008
• Collaboration Contact Christopher Freeman
  freemanch_at_niaid.nih.gov
• Licensing Contact Cristina Thalhammer-Reyero
  thalhamc_at_mail.nih.gov

48
Faster Cryo-Sample Processing
D. Dorward, V. Nair, E. Fischer National
Institute of Allergy and Infectious Diseases

• Device/method for microwave assisted cryo-sample
  processing
• Reduced time required for freeze substitution
  fixation from 2-6 days to 2-3 hours
• Equivalent preservation of morphology when
  compared to traditional freeze substitution
  fixation
• Superior preservation of morphology when compared
  to conventional fixation techniques using passive
  diffusion
• Value Proposition
• Enables microscopic examination of samples within
  hours of collection (eg. during surgery)
• Enables analysis of hydrogels not well preserved
  by traditional X-linking reagents
• Biological-cartilage, synovial fluid,
  extracellular matrices, biofilm
• Commercial-contact lenses, prosthetic devices
• RD Status Looking for partner to develop device
  prototypes
• IP Status Filed US Provisional Pat. Application
  61/112,575 on 11/7/2009
• Reference E-238-2008
• Collaboration Contact Christopher Freeman
  freemanch_at_niaid.nih.gov
• Licensing Contact RC Tang tangrc_at_mail.nih.gov

49
For information on these and other opportunities,
please contact Rosemary C. Walsh, Ph.D.
Phone[phone] Emailrcwalsh_at_niaid.nih.gov
To obtain copies of these slides, please visit
http//ttc.nci.nih.gov or http//ott.od.nih.gov
keyword BIO
50
Hot Technologies
at the National Cancer Institute John D.
Hewes, Ph.D.Technology Transfer
SpecialistTechnology Transfer CenterTel. (301)
435-3121email hewesj_at_mail.nih.govhttp//ttc.nci
.nih.gov
51
Why Collaborate ?
BUSINESS MODELS BASED ON COLLABORATION
From PriceWaterHouseCoopers Pharma 2020
Challenging Business Models, retrieved from
www.pwc.com/pharma
52
Why Collaborate with NCI?
TTC maintains an e-mail service to notify you of
new technology opportunities. Register at
http//ttc.nci.nih.gov
53
Marketed NCI-Licensed Technologies
Abbott/Others AIDS Test
Kits Schering AG/Berlex Fludara BMS
Videx (ddI) BMS Taxol
(paclitaxel) Roche Hivid (ddC) Millennium
Velcade Cell Therapeutics
Zevalin Amgen Kepivance 20/20
GeneSystems Multi-Replica Blotting
Kit Molecular Devices PixCell Laser Capture
Microdissection Merck Gardasil Medimmun
e Oncology NeuTrexin Monogram Biosciences
PhenoSenseTM HIV phenotype tests Isis
Vitravene Ortho Biotech Prezista
Biovest/Accentia BiovaxID Squirrel
Free Products Squirrel-free
capsaicin-treated birdseed Developed under
NCI CRADA
NCI has produced important drugs and technologies
through collaborations and licensing with the
private sector.
54
Chemical programming of antibodies through
selenocysteine
Christoph Rader, Ph.D. Experimental
Transplantation and Immunology Branch
Technology Cancer Therapeutics
(immunoconjugate/antibody-drug conjugate) An
engineered selenocysteine near the C-terminus of
an antibody, or antibody fragment, covalently
links the antibody and a small synthetic molecule
to produce hybrid molecules.
Value Proposition Combines advantages of small
synthetic molecules with monoclonal antibodies
Small synthetic molecules Monoclonal
antibodies Unlimited structural diversity
Prolonged and predictable in vivo half life Reach
recessed sites on macromolecules Potent
interference with macromolecular Straightforward
manufacturing interactions
Adjustable valence and effector
activity RD Status Pre-clinical in vivo
(mouse) toxicity, administration routes, and
pharmacokinetics IP Status PCT/US2008/059135
(4/2/08) U.S. Patent Application 60/909,665
(4/2/07) Reference E-146-2007 Collaboration
Contact John D. Hewes, Ph.D., hewesj_at_mail.nih.gov
, 301-435-3121 Licensing Contact Jennifer Wong,
wongje_at_mail.nih.gov, 301-435-463
55
Nitric Oxide-releasing Polymers
Larry K. Keefer, Ph.D. Laboratory of Comparative
Carcinogenesis

• Technology NO-releasing BiomaterialsPolymers
  containing the X-N2O2- functional group
  (NONOates, diazeniumdiolates) spontaneously
  generate bioactive NO at their surfaces on
  contact with physiological media for up to a
  month or more. NIH inventors have now produced
  and tested polymers in which the NO-releasing
  group is attached directly to the carbon backbone
  of many of the important workhorse industrial
  materials used in medicine to produce
• Polyacrylonitriles and Polyurethanes (tubing,
  textiles, vascular grafts, hemofilters, ECMO,
  antithrombotics, inhibition of neointimal
  hyperplasia)
• Polydiazeniumdiolated cyclic polyamines
  (multiphasic NO release)
• Polysaccharides (Cotton for bandages, surgical
  fabric, wound healing, tissue repair)
• Imidoester- and amidine-derived
  diazeniumdiolates (Antibacterial additives,
  platelet storage)
• Value Proposition Attaching NO-releasing groups
  onto biomaterials, which deliver NO to specific
  sites without systemic exposure to NO or its
  potentially toxic by-products
• RD Status Pre-clinical proof-of-concept
• IP Status U.S. Patents issued, U.S. and
  foreign patent applications
• Reference E-189-2002, E-276-2002, E-188-2004,
  E-248-2005, E-279-2005
• Collaboration Contact John D. Hewes,
  hewesj_at_mail.nih.gov, 301-435-3121
• Licensing Contact Steve Standley, 301-435-4074,
  sstand_at_mail.nih.gov

56
Prognostic for Prostate Cancer Treatment
William D. Figg, Pharm. D. Medical Oncology Branch

• Technology Cancer Biomarkers for
  androgen-independent prostate cancer (AIPC)
• a. CYP1B13 A genetic marker called CYP1B13 can
  predict survival in patients with prostate cancer
  prior to treatment with docetaxel. This genetic
  marker can be measured in DNA obtained from a
  blood sample. This technology can be potentially
  used to predict the patient's propensity to
  respond to docetaxel treatment when being treated
  for AIPC, which remains the second leading cause
  of cancer death in men in developed nations,
• b. SLCO1B3 Two polymorphic genetic markers in the
  SLCO1B3 gene, measured in genomic DNA obtained
  from a blood sample, can provide a correlation
  between clinical outcome of SLCOlB3 genotype with
  median survival of androgen independent prostate
  cancer. The genotype can also predict
  testosterone uptake, which is useful in clinical
  decisions regarding anti-androgen therapy.
• Value Proposition
• Potential to improve clinical diagnosis and
  prognosis for individual AIPC patients
• RD Status Pre-clinical in vitro analysis of
  patient samples
• IP Status a. U.S.11/991,878 filed 03/11/2008
  b. PCT/US2008/000310 filed 01/08/2008
• Reference a. E-307-2005 b. E-083-2007
• Collaboration Contact John D. Hewes, Ph.D.,
  hewesj_at_mail.nih.gov, 301-435-3121
• Licensing Contact Sabarni K. Chatterjee, Ph.D.,
  chatterjeesa_at_mail.nih.gov, 301-435-5587

57
Methods for Diagnosis and Prognosis of Lymphomas
Louis M. Staudt, M.D., Ph.D. Metabolism Branch

• Technology Microarray diagnostics
• Novel microarray for obtaining gene expression
  profile data for identifying lymphoma types and
  predicting survival in a lymphoma patient
• Established using a human genome gene chip set
  measuring the expression of over 27,000 genes in
  more than 500 lymphoproliferative tumor samples
• Describes a variety of methods for analyzing
  gene expression data obtained from a lymphoma
  sample, and specific algorithms for predicting
  survival and clinical outcome
• Value Proposition
• Allows clinicians to tailor drug treatments to
  an individuals unique lymphoma phenotype
• Enables the diagnosis of lymphoma subtypes that
  are indistinguishable by current methods but that
  are clinically distinct
• Designed to provide an all-in-one method for the
  diagnosis of all lymphomas
• RD Status Pre-clinical proof-of-concept with
  human tissue samples
• IP Status PCT Application No. PCT/US2004/029041
  (9/3/2004)
• Reference E-234-2003
• Collaboration Contact John D. Hewes, Ph.D.,
  hewesj_at_mail.nih.gov, 301-435-3121
• Licensing Contact Sabarni K. Chatterjee, Ph.D.,
  chatterjeesa_at_mail.nih.gov, 301-435-5587

58
Development of Novel Anti-HIV Compounds
Robert Shoemaker, Ph.D. and Alan Rein,
Ph.D. Developmental Therapeutics Program, HIV DRP
Retroviral Replication Laboratory
Technology HIV Therapeutic Active anti-viral
compound Stibavirin comprises aromatic,
antimony-containing compound that was shown to
inhibit viral particle assembly and inhibit the
binding of nucleocapsid protein to nucleic acid.
Also demonstrated was the capability of blocking
HIV-1 viral entry into CD4 cells through binding
to CD4 and inhibiting gp120-CD4 interaction.

• Value Proposition
• The mechanism of anti-HIV action of Stibavirin
  is different from current approved drugs.
• This suggests addition of Stibavirin to HAART
  regimen, in combination treatment of patients
  with AIDS, particularly those who have become
  resistant to other drugs. Well tolerated in
  vivo.
• RD Status Pre-clinical i