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U.S. Dept. of Health and Human Services ~ National Institutes of Health /2009 BIO 2009 Slide 1 BIO2009 Federal Science and Opportunities Track Hot Federal Biotechnologies Available for Collaboration and Licensing Tuesday, May 19, 2009 10:00AM – 11:30AM 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) ary Walsh (National Institute of Allergy and Infectious Diseases, NI John Hewes (National Cancer Institute, NIH) Suzanne Seavello Shope (Center for Disease Control)

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Page 1: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 1

BIO2009 Federal Science and Opportunities Track

Hot Federal Biotechnologies Available for Collaboration and Licensing

Tuesday, May 19, 2009 10:00AM – 11:30AM

You will hear about the innovative, cutting-edge research being conducted at Federal laboratories in the field of Biotechnology

Session ChairVio Conley (National Cancer Institute, NIH)

PresentersMelissa Maderia (National Cancer Institute, NIH)

Rosemary Walsh (National Institute of Allergy and Infectious Diseases, NIH)John Hewes (National Cancer Institute, NIH)

Suzanne Seavello Shope (Center for Disease Control)

Page 2: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 2

Technology Transfer atNational Institutes of Health (NIH)

Food and Drug Administration (FDA) Centers for Disease Control (CDC)

Technology Transfer atNational Institutes of Health (NIH)

Food and Drug Administration (FDA) Centers for Disease Control (CDC)

Work with Investigators on IP issuesEmployee Invention Reports (EIR)Transactional Agreements (CDA, MTA, CTA, CRADA)

Patent prosecutionLicensing/EnforcementPolicyMarketing

Page 3: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 3

http://ott.od.nih.gov/policy/research_tool.html

Peptides/Proteins

Nucleic Acids/VectorsAssays

Small Molecules

Animal Models

Antibodies

Cell Lines

Libraries

…and more!

Peptides/Proteins

Nucleic Acids/VectorsAssays

Small Molecules

Animal Models

Antibodies

Cell Lines

Libraries

Peptides/Proteins

Nucleic Acids/VectorsAssays

Small Molecules

Animal Models

Antibodies

Cell Lines

Libraries

…and more!

Many technologies are not patented, but are instead classified as Research Tools

Research Tools Available from the Public Health Service

Research Tools may include:

Not usually advertised or marketedDescribed in investigator’s publication

Freely available to non-profits and academiaAvailable via license to for-profit entities

NIH Research Tools Policy

Page 4: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 4

Genotoxin-Detecting Cell Lines – Myung (NHGRI), HHS Ref. No. E-108-2008/0Cell 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-261-2007/0Eleven murine cell lines expressing wild-type or mutant BRCA2

PAM212 Epidermal Keratinocyte Cell line - Yuspa (NCI), HHS Ref. No. B-003-1999/0For studies of inflammation and cancer

TNF-Sensitive Leukemia Cell Lines - Chan et al. (NIAID), HHS Ref. No. E-289 2003For screening of drugs that inhibit TNF-induced cell death

There are many more available cell lines!

In Stock: Cell Lines

Page 5: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 5

There are many more available nucleic acids and vectors!

In Stock: Nucleic Acids and Vectors

Recombineering Shuttle Vector – Casellas et al. (NIAMS), HHS. Ref. No. E-026-2009/0Highly 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 >100 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

Page 6: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 6

There are more mouse models for a variety of diseases and conditions!

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-187-2008/0Expresses 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-099-2004/0Floxed (conditional knockout) mouse model for cancer, hypertension, and diabetes

ARNT Mouse Model – Gonzalez (NCI), HHS Ref. No. E-047-2007/0Floxed (conditional knockout) mouse model for cancer, diabetes, and inflammation

Conditional LRRK2 transgenic Mouse Model – Cai (NIA), HHS Ref. No. E-015-2009/0Tet-responsive model for Parkinson’s disease and other inherited diseases caused by LRRK2 mutations.

Page 7: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 7

There are many more available antibodies!

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-119-2003/0Recognize MAD1,a human spindle assembly checkpoint protein involved in chromosomal segregation

Natural Killer Cell Monoclonal Antibodies – Ortaldo et al. (NCI), HHS Ref. No. B-015-1997/0Useful 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-061-2009/0Recognize 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

Page 8: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 8

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

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

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.

Value Proposition:

Technology:

R&D Status: completed; available for licensing/collaboration

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)

Reference #: E-171-2009/0Collaboration Contact Information: [email protected] Contact Information: [email protected]

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

Page 9: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 9

To obtain copies of these slides, please visit:

http://ttc.nci.nih.gov Or

http://www.ott.nih.gov/BIO2009

Orhttp://www.cdc.gov/tto

keyword: BIO

Page 10: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 10

BIO2009 Federal Science and Opportunities Track

Hot Federal Biotechnologies Available for Collaboration and Licensing

Melissa Maderia, Ph.D.

Technology Transfer SpecialistTechnology Transfer Center

National Cancer Institute

Competitive Service Center in support of National Institute of Neurological Disorders and Stroke

[email protected]://ttc.nci.nih.gov/

http://tto.ninds.nih.gov/

Page 11: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 11

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

R&D StatusDetection of CPE-∆N by RT-PCR in patient blood underway for early diagnosis of cancerPrediction of metastasis in patients with various other cancers underwayAvailable for licensing/collaboration.

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

IP Status: U.S. provisional patent application No.61/080,508 filed 2008

Reference #: E-234-2008Collaboration Contact Information: Y. Peng Loh, PhD. [email protected] Contact Information: Jennifer Wong. B.A. [email protected]

CPE splice variant CPE-∆N predicts metastasis in various human cancers

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

Page 12: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 12

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

PCR amplification by Y-family DNA Polymerases

Value Proposition

R&D Status: Expression and purification of enzymes and amplification of lesion-containing DNA demonstrated. Available for licensing/collaboration.

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

IP Status: PTC application filed May 2005United States Patent Application #: 20080193925, Reference #: E-Collaboration Contact Information: Dr. Roger Woodgate, [email protected] Contact Information:

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

Page 13: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 13

Jeff Duyn, Alan Koretsky, and Afonso Silva Lab of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke

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

Technology

R&D Status

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

Reference #: E-020-2007; E-099-2006; E-144-2008For Collaboration, please contact Melissa Maderia, Ph.D

301-451-3943 or [email protected] For Licensing, please contact John Stansberry, Ph.D.

301-435-5236 or [email protected]

MRI Techniques Providing Solutions in NeuroImaging

Multi-channel and birdcage coils arrays can be used to obtain improved homogeneity.

before after

(GND1)

Zp11

C4

T1

L2

C3

A

C1

L1

M

C2n

preamplifier

Inductively matched approach for decoupling MRI coil arrays.

Page 14: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 14

Alan Koretsky, John Moreland, Steve Dodd, and Gary ZabowNational Institute of Neurological Disorders and Stroke

National Institute of Standards and Technology

Technology

R&D Status

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

IP Status: PCT application claiming priority to provisional application filed 17 April 2008Reference #: E-081-2008For Collaboration, please contact Melissa Maderia, Ph.D

301-451-3943 or [email protected] For Licensing, please contact John Stansberry, Ph.D.

301-435-5236 or [email protected]

Microfabricated Magnetic Nanostructures

Applications: Magnetic Resonance ImagingCancerCardiovascular diseases imagingDrug developmentDrug candidate distribution trackingDiagnosticsMicrofluidics

Chemical shift imaging (CSI) of demonstration 1.25 mm-diameter particles magnetized by B0.

Several geometries have been microfabricated with varying materials of different properties

Biological compatibility and uptake in cells in progress

Page 15: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 15

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:

The current invention describes a simulation procedure in which several parameters can be used to model microarray image formation.

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

R&D 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 Jul;7(3):507–523.

IP Status: U.S. Patent No. 7,363,169 issued April 22, 2008Reference #: E-089-2003/0Contact: Jeffrey A. James, Ph.D.; 301-435-5474; [email protected]

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).

A Parameterized Model for Simulating MicroarraysYidong Chen et al.

Cancer Genetics Branch, NCI

Page 16: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 16

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

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

cNGR

Antibody cNGR

Good binding

cNGRliposome

Linear NGRliposome

Targeted liposome

Improved avidity

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

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

R&D Status: Synthesis and characterization demonstrated. Animal studies are underway.IP Status: U.S. Provisional Application filed June 2008Reference #: E-147-2008Contact: Michael Shmilovich; [email protected], 301-435-5019

Page 17: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 17

Encapsulated Nanoparticles for Computed Tomography Imaging

Ronald M. Summers et al. Clinical Center

Virtual Endoscopy and Computer-Aided Diagnosis Laboratory, Radiology and Imaging Sciences

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.

Optical Imaging of UEA-1 conjugated polymerized liposomes (targeted) binding the surface of a polyp found in APCMin/+ tissue.

Value Proposition:

Technology:

R&D Status: Discovery.

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.

IP Status: US Application #61/064,086 filed 15 February 2008Reference #: E-254-2007

Polyp

Polyp

Normal Cells

Contact: Michael Shmilovich; [email protected]; 301-435-5019

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 18

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

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.

Value Proposition:

R&D Status: Licensed.

Increase physician attention to polyp candidates in the cecum.

IP Status: US Applications #60/510,640 (10/10/2003); #7,440,601 (10/21/2008)

Reference #: E-174-2003

Contact: Jeffrey James; [email protected], 301-594-7219

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 19

Virtual Colonoscopy via WaveletsRonald 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).

Significantly reduce false positives by 41.5%

in a CTC CAD system for detecting 6-9 mm

polyps.

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.

Value Proposition:

R&D Status: Ready for Implementation in CAD Software.

Potential to improve specificity of CTC and reduce unnecessary colonoscopies.

IP Status: US Application #11/685,127 (3/12/2007)

Reference #: E-314-2006Contact: Jeffrey James; [email protected], 301-594-7219

Page 20: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 20

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)

IP Status: U.S. Provisional Application No. 61/055,328 filed 22 May 2008

Reference #: E-063-2008

Contact: Surekha Vathyam, Ph.D.; [email protected], 301-435-4076

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

R&D Status: Discovery Animal brain tumor regression studies underway

Page 21: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 21

Christy LudlowLaryngeal and Speech Section, National Institute of Neurological Disorders and Stroke

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 [email protected]

Non-Invasive Device and Methods for Swallowing Recovery Treatment and Training for Volitional Swallowing

Indications and Usesinitiation and retraining of swallowing

for these indications:post-strokepost-extubationneurologically impaired throat cancer

prevention of aspiration pneumonia

Advantages of Technologybutton press to initiate sensory stimulation and coordinate muscular movement to permit volitional swallowing sensor for monitoring pressure on the patient’s larynx and a swallowing motion detectormethods to produce vibratory stimulation, pressure stimulation, auditory stimulation, temperature stimulation, visual stimulation, olfactory stimulation, taste stimulation, or a combination of these

Current State of Development Two on-going clinical trials at the NIH to test device in dysphagic patients

Future Development NeededManufacture, market, and distribute deviceTechnological improvements based on current clinical trial results

Prototype of device currently being tested in patients

Device consists of --Device controller (including circuit and battery)Motor (vibrator)Adjustable, flexible keelPatient-controlled switch

Page 22: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 22

Colon Cancer Cells Normal Colon Cells

Nuc

lei

FA

CS

Selective Killing of Cancer CellsWenge Zhu & Melvin L. DePamphilisProgram on Genomics of Differentiation

National Institute of Child Health and Human Development

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

R&D Status Animal study in progress Available for licensing

IP Status: U.S. Provisional Application No: 61/106,465 Collaboration Contact Information: [email protected] Licensing Contact Information: Betty Tong ([email protected])

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

Page 23: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 23

Therapeutic Use of E-selectin For Treatment of Multiple Sclerosis and Prevention of Secondary Stroke

Hallenbeck, Shukaliak and TakedaNational Institute of Neurological Disorders and Stroke

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:

R&D StatusIn vivo and in vitro data are availableCollaborative opportunity – NINDS is actively seeking partners for further research, development, and commercialization

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

IP Status: National stage, with three issued patents in Secondary StrokeReference #: E-153-2005 (MS) and E-237-1999 (secondary stroke)Collaboration Contact Information: Laurie Arrants, [email protected], 301-435-3112Licensing Contact Information: Dr. Norbert Pontzer,[email protected] , 301-435-5502.

Intranasal delivery of E-selectin

Page 24: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 24

Jill Heemskerka, Jacquie Shukaliakb, and Gene Majorc

National Institute of Neurological Disorders and Stroke

Reference #: E-133-2006; E-187-2007; E-290-2007; E-179-2007

For Collaboration or Licensing, please contactMelissa Maderia 301-451-3943 [email protected]

Drug Treatment for Neurological Disorders

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 proteinPass through the blood-brain barrier

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 patientsUsed for prevention of PML in treatment therapies for MS patients

N

O

O

CH3

CH3

H3C

H3CO·

OH

NAnalogs based on

Indoprofen Template

Tempol

Page 25: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 25

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 Alzheimer’s 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 Alzheimer’s Disease, Parkinson’s Disease and other diseases.

R&D 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. [email protected]

Use of Razoxane for the Treatment of Alzheimer's DiseaseNigel H. Greig

Drug Design and Development Section, Laboratory of Neurosciences NATIONAL INSTITUTE ON AGING

Page 26: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 26

Method of Treating or Preventing Oxidative Stress-related Diseases Nigel H. Greig et al.

Drug Design and Development SectionLaboratory 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)

R&D 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. , [email protected] Contact: Norbert J. Pontzer, Ph.D., J.D., [email protected]

Page 27: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 27

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.

R&D 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: [email protected]

Drug Design and Development Section, Laboratory of Neurosciences, NATIONAL INSTITUTE ON AGING

Novel Inhibitors of p53 for Treatment of Neurodegenerative Disorders, Myocardial Infarction and Other Tissue Insults

Nigel H. Greig et al.

Page 28: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 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

R&D 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:

[email protected]

Page 29: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 29

Inhibitors of CD25 to Treat Autoimmune Diseases and Tumors Bibiana Bielekova

National Institute of Neurological Disorders and Stroke

Patent Status: U.S. Provisional Application No. 61/201,589 filed 12 Dec 2008 Reference #: E-007-2009For Collaboration, please contact Martha Lubet, Ph.D, 301-4435-3120; [email protected] For Licensing, please contact Suryanarayana (Sury) Vepa, Ph.D., J.D.; 301-435-5020; [email protected]

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

Dendritic Cell

CD25 Antagonists

T-cell Inhibition

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 30

A Novel & Efficient Technology for Targeted Delivery of siRNAArya Biragyn, Ph.D, et al.

National Institute on Aging (NIA), Laboratory of Immunology

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

Figure captionValue Proposition:

Novel compositions and methods for delivering inhibitory oligonucleotides to cells in a targeted and efficient manner

R&D Status: Animal studies in progress. The NIA is currently seeking licensing partners and/or collaborative partners for further development.

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

IP Status: PCT application; claiming priority to provisional application filed 15 April 2008Reference #: E-051-2008Collaboration Contact Information: Nicole Darack Guyton, Ph.D., [email protected] Contact Information: Surekha Vathyam, Ph.D.; [email protected]

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 (H&E-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.

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 31

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.

R&D 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: [email protected]

Treatment of Cocaine-Induced Fetal Brain Injury Chun-Ting Lee and William J. Freed Cellular Neurobiology Research Branch

National Institute on Drug Abuse

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 32

Ron McKay Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke

Reference #: E-001-2003; E-182-2007; E-239-2005

For Collaboration, please contact Martha Lubet, Ph.D, 301-4435-3120; [email protected]

For Licensing, please contact Fatima Sayyid, M.H.P.M., 301-435-4521; [email protected]

Targets for Treatment of Neurological Disorders Stem Cell Proliferation and Survival

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.

ApplicationsIncreased generation of stem cells in vitro for treatment of neurological disordersTreatment of neurodegenerative disorders, such as Parkinson’s disease, stroke, and spinal cord injury

Development StatusIn vitro method described in Nature 2006

Aug 17;442(7104):823-826. In vivo method validated in rodent

models of Parkinson’s disease and stroke.

Stroke

Parkinson

Spinal Cord Injury

CNS

Neural Stem Cells

HES 3

Shh

NOTCHligand

STAT3/Ser727

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 33

Zscan4: A Gene Critical for Early Embryonic DevelopmentMinoru S.H. Ko, M.D., Ph.D., et al.

National Institute on Aging (NIA), Laboratory of Genetics

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.

Figure caption

Value Proposition:

Zscan4 plays an essential role in early embryonic development, with potential applications for the development of stem cell therapeutics and assisted reproduction technologies.

R&D Status: Early stage development. Technology is available for licensing. 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-088-2007Contact: Tara Kirby, Ph.D.; [email protected]

Insert figure here

A schematic illustration of Zscan4 expression patterns.

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 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

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.

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).

Value Proposition:

Technology:

R&D Status: in progress, searching collaborations

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

IP Status: PCT/US2007/75724 Reference #: E-304-2005/0-PCT-02Collaboration Contact Information: [email protected] Contact Information: [email protected]

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.

A.

B.

C.

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 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.

Value Proposition:

R&D 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, 2008Reference #:E-162-2008/0

Contact: Cristina Thalhammer-Reyero, Ph.D., MBA; 301-435-4507; [email protected]

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

N

SPO

HNR

Phosphinic amides

N+NO

CN

O-

Furoxan (1)

S

SH

S S

Me S

O

O

SMe

NO

S

S

S S

NO

SMe

SH

S

S S

SMe

(MMTS)

Ascorbate

N S S Biotin

(Biotin-HPDP)

S

S

S S

SMe

S Biotin

Treatment of Schistosomiasis Using Substituted Oxadiazole 2-OxidesC.J. Thomas et al.

NIH Chemical Genomics Center

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

Technology:

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 36

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. R&D 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 15;18(4):1297–1303. 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; [email protected]

Substituted Triazolothiadiazines and TriazolopyridazinesC.J. Thomas et al.

NIH Chemical Genomics Center

Design and synthesis of novel Triazolothiadiazines and Triazolopyridazines as PDE4 Inhibitors

Log [10], M

%A

ctiv

ity

S

NN

NN

OMe

MeO

MeO

OO

PDE4A1APDE4B

IC50 (nM)

0.262.3

PDE isof orm

PDE4D 1.9PDE4B 1.6

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 37

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

notable inhibitors of cruzain

Value Proposition:

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

R&D 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, 2008Reference #: E-267-2008

Contact: Kevin W. Chang, Ph.D.; 301-435-5018; [email protected]

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

N

N

O

NH

O

S

O

O

N

HN N

NN

Bu

OO

FF

FF

1 2

Substituted Triazine and Purine Compounds, Methods of Inhibiting Cruzain and Rhodesain, and Methods of Treating Chagas Disease and African Trypanosomiasis

C.J. Thomas et al.

NIH Chemical Genomics Center

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

Page 38: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 38

Melissa Maderia, Ph.D. [email protected]

301-451-3943

To obtain copies of these slides, please visit: http://ttc.nci.nih.gov

orhttp://ott.od.nih.gov

orhttp://www.cdc.gov/tto

keyword: BIO

Contact Info

Page 39: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 39

BIO2009 Federal Science and Opportunities Track

Hot Federal Biotechnologies Available for Collaboration and Licensing

Rosemary C. Walsh, Ph.D.

Technology Development AssociateOffice of Technology Development

National Institute of Allergy and Infectious Diseases

[email protected]

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 40

Epitope-Transplant Scaffolds and Their Use Epitopes are removed from whole antigenand 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 vaccinesR&D Status: Pre-clinical

IP Status: Filed US & EP WO 2008/025015

Reference # E-302-2006/1

Collaboration Contact: Marguerite Miller; [email protected]

Licensing Contact: Cristina Thalhammer-Reyero; [email protected]

Peter D. Kwong, et al.National Institute of Allergy and Infectious Diseases

Novel Approach to Vaccine Design

Conserved neutralization epitope on

HIV-1 gp120

Page 41: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 41

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 bondsIP 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

R&D Status: Pre-clinicalCollaboration Contact: Marguerite Miller, MBA; [email protected]

Licensing Contact: Cristina Thalhammer-Reyero; [email protected]

Peter D. Kwong, et al.National Institute of Allergy and Infectious Diseases

Potential HIV Vaccine Immunogens

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 42

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

R&D 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; [email protected]

Licensing Contact: Cristina Thalhammer-Reyero; [email protected]

G. NableNational Institute of Allergy and Infectious Diseases

Chikungunya Vaccine

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 43

Polymorphic Membrane Protein D (PmpD) as vaccine candidate

>99% Sequence identity between serovariantsSurface located antigen Antibodies neutralize all 15 serotypes in vitroCan be expressed in E.coli and ModifiedVaccinia Ankara (MVA)

Value Proposition: Antigen common to all serotypesVaccination preferable to antibiotic intervention which can compromise development of immunity

R&D Status: preclinical

IP Status: Filed PCT application (WO 2008/048348) on1/9/07, priority date:1/9/06

Reference # E—031-2006

Collaboration Contact: Anna Amar; [email protected]

Licensing Contact: Peter Soukas: [email protected]

H. D. CaldwellNational Institute of Allergy and Infectious Diseases

Chlamydial Vaccine

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 44

Sialostatin L2 Mediation Controls Blood Feeding Success of Ixodes scapularisI. scapularis main vector of Lyme’s DiseaseSalivary secretions crucial for pathogen transmissionUse 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 bitesPotential as part of a multi-component vaccineEnvironmentally friendly alternative to acaricides(pesticides)

R&D 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: [email protected]

Licensing Contact: RC Tang; [email protected]

M. Kotsyfakis, J.M.C Ribeiro, J.G. Valenzuela, J. Anderson, J. AndersenNational Institute of Allergy and Infectious Diseases

S. Karim, T.N. Mather at the University of Rhode Island

Anti-tick Vaccine

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 45

Phenol-soluble modulin (PSM) polypeptides Secreted peptides that recruit, activate and lyse human neutrophilsEliminate main cellular defense against S. aureus infectionHigh PSM expression gives methicillin resistant S. aureus infections contracted in community settings greater virulence that MRSA found in health care settingsDeletion 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

R&D Status: Animal data available

IP Status: Filed International application on 5/8/2008; priority date:6/6/2007

Reference # E-239-2007/2-PCT-01

Collaboration Contact: Johanna Schneider; [email protected]

Licensing Contact: Cristina Thalhammer-Reyero; [email protected]

M. Otto National Institute of Allergy and Infectious Diseases

Novel Targets Against Staphlycocci Bacterial Infections

Page 46: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 46

Aegyptin, a collagen binding proteinSelectively inhibits collagen platelet aggregationBlocks interaction of collagen with its major ligands

Willebrand factor Glycoprotein VI (GPVI) Integrin a2β1

Applications: Adjuvant to “clot busting” therapeutics Prevention/treatment of cardiovascular/thrombotic diseaseTreatment for patients undergoing invasive cardio proceduresMay play role in treatment of pancreatic carcinoma

R&D 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-172—2007/1

Collaboration Contact: S. Dana Hsu: [email protected]

Licensing Contact: Jennifer Wong; [email protected]

E. Calvos, et al.National Institute of Allergy and Infectious Diseases

Platelet Aggregation Inhibitor

Platelet

Gp

Ib-V

-IX

Exposed Collagen

Endothelium

vWF

AggregationAggregation

Adhesion

Shape change

Release of granules content

GPVI

α 2β 1

Multiple receptors mediate platelet adhesion to collagen: GPVI, integrin alpha2beta1 and GPIb/vWF

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 47

MAOi(s) prevent HSV infection and may prevent periodic reactivation from latency Herpes viruses are repressed by host chromatin structures that wrap the viral genomeEnzymes (LSD1) are recruited to halt repressionLSD1 is inhibited by MAOi(s); expression of viral genes is inhibited

Application: May also prevent significant lytic replication of other herpes virusesMay reduce viral infection during transplantOther more specific drugs targeted to LSD1 may prevent other viral infections

R&D Status: Pre-clinical

IP Status: Filed US Provisional 61/111,109 on 11/4/2008

Reference # E275-2008

Collaboration Contact: Christopher Freeman; [email protected]

Licensing Contact: Cristina Thalhammer-Reyero; [email protected]

T. Kristie, et al.National Institute of Allergy and Infectious Diseases

Mono-amine oxidase inhibitors (MAOi) for treatment of herpes simplex infection

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 48

Device/method for microwave assisted cryo-sample processingReduced time required for freeze substitution fixation from 2-6 days to 2-3 hoursEquivalent preservation of morphology when compared to traditional freeze substitution fixationSuperior preservation of morphology when compared to conventional fixation techniques using passive diffusionValue 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

R&D 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; [email protected]

Licensing Contact: RC Tang; [email protected]

D. Dorward, V. Nair, E. FischerNational Institute of Allergy and Infectious Diseases

Faster Cryo-Sample Processing

Page 49: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 49

For information on these and other opportunities, please contact

Rosemary C. Walsh, Ph.D. Phone:301-451-3528

Email:[email protected]

To obtain copies of these slides, please visit: http://ttc.nci.nih.gov

orhttp://ott.od.nih.gov

keyword: BIO

Page 50: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 50

at the National Cancer Institute

John D. Hewes, Ph.D.Technology Transfer Specialist

Technology Transfer CenterTel. (301) 435-3121

email: [email protected]://ttc.nci.nih.gov

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 51

Why Collaborate ?Why Collaborate ?

BUSINESS MODELS BASED ON COLLABORATION

STRATEGIC TRENDS IN PHARMACEUTIC INDUTRYMarkets• Patients more informed • Patients paying more• Personalized medicine• Patient outcomes• Emerging markets

Health/Healthcare• Cost of chronic diseases• Payers establishing protocols• Pay-for-performance• Financial constraints of payers

Science/Technology• R&D becoming virtualized• R&D shifting to Asia• Remote monitoring• Data warehousing/sharing

IMPLICATIONS TO PHARMACEUTICAL INDUSTRYPharma goes beyond medicine• Outcomes, not products, become drivers• Prevention vs. cure• Flexible pricing pressure

R&D goes beyond the Lab• Data universe is growing• Virtual lab space is growing• Multi-disciplinary• Geographic expansion (Asia)• Bottom-line results

Value chains of Pharma & Healthcare more interlinked• Work with Regulators • Work with providers for trials• Dispersed services to coordinate

From PriceWaterHouseCoopers “Pharma 2020: Challenging Business Models,” retrieved from www.pwc.com/pharma

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 52

Why Collaborate with NCI?Why Collaborate with NCI?

Value PropositionIRP researchers can efficiently translate world-class discoveries into clinical applications using a broad infrastructure, such as that provided by NIH Clinical Center (world’s largest clinical research hospital). Accessible to industry through research collaborations and licensingLeverage the NCI's expertise, resources, and broad network of clinical researchers and sites Trials at the Clinical Center allows investigators from other NIH institutes to participate NIH can recruit patients from around the country, trials performed at the Clinical Center are more likely to enroll enough patients with rare diseases to provide the statistical power needed to produce meaningful results.

Intramural Research Program (IRP) ($718M in FY08) 10% of the NCI budget supports projects conducted by nearly 400 scientists in its own laboratories, most of whom are on the NIH campus in Bethesda or NCI-Frederick (MD).

TTC maintains an e-mail service to notify you of new technology opportunities.Register at http://ttc.nci.nih.gov

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 53

NCI has produced important drugs and technologies through collaborations and licensing with the private sector.

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®

Medimmune 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

Marketed NCI-Licensed TechnologiesMarketed NCI-Licensed Technologies

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 54

Chemical programming of antibodies through selenocysteine

Chemical programming of antibodies through selenocysteineChristoph 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 antibodiesUnlimited structural diversity Prolonged and predictable in vivo half lifeReach recessed sites on macromolecules Potent interference with macromolecular Straightforward manufacturing interactions

Adjustable valence and effector activity

R&D 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., [email protected], 301-435-3121

Licensing Contact: Jennifer Wong, [email protected], 301-435-463

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 55

Nitric Oxide-releasing PolymersNitric Oxide-releasing PolymersLarry 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

R&D 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, [email protected], 301-435-3121

Licensing Contact: Steve Standley, 301-435-4074, [email protected]

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 56

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

Technology: Cancer Biomarkers for androgen-independent prostate cancer (AIPC)

a. CYP1B1*3 A genetic marker called CYP1B1*3 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

R&D 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., [email protected], 301-435-3121

Licensing Contact: Sabarni K. Chatterjee, Ph.D., [email protected], 301-435-5587

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 57

Methods for Diagnosis and Prognosis of LymphomasMethods for Diagnosis and Prognosis of Lymphomas

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 individual’s 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

R&D 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., [email protected], 301-435-3121

Licensing Contact: Sabarni K. Chatterjee, Ph.D., [email protected], 301-435-5587

Louis M. Staudt, M.D., Ph.D.Metabolism Branch

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 58

Development of Novel Anti-HIV CompoundsDevelopment of Novel Anti-HIV CompoundsRobert Shoemaker, Ph.D. and Alan Rein, Ph.D.

Developmental Therapeutics Program, HIV DRP Retroviral Replication Laboratory

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.

R&D Status: Pre-clinical in vivo, incl. efficacy, pharmacokinetics, preliminary tox studies.

IP Status: U.S. application 10/528,747 filed 3/22/2005

Reference # E-121-2002

Collaboration Contact: John D. Hewes, Ph.D., [email protected], 301-435-3121

Licensing Contact: Sally Hu, Ph.D., MBA, [email protected], 301-435-5606

Technology: HIV TherapeuticActive 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.

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 59

HIV-1 Integrase Inhibitors for the Treatment of Retroviral InfectionsHIV-1 Integrase Inhibitors for the Treatment of Retroviral Infections

Technology: HIV TherapeuticsNovel HIV-1 integrase inhibitors that inhibit strand transfer (ST) of HIV viral DNA into the host genome

Value Proposition: Potential therapeutic and preventative value for AIDS and other retroviral infections Potential benefit for patients exhibiting resistance to current therapy regimes

R&D Status: Pre-clinical in vitro

IP Status: U.S. Provisional Application No 60/956,636 (08/17/2007)

Reference # E-237-2007

Collaboration Contact: John D. Hewes, Ph.D., [email protected], 301-435-3121

Licensing Contact: Sally Hu, Ph.D., MBA, [email protected], 301-435-5606

Terrence R. Burke Jr., Ph.D., Yves Pommier, M.D., Ph.D., et al.Laboratory of Medicinal Chemistry

HIV-1 Integrase Strand Transfer (ST) Inhibitory Potency (IC50) in the Presence of Mg2+ and Antiviral Inhibitory Potency (EC50) in HIV-1 Infected Cells

0.16 µM0.48 µM

OHOH

N

O

F

Cl

OHOH

N

O

F

IC50 (ST): 10 µMEC50: 0.77 µM

OHOH

N

O

2 µM0.62 µM

Cl

F

Page 60: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 60

Technology: HIV TherapeuticsNovel antibody-based technologies for the treatment of HIV/AIDs, including the first anti-HIV human domain antibody (m36), which can potentially be used alone or synergistically with other anti-HIV antibodies and antiretroviral drugs. Also included in this platform is a fusion construct that may elicit broad neutralizing antibodies and an HIV vaccine that is able to elicit a desired antibody against a target antigen.

Antibody-based HIV treatment and preventionAntibody-based HIV treatment and prevention

Applications: HIV treatment and prevention Ability to neutralize HIV isolates from different clades

R&D Status: Pre-clinical in vitro and in vivo

IP Status: US Patent Applications filed

Reference # E-043-2008, E-072-2008, E-322-2008

Collaboration Contact: John D. Hewes, Ph.D., [email protected], 301-435-3121

Licensing Contact: Sally Hu, Ph.D., MBA, [email protected], 301-435-5606

Dimiter S. Dimitrov, Ph.D.NCI CCR Nanobiology Program

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 61

Assay to detect Plk1 levels and activityAssay to detect Plk1 levels and activityKyung Lee, Ph.D.

Laboratory of Metabolism

Technology: Cancer DiagnosticMammalian polo-like kinase 1 (Plk1), a critical mitotic kinase, is upregulated in ~ 80% of human cancers. A growing body of evidence suggests that Plk1 plays a critical role in numerous mitotic events and cellular proliferation. Plk1 has been suggested as a biomarker for several types of human cancers and is considered an important potential target for anti-cancer therapy.

Value Proposition: Rapid and highly-sensitive ELISA that allows quantification of Plk1 activity with only several microgram of unpurified total lysates from cells and tissues. Provide broad clinical applications including prognosis of Plk1-associated cancers and assessment of early therapy response following anti-proliferative chemotherapy.

R&D Status: Pre-clinical in vitro analysis of patient samples

IP Status: U.S. Provisional Application No. 61/054,032 filed 16 May 2008

Reference # E-091-2008

Collaboration Contact: John D. Hewes, [email protected], 301-435-3121

Licensing Contact: Jennifer Wong, 301/435-4633, [email protected]

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 62

New Agents for Lab and Clinical ImagingMartin W. Brechbiel, Ph.D.

Radiation Oncology Branch

Technology: Imaging/Contract Agents Silica-encased, ultrasmall super-paramagnetic iron oxide (USPIONs) that can be detected through MRI, SPECT/PET and fluorescence simultaneously. Bifunctional chelate to sequester radiometals and conjugated to the mAb for targeted imaging or drug delivery. Novel method to embed fluorescent dyes in an ultrasmall particle, allowing better delivery in vivo.Value Proposition: Lab and clinical labeling at the cellular level for diagnostics and drug delivery. R&D Status: Pre-clinical in vitro and in vivoIP Status: U.S. and foreign patent applications

Reference # E-157-2007

Collaboration Contact: John D. Hewes, Ph.D., [email protected], 301-435-3121

Licensing Contact: John Stansberry, Ph.D., [email protected], 301-435-5236

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 63

3D Mapping of Cells at Nanometer ResolutionSriram Subramaniam, Ph.D.

NCI CCR Laboratory of Cell Biology, Biophysics Section

Technology: Imaging Strategies are being developed for automated, 3D visualization of cellular organelles using ion abrasion scanning electron microscopy (IA-SEM) combined with high resolution mass spectrometry to detect spatial distribution of proteins, metabolites and ions inside cells.

Potential applications: Spatial mapping of drug distribution and drug targets in mammalian cells within organelles Determination of metabolite and ion gradients

R&D Status: Pre-clinical prototypePilot experiments are underway for development and optimization of the technology using commercially available components and custom-designed technologies.

IP Status: US Patent Application # 60/906,166 (03/9/2007)

Reference # E-313-2007

Collaboration Contact: John D. Hewes, Ph.D., [email protected], 301-435-3121

Licensing Contact: Michael Shmilovich, J.D., [email protected], 301-435-5019

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U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 64

Technology: Cancer Therapeutics New strategy for treating cancers that over-express MDR1 Unlike most methods, this approach does not inhibit MDR1 function The anticancer effects of these novel agents depend on the overexpression of MDR1 These agents also appear to down-regulate MDR1 expression

Value Proposition: Capitalizes on the most common defense mechanism that cancer cells employ Correlation of effectiveness to level of expression increases specificity to cancer cells May avoid side effects seen with attempts to inhibit MDR1 function May re-sensitize cells to chemotherapeutics, allowing additional effective treatment

R&D Status: Pre-clinical in vitro

IP Status: PCT/US2009/000861(2/10 /09); US 61/027,712 (f/10/08)

Reference : E-017-2008

Collaboration Contact: John D. Hewes, Ph.D., [email protected], 301-435-3121

Licensing Contact: David Lambertson, Ph.D., [email protected]; 301-435-4632

New Strategy and Compositions for Treating Multidrug Resistant Cancer

Matthew D. Hall, Ph.D. et al.

Laboratory of Cell Biology

Page 65: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 65

John D. Hewes, [email protected]

301-435-3121

To obtain copies of these slides, please visit: http://ttc.nci.nih.gov

orhttp://ott.od.nih.gov

orhttp://www.cdc.gov/tto

keyword: BIO

Contact Info

TTC maintains an e-mail service to notify you of new technology opportunities.Register at http://ttc.nci.nih.gov

Page 66: Slide 1

U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 66

Centers for Disease Control and Prevention

Technology Transfer Office

Suzanne Seavello Shope, J.D.Technology Licensing and Marketing Scientist

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 67

Centers for Disease Control and Prevention

– A source of credible health information– Response to disease and disaster outbreaks– Source of national and international health

statistics– Development of new diagnostic and vaccine

technologies

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 68

CDC Research Areas

• All Infectious Diseases• Occupational Health• Toxic Chemicals at work, home and school• Injury prevention• Chronic Diseases• Health Statistics• Birth Defects

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 69

Examples of Non-patented Technologies

• Cell lines• Nucleic acids and vectors• Antibodies• PCR probe pairs

Page 70: Slide 1

U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 70

Sampling of Technologies filed with the USPTO

Vaccines:• I-015-07 M. Tuberculosis Proteins as Mucosal Vaccine Candidate Against TB • I-013-03 HIV-1 Multi-Clade, Multivalent (HIV-1MCMV) Recombinant Vaccine Construct • I-008-08 Development of Rift Valley Fever Virus Vaccines Utilizing Reverse Genetics• I-039-00 Peptide Vaccine Candidate Against Group A Streptococci• I-004-98 Recombinant Multivalent Malarial Vaccine Candidate against Plasmodium falciparum

Therapeutic:• I-030-04 Peptide from Streptococcus Pneumoniae Surface Adhesion A (PsaA) Protein Associated

with Adherence

Diagnostics:• I-001-05 Development of Real-time PCR Assay for Detection of Pneumococcal DNA and

Diagnosis of Pneumococcal Disease• I-010-05 Immunological Immobilization of Cardiolipin Antigen to a Solid Support• I-018-99 Diagnostic Antigens for the Identification of Latent Human Tuberculosis

Animal:• I-025-06 Rabies Virus Recombinant Immuno-Contraceptive Vaccine Candidate

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 71

Identification of M. Tuberculosis Proteins as MucosalVaccine Candidate Against TB

Suraj Sable, Tom Shinnick, Bonnie B. Plikaytis, and Mani Cheruvu NCHHSTP, CCID

Technology:Effective mucosal vaccine for TB: Strong cell mediated immune cytokine response Intranasal delivery of a single moderate dose of the BCG or a multi-component subunit vaccine induced a stronger and more sustained Mycobacterium Tuberculosis-specific T cell response in lung parenchyma and cervical lymph nodes than vaccines delivered subcutaneously The alanine protein rich antigen (APA, Rv1680) was highly antigenic following intranasal vaccination

Value Proposition: Strong need for new tuberculosis (TB) vaccines There is currently only one approved vaccine and it is not considered to be very effective Estimated market size to be $300 million (India is expected to account for 23% sales) A group of countries committed $1.5 billion for vaccines for diseases including TB (2007) The Gates Foundation has pledged $900 million to fight TB with the goal of eradicating it by 2015

R&D Status: Looking for a licensee or collaborating partner for animal studies/human trialsIP Status: PCT Patent Application was filed in January 2009CDC Reference # I-015-07; contact CDC Technology Transfer Office 770-488-8600

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 72

Development of a HIV-1 Multi-Clade, Multivalent (HIV-1MCMV) Recombinant Vaccine ConstructRenu B. Lal, Michele Owen, NCHHSTP, CCID

Value Proposition:A successful vaccine has huge potential throughout the worldThis candidate overcomes some past challengesExpanded funding opportunities from private foundations and federal government

R&D Status: Looking for a licensee or collaborating partner for animal studiesIP Status: Patents issued in US (7,425,611) and India, pending in Canada, Australia and EuropeCDC Reference # I-013-03; contact CDC Technology Transfer Office 770-488-8600

B-cell Epitopes

Tat EnvCCR5

T-helper Epitopes

Gag Vpr

Rev

+/- LysosomalTargeting

Pol

Env

CTL-Epitopes

Nef

+/- Proteosome

Targeting

GagPol

Env

= Unique restriction site for cloning into vectors

Technology:Multiple conserved epitopes provide broad immune responses less subject to subtype variationsCarefully fabricated strings of T- and B- cell epitopes designed with appropriate spacers and armed with cellular targeting sequences for inducing both T- and B- cell immune responses Constructed to allow easy addition, substitution or deletion of epitopes for optimization of antigen recognition and processingDesigned for use as a DNA vaccine and as an expression construct for recombinant antigens

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 73

Development of Rift Valley Fever Virus Vaccines Utilizing Reverse Genetics Brian H. Bird, Stuart T. Nichol, Cesar G. Albarino, and Thomas G. Ksiazek

Special Pathogens Branch, DVRD, NCZVED, CCID

Technology:Rift Valley Fever (RVF) Vaccine Single vaccine dose generates robust protective immune response (strong neutralizing antibody response) Survival of vaccinated rats after lethal virus challenge Ability to discriminate natural infection and vaccines Defined attenuated vaccine constructs Potential for use to prevent and control RVF infections

Value Proposition: Rift Valley Fever is prevalent in Africa and occasional outbreaks have occurred in the Middle East Highly contagious nature, healthcare burden, impact on veterinary and meat industry and potential as a biological threat agent Potential for the virus to spread to Europe, Asia, North America and other parts of the worldCommercial potential in Europe, the Middle East and in the US (USDA, Homeland Security stockpile)

R&D Status: Large animal studies are underway; looking for a licensee.IP Status: PCT Patent Application was filed in Dec 2008CDC Reference # I-008-08; contact CDC Technology Transfer Office 770-488-8600

Countries with endemic disease and substantial outbreaks of RVF

Countries known to have some cases, periodic isolation of virus, or serologic evidence of RVF

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 74

Peptide Vaccine Candidate Against Group A StreptococciBernard W. Beall, George M. Carlone, Jacquelyn S. Sampson, Edwin W. Ades

Meningitis And Vaccine Preventable Diseases Branch, DBD, NCIRD, CCID

Technology:Synthetic Group A streptococci Immunoreactive peptides of the M proteins of the most prevalent group A strep serotypes in the USPotential multi-antigenic peptide vaccine that has the ability to protect against 10 most common strains of Group A streptococciSynthetic peptide strategy circumvents previous problemsFunctional antibody response shown in mice which decrease the amount of nasopharyngeal colonization

Value Proposition: >9500 cases per year in the US with approximately 1300 deaths Difficulties with producing vaccine in the past include >80 serological M types and some M proteins cross-react with human tissue Simple vaccine design strategy could result in inexpensive vaccines, with versatility for altered formulations applicable for use in developed and undeveloped countries.

R&D Status: Requesting a CRADA partner to develop vaccine components and do animal studiesIP Status: Patent issued in US (7,407,664), pending in Canada, Australia and EuropeCDC Reference # I-039-00; contact CDC Technology Transfer Office 770-488-8600

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 75

Recombinant Multivalent Malarial Vaccine against Plasmodium falciparum

Ya Ping Shi, Altaf A. Lal, Seyed E. Hasnain Division of Parasitic Diseases, NCZVED, CCID

Technology:Multivalent Malaria Vaccine Recombinant, multi-valent and multi-stage malaria vaccine antigen more specifically useful for preventing or treating P. falciparum malarial infections in all three stages Effective in inhibiting reproductive growth of the parasite after initial infection Includes antibodies against a recombinant protein containing antigenic epitopes useful as research or diagnostic reagents

Value Proposition: There are 350-500 million cases of malaria worldwide each year and >1 million deaths Extensive potential for safe and effective vaccine, particularly in India (private market healthcare) In addition to the local population in the endemic areas, governments, travelers and military are potential large scale customer base Gates Foundation supports substantial founding and targets reduction in death by 2015R&D Status: Stability at large scale preparation has been shown; need a partner for animal studies and clinical trialsIP Status: Patents issued in US (6,828,416), India and Australia, pending in Canada and EuropeCDC Reference # I-004-98 (and I-019-03, I-021-03) ; contact CDC Tech Transfer Office 770-488-8600

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 76

Peptide from Streptococcus Pneumoniae Surface Adhesion A (PsaA) Protein Associated with Adherence

Edwin W. Ades, Jacquelyn S. Sampson, Sandra Steiner, George M. Carlone, Joseph J. Caba, and Gowrisankar Rajam

Meningitis And Vaccine Preventable Diseases Branch, DBD, NCIRD, CCID

Technology: P4 peptide from PsaA used for therapeutic intervention through augmented passive immunotherapy Multilineage cell activator in vitroHypothesize P4-mediated activation of phagocytic cells could rapidly and substantially increase opsonophagocytosis of bacteria to decrease fatal pneumococcal infection

Value Proposition:Animal studies show 100% remission of bacteremia and rescued 80% of mouse models

R&D Status: Have animal study data, need a partner for clinical trials and to make the material as GMP

IP Status: Patents pending in the US, Canada, Australia, Hong Kong and Europe

CDC Reference # I-030-04; contact CDC Technology Transfer Office 770-488-8600

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 77

Development of Real-time PCR Assay for Detection of Pneumococcal DNA and Diagnosis of Pneumococcal DiseaseEdwin Ades (DBD, NCIRD, CCID), Nadine Rouphael (CDC, Emory), and

Harry Keyserling (Emory)

Technology: Pneumococcal disease detection Unique primers and probes (PsaA) for a real-time PCR assay for detection of pneumococcal DNA Great tool for routine diagnostics as well as to test the efficacy of new pneumococcal vaccines

Value Proposition: Detection of pneumococcal pneumonia is limited by the lack of a sensitive, specific, and accurate laboratory assays Strong need for sensitive, real-time assays for pneumococcal infections Roughly 21-33 instances annually of S. Pneumoniae for every 100,000 members of the population. Assuming that each of these required a diagnosis, market projection is between 600,000-1,000,000 tests annually Real time PCR becoming common in hospitals and clinical labs, hence adoption of this technique rather easy

R&D Status: assays in mouse model have been completed, available for licensing to produce and distribute a kitIP Status: Patent issued in US (7,476,733), pending in Canada, Australia, Brazil, Japan and Europe CDC Reference # I-001-05; contact CDC Technology Transfer Office 770-488-8600

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 78

Immunological Immobilization of Cardiolipin Antigen to a Solid Support

Arnold Castro, Robert W. George, Victoria Pope DSTDP, NCHHSTP, CCIDTechnology:Sensitive dual detection of syphilis infection Ability to detect treponemal antibodies and anti-lipoidal antibodies to differentiate previous and new infections Opportunity to treat the new infection and prevent further spread Easy-to-read Color Band Signal with Built-in Test Control Immobilizing these antigens onto solid support media such as nitrocellulose make it an inexpensive assay tool 

Value Proposition: Rates of syphilis - once on the verge of elimination -- rose for the seventh consecutive year Demand for more sensitive tests expected to increase as more and more cases are reported Need to differentiate previous and new infections to treat the new infection to prevent further spreadSimultaneous screening and confirmatory test (currently a two-stage process) Potential to develop as a point of care, visually inferable test

R&D Status: Ready to license, have one non-exclusive licensee, looking for additional licenseesIP Status: Pending in US (2), Brazil, India, ARIPO regional, China, Canada, Australia and EuropeCDC Reference # I-010-05; contact CDC Technology Transfer Office 770-488-8600

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 79

Diagnostic Antigens for the Identification of Latent Human TuberculosisKristin A. Birkness, Fred D. Quinn, David S. Beall, Manon Deslauriers, Peter King

Mycobacteriology Laboratory Branch, DTE, NCHHSTP, CCIDTechnology:Detection of proteins expressed by M. tuberculosis: This invention focuses on the detection of proteins expressed by M. tuberculosis only while in a non-replicating state and therefore would serve as an indicator of latent infectionDetection of these proteins can be adapted to standard diagnostic methods for clinical use

Value Proposition: Ability to distinguish between active or latent TB infections Ability to determine BCG vaccine exposure and TB infection Ability to distinguish non tuberculosis mycobacteria infections Need to positively identify M. tuberculosis infections in immunosuppressed individuals

R&D Status: Ready to license, have one non-exclusive licensee, looking for additional licensees

IP Status: Patents issued in US (7,425,611), JP and Australia, pending in Canada, Australia and Europe

CDC Reference # I-018-99; contact CDC Technology Transfer Office 770-488-8600

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 80

Rabies Virus Immuno-Contraceptive Vaccine CandidatesCharles Rupprecht, Xianfu Wu

Rabies program/PRB, DVRD, NCZVED, CCID

Technology:Effective contraceptive vaccine for rabies: By incorporating a main immunocontraceptive gene into the rabies virus ERA genome, this invention provides a recombinant immuno-contraception vaccine for population management and rabies protection.

Value Proposition:More than 55,000 people die of rabies each year. About 95% of these occur in Asia and AfricaMore than 90% of human rabies are caused by rabid dog biting. Once the signs and symptoms of rabies start to appear, the disease is almost always fatal. Globally, the most cost-effective strategy for preventing human rabies is by eliminating rabies in dogs through animal vaccinations. http://www.who.int/mediacentre/factsheets/fs099/en This vaccine can prevent rabies and simultaneously control animal populationsThe vaccine is inexpensive and can be used on many animals including dogs, cats, raccoons, and other wild animals that spread rabies R&D Status: Animal study data is available; technology is available for licensing or collaborationIP Status: Provisional Patent Application filed September 2008CDC Reference # I-025-06; contact CDC Technology Transfer Office 770-488-8600

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U.S. Dept. of Health and Human Services ~ Centers for Disease Control and Prevention05/19/2009 BIO 2009 Slide 81

Centers for Disease Control and PreventionTechnology Transfer Office

Visit us at the Georgia Pavilion

Suzanne Seavello Shope, J.D.Technology Licensing and Marketing Scientist

Sources: www.who.intwww.cdc.gov

Internal marketing reports

Page 82: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 82

Unique Opportunity to Learn about Federal Science in Bio-Imaging

Page 83: Slide 1

U.S. Dept. of Health and Human Services ~ National Institutes of Health 05/19/2009 BIO 2009 Slide 83

To obtain copies of these slides, please visit:

http://ttc.nci.nih.gov Or

http://www.ott.nih.gov/BIO2009

Orhttp://www.cdc.gov/tto

keyword: BIO