Mobilizing the Body to Fight Cancer:

1
Mobilizing the Body to Fight Cancer Adoptive
Cell Transfer Immunotherapy SA Rosenberg, ME
Dudley, K Liu, RA Morgan, MR Parkhurst, NP
Restifo, PF Robbins, JC Yang, et al. NCI CCR
Surgery Branch, Tumor Immunology Section

• TechnologyPromising immunotherapeutics and
  cancer treatment strategy whereby
• Immune cells are isolated from a cancer patient
• Isolated cells are enhanced for anti-cancer
  activity and survival and proliferated ex vivo
• Cells are transferred back into the patient to
  attack tumors

• Value Proposition
• Enhanced Anti-Cancer Activity
• Directs the bodys immune system to target tumors
• Patient-specific and tumor antigen-specific
  treatments
• Reduced Side-Effects compared to conventional
  chemotherapy
• Enhanced Effectiveness of Transferred Cells
• Patient pre-treatment with lymphodepleting
  chemotherapy
• Genetically-engineered immune cells have
  prolonged survival, enhanced proliferation in
  patients, and increased reactivity to tumor
  antigens
• RD Status Ongoing clinical trials. Objective
  clinical responses observed in treated patients.
• IP Status US Applications 10/526,697,
  10/531,145, 11/575,077, 11/576,621, 12/205,106,
  12/443,111, 61/147,846, PCT/US08/77333, and
  foreign counterparts
• Reference No. E-275-2002, E-297-2002, E-106-2004,
  E-340-2004, E-090-2006, E-304-2006, E-059-2007,
  E-312-2007, E-043-2009

(From Rosenberg SA, et al. Nat. Rev. Cancer
(2008) 8305)
2
Nucleosides for Imaging and Treatment
ApplicationsJerry Collins et al.

• TechnologyNucleosides that provide for
• External imaging of tumor cell proliferation
• Noninvasive determination of which tumors would
  be sensitive to drug therapy
• Potential utility as a novel antitumor treatment

Whole body image of a patient with colorectal
cancer and liver metastasis
Low Uptake In Bone Marrow

• Value Proposition
• Rapid evaluation of treatment outcome during
  therapy
• Nucleosides are directly targeted towards
  specific events
• No current treatment for tumors with high levels
  of drug resistance, specifically thymidylate
  synthase
• On-going clinical studies sponsored by NCI for
  the nucleosides as imaging agents.
• Therapeutic IND filed in 2008 and NCI sponsored
  clinical studies expected to start in 2009.
• RD Status Pre-clinical and Clinical Data
  available
• IP Status US Patent Nos. 6,677,314 6,677,315
  6,753,309 6,682,715 6,683,045 6,703,374 and
  foreign counterparts.
• Reference E-058-1997

Low Uptake In Bone Marrow
3
Antiangiogenic and Antitumor Therapy using
FILIP1L Fragments Steven Libutti et al.

• TechnologySmall cDNA fragments of the coding
  region for wild type filamin A interacting
  protein 1-like (FILIP1L) and variant 2 of FILIP1L
  genes that encode proteins that inhibit cell
  proliferation and migration, and induce cell
  apoptosis
• Promising antivascular therapy for cancer and
  diseases related to abnormal vessel development.

Vessel density was significantly decreased in
tumors From FILIP1L fragment-treated mice
FILIP1L Fragment-Treated

• Value Proposition
• FILIP1L fragments have been delivered
  successfully to tumor-associated endothelial
  cells in vivo and demonstrated significant
  anti-tumor activity.
• Inventors have expressed the recombinant protein
  and developed antibodies to detect the protein
  fragments by Western, ELISA and
  immunohistochemistry.

Control

• RD Status Pre-clinical development
• Reference E-166-2007
• IP Status PCT Application No. PCT/US08/085825
  filed 12/03/2008

4
Cancer Detection Based on Spatial Genome
Organization in the Cell NucleusTom Misteli et
al.

• TechnologyDetects abnormal cells and identifies
  gene markers by the spatial arrangement of genes
  within the nucleus of the cell
• Diagnostic test for cancer using tumor biopsies

Normal

• Value Proposition
• Sensitive detection of cancer
• Very small sample needed (100-200 cells)
• Probes to all genomic regions are available
• Measures metastatic potential of cancer cells
• Determines tumor type
• Does not require mitotic chromosomes
• Alternative or complementary to conventional
  diagnostics
• Single cell assay allows analysis of
  subpopulations from biopsy
• RD Status Assay validation using a large set of
  tumor samples
• IP Status US Application No. 61/094,318 filed
  09/04/08
• Reference E-283-2008

Cancer
Spatial Gene positioning
5
A Novel Therapeutic Strategy for the Treatment of
Melanoma and HyperpigmentationVincent Hearing et
al. (NCI)

• TechnologySOX9 for the treatment of melanoma
  and hyperpigmentation
• SOX9 is expressed by normal human melanocytes in
  vitro and in the skin in vivo, and
  over-expression of SOX9 decreases the
  proliferation of mouse and human melanoma cell
  lines via several pathways
• Describes new insights into Melanoma development
  and new therapeutic approaches

• Applications
• Inhibiting the proliferation of melanoma cells
• Increasing sensitivity to retinoic acid
• Increasing skin pigmentation in hypopigmentary
  disorders

Passeron T, Valencia J, Namiki T, Vieira W,
Passeron H, Miyamura Y, Hearing VJ. Upregulation
of SOX9 inhibits the growth of human and mouse
melanomas and restores their sensitivity to
retinoic acid. J. Clin. Invest. 119954-963,
2009.
RD Status Animal model studies IP Status
International Application No. PCT/US08/009762
filed 08/03/08 Reference E-150-2007 Licensing
Contact Whitney Hastings
hastingw_at_mail.nih.gov
6
Prevention of Head and Neck Cancer Using
Rapamycin and Its AnalogsJ. Silvio Gutkind et
al. (NIDCR)

• TechnologyPreventing or treating head and neck
  squamous cell carcinoma (HNSCC) through the
  inhibition of mTOR activity.
• Pre-clinical Results
• Rapid regression of genetically-defined mouth
  tumors in mice (Cowdens syndrome and
  ras/p53-induced carcinomas).
• Potential for prevention and treatment of HNSCC
  caused by chronic exposure to tobacco-related
  carcinogens.

• Market
• Approximately 500,000 new cases of HNSCC arise
  every year making it the 6th most common cancer
  in the world.
• Frequently, prognosis is poor due to late
  detection of cancer.
• IP Status US Application No. 61/090,414 filed
  08/20/08
• Reference E-302-2008

Tongues of the mice afflicted with cancer caused
by tobacco-related carcinogens
7
Pharmacodynamic Assay to Monitor HDAC
InhibitorsEun Joo Chung and Jane Trepel (NCI)
New Protocol

• TechnologyRapid, simple, sensitive flow
  cytometric assay for the pharmacodynamic analysis
  of histone deacetylase inhibitors (HDAC) in
  clinical development as novel anti-cancer agents.
• Excellent tool for accelerating drug development
  from preclinical animal studies to Phase III
  trials

Blood draw

• Value Proposition
• Screens large numbers of mixed cell samples
• Identifies different cell types
• Monitor the effects of multiple classes of drugs
  simultaneously, i.e combination therapy
• Quantifies the proportion and type of cells
  exhibiting a response
• Sensitive measurement of protein acetylation
• Requires only 50 microliters of whole blood (a
  finger stick)
• RD Status Assay validated in clinical trials
• IP Status US Application No. 11/467,080 filed
  August 24, 2006 and foreign counterparts
• Reference E-094-2004

Fixation/Permeabilization Staining Analysis
HDACi Response 7-Parameter Analysis
Pretreatment
24 h-post MS-275
Acetylated lysine
Acetylated lysine
CD3
CD3
8
Antiangiogenic and Antitumor Therapy using DOC1
Fragments Steven Libutti et al.

• TechnologySmall cDNA fragments of the coding
  region for wild type filamin A interacting
  protein 1-like (FILIP1L), previously known as
  down-regulated in ovarian cancer 1-like (DOC1)
  and variant 2 of FILIP1L genes that encode
  proteins that inhibit cell migration and
  motility, induce cell apoptosis and inhibit cell
  proliferation
• Promising antivascular therapy for cancer and
  other diseases related to abnormal vessel
  development such as retinopathies.

• Value Proposition
• DOC1 fragments have been delivered successfully
  to endothelial cells and tumor cells both in
  vitro and in vivo and demonstrated significant
  anti-tumor activity.
• Inventors have expressed the recombinant protein
  and developed antibodies to detect the protein
  fragments by Western, ELISA and
  immunohistochemistry.
• RD Status Pre-clinical development
• IP Status PCT Application No. PCT/US08/085825
  filed Dec. 3, 2008
• Reference E-166-2007

9
Nucleosides for Imaging and Treatment
ApplicationsJerry Collins et al. (FDA)

• TechnologyNucleosides that provide for
• External imaging of tumor cell proliferation
• Noninvasive determination of which tumors would
  be sensitive to drug therapy
• Potential utility as a novel antitumor treatment

• Value Proposition
• Rapid evaluation of treatment outcome during
  therapy
• Nucleosides are directly targeted towards
  specific events
• No currently treatment for tumors with high
  levels of drug resistance, specifically
  thymidylate synthase
• On-going clinical studies sponsored by NCI for
  the nucleosides as imaging agents.
• Therapeutic IND filed in 2008 and NCI sponsored
  clinical studies expected to start in 2009.
• RD Status Pre-clinical and Clinical Data
  available
• IP Status US Patent Nos. 6,677,314 6,677,315
  6,753,309 6,682,715 6,683,045 6,703,374 and
  foreign counterparts.
• Reference E-058-1997

10
Pharmacogenetic Markers for Anticancer Treatment
OutcomeW.D.Figg et al. NCI CCR, Molecular
Pharmacology Section, Medical Oncology Branch and
Affiliates
Technology Polymorphic genetic markers in the
ABCB1, SLCO1B3 (formerly SLC21A8) and CYP1B13
genes that can be measured in genomic DNA
obtained from a blood sample. Can predict
survival from diagnosis, and duration of androgen
deprivation therapy in individuals with prostate
cancer (SLCO1B3), predict taxane-mediated
toxicity (ABCB1), and survival to docetaxel
treatment in androgen independent prostate cancer
(CYP1B13).
1 of 4
11

• Value Proposition
• Gene chip technology allows for the combination
  of multiple genotype assays in a single genetic
  test kit.
• Validated assays are easy to perform with minimal
  invasiveness (i.e. germline DNA is obtained via a
  simple blood).
• Low cost genotyping strategies are available
• Multiple genetic markers can be genotyped on a
  single chip to provide a multigenic approach to
  diagnostics
• Minimizing adverse events during therapy can
  reduce overall costs to clinics and the
  pharmaceutical industry, and potentially reduce
  the time to FDA approval during drug development.

RD Status Discovery, Preclinical and Clinical
Development Stage IP Status U.S. application no.
60/879,503 U.S. application no. 12/304,071 U.S.
application no. 11/991,878 and foreign
equivalents. HHS Ref. Nos. E-083-2007/0
E-237-2006/0 and E-307-2005
2 of 4
12
Pharmacogenetics Applications
3 of 4
13

• Collaborative Opportunities
• ABCB1 genotyping to predict taxane-mediated
  toxicity
• SLCO1B3 (OATP1B3) genotyping to predict survival
  after diagnosis of prostate
• cancer, and duration of androgen deprivation
  therapy (time to androgen independence).
• Use of CYP1B13 Genotyping to Predict Survival to
  Docetaxel
• Treatment in Androgen-Independent Prostate Cancer
• Retrospective validation in larger patients
  cohorts from different cancer
• types.
• In vitro and in vivo models
• Preclinical testing
• Determination of most effective therapeutic
  strategies for individuals with
• a specific genetic background.
• Determine genetic modifiers
• Prospective clinical trials

Contact Information Sabarni K. Chatterjee, Ph.D.
NIH Office of Technology Transfer 6011 Executive
Blvd, Suite 325 Rockville, MD 20852-3804 (301
)435-5587 chatterjeesa_at_mail.nih.gov
4 of 4
14
New Strategy and Compositions for Treating
Multidrug Resistant CancerHall et al.

• Technology
• New strategy for treating cancers that
  overexpress MDR1
• Unlike most methods, this approach does not
  inhibit MDR1 function
• The anticancer effects of these agents depend on
  the overexpression of MDR1
• These agents also appear to down-regulate MDR1
  expression
• Advantages
• 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
• RD Status Pre-Clinical Development.
• IP Status PCT/US2009/000861(filed 10 Feb. 2009)
  US 61/027,712 (files 10 Feb. 2008)
• HHS Reference No. E-017-2008/0

15
TRICOM A synergistic triad of costimulatory
molecules used in Cancer Vaccines for the
Prevention and Treatment of Cancer Jeffrey
Schlom et al. NCI, CCR, Laboratory of Tumor
Immunology and Biology

• Advantages
• The technology is beyond proof-of concept,
  supported by laboratory and clinical trial
  results and numerous publications.
• Recent Phase II clinical data are also available
  (to qualified licensees) employing TRICOM based
  vaccines.
• Further clinical studies are ongoing.
• Given the relatively more advanced stage of
  development of this technology, fewer validation
  studies are required compared to other
  immunotherapy related technologies.

• Technology
• TRICOM is a triad of costimulatory molecules used
  in vector-based cancer vaccines that employ a
  combination of T-cell costimulatory signals in
  combination with tumor associated antigens (TAAs)
  to greatly enhance the immune response against a
  variety of cancers. Already several TRICOM-based
  cancer vaccines incorporating TAAs have shown
  promising results during clinical stage
  development. Pre-clinical development of other
  TRICOM-based vaccines continues, which makes use
  of newly discovered TAAs and T-cell activating
  peptides derived from TAAs that would allow
  targeting cancers expressing poorly immunogenic
  TAA. Certainly, this cancer vaccine technology
  has a high potential for leading to a new
  approach in the prevention and/or treatment of
  cancer.

Success Story of TRICOM Technology Encouraging
Results for Prostate Cancer Vaccine Released Dr.
Jeffrey Schlom, Chief of the Laboratory of Tumor
Immunology and Biology at the National Cancer
Institute, National Institutes of Health (NIH),
led the scientific team that developed PROSTVAC,
a prostate cancer vaccine technology. PROSTVAC
is currently Bavarian Nordics (BN) lead prostate
cancer vaccine candidate. Bavarian Nordic
Immunotherapeutics (BNIT, U.S. subsidiary of BN)
has a license from the NIH to further develop
TRICOM based vaccines for use in prostate cancer.
BN recently released encouraging clinical data
for the vaccine at the Genitourinary Cancers
Symposium (GU) on February 26-28, 2009 in
Orlando, Florida. This announcement is the first
among several other study results that are
expected to be released in 2009.
Selected Relevant Patents U.S. Patent Nos.
6,969,609, 6,756,038, 6,001,349 7,118,738
7,410,644 6,946,133 6,893,869, 6,548,068 and
6,045,802 HHS Ref. Nos. E2561998/0,
E-099-1996/0 E-200-1990/0, E-154-1998/0,
E-260-1994/0.
16
Small-Molecule Activators of Pyruvate Kinase
Isoform M2Inventor Craig J. Thomas et
al. National Human Genome Research Institute
(NHGRI)
Background Cancer cells exploit pyruvate kinase
isoform M2 (PK-M2). PK-M2 inactivation leads to
buildup of metabolic intermediates, which cancer
cells use to proliferate. PK-M2 is expressed but
inactive in all cancer cells and is not expressed
in normal post-embryonic cells. Activation of
PK-M2 may stall tumor cell proliferation or
destroy the tumor cells. This invention
represents a novel, non-cytotoxic anti-cancer
approach with wide potential therapeutic
application.
PK-M2 is activated by our small molecules
PK-M2 is expressed but inactive in cancer cells

• The Invention
• Novel no other synthetic PK-M2 activators have
  been identified.
• Non-cytotoxic as PK-M2 is expressed only in
  cancer cells, this invention is not cytotoxic to
  normal, healthy cells.
• Wide potential therapeutic application all
  known cancer cells express but inactivate PK-M2.
• Development Status Early. This technology
  represents a collaborative opportunity - we are
  actively seeking partners for further research,
  development, and commercialization.
• Patent Status Provisional US 61/104,091
  (10/09/2008).
• For Further Information Please Contact Dr. Steve
  Standley, Licensing and Patenting Manager,
  sstand_at_mail.nih.gov, 301-435-4074.

Molecular graphics images of the PK-M2 x-ray
crystal structure 1T5A were produced using the
UCSF Chimera package from the Resource for
Biocomputing, Visualization, and Informatics at
the University of California, San Francisco
(supported by NIH P41 RR-01081).
17
Cyclized NRG Peptide for Tumor TargetingBradford
Wood et al. NIH Clinical Center
kNRG peptides
TechnologyCancer targeting cyclic peptides that
bind to aminopeptidase N isoform CD13. Can be
conjugated to chemotherapeutics, entrapped in a
liposome and conjugated to an imaging agent.

• Value Proposition
• High target specificity and affinity
• RD Status Discovery, Synthesis demonstrated.
• IP Status US Provisional Patent Applications
  61/074,864 filed June 23, 2008, and 61/106,722
  filed October 20, 2008.
• Reference HHS Ref. E-147-2008/0,1

04/02/2009
http//www.ott.nih.gov
18
Noninfectious Vaccine Against West Nile VirusT.
Liang, M. Qiao, A. Mundrigi, and W. Lipkin NIDDK
Liver Diseases Branch

• Technology West Nile Virus-Like Particles for
  Vaccine
• Competitive Advantages
• Strongly immunogenic
• Noninfectious
• Inexpensive and easy to manufacture usinginsect
  cells
• Current Market No approved human
  vaccineexists horse vaccine (live attenuated)
  exists butefficacy not measured
• RD Status tested in mouse model inventors
  open to collaborations
• IP Status US 2008/0118528, EP 05746277.2(priorit
  y date 4 May 2004)
• HHS Reference E-352-2008/0
• Contact
• Bruce Goldstein 301/435-5740 goldsteb_at_mail.nih.g
  ov

Figure Detection of West Nile virions and viral
RNA after viral challenge, in the serum, spleens,
and brains of mice immunized with CprME-LP or
prME-LP (with and without AS01ß adjuvant). The
Y-axis scales are constructed to start with a
value near the threshold of detection of each
assay (plaque-forming or real-time RT-PCR).
M Qiao, et al., Induction of Sterilizing
Immunity against West Nile Virus (WNV), by
Immunization with WNV-Like Particles Produced in
Insect Cells, J Infect Dis 190(12)2104-2108
(2004)
19
Nanoparticles for Imaging and Treatment of Brain
Tumors Hemant Sarin, M.D., NIH Clinical Center

• Technology Nanoparticles selectively cross the
  blood-brain tumor barrier (BBTB) of brain tumors
  but not the normal blood-brain barrier (BBB)
• Particle size only increases 1 to 2 nm per
  generation (G) even when functionalized with
  small agents (i.e. Gd-DTPA)

In vitro. Functionalized PAMAM dendrimers within
any particular generation are uniform in size,
shape and density. Panel A naked PAMAM
dendrimers. Panel B dendrimer functionalized with
Gd-DTPA. Panel C Electromicrograph of Gd-G5,
Gd-G6, Gd-G7 and Gd-G8 dendrimer generations.
Scale bar 20 nm. (Adapted from Journal of
Translational Medicine 2008, 680)

• Advantages
• Particle Size Adjustable to achieve the desired
  particle blood half-life
• 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 chemotherapy delivery

Development animal glioma regression studies
underway with chemotherapy carrying
nanoparticles Patent Status Provisional
61/055,328 (May 22, 2008) Reference No.
E-063-2008 Contact Surekha Vathyam, Ph.D.
(vathyams_at_mail.nih.gov [phone])
In vivo. Gd concentration maps showing
Gd-dendrimer distribution within the largest and
smallest gliomas of each generation over time. A)
Gd-G5, Gd-G6, and Gd-G7 dendrimers slowly
accumulate within the extravascular tumor space
of the largest RG-2 gliomas within the size range
of tumors in the study. Gd-G8 dendrimers remain
intravascular. B) Gd-G5 and G6 dendrimers still
slowly accumulate within tumor tissue of the
smallest RG-2 gliomas, which have a minimally
compromised blood-brain tumor barrier. Gd-G7
dendrimers are impermeable to the BBTB of the
smallest RG-2 gliomas and remain intravascular.
Gd-G8 dendrimers continue to be impermeable to
the blood-brain tumor barrier of the smallest
RG-2 gliomas. (Adapted from Journal of
Translational Medicine 2008, 680)
20
ABC Transporter Inhibitors Nadya Tarasova et
al. NCI CCR, Cancer and Inflammation Program
Technology ABC transporters pump a variety of
compounds from the cytoplasm out of the cell
thereby modulating numerous cell functions.
However, these receptors also mediate the efflux
of chemotherapeutics resulting multidrug
resistant cancer cells. A portfolio of synthetic
peptide analogs targeting BCRP, MDR1, MRP1, MRP2,
BCRP/MXR/ABCP receptors have been developed to
counteract this effect.

• Value Proposition
• Sensitizes drug resistant tumor cells to
  chemotherapeutics
• RD Status Pre-clinical
• IP Status US Patent No. 7,517,849 issued April
  14, 2009
• Reference E-019-2000

http//ott.od.nih.gov
21
Mouse Embryonic Stem Cells to Evaluate BRCA2
Mutations Shyam Sharan et al. NCI Mouse Cancer
Genetics Program, Genetics of Cancer
Susceptibility Section
TechnologyWild-type and eleven mutant BRCA2
cell lines were developed from a mouse embryonic
stem cell and bacterial artificial chromosome
based assay to express mutations in human BRCA2

• Applications
• Evaluate the effect of DNA damaging agents and
  genotoxins
• Screening tool for chemotherapeutic agents
• Radiation, homologous recombination and
  karyotyping assays
• Reference E-262-2007

http//ott.od.nih.gov
22
Chemical programming of antibodies through
selenocysteine Christoph Rader et al. NCI CCR,
Experimental Transplantation and Immunology
Branch

• Technology
• Hybrid molecules composed of an antibody, or
  antibody fragment, and a small synthetic molecule
  covalently linked at an engineered selenocysteine
  near the C-terminus of the antibody

• 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 interactions
• Inexpensive manufacturing Adjustable valence and
  effector activity
• Applications
• Improve pharmacokinetics and activity of small
  synthetic molecules
• Improve monoclonal antibody activity
• RD Status Pre-clinical development
• IP Status PCT Serial No. PCT/US2008/059135
  (4/2/08) U.S. Patent Application No. 60/909,665
  (4/2/07)
• Reference E-146-2007

23
Detection of Dihydropyrimidine Dehydrogenase
(DPD) Mutations For Clinical UseF. Gonzalez, et
al. NCI Center for Cancer Research, Laboratory of
Metabolism
TechnologyDPD is responsible for the metabolism
of fluoropyrimidine drugs, such as the much used
chemotherapeutic agent 5-fluorouracil. Detection
of DPD mutations can reduce the risk of severe
toxic reactions suffered by cancer patients
treated with 5-fluorouracil and lack of DPD
enzymatic activities.

• Applications and Advantages
• Molecular diagnostic of patients lack of DPD
  enzyme activity
• Reduction of severe toxic reaction in cancer
  patients caused by fluorouracil
• IP Status A multitude of issued patents in
  jurisdictions including the US, Europe, Canada,
  and Australia.
• HHS Reference E-157-1994
• Licensing Contact Betty B. Tong, Ph.D.
  301-594-6565 tongb_at_mail.nih.gov

24
Identification of Individuals Likely to Benefit
from Statin TherapyL. Kopelovich, et al. NCI
Division of Cancer Prevention, Chemopreventive
Agent Development Research Group
TechnologyPharmacogenetic method to identify
candidates who are most likely to benefit from
treatment with statins to reduce cancer risk, and
to minimize unnecessary cost and side effects.

• Applications and Advantages
• Identification of individuals most likely to
  benefit from statin use for reduction of cancer
  risk in addition to lowering cholesterol
• Cost and side effects reduction for statin use
• Potential expansion of statin market
• Development Status Genetic variants of HMG
  coenzyme A reductase gene were identified and
  studied for functional significance in vitro.
• IP Status PCT Application filed Nov.4, 2008,
  Application PCT/US2008/082359
• HHS Reference E-328-2007
• Licensing Contact Betty B. Tong, Ph.D.
  301-594-6565 tongb_at_mail.nih.gov

25
Treating Cancer with Inhibitors of Wip1Appella
et al.

• Technology
• This technology concerns small molecule
  inhibitors of Wip1
• Wip1 is overexpressed in several cancers,
  including breast and ovarian cancer
• Wip1 inhibits the tumor suppressor protein p53
• Inhibition of Wip1 may be a valuable anti-cancer
  agent by relieving the suppression of p53
• Advantages
• The structures of the inhibitors allow the
  specific targeting and inhibition of Wip1,
  reducing the possibility of undesired side
  effects
• Small molecules are stable and able to penetrate
  cells, allowing efficient delivery of the agent
• RD Status Pre-Clinical Development.
• IP Status PCT/US2008/074864 (filed 29 Aug.
  2008) US 60/969,258 (29 Aug. 2007)
• HHS Reference No. E-302-2007/0
• Licensing Contact David Lambertson, Ph.D.,
  lambertsond_at_mail.nih.gov 301-435-4632

26
New Diagnostic for Lung Cancer (NSCLC)Dracheva
et al.

• Technology
• New biomarker for non-small cell lung carcinoma
  (NSCLC)
• NSCLC is difficult to detect before the disease
  progresses significantly
• Prognosis is tied to early detection of NSCLC
• The LELA1 (CCDC6) gene is inactivated in many
  NSCLC cells
• Chromosomal loss of one copy
• Gene inactivation of the second copy through
  promoter functional loss
• Detection of the gene inactivation may lead to
  early diagnosis of NSCLC
• Advantages
• Diagnosis can be performed prior to significant
  disease progression
• Early diagnosis may result in better prognosis
  for patients
• Non-invasive method affords greater patient
  comfort
• RD Status Pre-Clinical Development
• IP Status PCT/US2008/059800 (filed 9 April 2008)
• HHS Reference No. E-265-2007/0
• Licensing Contact David Lambertson, Ph.D.,
  lambertsond_at_mail.nih.gov 301-435-4632