University of California-Davis Patents 2007

The following is a list of the patents attributed to your Program.
Please verify that the patents we have listed are correct, and add any
new patent information to the list. Please be sure that \"track
changes\" is on before making any additions.

Bioassay for detecting 2,3,7,8-tetrachlorodibenzo-para-dioxin and
TCDD-like compounds and novel recombinant cell line useful therefore

Number: 5,854,010

Year: 1998

Authors: Denison, M.S., A. Brouwer, G.C. Clark

# Compact assay system with digital information 

Number: 6,342,395

Year: 2002

Authors: Hammock, B.D., H. Kido, A. Maquieira

# Cyanohydrin ethers and esters as high-sensitivity enzyme substrates 

Number: 6,710,200

Year: 2004

Authors: Hammock, B.D., G. Shan, R. Zhang

**Cyanohydrin ethers and esters as high-sensitivity enzyme substrates**

Number: 6,528,675

Year: 2003

Authors: Bruce D. Hammock, Guomin Shan, Rong Zhang

# Diagnostic microarray apparatus 

Number: 6,395,562

Year: 2002

Authors: Hammock, B.D., H. Kido, A. Maquieira

Enzyme amplified, complex linked, competitive and non-competitive assays
for the detection of metal ions

Number: 5,459,040

Year: 1995

Authors: Hammock, B.D., F. Szurdoki, H. Kido

# Epoxide hydrolase complexes and methods therewith 

Number: 6,150,415

Year: 2000

Authors: Hammock, B.D., C. Morisseau, J. Zheng, M.H. Goodrow, T.
Severson, J.R. Sanborn

# Epoxide hydrolase inhibitor methods 

Number: 6,174,695

Year: 2001

Authors: Hammock, B.D., M.F. Moghaddam, J.M. Cheek, B. Borhan, J.
Fergusson, D.F. Grant, J.F. Greene, K. Matoba, J. Zheng, M.F. Sisemore

# Inhibition of glutathione transferase by haloenol lactones 

Number: 6,103,665

Year: 2000

Authors: Jones, A.D., A.E. Mitchell, B.D. Hammock, J. Zheng

# Inhibition of glutathione transferase by haloenol lactones 

Number: 5,767,147

Year: 1998

Authors: Jones, A.D., A.E. Mitchell, B.D. Hammock, J. Zheng

**Inhibition of glutathione transferase by haloenol lactones**

Number: 6,495,370

Year: 2002

Authors: A. Daniel Jones, Alyson E. Mitchell, Bruce D. Hammock, Jiang
Zheng

# Inhibitors of epoxide hydrolases for the treatment of hypertension 

Number: 6,693,130

Year: 2004

Authors: Kroetz, D.L., D.C. Zeldin, B.D. Hammock, C. Morisseau

Linoleic acid diol and glucuronide conjugate levels as diagnostic
markers of disorders of abnormal regulation of cytochrome P450
metabolism of unsaturated fatty acids

Number: 6,756,210

Year: 2004

Authors: Hammock, B.D., G. Zurek, S.J. Gee, J.W. Newman, J. Zheng

**Method of predicting and enhancing success of IVF/ET pregnancy**

Number: 5,994,148

Year: 1999

Authors: Dennis R. Stewart, Catherine A. Vandervoort

**Methods for classifying high-dimensional biological data**

Number: 7,062,384

Year: 2006

Authors: David M. Rocke, Danh V. Nguyen

# Recombinant soluble epoxide hydrolase 

Number: 5,445,956

Year: 1995

Authors: Hammock, B.D., D.F. Grant, J.K. Beetham

**Relaxin levels corrlelated to IVF/ET pregnancy success**

Number: 6,660,531

Year: 2003

Authors: Dennis R. Stewart, Catherine A. Vande Voort

**[Additional Information (including Patents Pending)]{.underline}**

**NON-CONFIDENTIAL DESCRIPTION**

**Technology Description**

Methyl-*tert*-butyl ether (MTBE) is a water-soluble gasoline additive
that is now causing significant contamination of ground and surface
water supplies. Originally introduced as an octane booster, it has more
recently been mandated in certain jurisdictions (notably California) in
reformulated gasolines in order to reduce carbon monoxide pollutant
levels resulting from gasoline combustion. However, MTBE is not easily
biodegraded or otherwise removed from the environment, and gasoline is
an ubiquitous and widespread substance that is discharged in large
quantities, making it impossible to prevent environmental exposure of
gasoline components. There is an urgent need for new decontamination
techniques to offset the threat to water-quality posed by air-quality
mandates.\
A new bacterial strain with high biodegradation activity on MTBE has
been isolated by researchers at the University of California, Davis. A
unique aspect of these bacteria is that they can use MTBE as their sole
carbon and energy source, metabolizing MTBE to carbon dioxide. Also,
these bacteria degrade concentrations of MTBE as high as 500 micrograms
per milliliter solution, meaning that they tolerate the high MTBE
concentrations associated with very contaminated soils and water.

**Applications**

The UC bacteria can biodegrade MTBE when inoculated into soil and
groundwater samples, which suggests that they have a strong potential
for employment with *in situ* decontamination processes as well as in
bioreactors and other treatment systems.

  -----------------------------------------------------------------------
  Inventors

  \- Jessica Hanson\
  - Kate Scow

  UC Case Number(s)

  \- 1999-073

   
  -----------------------------------------------------------------------

**NON-CONFIDENTIAL DESCRIPTION**

**Technology Description**

New, highly efficient nanoparticle phosphors for use in biological
fluorescent labeling have been developed by researchers at the
University of California, Davis. In this novel method, nanoparticles of
silica, yttria or gadolinium oxide are created through a one-step,
gas-phase synthesis process allowing for the introduction of lanthanide
elements into the resulting particles.\
\
A novel technique was developed for surface coating of the nanoparticles
with polymers containing different functional groups such as amino and
carboxyl groups. They are used for surface modification of the particles
with a variety of biomolecules like different proteins, antibodies and
also small molecules. In addition, a method was developed for precise
quantification of the molecules on the particle surface giving the
possibility for optimization of assay protocols.

**Related Technologies**

-   [[2006-393]{.underline}](http://ovcr.ucdavis.edu/ncd.cfm?caseno=2006-393) -
    Significantly Faster Microchannel Based Immunoassays

    **Advantages**

Some of the advantages of the UC Davis method over existing methods
include:

-   The particles have been successfully applied as labels for
    immunoassays

-   The particles are free of aggregation, clean of harmful contaminants
    and amenable to all applications involving fluorescent nanoparticles

-   They have long life times that make them useful in time gated
    detection methods

-   They do not photobleach

-   They are cheap to produce in significant amounts

-   They can be synthesized with magnetic cores for separation and
    manipulation

-   Doping with multiple lanthanides is possible, permitting ratioing of
    multiwavelength emissions that offers potentially thousands of
    distinct labels for microarrays

-   The particles have been used with protein microarrays that
    demonstrated the use of an internal standard for quantification

-   Immunoassays have been carried on the top of freely moving fluoro
    nanoparticles that are magnetic. After binding with antigens, the
    particles are recalled magnetically for optical interrogation. The
    nanoscale format provided a huge surface area for immobilization of
    multiple antibodies

    Patent Status

  ------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  **Canada**    Patent Pending

                

  **United      2 Patents Pending
  States**      

  Reference     PCT publication [[WO 05/040756
                A3]{.underline}](http://www.wipo.int/pctdb/en/search.jsp?query=PCT/US04/35295 &DBSELECT2=PCT&SEARCH_PAGE=simp&SERVER_TYPE=19&BRIEF_ELEMENT_SET=HITNUM,B-ENG,DP,MC,PA,ABSUM-ENG)
                published May 06,2005
  ------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

  -----------------------------------------------------------------------
  Inventors

  \- Dosi Dosev\
  - Bing Guo\
  - Ian Kennedy\
  - Darina Melnikova\
  - Mikaela Nichkova

  UC Case Number(s)

  \- 2004-167
  -----------------------------------------------------------------------

**NON-CONFIDENTIAL DESCRIPTION**

**Technology Description**

Researchers at UC Davis have developed a microchannel based immunoassay
using magnetic/luminescent core/shell nanoparticles as antibody carriers
and labeling. The magnetic/luminescent particles serve as carriers for
the antibodies and as an internal luminescent standard. The researchers
have developed techniques and used additional technology that
significantly increase the speed of the immunoreaction as well as the
level of diffusion during the incubation steps. Coupled with the small
volume of the single microchannel, the immunoassay times are
significantly reduced to about 5 minutes.

**Related Technologies**

-   [[2004-167]{.underline}](http://research.ucdavis.edu/ncd.cfm?caseno=2004-167) -
    Nanoparticle Fluors and Functionalization Techniques for use in
    Fluorescent Labeling

    **Advantages**

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-   The whole assay is performed in very small volumes using very small
    amounts of reagents

-   The speed of the assay is significantly increased, with incubation
    times in the range of several minutes

-   The luminescence of the particles serves as an internal calibration
    for the assay and helps to avoid experimental error for particle
    loss.

    Patent Status

  ---------------------------------------------- ------------------------
  **Patent Cooperation Treaty**                  Patent Pending

  ---------------------------------------------- ------------------------

  -----------------------------------------------------------------------
  Inventors

  \- Dosi Dosev\
  - Ian Kennedy\
  - Mikaela Nichkova\
  - Vishal Talwar
  -----------------------------------------------------------------------

**NON-CONFIDENTIAL DESCRIPTION**

*Allosteric Competitive Inhibitors of the N-Terminal Phosphatase
Activity of sEH to Mitigate Pathophysiological Conditions*

**Technology Description**

Soluble epoxide hydrolase (sEH) is an enzyme that has two catalytic
activities: a phosphatase activity associated with the N-terminal domain
(Nterm-Phos) and an epoxide hydrolase activity associated with the
C-terminal domain (Cterm-EH). The C-terminal domain is related to blood
pressure and inflammation regulation through the hydrolysis of
epoxy-fatty acids. The role of the phosphatase activity is as yet
unknown. UC Davis researchers have discovered novel ligands of the
N-terminal phosphatase active site. These compounds are allosteric
competitive inhibitors which alter enzyme phosphatase activity, and will
have uses to understand the mechanism and biological role of the
sEH-N-terminal phosphatase activity.

**Applications**

The compounds may have immediate use as biochemical tools to investigate
the mechanism and role of numerous phosphatases including the
phosphatase activity of the soluble epoxide hydrolase. Inhibition of
phosphatase activity may lead to novel therapeutic agents for
pharmacological tools for therapy. Furthermore, these compounds could
also mitigate the C-terminal EH activity through a non-competitive
mechanism that could be useful to treat inflammation and cardiovascular
diseases.

**Advantages**

Soluble epoxide hydrolase is a particular enzyme that has two enzymatic
activities. Previously described inhibitors only reduced the epoxide
hydrolase activity (Cterm-EH) of the enzyme. The compounds in this
application are the first described that can inhibit the
N-terminal-phosphatase activity of sEH.

**References**

[[Laboratory of Pesticide and
Biotechnology]{.underline}](http://www.biopestlab.ucdavis.edu/)

[[Tran KL, Aronov PA, Tanaka H, Newman JW, Hammock BD, and Morisseau C.
2005. Lipid Sulfates and Sulfonates are Allosteric Competitive
Inhibitors of the N-terminal Phosphatase Activity of the Mammalian
Soluble Epoxide Hydrolase. Biochemistry.
44(36):12179-87.]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16142916&query_hl=2&itool=pubmed_docsum)

Patent Status

  ---------------------------------------------- ------------------------
  **Patent Cooperation Treaty**                  Patent Pending

  ---------------------------------------------- ------------------------

  -----------------------------------------------------------------------
  Inventors

  \- Bruce Hammock\
  - Christophe Morisseau\
  - John Newman

  UC Case Number(s)

  \- 2005-597
  -----------------------------------------------------------------------

**NON-CONFIDENTIAL DESCRIPTION**

*Combination Therapy of NSAIDs and sEHIs Produce Analgesic and
Anti-Inflammatory Effects*

**Technology Description**

Non-steroidal anti-inflammatory drugs (NSAIDs) alleviate pain and
inflammation by counteracting cyclooxygenase (COX) enzymes and thereby
decreasing production of metabolites that lead to pain and
inflammation.  Although NSAIDs are highly effective in their ability to
reduce pain and inflammation, they cause a wide variety of undesired
side effects such as aggravation of congestive heart failure, dyspepsia,
renal failure, uncontrolled hypertension, and peptic uleration
hemorrhage and perforation.\
\
Researchers at the University of California, Davis have discovered that
combination therapy of soluble epoxide hydrolase inhibitors (sEHIs) and
NSAIDs produce significantly beneficial effects that are additive for
controlling pain and inflammation while reducing NSAID side effects.  UC
Davis researchers have demonstrated this in lipopolysaccharide (LPS) -
challenged mice.  In addition, UC Davis Researchers have discovered that
sEHIs may synergize COX inhibitors like NSAIDs in their action without
increasing side effects.

**Applications**

Pain relief for sufferers of arthritis and other inflammatory diseases
(*i.e.*, rheumatoid arthritis, osteoarthritis, psoriasis, etc.).

**Advantages**

-   sEHIs can enhance the effects of NSAIDs for the same therapeutic
    effect;

-   sEHIs may have greater potency in reducing inflammation compared to
    conventional NSAIDs; and,

-   sEHIs combined with conventional NSAIDs may be useful agents for the
    treatment of pain and inflammation.

    **References**

[[Schmelzer KR, Inceoqlu B, Kubala L, Kim IH, Jinks SL, Eiserich JP, and
Hammock BD. 2006. Enhancement of Antinociception by Coadministration of
Nonsteroidal Anti-Inflammatory Drugs and Soluble Epoxide Hydrolase
Inhibitors. Proc Natl Acad Sci USA.
103(37):13646-51.]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16950874&query_hl=2&itool=pubmed_docsum)

Patent Status

  --------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
  **Canada**            Patent Pending

  **European Patent     Patent Pending
  Office**              

  **Japan**             Patent Pending

                        

  **United States**     Patent Pending

  Reference             PCT publication [[WO
                        2006/086108]{.underline}](http://www.wipo.int/pctdb/en/search.jsp?query=PCT/US06/00914 &DBSELECT2=PCT&SEARCH_PAGE=simp&SERVER_TYPE=19&BRIEF_ELEMENT_SET=HITNUM,B-ENG,DP,MC,PA,ABSUM-ENG)
                        published Aug 17,2006
  --------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

  -----------------------------------------------------------------------
  Inventors

  \- Bruce Hammock\
  - Ahmet Bora Inceoglu\
  - Kara Schmelzer

  UC Case Number(s)

  \- 2005-253
  -----------------------------------------------------------------------

**NON-CONFIDENTIAL DESCRIPTION**

*sEH Inhibitors as Pain Reducing Analgesic Agents*

**Technology Description**

Analgesic compounds have very wide applications in human and animal
health.  Many analgesic compounds exist on the market for pain control,
however, not all types of pain are currently controlled by available
pharmaceuticals. \
\
Researchers at the University of California, Davis have discovered a
novel use of soluble epoxide hydrolase inhibitors (sEHIs) as pain
reducing analgesic agents.  sEH inhibitors, with a unique mechanism of
action, have pain reducing effects that appear to be independent from
blocking inflammation.

**Applications**

Pain reduction and therapeutic efficacy in the treatment and management
of acute and chronic pain.

**Advantages**

-   First case of a novel mechanism of analgesic activity independent
    from inflammatory pain;

-   sEH inhibitors offer unique advantages as stand-alone or as
    synergistic therapeutic agents; and,

-   sEH inhibitors can be used therapeucially or prophylactically for
    the treatment of acute and chronic nociceptive pain.

    **References**

[[Inceoglu B, Jinks SL, Schmelzer KR, Waite T, Kim IH, Hammock BD. 2006
\"Inhibition of Soluble Epoxide Hydrolase Reduces LPS-Induced Thermal
Hyperalgesia and Mechanical Allodynia in a Rat Model of Inflammatory
Pain\" Life Sci.
79(24):2311-9.]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16962614&query_hl=2&itool=pubmed_docsum)

Patent Status

  ------------- ------------------------------------------- -- ------------------------
  **Patent                                                     Patent Pending
  Cooperation                                                  
  Treaty**                                                     

                Inventors                                      

                \- Bruce Hammock\                              
                - Ahmet Bora Inceoglu                          

                UC Case Number(s)                              

                \- 2005-681                                    

                                                               
  ------------- ------------------------------------------- -- ------------------------

**NON-CONFIDENTIAL DESCRIPTION**

*Allosteric Competitive Inhibitors of the N-Terminal Phosphatase
Activity of sEH to Mitigate Pathophysiological Conditions*

**Technology Description**

Soluble epoxide hydrolase (sEH) is an enzyme that has two catalytic
activities: a phosphatase activity associated with the N-terminal domain
(Nterm-Phos) and an epoxide hydrolase activity associated with the
C-terminal domain (Cterm-EH). The C-terminal domain is related to blood
pressure and inflammation regulation through the hydrolysis of
epoxy-fatty acids. The role of the phosphatase activity is as yet
unknown. UC Davis researchers have discovered novel ligands of the
N-terminal phosphatase active site. These compounds are allosteric
competitive inhibitors which alter enzyme phosphatase activity, and will
have uses to understand the mechanism and biological role of the
sEH-N-terminal phosphatase activity.

**Applications**

The compounds may have immediate use as biochemical tools to investigate
the mechanism and role of numerous phosphatases including the
phosphatase activity of the soluble epoxide hydrolase. Inhibition of
phosphatase activity may lead to novel therapeutic agents for
pharmacological tools for therapy. Furthermore, these compounds could
also mitigate the C-terminal EH activity through a non-competitive
mechanism that could be useful to treat inflammation and cardiovascular
diseases.

**Advantages**

Soluble epoxide hydrolase is a particular enzyme that has two enzymatic
activities. Previously described inhibitors only reduced the epoxide
hydrolase activity (Cterm-EH) of the enzyme. The compounds in this
application are the first described that can inhibit the
N-terminal-phosphatase activity of sEH.

**References**

[[Laboratory of Pesticide and
Biotechnology]{.underline}](http://www.biopestlab.ucdavis.edu/)

[[Tran KL, Aronov PA, Tanaka H, Newman JW, Hammock BD, and Morisseau C.
2005. Lipid Sulfates and Sulfonates are Allosteric Competitive
Inhibitors of the N-terminal Phosphatase Activity of the Mammalian
Soluble Epoxide Hydrolase. Biochemistry.
44(36):12179-87.]{.underline}](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16142916&query_hl=2&itool=pubmed_docsum)

Patent Status

  ------------- ------------------------------------------- -- ------------------------
  **Patent                                                     Patent Pending
  Cooperation                                                  
  Treaty**                                                     

                Inventors                                      

                \- Bruce Hammock\                              
                - Christophe Morisseau\                        
                - John Newman                                  

                UC Case Number(s)                              

                \- 2005-597                                    
  ------------- ------------------------------------------- -- ------------------------

**NON-CONFIDENTIAL DESCRIPTION**

*Novel PCR Primer Pair and Real-Time qPCR Assay for Detecting and
Quantifying Perchlorate-Reducing Bacteria in Environmental Samples*

**Applications**

The novel PCR primer pair and real-time qPCR assay may be used to detect
and quantify perchlorate-reducing bacteria in microbial communities
(*e.g.*, bioremediation of soil and groundwater contaminants).

**Advantages**

Traditional culture-based methods are time-consuming, especially for
anaerobic microorganisms such as perchlorate-reducing bacteria.  This
method enables the rapid detection and quantification of genes, and
hence number of perchlorate-reducing bacteria, in a sample.

Patent Status

  ---------------------------------- ------------------------------------
  **United States**                  Patent Pending

  ---------------------------------- ------------------------------------

  -----------------------------------------------------------------------
  Inventors

  \- Krassimira Hristova\
  - Mamie Nozawa-Inoue\
  - Kate Scow

  UC Case Number(s)

  \- 2006-736
  -----------------------------------------------------------------------

**NON-CONFIDENTIAL DESCRIPTION**

*Lanthanide Nanoparticle Labels of DNA Probes for Fluorscence-based
Microarray and Hybridization in Solution Analyses*

**Technology Description**

Researchers at the University of California, Davis have developed a
method for the attachment of DNA oligoprobes to
NeutrAvidin-functionalized lanthanide nanoparticles. In addition,
protocols were developed and optimized for utilizing these novel DNA
probes for detection of target genes in microarray-based and direct
hybridization-in-solution assays. This method provides very stable
luminescent DNA labels in a non-PCR based approach for detection of
target genes in environmental, clinical and food safety diagnostics. UC
Davis researchers have demonstrated the first successful DNA application
for nano-scale lanthanide oxide particle as a substitution for
conventional fluorescent organic dye via this method.

**Applications**

This method may be used as a substitution of conventional organic
fluorescent dye and for detection and quantification of low bacterial
numbers or gene copies in a non-PCR approach of environmental,
biomedical, clinical and food safety fields. Additionally, this method
could be used for SNPs detection in clinical samples of patients with
genetic or cancer diseases.

**Advantages**

-   First successful DNA application for nano-scale lanthanide oxide
    particle as a substitution for conventional fluorescent organic dye

-   Provides very stable luminescent DNA labels in a non-PCR based
    approach

-   Overcomes photobleaching, spectral overlaps and poor photostability
    (*i.e.*, compared to organic fluorescent dye)

-   Lifetime reaches to 1-2 msec (vs. organic fluorescent dye which has
    1-10 ns of lifetime)

-   Improves the capability of DNA probes for accurate quantification of
    low gene copies in a high throughput microarray format

-   Based on the magnetic properties of the nanoparticles, provides
    fast, simple and reproducible assay in the format of hybridization
    in solution

    **References**

[[Dosev D, Nichkova M, Dumas RK, Gee SJ, Hammock BD, Liu K and Kennedy
IM. 2007. Magnetic/luminescent core/shell particles synthesized by spray
pyrolysis and their application in immunoassays with internal standard.
Nanotechnology 18,
055102-055107.]{.underline}](http://ej.iop.org/links/rwwvRbNEG/EJCZG_0k3BGSF6fUav5vpA/nano7_5_055102.pdf)

Patent Status

  ------------------------------- ---------------------------------------
  **United States**               2 Patents Pending

  ------------------------------- ---------------------------------------

Inventors

\- Dosi Dosev

\- Krassimira Hristova

\- Ian Kennedy

\- Mikaela Nichkova

\- Kate Scow

\- Ahjeong Son