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Technologies Available for License
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The following NIMH technologies are available for license inquiries. Please direct your queries to the NIMH Technology Transfer Office.� For additional information, see our
Licensing Information page. To review model PHS license agreements, please stop by our Downloadable Forms and Viewers page.
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For written inquiries, please contact the NIMH Technology Transfer Office at the
following mailing Address: Building 10, Room 4N222 [MSC 1381], National
Institutes of Health, Bethesda, MD 20892-1381. Thank you.
DNA Microarrays:� Modified Random Primers Increase Sensitivity of Detection
Patent Pending
Long-term potential applications:
DNA Microarray technology has become one of the most important tools for high
throughput studies in medical research with applications in the areas of gene
discovery, gene expression and mapping. The suitability of DNA Microarray for
profiling diseases and for identifying disease-related genes has also been well
documented. Following the rapid pace of gene sequence availability, Microarrays
have grown very rapidly in popularity and they seem to still hold considerable
untapped potential. Companies such as Affymetrics, Incyte and others have
commercialized DNA Microarrays for a variety of applications, and new
applications and products are on the rise.�
However, a major problem with most DNA Microarrays is one of sensitivity and the
requirement of larger sample sizes.� The technology profiled here addresses the
sensitivity issue head-on, making the Microarray technology even more valuable
in a variety of disease areas, such as cancer, infectious diseases and general
medicine.
The present invention relates to a new method of preparing cDNA probes from RNA,
that demonstrates an order of magnitude enhanced sensitivity compared to current
methods. The method utilizes random modified primers, which leads to the
incorporation of the fluorescent dye in multiple sites in the probe. Coupling of
the fluorescent dye to the reactive group on these random primers is performed
separately after the synthesis of the cDNA. These advances result in the
following benefits:
- Enhanced detection sensitivity by at least an order of magnitude means smaller sample size requirements, greater dynamic range of detection and smaller detection limits
- No base sequence dependence means better reproducibility, wider applicability and better normalization of signals
- Simplicity of method means a less expensive, more flexible method
- Greater stability of the reaction intermediates means greater efficiencies and better results
For licensing information contact: Uri Reichman
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Diagnostic Test For Creutzfeldt-Jakob Disease
US Patent No. 4,892,814
A novel assay for distinguishing Creutzfeldt-Jakob disease from other causes of
human dementia offers to significantly improve the early detection of this
disorder. Previously available methods for detecting this disease have had
limited utility because they require a biopsy of live brain tissue; because this
is such an invasive procedure, it is typically done late in the course of the
disease. This new assay can detect the presence of two distinctive proteins in
the cerebral spinal fluid of patients infected with the Creutzfeldt-Jakob prion
and, therefore, can be done as soon as the disease is suspected.�
For licensing information contact: Peter Soukas
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Decoding Neuronal Signals
Patent Pending
This invention provides a method of creating instructions for a prosthetic
device by monitoring and correlating the neuronal impulses associated with a
specific motor task. Which motor task is desired is formulated by monitoring
neuronal impulses from the wearer of the prosthetic device and relaying to the
mechanical motors of the prosthesis which motor task is desired. It appears that
this technology will have significant pioneer status, and it may be expected
that advances in this area will rely substantially on the development
represented by this invention
The invention is a new algorithm for decoding neuronal responses based on the
discovery that neuronal spike trains can be described using order statistics.
The device has applications in the direct control of prosthetic limbs by
neuronal signals originating from electrodes placed in the brain. The method
allows for decoding neuronal responses by monitoring sequences of potentials
from neurons while specific motor tasks are carried out. The sequences are then
characterized using the innovative technique of applying order statistics to the
spike train, such that subsequent action potentials representing unidentified
motor tasks can be decoded to determine the unknown task. The invention is of
substantial importance because it appears to have achieved a closed form
interpretation of neuronal responses upon which a motor prosthetic device might
be based.
For licensing information contact: Dale
Berkley
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Apparatus And Method For Transmitting Prosthetic Information To The Brain
US Patent No. 5,037,376
A novel apparatus for transmitting visual, audile, or tactile information to
the brain offers a means to significantly improve the utility of prosthetic
devices. There is presently no prosthetic device that can transmit a meaningful
sensory message to the brain. This new apparatus contains an array of sensory
elements that receive energy from an external stimulus and process those signals
via neural filters and neural waveforms to produce a pulse or "spike" train.
When applied to an appropriate area of the brain, these simulated spike trains
allow the subject to discriminate between various external stimuli.
For licensing information contact: Dale
Berkley
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Tissue Transplantation System
US Patent No. 5,004,457; 5,006,122
A novel apparatus for inserting brain tissue into the mammalian brain offers to improve neural tissue transplantation. Presently available methods for implanting tissue into the brain are cumbersome to use and often injure the transplanted tissue. This new apparatus uses a stereotaxic instrument to easily guide the tissue to the target site and two cannulas engaged in stylets, which apply minimal pressure to the transplanted tissue. Brain tissue can be inserted into the mammalian brain with minimal pressure and minimal disruption of the transplanted tissue. Tissue can be placed in multiple sites along a single tract or along multiple tracts. The apparatus can be used not only for fibrous tissue that holds together well but also for fragile embryonic brain tissue.
For licensing information contact: Dale
Berkley
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Catalyst For Preparing Polyacrylamide Gel Which Improves The Detection Of Biomaterials By Silver Staining
US Patent No. 5,292,665
A novel method for silver staining of polyacrylamide gels offers a quick,
sensitive method of visualizing proteins, polypeptides, and nucleic acids.
Present methods employ radioactive labeling of samples prior to electrophoresis
or staining of the gel with various dyes after electrophoresis. Although these
methods are powerful visualization tools, they are slow and complex and often
cannot detect samples at low concentrations due to background interference. By
adapting a histologic silver tissue stain for use with polyacrylamide gels, it
is possible to achieve as much as a 100-fold increase in sensitivity and obtain
an image in less than 6 hours. Background contamination is significantly reduced
by utilizing sample-specific crosslinking agents in the polyacrylamide gel.
For licensing information contact: Dale
Berkley
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Polyacrylamide Gels For Improved Detection Of Proteins
US Patent No. 5,283,196
A series of new crosslinking agents for polyacrylamide gels provide improved
reproducibility and accuracy in the separation and detection of proteins and
nucleic acids by silver staining techniques. Previously available crosslinking
agents interact with samples and silver staining and, thus, increase background
staining. These new crosslinking agents are tailored to the specific sample
being separated so that interaction with the samples or the silver stain is
minimized.
For licensing information contact: Dale
Berkley
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Method For Identifying Ligands And Antagonists Of Ligands
US Patent No. 5,532,157; 5,783,402
This invention describes a rapid and cost-effective method for
screening compounds for their ability to act as G protein-coupled receptor agonists or antagonists. The
method uses enzyme activity, as measured by simple colorimetric essays, to test ligand-binding capability.
Induction of b-galactosidase occurs if a specific agonist binds to a Gs-linked receptor, whereas Gi-coupled
receptor agonists inhibit forskolin-induced expression of b -galactosidase. These tests employ a
genetically engineered cell line with a cAMP-sensitive reporter construct (ie, increases in cAMP in this
cell line cause increased b -galactosidase activity). Currently available products, including stable cell
lines transfected with specific receptor cDNAs, are expensive and difficult to use.
For licensing information contact: John Rambosek
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cDNA Clone Of A Rat Serotonin Transporter, And Protein Encoded Thereby
US Patent No. 5,552,308
A novel cDNA encoding the rat serotonin transporter protein (5HHT) is
valuable for studies of the CNS and for screening therapeutic drugs. 5HHTs are responsible for removing
serotonin from the synoptic cleft of neurons, for storing serotonin in platelets, and are the site of
action for antidepressant drugs such as amphetamines and cocaine. There has previously been no method
available for studying the activity of these proteins in isolation. This 5HHT-encoding cDNA has been used
to create a permanent cell line that expresses this receptor and can be used for screening drugs that
affect the activity of 5HHT. The purified 5HHT can also be used for producing anti-5HHT antibodies for use
in diagnostic studies.
For licensing information contact: John Rambosek |
21 Highly Informative Microsatellite Repeat Polymorphic DNA Markers
US Patent Nos. 5,369,004; 5,378,602; 5,468,610; 5,721,100; 5,861,504
A novel group of 21 microsatellite repeat polymorphic DNA markers is valuable
for rapidly identifying and differentiating between individual human DNA sequences
for forensic, genetic, and human DNA mapping studies. Presently available methods
for studying differences in DNA structure between individuals -- such as DNA
sequencing, restriction fragment length polymorphism (RFLP) analysis, DNA
hybridization analysis, or primer extension analysis - are not practical for
comparing more than a few DNA sequences, take a long time to perform, or cannot
detect genetic differences that do not effect cleavage by a restriction endonuclease.
These new microsatellite DNA markers can be used as primers for rapid PCR amplification
of 27 unique human DNA polymorphisms, naturally occurring mutations in DNA sequences
that are often unique to each individual. The PCR-amplified DNA segments can then be
easily resolved on the basis of as little as a single nucleotide difference using
electrophoresis and autoradiography.
For licensing information contact: John Rambosek |
Human Olfactory Neuron Cultures
US Patent No. 5,869,266
Cultures of human olfactory neurons offer an improved method for screening
agents for treating neurologic diseases and disorders. Previously, rat and fetal
neurons have been successfully cultured; however, rats do not develop human
neurologic diseases, and neither rat nor fetal neurons replicate in culture, so
they die within a few months. These human olfactory neurons, which replicate in
culture, can be used for screening drugs that reverse or eliminate CNS diseases or
for testing drugs for neurotoxicity.
For licensing information contact: Norbert Pontzer |
Method For Treating Trichotillomania And Onchyphagia
US Patent No. 5,008,262
The drug clomipramine effectively treats trichotillomania (impulsive hairpulling)
and onchyphagia (pathologic nail-biting)not accompanied by any other mental or
obsessive-compulsive disorder. This invention provides a novel pharmaceutical approach
to treating primary hair-pulling and nailbiting. It is effective in individuals for
whom prior therapies have been unsuccessful.
For licensing information contact: Norbert Pontzer |
Antipsychotic Composition And Method For Treatment
US Patent No. 5,492,907; 5,663,167
This invention comprises a novel treatment method for patients suffering from
serious psychotic mental illness that offers to significantly improve the treatment
of such illnesses. Conventional antipsychotic drugs are effective in improving
symptoms of schizophrenia, but a significant number of patients have proven resistant
to such treatments. Recently, the drug clozapine has been found effective in treating
such drug-resistant patients; however, clozapine has severe toxic side effects. This
newly developed treatment method, which combines the use of an a2-adrenergic receptor
agonist with a standard antipsychotic drug, is effective in treating psychosis
without serious side effects. It is especially effective in patients who previously
had been resistant to treatment with standard antipsychotic drugs alone.
For licensing information contact: Norbert Pontzer |
Animal Model For Schizophrenia
US Patent No. 5,549,884
A newly developed animal model for schizophrenia is valuable for assaying
pharmaceutical compounds for treating this disorder. Schizophrenia is a neurologic
disorder characterized by bizarre behavior and/or hallucinations. previously, there
has been no satisfactory animal model for testing promising therapies for this
disorder. This newly developed animal model employs a neurotoxin that, when given to
a prepubescent mammal, causes brain lesions in the ventral hippocampus. Such animals
display many of the classic symptoms of schizophrenia and, thus, are ideal for
assaying the effectiveness of antischizophrenic drugs.
For licensing information contact: Norbert Pontzer |
Chromosomal Markers and Diagnostic Tests For Manic-Depressive Illness
Patent Pending
Bipolar disease, or manic-depressive illness, affects approximately 1% of the
population and is generally controlled through medication. Not all patients respond
similarly to a given medication. A medication that works well in one individual may
be ineffective in another individual. It is unclear why this is, but it has been
theorized that bipolar disease may involve multi-genes, possible on several
chromosomes. It is not known if one genetic locus dominates over another, but if one
does, then it may explain the variable medication effectiveness. One genetic locus
has been identified on chromosome 18 having allelic variations which may be used to
determine if an individual has an increased susceptibility to bipolar disease.
This method may be useful in determining if an individual has an increased
susceptibility to bipolar disease, or ultimately, it may provide a means to predict
which medication will provide the best treatment.
For licensing information contact: Norbert Pontzer
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Treatment For Cocaine Addiction
US Patent No. 4,942,182
Carbamazepine, a known anticonvulsant, offers an important new tool for the
treatment of cocaine addiction, for which there are presently no adequately effective
therapies. Carbamazepine blocks the reinforcing properties of cocaine and relieves
certai n responses from its use such as panic attacks. The drug must be given when
the patient is drug free, because carbamazepine worsens seizures and increases lethal
effects when given with cocaine.
For licensing information contact: Marlene Shinn
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Evaluative Means For Detecting Inflammatory Reactivity
US Patent No. 5,006,330; 5,209,920; 5,348,729
These novel diagnostic tests use CNS-directed therapeutic agents such as corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) to assess the susceptibility of individuals to inflammatory diseases, including rheumatoid arthritis, and depressive behavioral conditions, such as atypical depression. Potential drug responsiveness is determined by measuring plasma concentrations of specific hormones such as glucocorticoids or adrenocorticotropic hormone (ACTH) that will be directly affected by administration of the therapeutic agent. The closest known technologies include the administration of anti-inflammatory or antidepressant drugs or drug combinations that increase hypothalamic CRH responsiveness or that directly inhibit synovitis. Early clinical trials are promising and suggest that this new approach may improve diagnosis and choice of therapy.
For licensing information contact: Marlene Shinn
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Gibbon Ape Leukemia Virus-Based Retroviral Vectors
US Patent No. 6,033,905
New replication-defective retroviral vectors have been discovered to provide the
minimal DNA sequences required for efficient packaging of a gibbon ape leukemia
virus-based defective genome. These retroviral vectors consist of an improved
envelope, core, and defective genome -- where at least one of which is derived from
GaLV-to utilize the minimal cis-acting sequences from GaLV that allow packaging of
the defective genome in a hybrid virion. These retroviral vectors are suitable for delivering a variety of polynucleotides to cells, including transgenes for augmenting or replacing endogenous genes in gene therapy or for the production of transgenic animals. These GaLV-based replication-defective hybrid virions are as safe as murine retroviral vectors and provide a safe vehicle for delivery of genes for human gene therapy. The vectors may be used for gene therapy to treat congenital genetic diseases, acquired genetic diseases (eg, cancer), viral diseases (eg, AIDS, mononucleosis, herpesvirus infection), or to modify the genome of selected types of cells of a patient for any therapeutic benefit.
For licensing information contact: Fatima Sayyid
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Human-Mouse Hybrid Cell Line Expressing Monocyte-Macrophage Properties
US Patent No. 4,970,162
Twelve human-mouse hybrid cell lines that migrate to endotoxin-activated mouse
serum (EAMS) were isolated. Four of these lines also exhibited chemotaxis to
N-formylmethionine-leucine-phenylalanine (FMLP); one remained active in culture for at
least 20 passages. The hybrid consists of the stable and easily manipulated mouse
macrophage cell line RAW264, which lacks chemically defined attractants, and human
leukocytes for which FMLP is a defined attractant. These hybrid cell lines provide a
novel means of studying the mechanisms underlying the strong chemical attraction and
binding of N-formyl peptides to mammalian cells. They may also be useful in studying
inflammatory conditions in which macrophage chemotaxis plays an integral role.
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Protein Crosslinking Reagents Cleavable Within Acidified Intracellular Vesicles
US Patent No. 5,066,490
Novel protein crosslinking reagents that can be cleaved under acidic conditions
offer an improved method for delivering therapeutic agents to cells. Presently
available therapeutic delivery methods are not specific, do not adequately deliver
the drug a cross the cell membrane barrier, or modify the therapeutic agent during
the conjugation process. These novel protein crosslinking agents allow biologically
active compounds such as proteins, peptides, enzymes, drugs, or cell toxins to be
linked to mAbs without altering their biological activity. The cell-specific,
cross-linked compound is not cleaved until the therapeutic agent is deposited within
the cell.
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Stannylated 3-Quinuclidinyl Benzilates And Methods For Preparing *AQNB
US Patent No. 5,569,447
A unique method for synthesizing tomographic imaging agents has been developed
that offers to significantly improve the use of tomographic imaging in studying the
brain and other parts of the nervous system. Muscarinic cholinergic receptors (mAChrs)
play a vital role in a number of psychological and behavioral responses including
sleep, avoidance behavior, learning, and memory. Single-photon emission-computed
tomography (SPECT) has emerged as a leading diagnostic tool for diagnosing and
researching mAChr activity. At present, the potential of SPECT imaging of muscarinic
receptors as a diagnostic and analytical tool has not been fully attained, primarily
due to the high cost and difficulty of preparing the tomographic imaging agent *IQNB.
This invention overcomes such limitations by halogenating, particularly iodinating,
stannylated 3-quinuclidinyl benzilate compounds, which converts them to *AQNB
(wherein *A is a halogen). The halogenation of stannylated 3-quinuclidinyl benzilates
proceeds in as little as five minutes compared to up to an hour with previous methods.
In addition, radiolabeling with this method produces yields of *AQNB as high as 80
percent.
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Method For Screening Compounds, And Methods For Treating, Alzheimers Disease
Patent Pending
The present invention offers a method for screening therapeutic compounds or
compositions for their effectiveness in the treatment of Alzheimer's disease. In the
claimed methods, cells of an AD-affected patient are contacted with an effective
amount of the compound or composition to be screened and assayed for effects on the
amyloid precursor protein. The present invention also provides methods for screening
for AD, methods for decreasing the amount of the protein derivatives in AD-affected
cells, and methods for treating AD-affected patients by administering a compound that
increases the level of cyclic AMP in AD-affected cells or by administering a compound
found effective in decreasing the amount of certain protein derivatives as determined
by the screening methods set forth above.
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