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Office of Technology Transfer and Development
Pharmacological and Therapeutic Uses of Ultra-selective Opioidmimetic Peptides
Pharmacological and Therapeutic Uses of Ultra-selective Opioidmimetic Peptides
The National Institute of Environmental Health Science (NIEHS) is seeking a collaborative agreement with a company or organization to pursue the commercial development of highly selective delta opioid di- and tri-peptide antagonists. The opioidmimetic peptides exhibit a high selectivity, affinity and potency for the delta opioid receptor and may be beneficial in a number of distinct therapeutic and research applications including:
- The treatment of alcohol dependency, narcotic addiction and obesity
- The suppression of the immune response in organ transplants
- As a ligand for the characterization of the delta opioid receptor
Proposed Collaboration:
The NIEHS seeks a qualified commercial partner to assist in the further development of this technology either through a Cooperative Research and Development Agreement (CRADA) or the licensing of proprietary materials and methods associated with these inventions. It is anticipated that future studies will include:
The production of monoclonal antibodies against these peptides
The preparation of radiolabeled ligands for the biochemical characterization of the delta opioid receptor in animal tissues
The preparation of large quantities of highly pure peptide for pharmacological and physiological studies in both laboratory and clinical settings.
Patent protection is available with the possibility for non-exclusive or exclusive licensure.
Development of a Diagnostic for the Early Detection of Lung Cancer
Scientists at the National Institute of Environmental Health Sciences (NIEHS) have identified and partially characterized an enzyme that is selectively expressed at high levels in lung tumors. The development of an assay to measure levels of this enzyme may provide an efficient, non-invasive method for the diagnosis of lung cancer at early stages, leading to a more effective treatment of the disease. We also foresee the possibility of using this protein as a ligand to specifically target anti-tumor agents to affected tissue.
Proposed Collaboration:
The scope of the proposed collaboration would involve the development and evaluation of a non-invasive diagnostic assay for certain types of early stage lung disease and tumors. We are seeking a qualified company or organization to assist in the further development of this technology through a Cooperative Research and Development Agreement (CRADA). Future studies would involve the evaluation of tumor and tissue samples from both animal and human models and the development of monoclonal antibodies specific for the diagnostic protein. Patent protection is being sought for this invention.
Method for Diagnoses of XSCID
The XSCID diagnostic kit provides a method of diagnosing X-linked severe combined immunodeficiency (XSCID) in males or determining whether females are carriers. This method is based upon the presence of either a mutated or truncated IL-2R gene. The kit also discloses a method of treating XSCID as well as a method for monitering the therapy. Lastly, the diagnostic kit provides a promoter which regulates the expression of IL-2R , a vector comprising a DNA molecule operably linked to the promoter, a cell host that has been transformed with the vector, and a transgenic mouse comprising the promoter or a mutant IL-2R .
Advantages of XSCID Diagnostic Kit
- Diagnostic test is only definitive way of diagnosing XSCID
- Process for diagnosis is completely developed
The NHLBI is seeking to further develop this technology through collaboration in a Cooperative Research and Development Agreement (CRADA) or through the licensing of the methods, pharmaceutical compositions and kit related to the invention. Patent protection is being sought for this invention.
Adenovirus-Mediated Transfer of Recombinant Genes to the Lung
By using an adenovirus which infects the lung naturally to transfer the human cystic fibrosis gene to the epithelium of living animals, NHLBI researchers have discovered a way to produce therapeutic proteins in the lung. This new gene delivery system may be used to treat diseases such as cystic fibrosis, hereditary forms of emphysema, inflammatory lung diseases, asthma, adult respiratory distress syndrome and lung cancer.
Advantages:
- This system does not require the replication of the target cell for expression
- Recombination is rare
- No known associations with human malignancies
- The genome can be manipulated to accommodate foreign genes
- The adenovirus has been safely used as a human vaccine
In addition, adenovirus mediated gene transfer is advantageous over retro viral mediated gene transfer because genes can be transferred directly to targeted cells in vivo and the adenovirus vectors can be used to transform cells that retro viral vectors are unable to infect.
Expectations:
This vector is expected to expand upon the potential uses of gene therapy and will not directly compete with the use of retro viral vectors.
Proposed Collaboration:
The NHLBI is seeking to further develop this technology through collaboration in a Cooperative Research and Development Agreement (CRADA) or through the licensing of the methods, pharmaceutical compositions and kit related to the invention. Patent protection is being sought for this invention.
Adenovirus-Mediated Transfer of Genes to the Gastrointestinal Tract
Adenovirus mediated transfer offers a new method for introducing therapeutic proteins into the gastrointestinal tract. Currently, therapeutic proteins cannot be administered via oral or rectal routes because they will generally be degraded or not absorbed and thus not able to reach the circulatory system in an intact form. While recombinant adenoviruses can be used to produce human proteins in vivo, this method has heretofore been impractical because it required parenteral (intravenous, intratracheal) injection of the recombinant gene. Use of this replication-deficient adenovirus avoids this problem because it can be used to insert therapeutic genes directly into cells lining the gastrointestinal tract, from where the protein can be secreted into the system.
Advantages:
- Genes can be transferred directly to targeted cells in vivo
- Adenovirus vectors can be used to transform cells that retro viral vectors are unable to infect (retroviral vectors can deliver genes only to actively dividing cells)
- Efficient entry into most or all cell types. High titers and high level of expression
Proposed Collaboration:
The NHLBI seeks a qualified, domestic bio-pharmaceutical concern to develop this technology into products for the public health. NHLBI has an active research program in gene therapy and would be interested in receiving inquiries into specific projects that may be of interest to industry. Patent protection is available with the possibility for non-exclusive or exclusive licensure. Cooperative Research and Development Opportunity at the National Heart, Lung and Blood Institute.
Organ-Selective Delivery of Recombinant Genes and Other Therapeutic Agents to Hepatobiliary and Pancreatic Tissue
NHLBI researchers have developed novel ways to selectively deliver potentially therapeutic agents, including viral and non-viral gene transfer vectors, to hepatobiliary and pancreatic tissues in vivo, including the gallbladder, common bile duct, liver, exocrine pancreas, endocrine pancreas, and the duodenum. These discoveries may be used to develop new or improved treatments for many inherited and acquired diseases of these organs, such as hemophilia, cystic fibrosis, hepatitis, hepatocellular carcinoma, primary biliary cirrhosis, pancreatic carcinoma, diabetes mellitus, and opportunistic biliary tree infections associated with the Acquired Immunodeficiency Syndrome (AIDS).
Advantages:
- More effective method of delivery to intended tissue target(s)
- Facilitates in vivo evaluation of agents difficult to produce in large amounts
- Permits selective delivery to hepatocytes or intrahepatic cholangiocytes
- Local microenvironment can be changed before agent is administered
- Residual, non-absorbed agent can be removed following delivery
- Reduced systemic exposure to administered agent
- Makes possible rapid, effective in vivo screening of potentially therapeutic agents
- Includes proprietary systems for acute, intermittent, and chronic administration
Expectations:
As these systems were initially developed in mice, this technology makes it possible to evaluate the potential safety and efficacy of different agents for disease correction by using tissue-specific gene-knockout and transgenic models of human disease and agent delivery techniques analogous to those that may be ultimately used in human patients. This should lead to more rapid and clinically-relevant use of experimental animals in the initial in vivo screening of potentially therapeutic agents, thereby facilitating the ultimate development of new or improved treatments for human diseases of hepatobiliary and pancreatic tissues.
Proposed Collaboration:
The NHLBI is seeking to further develop this technology through collaboration in a Cooperative Research and Development Agreement or through the licensing of proprietary methods and materials related to these inventions.
A CRADA partner would be expected to facilitate the development of this technology. Examples of such potential assistance include:
- participating in the development of prototype delivery systems, including novel, proprietary catheter designs;
- providing novel agents, genes, vectors, and/or animal models for evaluation;
- facilitating production of viral or non-viral vectors;
- providing useful technical services, such as molecular biology, histopathological, or other important laboratory assistance.
- facilitating or conducting animal studies.
LCAT:Treatment of Atherosclerosis and LCAT Deficiency
In humans, the development of atherosclerosis is positively and inversely correlated with the plasma levels of low density lipoproteins (LDL) and high density lipoproteins (HDL) respectively. Lecithin cholesterol acyltransferase (LCAT), the major enzyme involved in the esterification of free cholesterol present in circulating plasma lipoproteins, is a major determinant of plasma HDL concentrations. Recent studies have established that transgenic rabbits overexpressing human LCAT have 6-7 fold higher plasma HDL levels than control, non-transgenic siblings. In addition, LCAT transgenic rabbits have reduced plasma concentrations of the atherogenic LDL and apoB-containing lipoproteins. This lipoprotein phenotype characterized by elevated plasma HDL and reduced LDL levels leads to marked protection against the development of diet-induced atherosclerosis in LCAT transgenic rabbits compared to control animals.
Proposed Collaboration
The NHLBI is seeking a collaborative partner for the development of different therapeutic modalities to raise plasma concentrations of LCAT for the treatment of atherosclerosis and LCAT deficiency. Using the strengths of the parties, the goals are to achieve one or more of the following:
- Evaluate the feasibility of gene therapy utilizing the LCAT gene and suitable vectors as a treatment approach for the prevention of atherosclerosis in animal models as well as patients with premature cardiovascular disease
- Evaluate the use of gene therapy to correct LCAT deficiency in LCAT knockout mice
- models systems and patients with LCAT deficiency
- Develop and evaluate the anti-atherogenic properties of pharmacological agents that raise plasma concentrations of LCAT
It is anticipated that the collaborator(s) will participate in ongoing studies on one or both of the research projects involving (1) the transfer of the human LCAT gene in animal models and patients with atherosclerosis or LCAT deficiency and (2) the development of pharmacologic agents that will increase plasma concentrations of LCAT. It is highly desirable that the collaborator have the resources to provide new, effective vectors for the long term in vivo expression of the LCAT gene. The collaborator may also be expected to contribute financial support under this CRADA for supplies and personnel. The NHLBI has applied for patents claiming this core technology.
