The NCI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize novel HIV and HCV therapeutics made from proteins and antibodies purified from cyanobacteria. If you feel your company or lab could contribute, their contact information is at the bottom of this article.
The emergence of mutant drug resistant strains of HIV has created the need for more effective and less toxic anti-HIV agents. This invention provides:
(1) Isolated and purified antiviral peptides or antiviral proteins named Scytovirins isolated and purified from aqueous extracts containing the cyanobacgteria, Scytonema varium.
(2) An antibody which binds an epitope of Scytovirin isolated and purified from Scytonema varium.
(3) A purified nucleic acid molecule that comprises a sequence which encodes an amino acid sequence homologous to Scytovirin.
(4) A vector comprising the isolated and purified nucleic acid molecule and a host cell or organism comprising the vector.
(5) A conjugate comprising the peptide and an effector component.
(6) A method of inhibiting a viral infection prophylatically and therapeutically.
Thus, this invention may represent potential new therapeutics for treatment of retroviral infections, including AIDS. Because the technology has its origin in natural products, the potential for development of less toxic HIV therapeutics is evident.
The inventors hav also demonstrated that Scuytovirin has potent anti-Hepatitis C virus (HCV) activity. Currently, there is neither effective treatment nor vaccine against HCV infection, which can lead to liver cancer and death. Scytovirin can be used alone or in combination with other anti-HCV drugs for HCV treatment and prevention.
Novel Method Of Preparing Vaccines
The National Cancer Institute’s Nanobiology Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize novel methods of preparing vaccines.
A major direction in the development of an effective HIV vaccine has been the search for vaccine immunogens that are able to elicit broadly cross-reactive HIV neutralizing antibodies (bcrnAbs). Such antibodies are rarely elicited in HIV-infected humans, and only a few such monoclonal bcrnAbs are known. Despite a tremendous amount of money and work being put forth, this approach has failed.
This invention describes methods to prepare vaccines for the treatment of human immunodeficiency virus (HIV) infections. The vaccine, which comprises a primary immunogen and a secondary immunogen, is able to effectively elicit broadly cross-reactive HIV neutralizing antibodies (bcrnAbs) against a target antigen. The primary immunogen is effective in eliciting B cell receptors (BCRs) that are on the maturational pathway of the desired antibody and have an intermediate degree of somatic mutational diversity (SMD). The secondary immunogen is able to provide additional diversification until the level of diversity typical for an HIV-specific bcrnAb is reached. By providing additional information to the immune system in the form of the primary immunogen, the number of possible combinations the immune system must face in attempting to identify pathways leading to bcrnAbs is significantly reduced. The conceptual approach described by this invention could also be used to develop cancer vaccines. (more…)
I’m amazed by how often the NCI is emailing me regarding collaborations now. Much more often than before. I would suspect it is a result of the $10 billion put aside for the NIH. This will be great for biotech employment and the recruiters that place people into life science, and the companies that sell products into the research market. Happy days are here again. Almost?
HIV Vaccine Vectors
The National Cancer Institute’s Animal Models & Retroviral Vaccine Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize HTLV-II vectored HIV vaccines.
This invention describes use of an HTLV-II viral vector. HTLV-II is a non pathogenic human virus that induces a gut immune response and infects mature dendritic cells in vivo. Because HTLV-II infects the gut like HIV, and because it induces maturation of dendritic cells, it may represent an excellent platform for the development of an HIV vaccine. Vaccines based on HTLV-II vectors have exhibited the capability of eliciting effective T cell response. Additionally, antibody response to the HTLV-II vector is almost undetectable. Because HTLV-II is a human retrovirus, it has no clear disease associations in either healthy or HIV infected individuals.
Most of the T-cell vaccines developed for HIV are based on microbial vectors that have limited replication capacity and do not persist in the host. The ability of these vaccines to protect against high virus load is merely transient (approximately six months). In addition, few of these vectors target mucosal sites, the first portal of HIV entry. In contrast, an HTLV-II based vaccine is anticipated to replicate at very low levels in lymphoid tissue and particularly in the gut which may enable them to effectively neutralize the virus. (more…)
Biomarkers For Breast Cancer Based On Genetic Instability
The National Cancer Institute’s Genetics Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize prognostic tests for breast cancer based on a 12-gene expression signature.
It is difficult to establish a prognosis for breast cancer because the clinical course and survival times of patients with the disease vary greatly. When cells are unable to repair minor damage to their DNA, genetic instability occurs, which can produce gross abnormalities in chromosomes and the onset of cancer. Because the magnitude of the abnormalities is strongly correlated with a negative prognosis for cancer, genetic instability can serve as a useful biomarker for establishing a prognosis for breast cancer patients. Presently, genetic instability is not directly accounted for in established prognostic tests.
Investigators at the National Cancer Institute (NCI) have developed a compact gene signature that identifies genome instability in breast cancer cells. By comparing changes in expression levels of only 12 genes in malignant tissue to levels in normal breast tissue, it is possible to detect the genetic abnormalities that are indicative of a poor prognosis. This method has the potential to improve markedly the forecasting of clinical outcomes for breast cancer and help improve treatment of this disease. (more…)
The NCI has been coming out with requests for collaborations a lot more all of a sudden. I wonder if it has anything to do with the stimulus package or is it just coincidence. I have several more that I will need to put up in the next day or so.
Compounds For The Prevention And Treatment Of Skin Tumors
The National Cancer Institute’s Laboratory of Cellular Carcinogenesis and Tumor Promotion is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics for treatment of skin diseases.
In recent years there has been a dramatic increase in the incidence of skin disease. Increase in exposure to UV light has contributed to the increase in premalignant skin lesions such as actinic keratoses. In the U.S., over 700,000 individuals suffer from superficial squamous and basal cell carcinoma. In addition, other skin diseases such as plantar and genital warts are extremely common. Currently, the treatment of these types of skin diseases includes surgical resection, tissue freezing, or application of acidic or cytotoxic topical treatments. However, surgical methods may be painful and the current topical treatments are not selective for hyperproliferative cells, not always curative, and may be toxic. This invention describes a series of compounds, hydroxylated aromatic protein cross-linking agents, that can be applied topically and are useful for premalignant and malignant superficial neoplasias of the skin and for the treatment of basal and squamous cell carcinomas. These compounds work through a protein crosslinking mechanism distinct from other therapeutics.
R and D Status: These compounds have proven to kill human and mouse skin cancer cells in vitro that are resistant to other potential therapeutic agents.
Further R&D Needed:
- Collaborative work on in vivo topical testing in animal models with de novo skin tumors or human skin tumor cells grafted to mice
- Potential use in other hyperproliferative skin diseases such as HPV induced warts and psoriasis needs testing in relevant animal models and cultured psoriatic and HPV infected keratinocytes. (more…)
The National Cancer Institute is looking for collaborators to work with them on HMGN polypeptides as immune enhancers or supressors.
Polypeptides For Stimulating Immune Responses
The National Cancer Institute’s Laboratory of Molecular Immunoregulation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize HMGN polypeptides as immune enhancers or immune suppressants.
HMGN polypeptides are multidomain proteins known to function by binding DNA to regulate the transcription of certain genes inside cells. When an HMGN polypeptide is released extracellularly, it acts as a potent activator of the immune system. Additionally, secreted HMGN acts as a potent recruiter and activator of dendritic cells, the cells principally responsible for initiating the immune response These activities make HMGN a potential candidate for a biological therapeutic for stimulating an immune response or as a vaccine against tumors. Investigators at the National Institutes of Health have developed compositions for using HMGN as immunoadjuvants in combination with microbial or tumor antigens.
Potential Commercial Applications
- Therapeutics for stimulating immune responses
- Immunostimulatory adjuvant to increase efficacy of vaccinations
- Attractant and activator of dendritic cells
- HMGN antagonist drugs to suppress inflammatory immune response (more…)
Novel Therapeutic For Inflammatory Disorders
The National Cancer Institute’s SAIC-Frederick Basic Sciences Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a novel inhibitor of the NF-kappa B signal transduction pathway, which leads to many inflammatory disorders.
Many tumors and blood cell cancers show over-activation of the NF-kappa B signal transduction pathway. This over-activation is associated with cancer forming in the colon, liver and other epithelial sites. In addition, there is evidence that over-activation leads to tumor formation and metastasis. However, this pathway is key for normal immunity, so any inhibition of NF-kappa B over-activation must avoid diminishing the body’s ability to fight infection. (more…)
Methods To Facilitate The Clinical Manufacture Of Proteins Used In Cancer Immunotherapy Development
The National Cancer Institute’s Biological Research Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods to facilitate pharmaceutical purification and processing of Interleukin-15 (IL-15).
Interleukin-15 (IL-15) is an immune system modulating protein (cytokine) that stimulates the proliferation and differentiation of T- lymphocytes. In the clinical context, IL-15 is being investigated for use in the treatment of diseases such as cancer. Manufacture of IL-15 for clinical use can be problematic.
Deamidation of IL-15 can lead to protein degradation that interferes with its pharmaceutical purification and processing. This invention describes substitutions of IL-15 amino acid sequences that are predicted to reduce deamidation of a specific amino acid residue found within the IL-15 protein. The substituted IL-15 amino acid sequences may advantageously facilitate the refolding, purification, storage, characterization, and clinical testing of IL-15. (more…)
Method For Effiecient Delivery Of Proteins Into Cells
The National Cancer Institute’s Protein Expression Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods for delivery of proteins using virus-like particles.
Proteins are critical to all biological manifestations from normal cell behavior to diseases including cancer. A convenient method to deliver proteins into cells would have wide ranging applications in cell biology including gene therapy and targeted killing of tumors. Current methods to deliver proteins include retrovirus, DNA transfection, protein transduction, microinjection, complexing the protein with lipids, etc. These methods are time and labor intensive, unsafe, inefficient, and can be toxic to cells. Protein transduction is an emerging technology for delivering proteins into cells that exploits the ability of certain proteins to penetrate the cell membrane. This technology has yet to become commonplace in biology because the majority of proteins remain trapped in the endosome of recipient cells.
This invention describes methods of delivering proteins into cells using virus-like particles (VLPs). VLPs consist of viral structural proteins that are capable of self-assembly into a nanoparticle, but are non-infectious because they lack viral nucleic acids. The present technology discloses a chimeric VLP that can be used to deliver functional fusion proteins or fully-processed proteins into target cells. By utilizing highly effective viral machinery, the problem of endosomal entrapment is eliminated and proteins can be delivered to target cells far more efficiently than existing protein transduction methods. In addition to protein therapy that can be used to treat numerous diseases and disorders, this technology can also be used for expansion of stem cells for transplantation as well as for the development of cancer vaccines. (more…)
Therapeutics To Treat Ocular Diseases
Keywords: Therapeutics, eye disease, macular degeneration
The National Eye Institute’s Section on Epithelial and Retinal Physiology and Disease (SERPD) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics for ocular diseases caused by accumulation of sub-retinal fluid.
The accumulation of subretinal fluid is associated with retinal injury, post-surgical complications, and numerous adverse ocular conditions, including chronic macular edema, age related macular degeneration, and diabetic retinopathy. Aberrant proliferation and migration of retinal pigment epithelial (RPE) cells is also associated with these conditions. Interferon gamma (IFN-gamma) has been implicated in the pathogenesis of a number of intraocular inflammatory or infectious diseases.
NIH inventors have shown that interferon-gamma (IFN-gamma) can significantly inhibit abnormal RPE proliferation and migration and can be used to remove subretinal fluid. The application of IFN-gamma may be by external application (e.g. eye drops or ointments) or by subretinal injection. This invention may be used to treat the debilitating complications of age-related macular degeneration, chronic macular edema, diabetic retinopathy, retinal detachment, glaucoma, or other diseases that are associated with abnormal fluid accumulation in the subretinal space. Additionally, the invention describes methods for treating decreases in visual acuity associated with this type of fluid accumulation.
Further R&D Needed:
- Pre-clinical trials
- Phase I clinical trial
R&D Status: Preclinical in vitro and animal model studies are in progress.
IP Status: U. S. Provisional Application No. 61/089,157 filed 15 Aug 2008
- Novel method to remove subretinal fluid to inhibit abnormal RPE proliferation and migration
- Potential to treat numerous ocular diseases and decreases in visual acuity by either external application or injection
- Ability to reduce retinal injury and post-surgical complications associated with accumulation of subretinal fluid
Alan Hubbs, Ph.D.
NCI Technology Transfer Center
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