Bioincept

Cherry Hill, NJ, United States

Bioincept

Cherry Hill, NJ, United States
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Embodiments are directed to a method of treating acute radiation syndrome comprising administering to a subject following exposure to radiation a PIF peptide. Some embodiments describe a method of treating acute radiation syndrome following radiation exposure comprising transplanting bone marrow that has been exposed to a PIF peptide prior to transplantation into a subject. Other embodiments describe a method of increasing engraftment of a transplanted organ, tissue, or cell by pre-exposing the organ, tissue, or cell to a PIF peptide.


Patent
Bioincept | Date: 2016-11-28

A novel class of embryo derived peptides are described (Preimplantation factor) that were generated synthetically and were tested on peripheral blood immune cells and shown to block activated but not basal immunity, inhibiting cell proliferation and creating a T_(H)2 type cytokine bias, in addition PIF enhance endometrial receptivity by increasing adhesion molecules expression. PIF biological activity appears to be exerted by specific binding to inducible receptors present on the several white cell lineages. PIF peptides, which are immune modulators therefore may have diagnostic and non toxic therapeutic applications in improving fertility, reducing pregnancy loss as well may be useful when administered for the treatment of autoimmune diseases and for prevention xenotransplants rejection.


Pre-implantation factor (PIF) may be used to treat intracellular damage. Aspects of the invention are directed to a method of treating intracellular damage comprising administering PIF to a subject in need thereof. Some aspects may be directed to methods of increasing cytokine secretion in response to intracellular damage comprising administering PIF to a subject in need thereof. The intracellular damage may be a result of a disease such as Listeria monocytogenes infection, malaria, Lyme disease, cardiovascular disease, duodenal peptic ulcer, atherosclerosis, peritonitis or tuberculosis. In some aspects, a method of treating tuberculosis is disclosed, comprising administering PIF to a subject in need thereof. In some aspects, a method of treating atherosclerosis is disclosed, comprising administering PIF to a subject in need thereof. In some aspects, a method of treating peritonitis is disclosed, comprising administering PIF to a subject in need thereof.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 298.31K | Year: 2015

DESCRIPTION provided by applicant Recent nuclear accidents and threats have highlighted the growing risk of widespread radiation exposure causing a potentially devastating public health emergency Acute radiation syndrome ARS develops after total body or partial body irradiation at a moderate to high dose and is especially damaging to the immune system Damage to the skin gut and central nervous system is also common Accordingly complex injuries such as burns multi organ injury and trauma increase the death rate from acute radiation syndrome Despite advances in understanding the biological basis of radiation injury medications that effectively treat radiation injury are limited Medical management of accidentally irradiated victims remains based on treatment with immune factors that enhance renewal of immune cells In more severe cases a bone marrow transplant may be performed but complications from graft immune rejection limit the utility of this approach Furthermore existing treatments have limited efficacy are difficult to administer and are expensive to produce Therefore there is an urgent need to develop new drugs to treat acute radiation syndrome that are both effective and easy to deploy in an emergency radiation exposure scenario The goal of this proposal is to test the ability of synthetic PreImplantation Factor sPIF a natural immune regulatory peptide to reverse ARS in mice when treatment begins hours after exposure to various levels of radiation The survival and health of mice will be monitored and blood marker profiles will be performed Additionally details of the molecular basis of radiation damage and sPIFandapos s protective effects on the immune system will be examined Specifically mice tissues will be scored for inflammation and organ damage The types of immune cells present and the expression of inflammatory markers and immune regulators will be determined The purpose of these studies will be to advance the development of sPIF as a treatment for ARS and to collect the necessary data for the submission of an investigational new drug IND application The use of sPIF could revolutionize the treatment of ARS Preclinical studies have demonstrated that sPIF completely protected mice from death when administered hrs following lethal radiation exposure Significantly the sPIF treated mice also maintained normal blood markers indicating sPIFandapos s underlying protective effect on immune function Additional studies showed sPIF accelerated recovery of white blood cells when administered hours following sub lethal radiation exposure Significantly this project will more fully evaluate sPIFandapos s potential as a non toxic effective treatment for radiation exposure that could be easily deployed during a public health emergency PUBLIC HEALTH RELEVANCE This project addresses the public need for an effective easily administered drug that increases survival following exposure to radiation Currently survival of radiation exposure from nuclear accidents or weapons mostly depends on the strength and distance of the radiation because available medical treatments are not able to sufficiently prevent and repair damage Therefore development of an effective drug to treat acute radiation syndrome that can be mass produced stored and easily administered during a radiation emergency has significant impacts on public health This project will build upon promising preliminary data to more fully evaluate the potential for synthetic Preimplantation Factor a natural immune regulatory peptide to serve as a non toxic effective treatment for radiation exposure


Patent
Bioincept | Date: 2014-10-22

Cells transfected with DNA sequences encoding for a PreImplantation Factor (PIF) or a PIF and one or more fusion tag(s) are disclosed. Also disclosed are DNA sequences encoding for synthetic PIFs, a PIF fusion peptide made of a PIF and one or more fusion tags, methods of treatment using the transfected cells that express a PIF, an R-I-K-P peptide, compositions containing the R-I-K-P peptide, and methods of identifying a compound that binds to an active site of an WX_(1)WX_(2)X_(3)X_(4)REWFX_(5)X_(6)X_(7)W receptor, wherein each X can be any amino acid.


The present invention relates to assay methods used for detecting the presence of PIF, and to PIF peptides identified using this assay. In particular, the present invention relates to flow cytometry assays for detecting PIF. It is based, at least in part, on the observation that flow cytometry using fluorescently labeled anti-lymphocyte and anti-platelet antibodies demonstrated an increase in rosette formation in the presence of PIF. It is further based on the observation that flow cytometry demonstrated that monoclonal antibody binding to CD2 decreased in the presence of PIF. The present invention further relates to PIF peptides which, when added to Jurkat cell cultures, have been observed to either (i) decrease binding of anti-CD2 antibody to Jurkat cells; (ii) increase expression of CD2 in Jurkat cells; or (iii) decrease Jurkat cell viability. In additional embodiments, the present invention provides for ELISA assays which detect PIF by determining the effect of a test sample on the binding of anti-CD2 antibody to a CD2 substrate.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: STTR | Phase: Phase I | Award Amount: 223.42K | Year: 2016

ABSTRACT Perinatal hypoxic ischemic encephalopathy HIE affects to infants per every born Mortality from HIE can be up to and approximately of survivors suffer significant long term disability including cerebral palsy epilepsy and developmental disorders Damage during the acute phase of HIE is caused by a deficit in oxygen and glucose in the brain However increasing evidence indicates that secondary and tertiary phases are responsible for significant ongoing damage After an initial insult oxidative stress increases and signaling cascades lead to cell death Elevated inflammation and epigenetic changes may be present months to years after initial injury as evidenced by myelin deficits reduced plasticity and altered cell number Recently hypothermia has been used to significantly reduce mortality and developmental complications in term infants with HIE However there are several limitations to this approach Treatment must be initiated within hours of injury to reduce metabolic damage and oxidative stress and of infants still die or suffer severe disability The National Institute of Child Health and Human Development recently reported an urgent need to develop neuroprotective combination therapies to be used hours to days after the insult in combination with hypothermia A number of known neuroprotective compounds erythropoietin stem cells xenon etc are being investigated alone or in combination with hypothermia but to date none have emerged as a more effective treatment for HIE Overall there is need for new adjuvant therapies in HIE This project will test the efficacy of moderate hypothermia plus an immunomodulatory compound synthetic PreImplantation Factor sPIF in a rat model of HIE that is equivalent in development to a term human infant brain BioIncept has published data demonstrating that PIF regulates both the innate and adaptive immune response Significantly PIF reversed neurological damage in a multiple sclerosis model and protected against oxidative stress in multiple disease models Recent studies in a model of encephalopathy of prematurity showed that PIF provided protection against neuro axonal injury In this project we will first perform a short term dose ranging study with sPIF plus hypothermia to determine what dose is most effective Then we will perform a longer term comparison of the selected sPIF dose plus hypothermia combination and compare the results to hypothermia alone We will use histology neurofunctional tests and magnetic resonance imaging MRI to compare the different treatments Overall we anticipate PIF plus hypothermia will affect all injury phases and will create an additive neuroprotective effect since these treatments target different pathways Clinical translation of PIF as a first line HIE treatment is promising if these preclinical evaluations are successful as BioIncept received FDA Fast Track designation for PIF treatment of autoimmune hepatitis clinical trial began in and Yale University collaborators provide additional obstetric and clinical expertise PROJECT NARRATIVE Perinatal hypoxic ischemic encephalopathy HIE can result in newborn death or long term disability including cerebral palsy epilepsy increased hyperactivity and developmental disorders Recently hypothermia treatment has been used to significantly reduce mortality and developmental complications from HIE but of infants still die or suffer severe disability The National Institute of Child Health and Human Development NICHD recently reported an urgent need to develop neuroprotective combination therapies to be used hours to days after the insult in combination with hypothermia This project will test the efficacy of hypothermia plus a novel immunomodulatory compound Preimplantation Factor PIF to develop a more effective combination treatment to prevent brain injury


Patent
Bioincept | Date: 2015-07-09

A novel class of embryo derived peptides are described (Preimplantation factor) that were generated synthetically and were tested on peripheral blood immune cells and shown to block activated but not basal immunity, inhibiting cell proliferation and creating a T_(H)2 type cytokine bias, in addition PIF enhance endometrial receptivity by increasing adhesion molecules expression. PIF biological activity appears to be exerted by specific binding to inducible receptors present on the several white cell lineages. PIF peptides, which are immune modulators therefore may have diagnostic and non toxic therapeutic applications in improving fertility, reducing pregnancy loss as well may be useful when administered for the treatment of autoimmune diseases and for prevention xenotransplants rejection.


The present invention relates to assay methods used for detecting the presence of PIF, and to PIF peptides identified using this assay. In particular, the present invention relates to flow cytometry assays for detecting PIF. It is based, at least in part, on the observation that flow cytometry using fluorescently labeled anti-lymphocyte and anti-platelet antibodies demonstrated an increase in rosette formation in the presence of PIF. It is further based on the observation that flow cytometry demonstrated that monoclonal antibody binding to CD2 decreased in the presence of PIF. The present invention further relates to PIF peptides which, when added to Jurkat cell cultures, have been observed to either (i) decrease binding of anti-CD2 antibody to Jurkat cells; (ii) increase expression of CD2 in Jurkat cells; or (iii) decrease Jurkat cell viability. In additional embodiments, the present invention provides for ELISA assays which detect PIF by determining the effect of a test sample on the binding of anti-CD2 antibody to a CD2 substrate.


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