SAN DIEGO, CA, United States

Allele Biotechnologyandpharmaceuticals Inc

www.ALLELEBIOTECH.COM
SAN DIEGO, CA, United States

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Patent
Allele Biotechnologyandpharmaceuticals Inc | Date: 2016-07-16

A multi-step method is disclosed for efficient selection of antibody or antibody fragments. In addition to the dramatically increased efficiency of finding antibodies against a given immunogen by the invented processes, the novel technology also differs from all previously known technologies in that the antibody or antibody fragments represent the most abundant antibodies induced by the immunogen, therefore having the highest potential of specificity and affinity. Utility of the invention can be found in virtually all areas that involve antibody or T cell receptor selection using any animal, against any immunogen.


Patent
Allele Biotechnologyandpharmaceuticals Inc | Date: 2013-05-13

The present disclosure relates generally to novel methods and compositions for using engineered reprogramming factor(s) for the creation of induced pluripotent stem cells (iPSCs) through a kinetically controlled process. Specifically, this disclosure relates to establishing combinations of reprogramming factors, including fusions between conventional reprogramming factors with transactivation domains, optimized for reprogramming various types of cells. More specifically, the exemplary methods disclosed herein can be used for creating induced pluripotent stem cells from various mammalian cell types, including human fibroblasts. Exemplary methods of feeder-free derivation of human induced pluripotent stem cells using synthetic messenger RNA are also disclosed.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2015

DESCRIPTION provided by applicant Alzheimerandapos s disease AD is the most common dementia in the elderly and imposes a tremendous burden to patientsandapos families and the society both financially and emotionally Currently there is no effective treatment available to cure the disease Pathologically AD is characterized by the presence of extracellular amyloid A plaques and intracellular tau neurofibrillary tangles in selected brain regions including cerebral cortex and hippocampus Multiple strategies targeting on A generation and clearance are being pursued vigorously in an effort to reduce A levels and A induced synaptic and neuronal toxicity However these attempts including those using anti A immunotherapies have not led to any FDA approved drugs to treat AD mainly due to toxic side effects and lack of efficacy Despite these failures anti A based immunotherapies have made progress Crenezumab a humanized monoclonal antibody targeting both monomeric and oligomeric forms of A by Genentech Roche inhibits A aggregation and promotes A disaggregation Although it missed its primary endpoints in a lately completed Phase II clinical trial crenezumab treatment in people with mild to moderate AD showed a trend toward slowing cognitive decline Most recently Biogen Idec has announced positive results from a Phase b clinical trial on its pipeline drug candidate aducanumab a human monoclonal antibody that binds aggregated forms of A with high affinity and plans to carry out a phase III study Therefore anti A immunotherapies are highly promising and improved anti A therapeutic reagents can help bring such therapies into clinic The purpose of this proposed project is to generate an advanced nano antibody for reducing amyloid A levels and preventing A plaque formation in AD Nan antibody nAb is a distinctive type of antibody fragment derived from camelid heavy chain only antibody HCAb As a therapeutic candidate nAb holds many superior properties that may enable some key improvement of current anti A reagents to help them succeed in clinical trials In this proposal we will develop engineered nano antibodies that will bind A and target it for degradation We will test the efficacy of such anti A reagents in cell and mouse models of Alzheimerandapos s disease We expect that this engineered anti A nAbs to have higher A binding affinity and greater A reduction efficiency but less toxic side effects compared to conventional antibodies PUBLIC HEALTH RELEVANCE Targeting amyloid peptide in its monomer form or aggregated form has the potential of slowing the progression of Alzheimerandapos s disease We propose to develop amyloid peptide targeting reagents by combining the specificity of novel nano antibodies or nanobodies and cellular degradation signals The work in this proposal can lay a foundation for further development of such reagents for clinical use


Patent
Allele Biotechnologyandpharmaceuticals Inc | Date: 2014-05-30

The present disclosure relates generally to novel methods and compositions for using engineered reprogramming factor(s) for the creation of induced pluripotent stem cells (iPSCs) through a kinetically controlled process. Specifically, this disclosure relates to establishing combinations of reprogramming factors, including fusions between conventional reprogramming factors with transactivation domains, optimized for reprogramming various types of cells. More specifically, the exemplary methods disclosed herein can be used for creating induced pluripotent stem cells from various mammalian cell types, including human fibroblasts. Exemplary methods of feeder-free derivation of human induced pluripotent stem cells using synthetic messenger RNA are also disclosed.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 222.17K | Year: 2016

Summary Statement and Abstract Stem cell technology is revolutionizing regenerative medicine and cell based therapies One of the promising applications of this technology is stem cell derived platelet Platelets are in high demand for a number of medical treatments but general or matching sources may be limited for various reasons A continuous donor independent and universally compatible supply of platelets are thus highly desirable We have previously developed a unique mRNA based technology of reprogramming somatic cells into iPSCs induced pluripotent stem cells with over efficiency in a short period of just days Together with our collaborators we have recently published a feeder free protocol to differentiate iPSCs to megakaryocytes MKs of purity and to universal i e HLA negative platelets with remarkable similarity and comparable purity to human platelets We propose the current phase I SBIR project to overcome the two remaining barriers in the translation of our technology into commercially viable clinical use One is the prohibitive cost of manufacturing iPSC derived platelets due to the high cost of GMP grade recombinant growth factors and cytokines amounting to $ dose The second barrier is the lack of automated large scale manufacturing of the stem cells differentiated cells and platelets We propose three aims The first aim will utilize our strength in mRNA based protein expression to manufacture growth factors cytokines in conditioned cell media at a fraction of the cost of GMP level recombinant growth factors cytokines These growth factors cytokines will be tagged with fluorescent proteins in Phase I so that we can monitor their concentrations during the differentiation culturing from iPSCs to platelets The second aim will optimize and improve the efficiency and yields of both megakaryocyte MK differentiation and platelet release from MKs To further reduce the production cost we will also titrate down the concentrations of growth factors cytokines needed for the manufacturing of platelets The third aim will implement the optimizations from the first aims in a large scale culture to manufacture platelets in quantity equivalent to at least two doses for human transfusion Through both increasing the yields of platelets and reducing the cost of supplying growth factors cytokines our goal is to bring the per dose cost of iPSC derived platelets low enough to start planning clinical trials Project Narrative The goal of the proposed research is to develop a novel large scale blood cell manufacturing system for stem cell based therapies The technology will have implications in regenerative medicine particularly for platelet transfusion


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2016

Abstract Alzheimerandapos s disease AD is the most common dementia in the elderly Currently there is no cure for the disease Pathologically AD is characterized by the presence of extracellular amyloid A plaques and intracellular tau neurofibrillary tangles in patientandapos s brain Although being vigorously pursued multiple attempts targeting on A generation clearance have been failed in Clinical trials mainly due to toxic side effects and lack of efficacy As reported recently in Scientific Reports we identified the human RPS RG gene with the ability to reduce A production and tau phosphorylation We also showed that RPS RG overexpression counteracted A oligomer oA induced synaptic loss and cognitive impairments by activating adenylate cyclase PKA signaling pathways which in turn caused the activation of CREB an important transcription factor regulating learning and memory and the inactivation of GSK an important kinase inducing tau hyperphosphorylation Thus RPS RG can be further exploited for its therapeutic potential in AD The purpose of this project is to generate an agonistic activating nanoantibody targeting RPS RG to promote RPS RG mediated synaptic and cognitive protection against AD Nanantibody nAb is a distinctive type of antibody fragment derived from camelid heavy chain only antibody HCAb As a therapeutic candidate nAb holds many superior properties over conventional antibodies In addition agonistic activating antibodies have been widely reported and used in many areas of research and therapy including those targeting G protein coupled receptors GPCRs In this proposal we will generate humanized nanoantibodies that will bind RPS RG and activate downstream signaling pathways We will examine the expression of RPS RG in AD postmortem brains and its correlation with the severity of premortem cognitive decline in human patients with severe memory loss mild memory impairment MCI or normal cognition as control We will also examine its ability to activate downstream signaling pathways to counteract synaptic and cognitive decline in both in vitro and in vivo animal models of AD We expect that RPS RG is downregulated in AD patient brains and its reduction correlates with the severity of dementia in AD and MCI patients and that agonistic RPS RG nanoantibodies reduce A and phosphorylated tau levels and mitigate synaptic loss and cognitive impairment in an PKA dependent manner in AD mice Our results should lay a foundation for the future development of RPS RG nanoantibodies as therapeutics in AD Narrative Synaptic deficits mediated by oligomeric A and hyperphosphorylated tau underlies cognitive decline in Alzheimerandapos s disease AD In this project we propose to develop biologics nanoantibodies targeting novel therapeutic target RSP RG to counteract AD associated synaptic and cognitive impairments The outcome of this study may lay a foundation for future development of therapeutic reagents in AD


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 199.94K | Year: 2013

DESCRIPTION (provided by applicant): The goal of the proposed project is to develop a commercial kit that will allow drug addiction researchers with ongoing projects using cell-based models to be able to successfully and conveniently produce human inducedpluripotent stem cells (iPSCs). Addiction to drugs destroys lives of substance abusers and their families, creating enormous social problems and exerting cost on the nation's health care system. Molecular mechanisms that contribute to the initiation and establishment of addiction are largely unknown, partially due to the lack of neural cell types from the patients. The technologies that made possible of human iPSCs opened the doors to new areas of direct interrogation of the pathophysiology of addiction byusing patient-specific cell sources. Currently, the NIDA is funding projects that rely on iPS technologies to: 1) characterize dopaminergic neurotransmission function of neurons derived from iPSCs with genomic aberrations, such as chromosomal polymorphismregions containing dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) genes; 2) identify genetic variations that can be functionally correlated to addiction in patient cell-derived neurons via iPSCs; 3) make dopamine neurons from patient iPSCs and expose them to methamphetamine and withdrawal in order to analyze the electrophysiological properties of patient-specific neurons versus controls, etc. Even though it is considered a technology with great potential in studies of addiction or other diseases, reprogramming of adult human cells to iPSCs is still an inefficient, tedious and costly process to most researchers. The currently prevailing methods of reprogramming have additional problems such as alteration of genomes or introduction of viruses that can complicate the interpretation of results from the cell-based assays. This project aims to develop a turn-key tool kit that will enable many biomedical researchers to generate iPSCs not only with 10 to 100 folds higher efficiency than othermethods, in less than 2 weeks, but also through a feeder-free, xeno-free and footprint-free procedure. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The goal of the proposed research is to develop a research tool kit for highly efficient generation of human induced pluripotent stem cells from adult cells. The technology will allow discoveries of novel therapies using stem cells or patient-specific disease models.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2014

DESCRIPTION (provided by applicant): The goal of the proposed Phase I research is to develop a set of commercial reagents for recognizing 2'-O-methyladenosine (Am), 2'-O-methylcytidine (Cm), 2'-O-methylguanosine (Gm) or 2'-O-methyluridine (Um), as well asindiscriminately to all four 2'-O-methyl ribose moiety. The core technologies that serve as the foundation of these new reagents are based on the unique properties of camelid antibodies, which have been well accepted as valuable binding reagents for proteins and haptens, but so far without any example for RNA modifications. The main advantage of the proposed single-domain (VHH) antibodies from camelidae is that they have very high affinity and specificity, and they are easy to reproduce as monoclonal antibodies, stable, and of very small size, enabling super-resolution imaging when conjugated to dye. Currently, affinity reagents of any type are only available for monitoring a handful among the more than 100 RNA modification moieties. The best examples o


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 153.06K | Year: 2014

Project Summary/Abstract The goal of the proposed Phase I research is to develop a set of commercial kits for footprint-free genome engineering. The core technologies that serve as the foundation of these kits are based on the CRISPR/cas system, which wasoriginally identified in bacteria and recently shown to also function in mammalian cells. The main advantage of the proposed gene targeting system is that the specificity of the target DNA sequence is dictated by a guide RNA, which can base-pair with onestrand of double-stranded DNA by forming an R-loop . Currently, zinc-finger nuclease (ZFN) and transcription activator-like effector nuclease (TALEN) provide possibilities to specifically and permanently modify the human genome. There are commercial reagents and services available for these two technologies. However, these two technologies are based on protein-DNA recognition, which requires designing and creating new enzymes every time a unique DNA sequence is to be targeted. The assembly of new ZFNs or


Patent
Allele Biotechnologyandpharmaceuticals Inc | Date: 2015-12-07

The present disclosure relates to methods and compositions comprising naturally occurring light absorbing molecules for preventing damages from light exposure. Specific embodiments of this disclosure include fluorescent proteins from Brachiostoma lanceolatum.

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