1996 |
Naleway, John J |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Marker Gene Directed Substrates For Cell Regulation @ Marker Gene Technologies |
0.904 |
1998 — 1999 |
Naleway, John J |
R44Activity Code Description: To support in - depth development of R&D ideas whose feasibility has been established in Phase I and which are likely to result in commercial products or services. SBIR Phase II are considered 'Fast-Track' and do not require National Council Review. |
Genetic Strategies For Drug Targeting @ Marker Gene Technologies
This Small Business Innovation Research Phase II project aims to investigate the use of developing new biological systems employing common marker gene expression in transformed cells to control the growth and character of cells in living tissue. Building on our successes in the Phase I effort, the proposed research will provide breakthroughs needed to advance new promising medical uses of recombinant genes. In Phase I, Marker Gene Technologies, Inc. established the feasibility of this technology by preparing new galactoside and Cephalosporin conjugates of common growth regulators, drugs and enzyme inhibitors, for administration to animal cells or bacteria that contain either the beta- galactosidase (lac Z) or ampicillin resistance (beta-lactamase, amp) genes as gene fusion markers. These new conjugates utilized these fusion systems in transformed cells to affect drug delivery and control selected biological properties. In Phase II, the new biological systems will be implemented in vivo for their ability to cause specific and localized effects on cell growth and to deliver activated drugs in a cell- or tissue-specific manner. In particular, the conjugates will be further tested in the significant medical areas of gene and immuno-therapy for cancer and proliferative diseases treatment. PROPOSED COMMERCIAL APPLICATION: The success of this project opens up enormous commercial possibilities in the fields of medical intervention in genetic diseases, gene and immuno- therapy for cancer treatment, biotechnological production of new proteins and drugs in cell-culture systems, and bacterial screening strategies. In addition, it contributes new information and techniques for basic cell-biology research.
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0.904 |
2001 |
Naleway, John J |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Live Cell Apoptosis Assay For High-Throughput Screening @ Marker Gene Technologies
DESCRIPTION (Applicant's Abstract): This Small Business Innovation Research Phase I project aims to investigate the feasibility of developing new compounds capable of measuring initial stages of apoptosis induction in living cells and tissues. If successful, the proposed research will provide breakthroughs needed to advance the discovery of promising new apoptosis modulating drugs for medical applications. In Phase I of this project, Marker Gene Technologies, Inc. proposes to establish the feasibility of the technology by preparing new fluorogenic peptidase substrates for the Caspase family of enzymes, for administration to living cells or tissues that either have been induced to initiate apoptosis or are of disease interest. These new substrates and the resulting detection systems will provide innovative methods to quantitate apoptosis induction and to screen for the influence of secondary drug or treatment administration. In Phase I, the new substrates will be assayed in vitro for their ability to measure specific and localized inhibition or induction of apoptosis in living cells and to do so in a cell- or tissue-specific manner. In Phase II, the substrates will be further tested as an analytical tool in vivo and in a variety of significant medical applications. PROPOSED COMMERCIAL APPLICATION: The success of this project opens up enormous commercial possibilities in the field of medical intervention in proliferative diseases such as cancer and degenerative diseasess such as Alzheimer's disease, screening of new proteins and drugs in cell-culture systems for efficacy in modulating apoptosis, and general new peptidase detection strategies. In addition, it will lead to licensable products in these areas.
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0.904 |
2002 |
Naleway, John J |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
New Labeling Reagents For Genetic Analysis @ Marker Gene Technologies
DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I project aims to investigate the feasibility of developing new, sensitive, accurate, and reliable detection methods for genomic DNA or RNA samples that are essential for genomic microarray analysis. If successful, the proposed research will help provide breakthroughs needed to advance the promising medical uses of genomic analysis to determine the pattern of gene expression in live cell assays. In Phase I of this project, Marker Gene Technologies proposes to establish the feasibility of the technology by preparing new labeling reagents and systems capable of directly modifying DNA or RNA oligomers for ultrasensitive fluorescence or chemiluminescent detection. These labeling reagents will be assayed in vitro for their ability to monitor gene expression events in response to biological effects on cell function and to monitor the change in gene expression upon application of drugs and bioactive compounds in a cell-specific manner. In Phase II, these and additional detection reagents and methods will be further tested in a variety of pre-clinical applications for genomic expression analysis combined with drug application. PROPOSED COMMERCIAL APPLICATION: The success of this project opens up enormous commercial possibilities in the fields of medical intervention in genetic diseases, genetic screening of new proteins and drugs in cell-culture systems, and new anti-bacterial and anti-viral agent discovery. In addition, it contributes new information and techniques for basic cell-biology research, and the labeling reagents and techniques produced can be marketed for these research and commercial uses.
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0.904 |
2002 |
Naleway, John J |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Luciferase Directed Substrates For Cell Regulation @ Marker Gene Technologies
DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I project aims to investigate the feasibility of developing new compounds capable of utilizing common marker gene expression in transformed cells to control the growth and character of cells in living tissue. If successful, the proposed research will provide breakthroughs needed to advance the promising medical uses of recombinant genes. In Phase I of this project, Marker Gene Technologies proposes to establish the feasibility of the technology by preparing new D-luciferin conjugates of common growth regulators, drugs and enzyme inhibitors, for administration to animal cells or bacteria that contain either the firefly luciferase gene (luc) as a gene fusion marker. These new conjugates will provide innovative methods of utilizing this reporter gene system in transformed cells to affect drug delivery and control selected biological properties. In Phase I, the new conjugates will be assayed in vitro and in vivo for their ability to cause specific and localized inhibition or improvement of cell growth and to deliver activated drugs in a cell- or tissue-specific manner, In Phase II, the conjugates will be further tested in a variety of significant medical applications.
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0.904 |
2005 |
Naleway, John J |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Positive Selection Systems Using Marker Genes @ Marker Gene Technologies
This Small Business Innovation Research Phase I project aims to investigate the feasibility of developing new compounds capable of utilizing common marker gene expression in transformed cells to control the growth and character of cells in cell culture and live tissue applications. If successful, the proposed research will provide breakthroughs needed to advance the promising medical uses of recombinant genes. In Phase I of this project, Marker Gene Technologies proposes to establish the feasibility of the technology by preparing new galactoside and Cephalosporin conjugates of common growth regulators, drugs and enzyme activators, for administration to animal cells or bacteria that contain either the beta-galactosidase (lacZ) or ampicillin resistance (Beta-lactamase, amp) genes as gene fusion markers. These new conjugates will be used to provide innovative methods of utilizing these fusion systems in transformed cells - to select for transgenic cells in a non-destructive fashion. In Phase I, the new conjugates will be assayed in vitro for their ability to cause specific and localized improvement of cell growth and to deliver the active agents in a cell- or tissue-specific manner. In Phase II, the conjugates will be further tested in a variety of significant medical applications. The success of this project opens up enormous commercial possibilities in the fields of cell selection, medical intervention in genetic diseases, immunotherapy for cancer treatment, biotechnological production of new proteins and drugs in cell-culture systems, and bacterial screening strategies, and the conjugates prepared can be marketed in these areas. In addition, it contributes new information and techniques for basic cell-biology research.
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0.904 |
2007 — 2008 |
Naleway, John J |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Live-Cells Assays For Lysosomal Enzyme Activity @ Marker Gene Technologies
[unreadable] DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I project aims to develop new targeted fluorogenic substrates capable of measuring lysosomal enzyme activity in living cells and tissues. If successful, the proposed research will provide breakthroughs needed to advance the discovery of promising new therapies and modulating drugs for lysosomal storage diseases and allied medical applications. In Phase I of this project, Marker Gene Technologies, Inc. will establish the feasibility of the technology by preparing new fluorogenic glycosidase substrates for lysosomal enzymes and demonstrating differential staining in living cells that are from normal or are of disease origin. In Phase II, these new substrates will be assayed in vitro and in vivo for their ability to measure specific and localized inhibition or induction of lysosomal enzymes in living cells as well as differentiate individual enzyme activities in a cell- or tissue-specific manner. The new substrates and the resulting detection systems will provide innovative methods to quantitate lysosomal enzyme function and to screen for the influence of secondary drug or protein administration, making them useful analytical tools for a variety of significant medical applications. The success of this project opens up enormous commercial possibilities in the fields of medical intervention in lysosomal storage diseases such as Sandhoff's disease, Tay-Sachs syndrome, Krabb[unreadable]'s disease and Gaucher's disease, as well as in the screening of new proteins and drugs in cell-culture systems for efficacy in modulating lysosomal enzyme activity in these diseases, and development of new, general and specific high-throughput lysosomal enzyme detection strategies. In addition, it will lead to commercial and licensable products in these areas. [unreadable] [unreadable] [unreadable]
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0.904 |
2012 — 2014 |
Naleway, John J |
R44Activity Code Description: To support in - depth development of R&D ideas whose feasibility has been established in Phase I and which are likely to result in commercial products or services. SBIR Phase II are considered 'Fast-Track' and do not require National Council Review. |
Live-Cell Assays For Lysosomal Enzyme Activity @ Marker Gene Technologies
DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase II project aims to develop new targeted fluorogenic substrates capable of measuring lysosomal enzyme activity in living cells and tissues. If successful, the proposed research will provide breakthroughs needed to advance the discovery of promising new therapies and modulating drugs for lysosomal storage diseases and allied medical applications. In Phase I of this project, Marker Gene Technologies, Inc. established the feasibility of the technology by preparing new fluorogenic glycosidase, esterase, phosphatase, lipase and sulfatase substrates for lysosomal enzymes and demonstrated differential staining in living cells that were from normal or were of disease origin or upon induction of inhibition of lysosomal enzyme activities. In Phase II, these and additional new substrates will be assayed in vitro for their ability to measure specific and localized inhibition or induction of lysosomal enzymes in living cells as well as differentiate individual enzyme activities in a cell- or tissue-specific manner. These new systems will be validated for use in high-throughput screening for drug discovery, for use in clinical diagnostics to evaluate the occurrence and progression of disease, and for use in monitoring the effectiveness of existing or emerging therapeutic interventions for these disorders. The new substrates and the resulting detection systems will also provide innovative methods to quantitate lysosomal enzyme function and to screen for the influence of secondary drug or protein administration, making them useful medical research tools for a variety of significant biochemical and medical applications. The company has engaged the collaboration of several noted research laboratories and institutions as well as major pharmaceutical companies in this arena, who are eager to test the methods and systems in their existing clinical applications. The resulting assays and products will be marketed to the research, pharmaceutical, biotechnology and diagnostic industries.
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0.904 |
2013 — 2018 |
Naleway, John J |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). R44Activity Code Description: To support in - depth development of R&D ideas whose feasibility has been established in Phase I and which are likely to result in commercial products or services. SBIR Phase II are considered 'Fast-Track' and do not require National Council Review. |
Live-Cell Assays of Er and Golgi Enzyme Activities @ Marker Gene Technologies
RESEARCH STRATEGY/PROJECT SUMMARY/ABSTRACT This Administrative Supplement to our Small Business Innovation Research Phase II project will take advantage of new advances in liquid handling instrumentation to augment our efforts in developing high-content (HCS) and high-throughput screening (HTS) systems for the discovery of novel therapeutics and/or modulating systems for use in the treatment of neurodegenerative disorders including Gaucher, Krabbe, Fabry, Tay-Sachs, Sandhoff and other lysosomal storage diseases as well as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Type 2 diabetes, Lowe syndrome, Huntington's disease and their allied medical conditions. The ability to accurately plate out equal numbers of live cells into 96-well or 384-well tissue culture plates for these HTS and HCS applications is paramount to obtaining consistent and reliable results. Robust and reliable methods for the manipulation of human cell lines by passaging, plating and labeling are required to enable consistent, reproducible screens to be performed. With the help of this supplement, we intend to develop procedures and processes to maximize the level of consistency of cell plating and analysis, to ensure that the assays which we are running on a routine basis remain consistent across multiple runs and to apply these methods in the screening of large libraries of compounds. These procedures involve a variety of fully or semi-automated steps, using high-quality commercially available liquid handling and dispensing technologies. Therefore, we propose the purchase of a Molecular BioProducts/Thermo- Fisher Versette? automated liquid handling instrument. The Versette? has replaced the Thermo- Electron Multidrop as the state-of-the-art cell dispensing technology at Thermo-Fisher research labs and at HCS screening facilities worldwide [1-5]. The Versette will be integrated with our existing Thermo- Fisher Countess II FL Cell Counter and CellInsight? CX5 High Content Screening (HCS) Platforms to provide absolute cell counts, measure viability, determine whether cells to be plated from suspension consist of single cells [6] and perform the HCS screening and analysis of potential drug candidates. The ultimate goal and the overall impact of this project is to provide an understanding of the dynamic processes that occur in intracellular enzyme and protein trafficking defects in human disease and to obtain information that will provide a pathway to the discovery of more efficacious treatment options. The use of these systems for screening libraries of potential drug candidates for their ability to modulate enzyme function, trafficking and intracellular localization will identify new small molecule therapeutic leads based on these parameters. These systems will be used in our CRO activities as well as for a variety of significant cell biology, biochemical, diagnostic and medical applications with our collaborators in both academia and industry.
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0.904 |
2015 |
Naleway, John J |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Targeted Pharmacological Chaperones For Neurological Diseases @ Marker Gene Technologies
? DESCRIPTION (provided by applicant): This Small Business Innovation Research Phase I project aims to develop new targeted pharmacological chaperones capable of modulating enzyme degradation in the Golgi apparatus and Endoplasmic Reticulum (ER) of living cells and tissues. If successful, the proposed research will provide breakthroughs needed to advance the discovery of promising new therapies and modulating drugs for neurodegenerative disorders including lysosomal storage diseases, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), myeloid leukemia, glioblastoma, Type 2 diabetes, Lowe syndrome and allied degenerative diseases and medical conditions involving protein misfolding. In Phase I of this project, Marker Gene Technologies, Inc. will establish the feasibility of the technology by preparing new targeted pharmacological chaperones, demonstrating improved loading and localized accumulation in the Golgi and ER and demonstrating efficacy for increasing lysosomal enzyme activity in living cells that are of disease origin in comparison to those from normal controls. In Phase II, these and additional new targeted drug conjugates will be evaluated in vitro and in vivo for their ability to affect specific and localized induction of tese enzymes in living cells as well as alleviate unwanted protein degradation or improve protein trafficking in a cell- or tissue- specific manner using a variety of delivery methods. These new pharmacological chaperones and the resulting targeting systems will provide innovative methods to modulate Golgi and ER organelle function and thereby screen for the influence of secondary drug or protein administration, affect intracellular trafficking of proteins or improve transport or secretion of proteins, making them useful analytical tools for drug discovery and basic research in a variety of significant medical applications. Our very preliminary results indicate the proposed methods have the potential to increase intracellular loading and targeting of pharmacological chaperones in human cell lines from patients with Gaucher disease, thereby providing a new tool to the arsenal of available therapeutics for clinical treatment of neurodegenerative disorders.
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0.904 |