Notice of Addition of High Throughput Screening to the Scope of PAR-15-070 "Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Assay Development and Therapeutic Agent Identification and Characterization to Support Therapeutic Discovery (R21/R33)"

Notice Number: NOT-NS-15-031

Key Dates
Release Date:   July 2, 2015

Related Announcements
PAR-15-070

Issued by
National Institute of Neurological Disorders and Stroke (NINDS)   

Purpose

The purpose of this Notice is to make a change in scope for PAR-15-070 "Innovation Grants to Nurture Initial Translational Efforts (IGNITE): Assay Development and Therapeutic Agent Identification and Characterization to Support Therapeutic Discovery (R21/R33)" to allow for high throughput screening (HTS).

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

The current language reads:

Examples of activities for R21 phase include, but are not limited to:

  • Development of assay(s) to support a succinct testing funnel, including for example, assays to measure specificity, potency, stability to protease and/or other metabolic enzymes, and cellular uptake.
  • A combination of assays may be developed to demonstrate relevant biological activity when a single assay may not provide adequate measurement of overall potency due to a complex mechanism of action or multiple activities of a biologic.
  • Development of in vitro or ex vivo potency/efficacy assay designed to indicate the specific ability of an agent to achieve a desired biological effect, for example: structural changes that may impact product quality, stability, and efficacy.
  • Development of assays to evaluate cellular uptake, engagement, infection, aggregation, downstream functional measures in vitro or ex vivo, purity, and specificity. Assays to measure DNA, RNA, and protein levels of either endogenous genes or delivered products, downstream in vitro or ex vivo functional read-outs, viral titer, viral particle load stability and specificity.
  • Development of assays to evaluate purity and identity of the therapeutic by surface markers or specific proteins, morphological measures, differentiation, purity, functional measures vitro or ex vivo, stability, and immunogenicity.

Examples of activities for the R33 phase include, but are not limited to:

  • Preparation and screening of select series of therapeutic agents using for example medicinal chemistry or biological processes.
  • Preparation of therapeutic agent(s) and confirmation of structure, sequence or biological characteristics
  • Development and selection of cell lines/vectors to produce bioactive agents with acceptable potency and stability, production, cellular uptake/engagement, or secondary in vitro functional assays.
  • Assessment of therapeutic agent’s properties using computational analysis and early physicochemical measurements, polar surface area, solubility, cell permeability and efflux.
  • Assessment of initial pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion (ADME).
  • Assessment of potential off target activities.
  • Optimization of therapeutic agent(s).

Examples of activities that are not appropriate for this FOA include, but are not limited to:

  • Studies designed to establish proof of concept for a biological target (covered by PA-13-302).
  • Development of assays or probes to support basic understanding of disease or other basic research. Basic research is supported in PA-13-302, Research Project Grant (Parent R01).
  • High-throughput screening (HTS), comprising screening of large random chemical libraries for activity against biological targets via the use of automation, miniaturized assays and large-scale data analysis. HTS is defined by the number of compounds tested in the range of 10,000–100,000 per day. (covered by PAR-14-284 ).
  • Assay development for HTS (covered by PAR-13-364 ).
  • Pharmacodynamics and in vivo efficacy studies (covered through companion PAR-15-071 ).
  • Development of devices, surgical procedures, diagnostics, and rehabilitation strategies.
  • Development of risk, detection, diagnostic, prognostic, predictive, and prevention biomarkers.
  • Studies of disease mechanism.
  • Studies or use of therapeutic agents to identify targets relevant to a disease.
  • Investigational New Drug (IND) enabling studies.
  • Manufacture of therapeutic agents for clinical use.
  • Clinical research and clinical trials.

The language has been modified and now reads:

Examples of activities for R21 phase include, but are not limited to:

  • Development of assay(s) to support a succinct testing funnel, including for example, assays to measure specificity, potency, stability to protease and/or other metabolic enzymes, and cellular uptake.
  • A combination of assays may be developed to demonstrate relevant biological activity when a single assay may not provide adequate measurement of overall potency due to a complex mechanism of action or multiple activities of a biologic.
  • Development of in vitro or ex vivo potency/efficacy assay designed to indicate the specific ability of an agent to achieve a desired biological effect, for example: structural changes that may impact product quality, stability, and efficacy.
  • Development of assays to evaluate cellular uptake, engagement, infection, aggregation, downstream functional measures in vitro or ex vivo, purity, and specificity. Assays to measure DNA, RNA, and protein levels of either endogenous genes or delivered products, downstream in vitro or ex vivo functional read-outs, viral titer, viral particle load stability and specificity.
  • Development of assays to evaluate purity and identity of the therapeutic by surface markers or specific proteins, morphological measures, differentiation, purity, functional measures vitro or ex vivo, stability, and immunogenicity.
  • Assay development for High-Throughput Screening (HTS).

Examples of activities for the R33 phase include, but are not limited to:

  • Preparation and screening of select series of therapeutic agents using for example medicinal chemistry or biological processes.
  • Preparation of therapeutic agent(s) and confirmation of structure, sequence or biological characteristics
  • Development and selection of cell lines/vectors to produce bioactive agents with acceptable potency and stability, production, cellular uptake/engagement, or secondary in vitro functional assays.
  • Assessment of therapeutic agent’s properties using computational analysis and early physicochemical measurements, polar surface area, solubility, cell permeability and efflux.
  • Assessment of initial pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion (ADME).
  • Assessment of potential off target activities.
  • Optimization of therapeutic agent(s).
  • HTS, comprising screening of large random chemical libraries for activity against biological targets via the use of automation, miniaturized assays and large-scale data analysis. HTS is defined by the number of compounds tested in the range of 10,000–100,000 per day.

Examples of activities that are not appropriate for this FOA include, but are not limited to:

  • Studies designed to establish proof of concept for a biological target (covered by PA-13-302 ).
  • Development of assays or probes to support basic understanding of disease or other basic research. Basic research is supported in PA-13-302, Research Project Grant (Parent R01).
  • Pharmacodynamics and in vivo efficacy studies (covered through companion PAR-15-071 ).
  • Development of devices, surgical procedures, diagnostics, and rehabilitation strategies.
  • Development of risk, detection, diagnostic, prognostic, predictive, and prevention biomarkers.
  • Studies of disease mechanism.
  • Studies or use of therapeutic agents to identify targets relevant to a disease.
  • Investigational New Drug (IND) enabling studies.
  • Manufacture of therapeutic agents for clinical use.
  • Clinical research and clinical trials.

All other aspects of this FOA remain unchanged.

Inquiries

Please direct all inquiries to:

Dr. Amir Tamiz
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1779
Email: amir.tamiz@nih.gov