Notice of Clarification of the Purpose and Research Objectives and Revised Research Strategy Instructions in PAR-16-115 "Optimization of Monoclonal Antibodies for Eliminating the HIV Reservoir (R01)"

Notice Number: NOT-AI-16-087

Key Dates
Release Date:  October 5, 2016

Related Announcements
PAR-16-115    

Issued by
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Mental Health (NIMH)

Purpose

On February 25, 2016, the NIAID issued Funding Opportunity Announcement (FOA) PAR-16-115 "Optimization of Monoclonal Antibodies for Eliminating the HIV Reservoir (R01)."  The purpose of this Notice is to alert the scientific community of a clarification in the purpose and research objectives and revision of research strategy instructions of this FOA.   

Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Purpose

Current Language:
The purpose of this Funding Opportunity Announcement (FOA) is to support the optimization of mAb or mAb derivatives that recognize and eliminate cells comprising the HIV reservoir.

Revised Language:
The purpose of this Funding Opportunity Announcement (FOA) is to support the optimization of mAb or mAb derivatives that recognize and eliminate cells comprising the HIV reservoir. For the purpose of this FOA, optimization refers to the molecular engineering of mAb and/or their modification during or after production such that they are no longer native.

Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

Specific Areas of Research Interest

Current Language:
This FOA will support applications that propose hypothesis-driven mechanistic studies aimed at the optimization of mAb or mAb derivatives that recognize and eliminate cells comprising the HIV reservoir. Areas of interest include, but are not limited to:

  • Generation of HIV-specific mAb or mAb derivatives with:
  • Improved Fab function to increase specificity, potency, avidity and breadth
  • Improved Fc effector function to eliminate cells expressing HIV proteins
  • Increased half-life and biodistribution
  • Studies of polyreactivity, autoreactivity (e.g. cross reactivity to human adult and fetal tissue) and immunogenicity (e.g. anti-antibodies)
  • Assessments of pharmacokinetics and efficacy (i.e. capacity of individual products or combinations of products to eliminate active and reactivating HIV reservoirs) in appropriate animal models

For the purposes of this FOA, the following HIV-specific mAb or mAb derivatives are within scope:

  • Broadly neutralizing or non-neutralizing mAb
  • Bispecific and multi-specific mAb
  • mAb conjugated to other proteins, peptides, or compounds

Applications proposing any of the following research topics will NOT be supported under this FOA:

  • Clinical Trials
  • Development of new animal models
  • Solely isolating and characterizing new mAb
  • cGMP product manufacturing

Revised Language:
This FOA will support applications that propose hypothesis-driven mechanistic studies aimed at the optimization of mAb or mAb derivatives that recognize and eliminate cells comprising the HIV reservoir. Areas of interest include, but are not limited to:

  • Generation of HIV-specific mAb or mAb derivatives with:
  • Improved Fab function to increase specificity, potency, avidity and breadth
  • Improved Fc effector function to eliminate cells expressing HIV proteins
  • Increased half-life and biodistribution
  • Studies of polyreactivity, autoreactivity (e.g. cross reactivity to human adult and fetal tissue) and immunogenicity (e.g. anti-antibodies)
  • Assessments of pharmacokinetics and efficacy (i.e. capacity of individual products or combinations of products to eliminate active and reactivating HIV reservoirs) in appropriate animal models

For the purposes of this FOA, the following HIV-specific mAb or mAb derivatives are within scope:

  • Broadly neutralizing or non-neutralizing mAb
  • Bispecific and multi-specific mAb
  • mAb conjugated to other proteins, peptides, or compounds

Applications proposing any of the following research topics will NOT be supported under this FOA:

  • Clinical Trials
  • Development of new animal models
  • Solely isolating and characterizing new mAb
  • cGMP product manufacturing
  • Evaluations of mAb or mAb combinations that have not been optimized by molecular engineering or modified during/after production such that they are no longer native
  • In vitro/ex vivo analyses lacking supporting studies of pharmacokinetics and efficacy in animal models

Part 2. Section IV. Application and Submission Information
Current Language:

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:  Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Revised Language:

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy:

  • Describe how the project will optimize mAb or mAb-derivatives by molecular engineering and/or modify them during/after production such that they are no longer native.
  • Describe plans to study pharmacokinetics and efficacy in appropriate animal models.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:  Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

All other aspects of this FOA remain the same.

Inquiries

Please direct all inquiries to:

Stephen Smiley, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID) 
Telephone: 240-627-3071
Email: stephen.smiley@nih.gov

Jeymohan Joseph, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 240-627-3869
Email: jjeymoha@mail.nih.gov