requests-for-proposal

Improvement of Pharmacokinetic Properties and Efficacy of Nucleic Acid Drug

Request Number REQ3342854
Due Date May 19, 2017
Author Seh-Rin Sung
Request for Proposal Details
RFP Title
Improvement of Pharmacokinetic Properties and Efficacy of Nucleic Acid Drug
RFP Description

NineSigma, representing a pharmaceutical company with special focus on nucleic acid therapeutics, seeks a technology to improve the pharmacokinetic properties of a nucleic acid drug, such as in vivo stability, prolonging blood circulation, tissue-specificity and cellular uptake.

Background

Nucleic acid drugs generally have poor pharmacokinetic properties, such as low in vivo stability, rapid blood clearance, and low cellular uptake. To resolve these problems, various approaches have been taken; however, no suitable technology has been established yet. With this as a background, the client wishes to collaborate with potential partners that possesses promising technology.

 

 

 

Key Success Criteria

Prerequisite

  • Type of nucleic acids: DNA, RNA and artificial nucleic acids such as morpholino nucleic acids
  • Administration route: Systemic administration by injection
  • Target tissue: All tissues except the liver

 

 

Possible Approaches

Assumed approaches to improve the pharmacokinetic properties and achieve high activity and low toxicity might include, but are not limited the following:

 

(1)Conjugation of compounds to nucleic acid

The nucleic acid drug conjugated other  compounds, sugar chains, peptides, and antibodies are included and the following requirements should be met:

  • Improved pharmacokinetics

    • At least one of the following pharmacokinetic properties should be improved: tissue-specificity (except for the liver), cellular uptake, or in vivo stability.

  • High efficacy

    • Conjugated compounds should not inhibit the efficacy.

    • In case of conjugation of high molecular compounds, an approach using the following mechanism is acceptable: once conjugated compounds are delivered to the inside of target tissue, the compounds will be removed.

  • High safety

[Exclusion] Cationic compounds

  • Owing to cytotoxicity concerns, it is desirable that no cationic compounds are included. However, these compounds can be acceptable if above concerns are avoidable.

 

(2)Chemical modification of nucleic acid

The nucleic acid drug of which the base moieties, phosphodiester linkage, and sugar moieties should be chemically modified and the following requirements should be met:

  • Improvement of efficacy or pharmacokinetics
    • The activity of siRNA and antisense and the target gene specificity should be improved.
    • At least one of the following pharmacokinetic properties should be improved: tissue-specificity (except for the liver), cellular uptake, or in vivo stability.
  • High safety
    • Immune response, nephrotoxicity, and hepatotoxicity should be avoided.

 

(3)Loading nucleic acid to the carrier

The technology should enable nucleic acid to be loaded to the carrier using a mechanism other than the commonly known electrostatic interaction method, and should meet the following requirements:

  • Improvement of pharmacokinetics
    • At least one of the following pharmacokinetic properties should be improved: tissue-specificity (except for the liver), cellular uptake, or in vivo stability.

[Exception] Carriers designed to deliver to solid tumors using the EPR effect

  • High efficacy
    • The carrier should not inhibit the efficacy.
  • High safety

[Exception] Cationic carriers

  • Owing to cytotoxicity concerns, it is desirable that no cationic compounds are included. However, these compounds can be acceptable if above concerns are avoidable.
  • High loading efficiency of nucleic acid
    • Loading efficiency of 50% or higher

 

Current level of the technology required in all approaches (1) through (3)

Approaches (1) through (3) should meet the following requirements:

  • Improvement of drug efficacy or pharmacokinetics should be confirmed in in vitro study, and more preferably, in in vivo study.
  • The minimum safety (cytotoxicity) should be confirmed in in vitro study, and more preferably, in in vivo study.
  • Synthesis and analysis methods should be established in the laboratory.
    • For approach (3), an established formulation preparative procedure should exist.

 

With regard to the above approaches, we also welcome technologies which have never been validated in nucleic acid if there is the potential for future application with rationale.

 

 

Approaches not of interest

The following approaches are not of interest:

  • Technologies and materials that use substances harmful to human body.

 

 

 

Preferred Collaboration types
Items to be submitted

Anticipated Project Phases or Project Plan

The proposing organization is required to submit proposals using the attached Response Template.

 

The client will review proposals and select suitable candidates for collaboration. Once candidates are selected, the client will execute confidential disclosure agreements (CDAs) in order to seek further information disclosure and discuss possible research approaches.

Once the best candidates have been determined, the client will execute licensing/joint/contract research agreements with partners.

 

Items to be Included in the Proposal

Responses will use the Proposal Template which is linked to the “attachments“ shown at the bottom of the link <REQ3342854 > and include the following items:

 

  • Type of proposed technology
  • Overview of the technology (background of technology development, assumed application for the development, uniqueness, etc.)
  • Mechanism that can improve the pharmacokinetic properties of a nucleic acid drug
  • Current performance
    • Base materials to be used
    • Type of nucleic acid
    • Track record of evaluation drugs
    • Specific diseases that the technology can be applied to
    • Data indicating improvement of drug delivery and pharmacological activity
    • Considerations on the safety
  • Current R&D stage
  • Current challenges and future development plans to meet the ultimate requirements
  • Any requests concerning the collaboration form
  • Contact and license agreements that the applicant currently has with other companies
  • Current status of intellectual property related to the proposed technology
  • Past research achievements

 

Area of Interest
Request Priority
Comments