Asset

  • No.

    121

  • Asset Title

    Development of Multi-Specific Antibody-Serum Albumin Fusion Proteins Targeting Multiple Human and Murine CXC (ELR+) Chemokines

  • Organization

    Massachusetts Institute of Technology

  • Product Type

    Antibody

  • Therapeutic Area

    Inflammatory disease

  • Development Stage

    Hit To Lead or Lead Optimization

  • Technical Summary

    • Ab binds multiple CXC chemokines to block the CXC inflammatory cascades.

    • This technology uses an antibody that promiscuously binds multiple CXC chemokines to block the CXC inflammatory cascades associated with RA. A panel of promiscuous antibodies was developed through three sequential rounds of PCR-mutagenesis and directed evolution by selecting for antibodies with both promiscuous binding tendencies (binding to multiple CXCLs), and high binding affinity against multiple CXCLs.

    • The antibodies were then fused to the serum albumin protein, which stabilizes the antibody in circulation and increases the in vivo half-life. The top three antibody hits from this directed evolution scheme blocked receptor activation in response to 2-5 different CXC ligands in vitro. 

    • The inventors performed proof of concept experiments in an in vivo mouse model of RA that demonstrated a complete resolution of RA disease burden in only 10 days in response to the top candidate antibody. 

      

  • Patent

    US20210246199A1

  • Publication

    Directed Evolution of Broadly Crossreactive Chemokine-Blocking Antibodies Efficacious in Arthritis. Nature Communications, (2018)

  • Attachment

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