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RCT demonstrates long half-life of CH2 domains


Research Corporation Technologies (RCT) and the Protein Interactions Group of the National Cancer Institute at the National Institutes of Health (NIH) have published the first studies in primates that characterize the long half-life of isolated CH2 domains, a new antibody-derived scaffold. The work was performed under a Cooperative Research and Development Agreement (CRADA) between RCT and the NIH. While therapeutic monoclonal antibodies are the most successful class of biologics in the last decade, their large size limits their ability to penetrate certain tissues and tumors effectively. Currently under development are several next-generation antibody-like drug platforms, such as antibody fragments and antibody-like scaffolds, which are much smaller in size than current monoclonal antibodies. These molecules’ smaller size may allow for better tissue penetration and new routes of administration. However, the small size of the newer scaffolds comes with a short serum half-life, typically less than one hour, once injected into patients. The CH2 domains (CH2D) described in the mAbs publication retain a small size and have a much longer half-life in both rodents and non-human primates, ranging from eight to 16 hours for those tested in the paper. “The small size coupled with the longer half-life makes the CH2D scaffold an ideal platform for the development of new therapeutic products. Moreover, this is the first report of a small protein scaffold having an extended half-life in non-human primates without modifications, such as pegylation,” said Kurt Gehlsen, Ph.D., Vice President and Chief Scientific Officer at RCT. RCT is developing a new biologics discovery platform based on engineered CH2 domains called ABDURINS™. The ABDURINS™ platform includes large, diverse libraries of engineered CH2 domains for screening against therapeutic targets of interest. RCT plans to make these novel libraries available to partners in both phage display and DNA display formats. To facilitate screening of the ABDURINS™ libraries, RCT has partnered with Isogenica (Isogenica.com) to provide interested parties access to a proprietary display and screening platform called CIS display. The CIS display system can screen significantly larger libraries and isolate and optimize lead binders in a fraction of the time it takes using phage display. RCT also has a partnership with IRBM (IRBM.it) that allows partners and licensees access to a broad ABDURINS™ product discovery and development program through early nonclinical testing. “We believe that our ABDURINS™ platform addresses several of the known short-comings of other small antibody-like fragments through its longer half-life, ease of production, and flexible formatting. We are looking forward to partnering with industry and developing the next generation of antibody-like therapeutics,” said Shaun Kirkpatrick, President and Chief Executive Officer of RCT.

About RCT

RCT is a Tucson-based technology investment and management company that provides early-stage funding and development for promising biomedical companies and technologies. RCT focuses on technology investments with origins from universities and research institutions worldwide. To learn more about RCT and the ABDURINS™ platform, see RCTech.com.

Read the mAbs article here:

Pharmacokinetics of engineered human monomeric and dimeric CH2 domains

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