Directhumab's Technology

• Antibodies derived from non-animal sources or transgenic animals carry a limited repertoire of human IgG gene family only and maintain artificial antibody sequences that neither exist in nature nor will be selected by murine antigen presenting cells in a murine environment.

• Non-nature-selected antibody sequences may work well in vitro but frequently they will behave completely different in vivo. One of the common problems of artificial antibodies used as medicines is a disadvantageous (clinical) pharmacokinetic profile. Often, such antibodies even disappear in vivo without trackable disposition. Furthermore antibodies carrying residual non-human sequences are more likely to induce anti-drug antibodies in humans, which may cause immunogenicity related adverse events.

• Reconstitution of immune-deficient mice* with human hematopoietic stem cells - e.g. CD133⁺ cells - develop a fully functional human immune system (humanized mouse).

• Following immunization the humanized mouse directly generates high quality, high-affinity, and fully human antibodies. These antibodies are pre-selected by human immune cells in vivo. Therefore in vitro affinity maturation and antibody humanization processes - a costly and tedious effort required following alternative approaches - can be avoided for antibodies envisaged as medicinal products in humans.

  

• Being not inbred, Humanized Mice have no blind spots in their immune repertoires, meaning that diverse antibodies covering virtually any target epitope can be found – even on highly complex targets.

• The variable (V) regions of conventional antibodies from Humanized Mice are naturally encoded by the complete repertoire of V genes found in humans – unlike transgenic mice.

• An in-depth characterization of the reconstituted immune system by data analysis of deep sequencing Ig repertoire validated the humanized mouse be immunological equivalent to human donors

• While proteins of therapeutic interest are often conserved between human and rodent and tolerated, they are not tolerated in Humanized Mice, based on the post-natal time point for the human immune system development where all differentiation/embryonic, oncofetal or developmental proteins are not expressed anymore. This makes Humanized Mice able to mount antibody responses against any therapeutic target 

• Directhumab holds IP-rights for this novel technology, which opens the direct access to fully human antibodies. 

• Our proprietary technology has expansive potential to immediately generate fully human antibodies against a wide range of antigens, including developmental and embryonic antigens.
   
• For research groups and biotechnology companies interested in the development of novel antibodies for medicinal use this is a unique opportunity to benefit from an independent IP-position.
   
• Inquiries to discuss modalities for collaboration are welcome.

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 * (e.g. Rag2^-/-gamma chain^-/- with inactivated mouse antibody machinery)