Discovery and bio‐optimization of human antibody therapeutics using the XenoMouse^® transgenic mouse platform

Abstract

Since the late 1990s, the use of transgenic animal platforms has transformed the discovery of fully human therapeutic monoclonal antibodies. The first approved therapy derived from a transgenic platform--the epidermal growth factor receptor antagonist panitumumab to treat advanced colorectal cancer--was developed using XenoMouse(®) technology. Since its approval in 2006, the science of discovering and developing therapeutic monoclonal antibodies derived from the XenoMouse(®) platform has advanced considerably. The emerging array of antibody therapeutics developed using transgenic technologies is expected to include antibodies and antibody fragments with novel mechanisms of action and extreme potencies. In addition to these impressive functional properties, these antibodies will be designed to have superior biophysical properties that enable highly efficient large-scale manufacturing methods. Achieving these new heights in antibody drug discovery will ultimately bring better medicines to patients. Here, we review best practices for the discovery and bio-optimization of monoclonal antibodies that fit functional design goals and meet high manufacturing standards.

The CGRP Pathway in Migraine as a Viable Target for Therapies

“…Eptinezumab employs the proprietary MabXpress antibody production technology which is considered to improve the efficiency of producing large molecule therapeutics . Erenumab was generated using the XenoMouse technology which delivers fully human mAbs . Galcanezumab was produced in BALB/c mice immunized with human CGRP conjugated to ovalbumin.…”

Recombinant Antibody Fragments for Neurodegenerative Diseases

“…Recombinant Ab fragments are promising alternatives to full-length immunoglobulins and offer important advantages compared with conventional monoclonal Abs: extreme specificity, higher affinity, superior stability and solubility, reduced immunogenicity as well as easy and inexpensive large-scale production [ 6 - 16 ]. Different antibody formats such as single-chain fragment variable (scFv), single-domain antibody fragments (VHHs or sdAbs), bispecific antibodies (bsAbs), intrabodies and nanobodies, are currently being studied in pre-clinical models of cancer as well as infectious and autoimmune diseases and many of them are being tested as therapeutics in clinical trials [ 4 , 16 - 22 ].…”

Nanodisc technology facilitates identification of monoclonal antibodies targeting multi-pass membrane proteins

“…This combined with fluorescently labelled antigen allows for single cell sorting of hybridoma producing IgG specific to the antigen of interest. The single cell sorted hybridoma can then be expanded in microtiter wells and specificity of IgG secreted into the culture media can be confirmed using standard screening techniques 8 .…”