GMP Biopharmaceuticals


Production of a monoclonal antibody for therapeutic use for the prevention of Graft-versus-Host-Disease (GvHD)

The aim of the project is the GMP-compliant production of a monoclonal antibody for the clinical trial for the prevention of Graft-versus-Host-Disease (GvHD) in allogeneic stem cell transplantation.

The project includes the following work packages:

  • Production of the master cell bank, its characterization and quality control
  • Process development of the upstream and downstream process
  • Formulation Development
  • Production of GMP-compliant batches for the preclinical and clinical trial
  • Establishment and validation of the approval-relevant analysis for quality control including in-process controls, as well as structural analyses and stability investigations including stress tests and long-term investigations
  • Contribution to the Investigational Medicinal Product Dossier (IMPD)

Process development, manufacturing and quality control of a chimeric Ficolin-Angiopoietin fusion protein

Homology model of the chimeric recombinant fusion protein Ang1 mimetic.
© Fraunhofer IZI
Homology model of the chimeric recombinant fusion protein Ang1 mimetic.

Even today, there is frequently no cure for glaucoma, an eye disease. Therefore, research efforts to find new treatments must be accelerated. In many cases, current treatments and surgical methods are not effective, show little success and, frequently, are not well tolerated. Therefore, new treatments for the continuously increasing number of patients suffering from glaucoma are needed – in particular, by ensuring the permanent reduction of intraocular pressure. To achieve this effect, the use of innovative molecules is aimed at stabilizing the vascular endothelium. 

This strategy is based on addressing a reversible small molecule inhibitor (vascular endothelial protein tyrosine phosphatase (VE-PTP)). A specifically developed fusion protein with a reinforced modulating effect on the signal path (referred to above) is intended to repair defective Schlemm canals in the eye - which leads to increased liquid flow. As a result, intraocular pressure would be reduced, which would, in principle, cure glaucoma. 

Moreover, this therapeutic principle is to be evaluated in the context of SARS-COV-2 infections. This infection frequently involves damage to the endothelium – particularly in lung tissue. A stabilization of the endothelium would, therefore, be very valuable here as well. 

For this reason, this project aims to establish a GMP-compliant production process (in particular as regards cell lines and master cell banks, as well as upstream and downstream process development) for the fusion protein. This includes the necessary quality control at Fraunhofer IZI so as to ensure the efficient and effective clinical application of the biomolecule.