Phar2912-Therapeutic proteins

• Pharmacokinetics


  The study of the movement of drugs within the body
• Biopharmaceuticals


  Biological medicines that contain one or more active substances made by or derived from a biological source (such as a bacterium or yeast), rather than a chemical source
• Biopharmaceuticals


  • They are larger and more complex than non-biological medicines
  • They may result in a degree of variability, particularly between batches of the medicine
• Therapeutic proteins


  Proteins that are engineered in the laboratory for pharmaceutical use
• Insulin was the first therapeutic protein introduced in the 1920s

  
• Recombinant DNA-technology


  Allows proteins to be generated in specific host cells (e.g. bacteria, yeast or mammalian cells)
• Mammalian cells


  The main host for therapeutic protein production as they allow post-translational modifications like glycosylation and sialylation, which have a big impact on the protein's pharmacokinetics and efficiency
• Monoclonal antibodies


  • Larger size (about 150 kDa)
  • Immunoglobulin structure
  • Cell-based production and purification from cell culture (complex)
  • High target specificity
  • Receptor-mediated distribution and elimination
  • Very limited central nervous system access
  • Weekly to monthly dosing

  
• Small molecule drugs


  • Smaller size (approx 0.5 kDa)
  • Chemical moiety structure
  • Controlled chemical synthesis (easy)
  • Lower target specificity
  • Hepatic metabolism and renal elimination
  • Possible central nervous system access
  • Usually daily dosing
• Antibody elimination


  1. Intracellular catabolism following fluid-phase or receptor-mediated endocytosis

  2. Receptor-mediated endocytosis of antibody following interaction with target epitopes on cell surfaces (target-mediated disposition)

  3. Target-mediated elimination is capacity limited (saturable) due to finite expression of the target
• Formation of non-neutralising anti-drug antibodies

  Increased clearance (reduced exposure)
• Formation of neutralising anti-drug antibodies

  Antibody unable to bind the target, decreased antibody activity
• Biosimilar medicine


  A version of an already registered biological medicine (the reference medicine) that has demonstrable similarity in physiochemical, biological and immunological characteristics, efficacy and safety
• Generic medicine


  A version of an original medicine that has the same chemical structure and can be developed to be the same as the reference medicine
• Biosimilars are similar, but not identical, versions of a biological medicine due to the degree of natural variability that occurs in their development and production