Development of a long acting human growth hormone analog suitable for once a week dosing

Bioorg Med Chem Lett. 2013 Jan 15;23(2):402-6. doi: 10.1016/j.bmcl.2012.11.104. Epub 2012 Dec 5.

Abstract

Human growth hormone was conjugated to a carrier aldolase antibody, using a novel linker by connecting a disulphide bond in growth hormone to a lysine-94 amine located on the Fab arm of the antibody. The resulting CovX body showed reduced affinity towards human growth hormone receptor, reduced cell-based activity, but improved pharmacodynamic properties. We have demonstrated that this CovX-body, given once a week, showed comparable activity as growth hormone given daily in an in vivo hypophysectomized rat model.

MeSH terms

  • Animals
  • Antibodies / metabolism
  • Crystallography, X-Ray
  • Disease Models, Animal
  • Drug Administration Schedule
  • Drug Design*
  • Fructose-Bisphosphate Aldolase / metabolism
  • Human Growth Hormone / administration & dosage*
  • Human Growth Hormone / analogs & derivatives*
  • Humans
  • Hypophysectomy
  • Models, Molecular
  • Molecular Structure
  • Rats
  • Time Factors

Substances

  • Antibodies
  • Human Growth Hormone
  • Fructose-Bisphosphate Aldolase