Comparing the antithrombotic efficacy of a humanized anti-factor IX(a) monoclonal antibody (SB 249417) to the low molecular weight heparin enoxaparin in a rat model of arterial thrombosis

Thromb Res. 2000 Oct 1;100(1):73-9. doi: 10.1016/s0049-3848(00)00299-1.

Abstract

A humanized inhibitory anti-factor IX(a) antibody (SB 249417) has been compared to enoxaparin (Lovenox) in a rat model of arterial thrombosis. Pretreatment of rats with either SB 249417 (3.0 mg/kg, i. v.) or enoxaparin (30.0 mg/kg, i.v. or s.c.) resulted in comparable and significant reductions in thrombus formation. However, the efficacious dose of enoxaparin resulted in >30-fold increase in the aPTT over baseline, while the efficacious dose of SB 249417 prolonged the aPTT by only approximately 3-fold. Additionally, pretreatment with SB 249417 resulted in sustained blood flow and arterial patency throughout the experiment in >80% of rats treated. In contrast, <30% of rats pretreated with enoxaparin remained patent throughout the experiment. The data in this report indicate that the selective inhibition of factor IX(a) with the monoclonal antibody SB 249417 produces a superior antithrombotic profile to that of the low molecular weight heparin enoxaparin.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Blood Coagulation Tests
  • Blood Flow Velocity / drug effects
  • Carotid Artery Thrombosis / chemically induced
  • Carotid Artery Thrombosis / drug therapy*
  • Coronary Disease / drug therapy*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enoxaparin / pharmacology*
  • Enoxaparin / standards
  • Enoxaparin / therapeutic use
  • Factor IXa / immunology*
  • Fibrinolytic Agents / pharmacology*
  • Fibrinolytic Agents / standards
  • Fibrinolytic Agents / therapeutic use
  • Heparin, Low-Molecular-Weight / immunology
  • Heparin, Low-Molecular-Weight / pharmacology
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Enoxaparin
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • Factor IXa