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.
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.
Toomey
J R
JR
Departments of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Rd., King of Prussia, PA 19406, USA. John_R-Toomey@sbphrd.com
Blackburn
M N
MN
Storer
B L
BL
Valocik
R E
RE
Koster
P F
PF
Feuerstein
G Z
GZ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D001780:Blood Coagulation Tests; D001783:Blood Flow Velocity / Q000187:drug effects; D002341:Carotid Artery Thrombosis / Q000139:chemically induced / Q000188:drug therapy*; D003327:Coronary Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000494:pharmacology* / Q000592:standards / Q000627:therapeutic use; D015949:Factor IXa / Q000276:immunology*; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000592:standards / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000911:Antibodies, Monoclonal; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D015949:Factor IXa