Patents erythropoietin

A group of benzimidazole-2-pyrazole PHD2 inhibitors appeared in a recent patent application, with IC50 values as low as 16 nM for compound 43 in a [14C]-based enzymatic assay [64]. Furthermore, members of this class of compounds were reported to stimulate erythropoietin secretion from PIep3B cells by up to 150% at 100 pM concentrations. 

To date, three pharmaceutical companies have entered clinical trials with PHD inhibitors for the treatment of anemia with the most advanced being FG-2216. In clinical studies, compound 2 (likely FG-2216) showed a dose- and time-dependent elevation of plasma erythropoietin after oral administration [66]. Healthy volunteers were orally administered various doses of compound 2 and serum erythropoietin (EPO) concentrations were measured at various times. Compound 2 increased serum EPO levels in a dose-dependent manner and, following administration of the 20 mg/kg dose, a 5-fold increase of EPO levels was observed after 12 h. In the same patent application, the effect of 2 on anemic predialysis patients with no previous rh-EPO exposure was also disclosed. Patients were treated with 2 three times/week for 4 weeks (no dose reported) and the hemoglobin levels were assessed on day 42. The patients who received treatment showed a mean increase in hemoglobin of 1.9 g/dL from baseline values, whereas subjects who received placebo showed a mean decrease of 0.35 g/dL from baseline levels. These data suggest for the first time that an oral PHD inhibitor could be effective for the treatment of anemia. 

Using the same logic, the US PTO has, for example, granted patents for pure cultures of specific microorganisms, as well as medically important proteins [e.g. factor VIII, purified from blood (Chapter 9) and erythropoietin, purified from urine (Chapter 6)]. 

In Brazil, for instance, the recombinant form of molecules such as IFN-alpha and human erythropoietin can be patented, as well as the processes for obtaining them using animal cells. However, the natural forms of these molecules, as well as the animal cells used to obtain these molecules, are not patentable. 

Erythropoietin (Epoetin, EPO) had a global market of US 11.1 billion in 2004 (Research and Markets, 2005b) and was the top-selling biopharmaceutical worldwide. The patent on this biopharmaceutical, owned by the company Amgen, expired in 2004, paving the way for new companies to enter the market. 

Alliger, P. Palma, N. Chromatographic Purification of Recombinant Human Erythropoietin. WO Patent 03045996, 2003. 

Erythropoietin, Lipitor, and TNF inhibitors are likely to cross the 15 billion mark within the next few years. Amgen commercial success with its EPO brands has attracted several competitors with which Amgen has been involved in costly and protracted patent and marketing litigation to protect its franchise. Erythropoietin... 

Bernstein, H., Mathiowitz, E., Monel, E., and Brickner, A., 1993, Erythropoietin drug delivery system. International Patent Application WO 93/25221, date of publication December 23, 1993. 

P.S. Bailon, Erythropoietin conjugates, U. S. Patent 6583272, assigned to Hoffman-La Roche Inc., June 24, 2003. 

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