Risedronate is used for the treatment of Paget’s disease of bone, a disease in which the formation of bone is abnormal, and for treating sufferers of osteoporosis in which the density and strength of bones are reduced. By slowing down the rate at which bone is dissolved, risedronate increases the amount of bone. The FDA approved risedronate for treatment of Paget’s disease in 1998 and for the prevention and treatment of osteoporosis in 1999. The drug is marketed as Actonel.
Proctor & Gamble filed worldwide patents titled for WO/2001/056983 ”Selective Crystallization of 3-Pyridyl-1-Hydroxyethylidene-1,1-Bisphosphonic Acid Sodium as the Hemipentahydrate or Monohydrate.” This patent has issued in Korea, Europe and the US. After allowance in Israel, it published for Opposition purposes and Unipharm filed an opposition. The claims in Israel were those allowed in the US.
The main claim is:
A process for selectively producing 3-pyridyl-1-hydroxyethlidene-1,1-bisphosphonic acid sodium hemipentahydrate and monohydrate comprising the steps of:
a) providing an aqueous solution of 3-pyridyl-1-hydroxyethlidene-1,1-bisphosphonic acid sodium;
b) heating the aqueous solution to a temperature from about 45° C. to about 75° C.; c) adding a solvent to the aqueous solution; and
d) optionally cooling the aqueous solution.
The Opposer claimed that the applicant knew full well that the hydrated salt was a mixture of the hemipentahydrate and the monohydrate and that the method of crystallization was the standard method of dissolution and was totally lacking in inventive step. The Applicant claimed not to have been aware of the monohydrate, although it is apparently always precipitated with the hemipentahydrate.
Deputy Commissioner Noach Shalev Shlomovits who heard the opposition, was apparently impressed by the fact that neither in the application nor during the opposition proceedings, did the applicant produce any crystallographical evidence, but simply deduced the two salts from the weight of the crystals, estimating the water of crystallization. Without any other evidence, it is clear that both crystal forms must have been known, and it appears that the general observation of controlling the rate of cooling and concentrations does not involve an inventive step. Shlomovits ruled that not only was there a lack of inventive step, but that the application was not properly enabled. Furthermore, he states that the claimed invention is not fairly based on the specification. Additionally, for greediness in clearly claiming more than is entitled, the Deputy Commissioner ruled that the application should be rejected. Finally, he stated that the scope of the composition claims include the pure hemipentahydrate which the applicant accepted was previously known since it was claimed in an earlier application.
The decision is resplendent with words like obvious’ and clearly, yet it should be noted that other, significant examining jurisdictions did allow the patent. Nevertheless, claims 16 to 18 relate to mixtures of from 50%-100% hemipentahydrate which does indeed lack novelty due to previous patents for the salt. Is this an attempt at ever-greening? Perhaps. If the applicant is dissatisfied with the Deputy Commissioner’s analysis, this decision will be appealed to the courts.
It should be noted that Teva tried unsuccessfully to invalidate the main Actonel patent in 2008. Earlier this year Teva was sued by Roche and by Warner Chilcott for patent infringement when trying to obtain FDA approval for a generic version of the drug.