Pfizer on top in Norvasc API patent dispute
prescribed branded medicine for treating hypertension after a US
court ruled that Dutch drugmaker Synthon's generic copy of Norvasc
(amlodipine besylate) infringed upon a US patent pertaining to the
drug's active pharmaceutical ingredient (API).
A federal court in North Carolina upheld Pfizer's patent covering amlodipine besylate, prohibiting the US subsidiary of Synthon from launching a generic version of the drug until September 2007.
The patent covers the besylate salt of amlodipine, its pharmaceutical composition with a diluent or carrier, and its tablet formulation consisting of an anti-hypertensive, antiischemic or angina-alleviating effective amount of the API.
Two weeks ago a federal court jury in Virginia ruled that Pfizer did not infringe on another patent owned by Synthon covering a process which Pfizer has been using for over 15 years for making amlodipine, and found that patent invalid on multiple grounds.
"We had to protect Norvasc after Synthon filed a request with the US Food and Drug Administration (FDA) for approval of their drug," Pfizer spokeswan Bryant Haskins told In-PharmaTechnologist.com.
"This latest ruling reaffirms that our amlodipine patent is valid and we are determined to protect it from future challenges."
Synthon unsuccessfully argued that Pfizer's patent is invalid because of obviousness and the lack of adequate written description.
The court ruling in North Carolina is subject to appeal but a Synthon representative could not be reached to comment on the company's intentions.
Thus, the world's biggest drugmaker has ensured that Norvasc, which made up $4.71bn (€3.66bn) out of Pfizer's $51.3bn 2005 revenue, is safe for now.
When Norvasc was being developed in the 1980s, Pfizer had originally intended to use the maleate salt of amlodipine in its tablet formulation, but decided to switch to amlodipine besylate because of the chemical instability and sticking to the tabletting machinery that were observed with the maleate salt.
This was an unprecedented move back then, since in order to facilitate the scaling up of manufacturing operations, Pfizer had to abandon its maleate formulation, which had reached Phase III clinical studies, and instead develop the besylate formulation, which required repeated testing for it to be approved by the FDA and risked substantially delaying Norvasc's commercial launch.
Nevertheless, the move paid off, as Pfizer's formulation scientists were able to produce large commercial batches of amlodipine besylate tablets by direct compression on high-speed tablet presses without disruption, unlike their attempts to do so with the maleate salt of amlodipine.
Amlodipine besylate however is used not just in Norvasc but also in Caduet (amlodipine besylate/atorvastatin calcium), a multi-target single pill combining Norvasc and Lipitor, used for treatment of elevated cholesterol levels in the blood.
In January 2006, Pfizer's Norvasc API patent was held valid and infringed by Canadian company Apotex in a decision by the Northern District Court of Illinois.
The challenges to the patent could continue though as its expiration date approaches and generic drugmakers are positioning themselves to reach the market first with their copy of the drug.
