We reported earlier that the U.S. Patent and Trademark Office (USPTO) issued a ruling against one of several patents that Pfizer holds on Lipitor (atorvastatin), its top-selling cholesterol drug. In the reexamination proceeding initiated last year by the Public Patent Foundation (“PUBPAT”), the USPTO rejected all 44 of the claims of U.S. patent 5,969,156 when it ruled that Pfizer’s arguments for securing the patent in 1999 were invalid. PUBPAT’s Request for Re-examination alleged that the claims of the ‘156 patent are anticipated by U.S. patents 5,273,995 and 5,686,104 as having disclosed crystalline atorvastatin.
Now, the tide has turned. On Nov. 23, 2005, the Examiner issued a Notice of Intent to Issue Ex Parte Re-Examination Certificate. Included in the allowed claims are 21 of the original claims, 13 amended claims and 73 newly presented claims!
In the Statement of Reasons for Patentability and/or Confirmation, the Examiner stated that:
Claims 1-117 are allowed because they are directed to crystalline forms of atorvastatin which are not found in the prior art. More specifically, the prior art form of atorvastatin found in Mills et al (US 5,686,104) and Roth (US 5,273,995) are amorphous compared to the instant claims which are crystalline forms of the same compound.
In its response, Pfizer submitted declarations showing the x-ray powder diffraction analysis of the atorvastatin calcium compounds of the prior art as compared to the compounds claimed in the ‘156 patent. Claims 2, 4, 5, 9 and 31 were amended to correct a typographical error while claims 1, 28, 29, 36 and 38 were amended. In doing so, Pfizer admitted that “it has now been determined that it is possible, although unlikely, that certain lots of atorvastatin calcium used in early clinical trials might be argued to fall within the scope of some of the broad originally issued claims of the ‘156 patent.” The claims have now been amended to limit the claims to a crystalline Form I atorvastatin hydrate having an X-ray powder diffraction containing the following 2-theta value measured using CuK-alpha radiation: 22.0.
In its response, Pfizer stated that atorvastatin is an “unusual” molecule that exists in a large number of polymorphs with various “amorphous” forms and a greater number of different crystalline forms but that Form I crystalline atorvastatin calcium trihydrate is the active ingredient in Lipitor and the only form ever marketed by Pfizer. They also stated that the original atorvastatin calcium utilized by Pfizer in early development was an amorphous solid. Pfizer then points out the differences between the amorphous and crystalline atorvastatin, including chemical stability, impurities, particle size and dissolution profiles.
The ‘156 patent at issue with the current re-exam is set to expire in 2017, thus extending the useful patent protection of the drug (keep in mind that Lipitor is set to become the world’s first $10-billion-a-year drug so the stakes are extremely high).
Although the ‘156 patent is one of five patents listed by Pfizer with the U.S. Food and Drug Administration (FDA) for atorvastatin, it is the only one asserted by Pfizer in patent infringement lawsuits filed last year against web sites selling generic atorvastatin to Americans. Two are under review by a Delaware court and the remaining two have never been asserted by Pfizer against any competitor to Lipitor.
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Dowload the Notice of Intent to Issue Ex Parte Re-Examination Certificate here.
