The U.S. of Appeals for the Federal Circuit invalidated U.S. Patent No. 5,994,329 (the ‘329 patent), covering the  osteoporosis drug Fosamax made by Merck & Co.  The court reversed and vacated an earlier ruling by the U.S. District Court in Delaware that had upheld the validity of the patent.

The patent is listed in the U.S. Food and Drug Administration’s Orange Book for Merck & Co.’s 35 mg and 70 mg Fosamax for which Teva Pharmaceutical Industries Ltd. has filed an Abbreviated New Drug Application to market a generic version. The district court found that Teva’s Abbreviated New Drug Application (ANDA)  constructively infringed the ‘329 patent claims 23 and 37 under 35 U.S.C. 271(e)(2)(A) of the Hatch-Waxman Act.

The ‘329 patent, entitled Method for Inhibiting Bone Resorption teaches a method of treating and preventing osteoporosis through less-than-daily administration of bisphosphonate compounds.  Bisphosphonates are a family of chemical compounds that are known to selectively inhibit the bone destruction process that contributes to osteoporosis and other bone diseases. At issue in this case are once-weekly dosages of alendronate monosodium trihydrate.

Since bisphosphonates are not readily absorbed by the gastrointestinal (‘GI’) tract, a patient must take the medicine on an empty stomach and remain upright and fasting for thirty minutes after ingestion.   The ‘329 patent provided a reduced-frequency dosing schedule to alleviate  the irritating effect of the compounds.
This case involves dependent claims 23 and 37 of the ‘329 patent, as below:

23.       A method for treating osteoporosis in human comprising orally administering about 70 mg of alendronate monosodium trihydrate, on an alendronic acid basis, as a unit dosage according to a continuous schedule having a dosing interval of once-weekly.

37. A method for preventing osteoporosis in human comprising orally administering about 35 mg of alendronate monosodium trihydrate, on an alendronic acid basis, as a unit dosage according to a continuous schedule having a dosing interval of once-weekly.

Relying on a construction of “about”, the district court dismissed Teva’s allegations that the claims were anticipated or obvious.

In reviewing the lower court’s holding, the Fed. Cir. stated that:

According to the district court’s opinion, the patentee uses the phrase about 35 [or 70] mg to account for variations in the molecular weight of the different derivatives of alendronic acid and to deliver exactly 35 (or 70) mg of alendronic acid.  Merck, 288 F. Supp. 2d at 613.  For example, the court noted that alendronate monosodium trihydrate, which is used in Fosamax, requires an atom of sodium for each molecule.  Id. at 613-14. 

If a heavier metal were chosen, such as potassium, the weight of the derivative compound would have to increase to deliver exactly the same number of molecules of the active alendronate compound found in 35 [or 70] mg of alendronic acid.  Id. at 614.  The district court thus construed the term “about 35 [or 70] mg” to mean the amount of the derivative compound that gives exactly 35 [or 70] mg of the active compound.

We reverse the district court’s construction of about and hold that such term should be given its ordinary meaning of approximately.

When a patentee acts as his own lexicographer in redefining the meaning of particular claim terms away from their ordinary meaning, he must clearly express that intent in the written description.  See, e.g., Bell Atl. Network Servs. v. Covad Communications Group, Inc., 262 F.3d 1258, 1268 (Fed. Cir. 2001).  We have repeatedly emphasized that the statement in the specification must have sufficient clarity to put one reasonably skilled in the art on notice that the inventor intended to redefine the claim term.  Id."

The trial court held a July 1996 article does not ‘expressly or inherently disclose the dosage amounts for alendronate in claims 23 and 37’ because there was no evidence that 40 mg and 80 mg of alendronate contains ‘the same number of alendronate core molecules’ as found in 35 mg and 70 mg, respectively, of alendronic acid and that the suggestion of weekly treatment was not ‘clinically useful or obvious in July 1997 because of the known dose-related gastrointestinal side effects’ associated with the daily formulation of Fosamax. Teva argued that the 40 mg and 80 mg amounts were recommended because 40 mg tablets of alendronate monosodium trihydrate were commercially available and exact multiples of the standard daily dose corresponding to the amount of Fosamax administered in a week, i.e., 35 mg or 70 mg, were not commercially available at the time of the 1996 articles.

In holding that the passage cited by the district court from the specification for Merck’s definition of ‘about’ is ambiguous, the court stated that it fails to redefine ‘about’ to mean ‘exactly’ in clear enough terms to justify such a counterintuitive definition of ‘about.’  The court also stated that:

Finally, our construction of ‘about’ eliminates the problem pointed out by Teva that the district court’s construction of the term ‘about’ renders other parts of the claim superfluous.  As Teva notes, the specification uses both the term ‘about’ and ‘on an alendronic acid basis’ at least 15 times to describe a dosage strength.  If, as Merck urges, “about 35 [or 70] mg” means exactly 35 (or 70) mg of alendronic acid, then the oft-repeated phrase “on an alendronic acid active basis’ would be unnecessary since such an understanding would be clear simply by using the term “about.”  A claim construction that gives meaning to all the terms of the claim is preferred over one that does not do so.  Elekta, 214 F.3d at 1307 (construing claim to avoid rendering the 30 degree claim limitation superfluous); Gen. Am. Transp. Corp. v. Cryo-Trans, Inc., 93 F.3d 766, 770 (Fed. Cir. 1996) (rejecting the district court’s claim construction because it rendered superfluous the claim requirement for openings adjacent to the end walls).  By construing ‘about’ to mean its accepted and ordinary meaning of “approximately,” the phrase “alendronic acid basis” is no longer excess verbiage, but is instead necessary because it is the noun that “about 35 [or 70] mg” modifies. 

In light of the corrected claim construction the court reversed the district court’s obviousness analysis holding that:

The central issue concerns the differences between the aspects of the invention claimed at claims 23 and 37, and the teachings of the Lunar News articles.  As the district court necessarily recognized, there are more similarities than differences.  These claims, and the July 1996 article, both teach administering alendronate once a week instead of once a day.  These claims read in light of the specification, and the July 1996 article, both indicate and it has been conceded as known in the art at the time that for treating or preventing osteoporosis a once-weekly dosage at seven times the daily dose would be as effective as seven daily doses.  The ‘329 patent, and both the April and July 1996 articles, explain the motivation for a once-weekly dose as increasing patient compliance, by making it easier to take the drug (and incur the inconvenience of the rigorous dosing regimen less frequently).  Although the claims teach 70 or 35 mg doses rather than the 80 or 40 mg doses disclosed in the July 1996 article, Dr. Arthur C. Santora, one of the co-inventors on the ‘329 patent admitted against Merck’s interest that a once-weekly 40 mg dose would be as effective as seven daily 5 mg doses, and a once-weekly 80 mg dose would be as effective as seven daily 10 mg doses, in preventing or treating osteoporosis.  There was no great leap required of those skilled in the art to go from 40 or 80 mg once a week, the pills available at the time to treat patients with Paget’s disease, to a 35 or 70 mg pill once a week.  The district court’s conclusion that the claims are not obvious cannot rest on any of these similarities between the claimed invention and the two Lunar News articles.

In short, the district court clearly erred in distinguishing the claimed invention from the two Lunar News articles offered as section 103 prior art.  Contrary to the district court’s findings, these articles support the conclusion that Merck’s claims 23 and 37 are invalid as obvious. 

The dissent, however, looked at the terms of the entire phrase “about 70 [35] mg of alendronate monosodium trihydrate, on an alendronic acid basis.”  Judge Rader warned:

1.  "Elect the Lexicographer Option at Your Own Risk"   With this court’s claim constructions wavering between the plain meaning rule … and the “specification” rule … , a patent applicant might suppose that the best option to define the scope of the claim language might be the lexicographer rule.  In this case, the patentee used the lexicographer rule to define a lengthy phrase.  …   In its definition, the patentee defined the phrase with precise values.  The patentee’s definition, however, fell five letters short of success because the phrase included the word “about.”  This court seized on that word, gave it an ordinary meaning, and cast aside the lexicographer rule without a convincing explanation.  Moreover, this court overturned the result of a lengthy district court trial for the sole reason that the trial court applied this court’s lexicographer rule.  I find it hard to explain to the district court how it erred by following this court’s rules. 

2.  "Deference to Trial Courts: Time for ‘Truth in Advertising’" Despite the district court’s superior tools and time to evaluate the complete record, to hear and inquire from expert and fact witnesses, to delve into countless related details, to probe the scientific and semantic context, and to entertain argument as long as necessary for clarity, this court with its reading three briefs before its half-hour hearing becomes enamored with its own analysis of a very close issue and reverses the district court.  Either the Federal Circuit accords deference in accordance with its public protestations or it does not in accordance with its legal standard barring any deference.  If the former, this court has a “truth in advertising” problem.  Its actual practice clashes with its professed legal duty.  If the latter, this court has a different kind of “truth in advertising” problem.

This should allow Teva’s ANDA to be eligible for Final Approval in February 2008 when U.S. Patent No. 4,621,077 expires, instead of 2018. The main patent for the daily 5 milligram and 10 milligram versions of the drug already was set to expire in February 2008.

Merck reported total sales of $3.16 billion US for Fosamax last year, more than 90 per cent of which were for the once-a-week version. This comes on top of the withdrawal of Vioxx from the market and the loss of the Zocor patents in the middle of 2006. Zocor, for high cholesterol, is Merck’s biggest drug, with $5.2 billion in sales last year.

See more here.

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