Please welcome Daniel Shelton, an associate in the Chemical, Biotechnology and Pharmaceutical Practice of Foley & Lardner LLP, as a new author for PharmaPatentsBlog.

In Teva Pharmaceuticals USA, Inc. v. Sandoz, Inc., the Federal Circuit invalidated a number of claims directed to a polymer defined by its “molecular weight” because the term was ambiguous, and Applicants’ conflicting statements during prosecution as to the meaning of “molecular weight” made the term insolubly ambiguous. On the other hand, the court found that similar statements regarding “molecular weight” did not give rise to prosecution disclaimer with respect to other claims that were not invalidated. The court agreed that those claims were infringed, thus making it likely that Teva will be able to keep generic versions of Copaxone® off the market until its patents expire in May of 2014.

The Patent At Issue

The Teva  patents at issue relate to the drug Copaxone®, which is marketed for treating multiple sclerosis. Copaxone® comprises “copolymer-1,” which is a random copolymer of four different amino acids in a particular ratio. According to the patents, Teva discovered that copolymer-1 molecules of a certain molecular weight achieve improved treatment.

Would-be generic competitors submitted Abbreviated New Drug Applications (ANDAs) seeking approval to market generic versions of Copaxone®. In response, Teva brought an infringement action asserting nine patents:

U.S. Patent Nos. 5,800,808; 5,981,589; 6,048,898; 6,054,430; 6,342,476; 6,362,161; 6,620,847; 6,939,539, and 7,199,098.

The patents all stem from the same application disclosure, and recite copolymer-1 through two distinct groups of claims (referred to by the court as “Group I” and “Group II”).

A representative claim from Group I is claim 1 of U.S. Patent No. 5,981,589:

Copolymer-1 having a molecular weight of about 5 to 9 kilodaltons, made by a process comprising the steps of:
reacting protected copolymer-1 . . . ; and
purifying said copolymer-1, to result in copolymer-1 having a molecular weight of about 5 to 9 kilodaltons.

 A representative claim from Group II is claim 1 of U.S. Patent No. 6,054,430:

 Copolymer-1 having over 75% of its mole fraction within the molecular weight range from about 2 kDa to about 20 kDa . . . .

The Federal Circuit held the Group I claims indefinite, but upheld the Group II clams.

The Federal Circuit Decision On Indefiniteness–Insoluble Ambiguity

The Federal Circuit reiterated its recent holding in Biosig Instruments, Inc. v. Nautilus, Inc., that “A claim is indefinite only when it is not amenable to construction or insolubly ambiguous.” As summarized by the court, to prove indefiniteness, “an accused infringer must demonstrate by clear and convincing evidence that one skilled in the relevant art could not discern the boundaries of the claim based on the claim language, the specification, the prosecution history, and the knowledge in the relevant art.”

With regard to the Group I claims, the term “a molecular weight of about 5 to 9 kilodaltons” was construed to refer to the average molecular weight of the copolymer-1 material. However, the court found that, as used in the art, the average molecular weight of polymeric materials can be measured in a number of different manners, including peak average molecular weight (Mp), number average molecular weight (Mn), and weight average molecular weight (Mw). Thus, the term “molecular weight” in the Group I claims was ambiguous, because the term did not indicate which of Mp, Mn and Mw was meant. The court turned to the specification and prosecution history for guidance in this regard, but found two directly contradictory statements in the prosecution history which rendered the claims insolubly ambiguous.

In one case, Teva stated in response to an indefiniteness rejection that “[o]ne of ordinary skill in the art, upon reviewing the specification, would understand that ‘average molecular weight’ refers to the molecular weight at the peak of the molecular weight distribution curve shown in Figure 1,” i.e., Mp. The claims were allowed.

In a second case, Teva overcame a similar indefiniteness rejection by arguing, “[o]ne of ordinary skill in the art could understand that kilodalton units implies [sic] a weight average molecular weight,” i.e., Mw. The claims were allowed.

The Federal Circuit could not reconcile these two different definitions.

Teva tried to support the “Mp” definition with expert testimony that the molecular weight distribution curves and accompanying legend of Figure 1 of the patents would lead a skilled artisan to understand that the claim terms “molecular weight” and “average molecular weight” denote Mp. While the district court determined that Teva’s evidence was sufficient, the Federal Circuit applied de novo review, scrutinized the data, and determined that it “does not save Group I claims from indefiniteness.”

Thus, the Federal Circuit held that the Group I claims are invalid as indefinite.

In contrast to the Group I claims, the Group II claims were not construed as reciting the average molecular weight of the polymer. As the Federal Circuit explained,

Instead of describing copolymer-1 in terms of a statistical measure, such as Mw, Group II claims recite the percentage of copolymer-1 molecules in a sample falling within an arbitrarily set molecular weight range. The numbers that set the boundaries of that range, such as “2 kDa” and “20 kDa” in the ’430 patent claim 1, refer to precise points on the “Molecular Weight” axis, rather than to statistical properties of the polymer molecular weight curves. Like the numbers 10,000 (i.e., 10 kDa) and 20,000 (i.e., 20 kDa) in the figure above, “2 kDa” and “20 kDa” refer to exact values rather than statistical measures.

Thus, claims of Group II were held not to be invalid for indefiniteness. The court also upheld the Group II claims over the enablement and obviousness challenges.

The Federal Circuit Decision On Infringement–Prosecution Disclaimer 

The would-be generic competitors sought to establish that their generic products would not infringe the Group II claims because Teva had disclaimed copolymer-1 compositions having Mw greater than 10 kDa, and their proposed generic products have Mw greater than 10 kDa.

During prosecution of several of the asserted patents, Teva overcame prior art rejections by arguing that, in contrast to the prior art’s copolymer-1 which had a “minimum molecular weight of 10 kilodaltons,” the pending claims cover “copolymer-1 having a molecular weight of about 5 to 9 kilodaltons.” The prior art does not explain whether its references to “molecular weight” means Mp or Mw, but cites an article that describes the measurement process in more detail. The would-be generic competitors argued that the technique described in the article only measures Mw, such that these arguments surrendered coverage of any copolymer-1 with Mw greater than 10 kDa

The Federal Circuit disagreed. The court noted that the statements made by Teva did not “expressly refer to any specific molecular weight measurement.” In this regard, the court referred to its finding that the Group I claims are indefinite because of the ambiguity in the meaning of “molecular weight.” The court found that the connection between Teva’s statements and the article cited in the prior art was “too attenuated to limit the scope of the claims to copolymer-1 with Mw less than 10 kDa.” The court also disagreed that the technique discussed in the cited article only can yield Mw. Thus, the Federal Circuit refused to find clear and unmistakable disclaimer.

The Value Of A Variety Of Claims 

For patent holders, this case illustrates the value of securing claims of varying scope using different terminology. While a number of Teva’s claims were found to be invalid, Teva was left with claims that likely will prevent its generic competitors from entering the market until the patents expire. For patent challengers, this case demonstrates the tension between attacking claims based on indefiniteness, which requires insoluble ambiguity, and seeking to limit claim scope based on prosecution disclaimer, which requires clear and unmistakable disclaimer.