By Kevin E. Noonan --
On October 2, 2008, Judge William Young of the District Court of the District of Massachusetts issued his 150-page opinion in Amgen Inc. v. F. Hoffmann-La Roche Ltd. , Amgen's patent infringement suit over Roche's Mircera® drug product (see "Victory for Amgen in District Court Decision - Part I"). On October 23, 2007, Amgen received a jury verdict that Amgen's patents-in-suit (U.S. Patent Nos. 5,547,933; 5,441,868; 5,618,698; 5,955,422; and 5,756,349) were not invalid and Mircera® infringed the claims of the '933, '868 and '698 patents (see "Amgen Survives Another EPO Challenge"). Thereafter, Judge Young entered a preliminary injunction to prevent Roche from putting Mircera® on the market while the Court prepared its opinion. On Friday, the Federal Circuit affirmed the preliminary injunction without an opinion, under Federal Circuit Rule 36 (see "Amgen v. Hoffmann-LaRoche: Back to the District Court").
The Federal Circuit considered none of Judge Young's findings of fact and conclusions of law, maintaining that none of these issues were before the CAFC since Judge Young was precluded from entering a final judgment until after the Federal Circuit made its decision and returned jurisdiction to the District Court. These decisions by the District Court included: 1) affirming the jury's infringement decision by denying Roche's motion for judgment as a matter of law (JMOL); 2) reaffirming its pretrial decision to grant summary judgment regarding infringement of claim 1 of the '422 patent; 3) "explaining" its reasoning for ruling, also pretrial, that the claims of Amgen's patents-in-suit are not invalid for obviousness-type double patenting (despite the intervening Federal Circuit decision in Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc.); 4) denying Roche's motion for JMOL that claim 1 of the '422 patent and claims 3, 7, and 9 of the '933 patent are not invalid for indefiniteness for reciting the term "human erythropoietin"; and 5) granting Amgen a permanent injunction. Previous Patent Docs posts have discussed the obviousness-type double patenting (Part I) and permanent injunction (Part II) aspects of the District Court's decision. Here, we discuss some of the remaining grounds for the Court's deciding this case in Amgen's favor.
The Court denied Roche's motions for judgment as a matter of law (JMOL) that Amgen's claims were invalid. Although the Court noted that Roche's motion raised issued of invalidity on the grounds of anticipation, obviousness, indefiniteness, and non-enablement, the Court addressed two of these arguments: first, that the claims of the '422 patent were anticipated by the Goldwasser study, and second that the term "human erythropoietin" is indefinite.
Regarding the anticipation argument, this was ground well-traveled and familiar to the Court. Hoechst Marion Roussel (HMR) used the same prior art study of Goldwasser to support the same anticipation argument in Amgen Inc. v. Hoechst Marion Roussel, Inc., and the court there, as the Court here, found claim 1 of the '422 patent not to be anticipated when the Goldwasser study was applied as a § 102 reference. In this case, the Court gave effect to the limitation "purified from mammalian cells grown in culture" to distinguish over the Goldwasser EPO preparations that were made from urine, as a matter of law based on the Court's claim construction. The Court construed claim 1 of the '422 patent as reciting 5 elements:
A [1] pharmaceutical composition comprising a [2] therapeutically effective amount of [3] human erythropoietin and a [4] pharmaceutically acceptable diluent, adjuvant or carrier, wherein said erythropoietin is [5] purified from mammalian cells grown in culture.
The Court said that Roche tried to improperly shift the invalidity burden to Amgen, by arguing that Amgen was required to show that the "source" limitation "imparts novel structure to an otherwise non-novel product." As for the propriety of finding that the process/source limitation was a substantive limitation, the Court found that it was a well-established way of distinguishing claimed subject matter over the prior art. This conclusion was based, in part, on Dr. Lin's testimony that "'the only way [to] characterize [his claimed] product is by the way they were making [it]'." This claim construction was affirmed by the Federal Circuit in Amgen Inc. v. Hoechst Marion Roussel, Inc. (although in that case the issue was whether the term could be construed to mean that the EPO product was purified from the culture media as opposed to being purified from the cells themselves). The Court also noted that there were "observed distinctions" between "recombinant EPO [rEPO] and the urinary EPO [uEPO] employed by Goldwasser." These included what the Court termed "critical distinctions" in glycosylation and specific activity in vivo, which "may . . . reflect recombinant EPO's resistance to degradation in the human body," which the Court cited as reasons for imbuing the source limitation as a real limitation on the EPO product claim
"It is also significant that the source is what enables mass production and commercial viability," according to the Court. In the Court's view, the simple fact is that the prior art Goldwasser method would require a drug manufacturer to "scour the world" for aplastic anemia patients whose urine could be processed to produce purified uEPO, "transforming the company into a glorified urine collection agency." The "genius," in part, of rEPO is that it frees drug manufacturers from this dependency on urine as a source of EPO, according to the opinion.
Procedurally, the Court also disagreed with whether the issue was a question of fact for the jury, casting the question not as whether Amgen's claim 1 of the '422 patent was anticipated but on the question of claim construction. The Court said that Roche's arguments were contrary to Markman v. Westview Instruments, Inc., wherein the meaning of claims is a question of law solely within the province of the court. According to the District Court, having construed the "purified from mammalian cells grown in culture" limitation as discussed above, no jury could decide that the Goldwasser reference anticipated, since Goldwasser taught uEPO, and the Court cited In re Luck for the principle that process limitations in a product claim "must be given the same consideration as traditional product characteristics."
The Court also based its decision on its conclusion that imposing on Amgen the burden argued by Roche would contravene the statutory presumption of validity. The Court distinguished Roche's authority to the contrary, In re Moeller, 117 F.2d 565 (CCPA 1941), by pointing out that the Moeller case was an appeal from a decision of the PTO Board of Appeals, where the presumption of validity does not apply. The Court was also unpersuaded by Roche's argument that the distinctions between rEPO and uEPO were undefined, and that it was possible that an rEPO preparation could be identical to the uEPO preparation of Goldwasser, saying that any such speculation failed to satisfy Roche's burden of establishing invalidity by clear and convincing evidence.
Finally, the Court noted that its construction, that the source is a substantive limit on the product in the claim, has been twice appealed to the Federal Circuit and twice affirmed:
As to the '422 patent, the limitation "purified from mammalian cells grown in culture" in claim 1 clearly limits the source of the EPO used in the claimed "pharmaceutical composition." The limitation only speaks to the source of the EPO and does not limit the process by which the EPO is expressed. Rather, the claim is broadly drawn to a "pharmaceutical composition" having certain elements, one of those being EPO "purified from mammalian cells in culture." This reading is in line with the district court's construction.
Turning to Roche's allegations that the claims of the '422 patent (claim 1) and '933 patent (claims 3, 7, and 9) were indefinite for reciting "human erythropoietin," the Court said that the "touchstone" of the indefiniteness inquiry is whether the skilled worker would understand what was being claimed. This question, according to the Court, was addressed by competing expert testimony (Dr. Lodish for Amgen and Dr. Flavell for Roche). However, the Court said that its role was not to re-weigh the evidence but to determine whether the evidence provided "a sufficient basis for a reasonable jury to conclude Roche failed to prove indefiniteness by clear and convincing evidence." The Court found that it did, saying that the claims are sufficiently definite even if the specification is unclear on whether it is 165-166 amino acids. Part of the basis for the Court's decision is that "in fields of new and evolving knowledge . . . claims can be no more precise than the knowledge of the field permits" (citing PharmaStem Therapeutics Inc v. Viacell, Inc., 491 F.3d 1342, 1373 (Fed. Cir. 2007)). Roche argued that the disclosure in the specification of undefined "mutants, analogs and allelic variants" as falling within the scope of the term "human erythropoietin" was enough to render the term indefinite, and the Court disagreed. The Court also opined that Roche's "focus on the number of amino acids" (165 or 166) was "misplaced," since the Court's construction of the phrase did not require that the amino acid sequence have a precisely-defined length.
Finally, the Court denied Roche's motion for JMOL on the question of infringement, based on evidence that Roche's Mircera® drug product contained erythropoietin that fell within the scope of Amgen's claims. In doing so, the Court rejected Roche's theory that Mircera® should be considered as a "single molecule" (i.e., peg-EPO), but rather characterized it as rEPO modified by conjugation with polyethylene glycol. In the Court's view, "[p]egylation merely attaches a sugar, via a single carbon bond, to a recombinant glycoprotein with the patented amino acid sequence; it does not alter the patented properties of EPO." This alteration was not sufficient for the Court to overturn the jury verdict of infringement. In support of its decision, the Court cited testimony, internal Roche documents, and Roche's representations to the FDA to the effect that peglylating rEPO did not change its "amino acid sequence, glycosylation or carbohydrate content," i.e., that Mircera® retained rEPO's biological properties.
For additional information regarding this topic, please see:
• "Amgen v. Hoffmann-LaRoche: Back to the District Court," October 10, 2008
• "Victory for Amgen in District Court Decision - Part III," October 9, 2008
• "Victory for Amgen in District Court Decision - Part II," October 8, 2008
• "Victory for Amgen in District Court Decision - Part I," October 6, 2008
• "BIO Submits Amicus Brief in Amgen v. Hoffman-LaRoche," July 7, 2008
• "Glasses Half-full or Half-empty: Hoffman-LaRoche's Different Interpretation of Pfizer v. Teva," April 15, 2008
• "Hoffmann-LaRoche Can't Wait, Files Notice of Appeal to the Federal Circuit," April 11, 2008
• "Will the Federal Circuit's Pfizer v. Teva Decision Spell the End of Amgen's Patent Rights to Recombinant Human Erythropoietin?" March 31, 2008
• "Court Still Cannot Decide on Amgen's Permanent Injunction," March 26, 2008
• "Amgen Inc. v. International Trade Commission (Fed. Cir. 2008)," March 20, 2008
• "Roche Agrees to Court's Conditions for Modifying Preliminary Injunction," March 20, 2008
• "Roche's Mircera® Remains Off the Market (For Now)," March 2, 2008
• "Amgen Survives Another EPO Challenge," October 28, 2007
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