Claims 16 and 17 are process claims that read:
16. A process for stabilizing an ACE inhibitor drug against cyclization which comprises the step of contacting the drug with:
(a) a suitable amount of an alkali or alkaline earth metal carbonate and,
(b) one or more saccharides
17. The process of claim 16 wherein the drug is selected from the group consisting of quinapril, enalapril, and indolapril, or a pharmaceutically acceptable acid addition salt thereof.
After holding a hearing in accordance with Markman v. Westview Instruments, Inc., 517 U.S. 370 (1996), aff’g 52 F.3d 967 (Fed. Cir. 1995) (en banc), the court construed the phrase “an alkali or alkaline earth metal carbonate” as used in claims 1 and 16 of the ’450 patent to include only a carbonate and as not including a bicarbonate. In a related case, Schwarz Pharma, Inc., Schwarz Pharma AG and Warner Lambert Company v. Teva Pharmaceuticals USA, Civil No. 01-4995, the court granted Teva’s motion for summary judgment based on the same construction of “carbonate.” The Court of Appeals reversed, Schwarz Pharma, Inc. v. Teva Pharmaceuticals, USA, Inc., 2004 WL 193228 (Fed. Cir. Jan. 29, 2004), construing “the term ['carbonate'] to include both the carbonate and bicarbonate ions.”
After discovery in this case had been completed (but before the decision of the Federal Circuit Court of Appeals in the Schwarz Pharma action), Warner-Lambert and Teva filed motions for summary judgment. The court set forth its findings of fact and conclusions of law in an opinion dated October 2, 2003. Finding that there are no genuine issues of material fact with respect to infringement, the court denied Teva’s motion for summary judgment of noninfringement of claims 1, 4-10 and 12 of the ’450 patent and granted Warner-Lambert’s motion for summary judgment of infringement of claims 1, 4-10, 12, 16 and 17 of the ’450 patent.
Finding that there are no genuine issues of material fact with respect to the validity of claims 1, 4-10 and 12 of the ’450 patent, the court granted Warner-Lambert’s motion for summary judgment of validity as to those claims. Finding that there are genuine issues of fact concerning whether claims 16 and 17 were obvious to a person skilled in the art, the court denied Warner-Lambert’s motion for summary judgment of validity of claims 16 and 17.
The court found that Merck’s pre-existing Vasotec tablet, which Warner-Lambert did not disclose to the Patent and Trademark Office (PTO), was highly material in that a reasonable examiner would have considered the Vasotec product important in deciding whether to allow the application to issue as a patent. However, the court concluded that whether Warner-Lambert’s inventors intended to deceive the PTO by withholding information concerning Vasotec raised questions of material fact. Therefore, the court denied Teva’s motion for summary judgment that the ’450 patent is unenforceable due to Warner-Lambert’s inequitable conduct and denied Warner-Lambert’s motion for summary judgment of no inequitable conduct.
The subsequent decision of the Federal Circuit Court of Appeals in the Schwarz Pharma action did not affect these rulings. There remained for trial the issues of anticipation and obviousness of claims 16 and 17 of the ’450 patent and the issue of whether the ’450 patent is unenforceable because Warner-Lambert withheld from the PTO the existence of Vasotec with an intent to deceive the PTO. A trial was held on May 3-6, 2004.
Held: The evidence establishes that the ’450 patent was neither obvious nor anticipated in the prior art nor did Warner-Lambert’s inventors act with an intent to deceive the PTO by failing to call to the patent examiner’s attention the Merck Vasotec product.
II. ACE inhibitors are a class of drugs used for treatment of hypertension. Squibb introduced captopril, the first ACE inhibitor tablet marketed in the United States, by the early 1980s.
Merck developed the next ACE inhibitor, enalapril, which it sold under the trade name Vasotec in the United States beginning in January 1986. Warner-Lambert’s ACE inhibitor, quinapril hydrochloride, an acid salt of quinapril, received FDA approval in November 1991 and was marketed under the name Accupril.
The process for formulating Merck’s Vasotec and the process for formulating Warner-Lambert’s Accupril have several common features. Each involves a process for stabilizing an ACE inhibitor against cyclization; each involves contacting the ACE inhibitor with a carbonate that includes the carbonate or bicarbonate ion; each involves contacting the ACE inhibitor with a saacharide. Critical to the issues addressed at trial is the extent of the knowledge Warner-Lambert’s scientists had at the time of filing the application for the ’450 patent about the stability or instability of Merck’s enalapril product and about how Merck solved any instability problems. Also critical to the issues addressed at trial is the extent to which information about the Merck solution of instability problems was in the public domain and available to persons of ordinary skill in the art.
III. A. Teva relies heavily on the testimony and expert opinion of Joseph Schwartz, Ph.D., to establish that for purposes of novelty and anticipation the date of invention is presumed to be the filing date of the patent application — in this case, February 24, 1987.
The date of invention for purposes of novelty and anticipation is presumed to be the filing date of the patent application. A patentee has an initial burden of coming forward with evidence of conception, and the court must consider all of the evidence so that an evaluation can be made of the inventor’s claim of conception.
An invention is conceived when the inventor forms in his mind a definite and permanent idea of the complete and operative invention as it is thereafter to be applied in practice. Conception is complete when one of ordinary skill in the art could carry out the conceived idea without unduly extensive research or experimentation that would undermine the specificity of the conception.
Dr. Schwartz’s understanding of the legal concept of conception was flawed. There was no requirement that conception could occur only after the inventors had produced sufficient stability data to convince the FDA that Warner-Lambert was entitled to approval of its Accupril product. An inventor need not know that his invention will work for conception to be complete. He need only show that he had the idea; the discovery that an invention actually works is part of its reduction to practice.
A September 4, 1986, memo of Dr. Michael Ray Harris, one of the inventors named in the ’450 patent, set forth the details of the successful studies of the stabilizing effects of magnesium carbonate and lactose. Dr. Harris testified that “[a]t this point we’re just tweaking. No major changes. Just tweaking to finalize.” The studies to which the September 4 memo referred had to have taken place no later than August 1986. Conception had taken place at that time and was reflected in the August 20 memo. The conception date of the invention described in the ’450 patent was no later than September 4, 1986.
B. Teva claims that the ’450 patent is unenforceable due to Warner-Lambert’s inequitable conduct before the PTO, specifically, its failure to disclose the existence of Vasotec as prior art.
The testimony of Dr. Kuchi S. Murthy, another inventor of the ’450 patent, that Vasotec and enalapril were not discussed among the inventors (they “fell off the table”) after the failure to stabilize quinapril by adjusting its pH through the use of sodium bicarbonate is supported by the testimony of Dr. Harris, who recalled no discussion of Vasotec after the failure of the pH studies called for in the May 7, 1986 memo.
The sequence of events extending from May 1996 through the filing of the patent application is consistent with Drs. Murthy and Harris’s testimony about their discussions of Vasotec. Vasotec was a subject of interest to them when they ascertained the pH of the Vasotec tablet in solution, when they entertained the hypothesis that adjusting the pH of quinapril would solve the problem of cyclization degradation and when they sought to achieve a suitable pH through the use of sodium bicarbonate. When they failed to achieve stability through adjustment of the pH of quinapril, they turned their efforts toward finding an excipient that would stabilize quinapril. By late June or July 1986 Vasotec and its use of sodium bicarbonate were no longer of interest to the Warner-Lambert scientists and they had no reason to discuss Vasotec.
The fact that Warner-Lambert’s quest for stability took place in two stages and the fact that Vasotec was of interest to the Warner-Lambert scientists only during the first, unsuccessful stage were not fully recognized in the October 2, 2003, opinion deciding the parties’ summary judgment motions and were only fully appreciated by the court after considering the testimony and other evidence presented at the trial. Consequently, some of the factors set forth in the earlier opinion as indicative of an intent to deceive are not in fact evidence of such an intent. That Warner-Lambert scientists kept themselves informed about the ‘pril competition, including Merck’s efforts, is neither surprising or reprehensible. There was no reason why Warner-Lambert should not have continued its efforts to stabilize quinapril after Merck released Vasotec in January 1986. Knowledge that Vasotec contained sodium bicarbonate did not disclose the manner, if any, in which it contributed to stabilization of enalapril, and the Warner-Lambert scientists simply used sodium bicarbonate to achieve various pH levels, a technique that failed to achieve stability and that (unknown to the Warner-Lambert scientists) had failed to achieve stability when the Merck scientists pursued the same route to stabilization.
The Warner-Lambert scientists knew that sodium bicarbonate was used in the Vasotec formulation but did not know its function. In fact, during the course of Merck’s development of a stable formulation its scientists at first used sodium bicarbonate to adjust enalapril’s pH; later during their analysis of the chemistry of the cyclization degradation process they employed sodium bicarbonate in connection with the reaction that converted enalapril maleate to a stable enalapril sodium. There is no evidence that the Warner-Lambert scientists were aware of this function of sodium bicarbonate in Vasotec.
Having achieved success with magnesium carbonate, it is natural that the failed sodium bicarbonate no longer seemed relevant to the Warner-Lambert scientists. Notwithstanding the construction that the Court of Appeals has given to the word “carbonate,” it was not the intent of the ’450 patent inventors to claim either the Vasotec formulation or sodium bicarbonate. The evidence does not support Teva’s argument that failure to disclose Vasotec, which contained sodium bicarbonate, was intended to deceive the PTO.
C. In the October 2, 2003, opinion the court found that in Warner-Lambert’s formulation lactose serves the function of inhibiting hydrolysis and that there is no evidence that the lactose contained in Merck’s Vasotec tablets serves that function or that Warner-Lambert’s scientists thought that it did. Consequently, summary judgment of validity was entered with the respect to claims 1, 4-10 and 12 of the ’450 patent.
There remained for trial Teva’s contention that claims 16 and 17 of the ’450 patent were obvious in light of Merck’s Vasotec tablets.
In the early 1980s when Merck and Warner-Lambert commenced their efforts to stabilize an ACE inhibitor (enalapril in the case of Merck and quinapril in the case of Warner-Lambert), none of the scientists at either company had any knowledge of cyclization degradation. In contrast to hydrolysis, the most common degradation pathway, none of them had addressed cyclization degradation in any drug on which they had worked, nor had they known of any drug that degraded via cyclization, nor had they seen anything concerning it in the literature. Likewise, Teva’s expert, Dr. Schwartz, in his 35 years of drug formulation experience had never before encountered a drug that degraded via cyclization. He testified that in 1986 it was generally believed that carbonates and sodium carbonates promoted degradation via cyclization rather than promoting stability.
At the time in question next to nothing was known about cyclization. It took both the Merck and Warner-Lambert scientists years of trial and error before they could develop means to stabilize enalapril in the case of Merck and quinapril in the case of Warner-Lambert. Even after Merck developed its basic process of neutralizing enalapril and converting enalapril to enalapril sodium, it was necessary to refine the process through adjustment of the duration of mixing, temperature, holding time in the mixer and particle size. When giving his opinion Dr. Schwartz had the benefit of confidential information Merck provided to him in 1994 about Merck’s development of Vasotec and its use of sodium bicarbonate. One cannot help but conclude that his opinion benefits from hindsight and does not reflect the position of a person skilled in the art in 1986.
Merck’s decision to treat Vasotec and the process for manufacturing it as a trade secret rather than seeking a patent is strong evidence that a person skilled in the art could not have replicated the drug or the process using publicly available information. This was a decision made at the highest level of Merck’s research management.
Claims 16 and 17 of the ’450 patent would not have been obvious at the time the invention was made to a person having ordinary skill in the art and consequently are not invalid under 35 U.S.C. � 103.
D. Teva contends that claims 16 and 17 of the ’450 patent are invalid under 35 U.S.C. � 102(g)(2). Anticipation under this section requires that a single prior art reference disclose each element of the claimed invention.
The alleged prior art in this case did not disclose the function of sodium bicarbonate in Vasotec nor did it disclose the process by which Merck stabilized enalapril against cyclization degradation. That stabilization process depended on the extent to which an in-situ deprotonation reaction between enalapril and sodium bicarbonate went to completion in the limited water of wet granulation. Numerous factors had to be controlled. Merck had developed its own proprietary test to determine the extent of the reaction.
The conception date of Warner-Lambert’s invention was in August 1986, and by the end of August the Warner-Lambert scientists had demonstrated that it worked for its intended purpose. At that time the availability of a Vasotec tablet and knowledge of the tablet’s starting components would not have enabled one skilled in the art to ascertain the complex process by which the Merck scientists formulated a stable enalapril tablet.
By its terms � 102(g) bars a patent if a prior invention was made by an inventor who had not suppressed or concealed it. Before Warner-Lambert’s invention in August 1986, Merck had made a deliberate decision to forgo patent protection and instead to conceal from the public as a trade secret its process for stabilizing Vasotec using sodium bicarbonate. In a previous section of this opinion there is described the success that Merck achieved in maintaining the process as a trade secret to the late 1980s or early 1990s and the continuing efforts on Merck’s part during the 1994 Canadian litigation to withhold the role of sodium bicarbonate in that process.
At the time the invention disclosed in the ’450 patent was conceived there were available to the public only the Vasotec tablet, the package insert, the 1985 edition of the European Dictionnaire Vidal, the Dutch publication Pharmaceutisch Weekblad, and an article by Toshihiro Kato of Nippon Merck-Banyu Co., in Japan. In their totality they disclosed most of the starting components of Vasotec and that enalapril was susceptible to cyclization.
Thus, before (and for a considerable time after) the conception of the invention disclosed in the ’450 patent, Merck’s Vasotec process had been deliberately suppressed and concealed. The available information concerning Vasotec did not enable one of skill in the art to practice claims 16 and 17 of the ’450 patent nor did it enable such a person to practice a process of stabilizing an ACE inhibitor against cyclization. Teva has failed to prove that claims 16 and 17 were anticipated by the Merck Vasotec process.
— Digested by Steven P. Bann
[The slip opinion is 38 pages long.]
For plaintiff Warner-Lambert — Melissa L. Klipp (Drinker Biddle & Reath) and Joseph M. O’Malley Jr., Herbert W. Rea, Bruce M. Wexler, Robert L. Baechtold and Nicholas M. Cannella, of the N.Y. bar (Fitzpatrick, Cella, Harper & Scinto). For defendant Teva Pharmaceuticals USA, Inc. — Arnold B. Calmann (Saiber Schlesinger Satz & Goldstein), David M. Hashmall, of the N.Y. bar (Goodwin Procter), Henry C. Dinger, of the Mass. bar, W. Edward Bailey and A. Joy Arnold, of the N.Y. bar (Fish & Neave). For third-party interveners Schwarz Pharma, Inc. et al — Charles M. Lizza and Robert C. Brady (Leboeuf, Lamb, Greene, & MacRae) and F. Dominic Cerrito, Michael W. Vary and Isaac Mosner, of the N.Y. bar (Jones Day).
