Full opinion text
OPINION FAENAN, District Judge. I. Procedural Background Plaintiff, Merck & Co., Inc. (“Merck”) is a Delaware corporation with its principal place of business in New Jersey. Defendant, Teva Pharmaceuticals USA, Inc. (“Teva”) is a New Jesey corporation with its principal place of business in Pennsylvania. Merck is the owner of the entire right, title and interest in United States Patent No. 5,994,329, entitled “Method for Inhibiting Bone Resorption” (the “ ’329 Patent”), which issued November 30, 1999, naming as inventors Anastasia G. Daifotis, Arthur C. Santora II, and John Yates. Merck filed the application for the ’329 Patent on July 22, 1997. The ’329 Patent is set to expire on August 14, 2018. (PTX 1). Merck listed the ’329 Patent in the Federal Drug Administration’s (“FDA”) publication “Approved Drug Products with Therapeutic Equivalence Evaluations” (the “Orange Book”) in connection with its 70 mg and 35 mg dosage for alendronate sodium, which Merck markets under the name “Fosamax.” On October 3, 2000, Teva filed a supplement to an existing Abbreviated New Drug Application (“ANDA”) seeking FDA approval to market generic versions of Merck’s 70 mg alendronate sodium product for weekly administration. Included with Teva’s ANDA filing were “paragraph IV” certifications (21 U.S.C. § 355(j)(2)(A)(vii)(IV)) asserting that the Patents listed in the Orange Book, including the ’329 Patent, are invalid, unenforceable or would not be infringed by the commercial marketing of Teva’s proposed product. Merck filed this action on January 21, 2001, alleging that Teva’s filing of its supplement was an act of infringement under 35 U.S.C. § 271(e)(2)(A). Thereafter, Merck listed U.S. Patent No. 6,225,294 (the “ ’294 Patent”) in the Orange book and Teva filed a paragraph IV certification asserting that the ’294 Patent is invalid, unenforceable or would not be infringed by the commercial marketing of Teva’s proposed 70 mg alendronate sodium product. On October 4, 2001, Merck filed Civil Action No. 01-675-JJF, alleging that Teva’s filing of its supplemental ANDA was an act of infringement of the ’294 Patent under 35 U.S.C. § 271(e)(2)(A). Subsequently, Teva filed another supplement to its ANDA, seeking approval to market a generic version of Merck’s 35 mg Fosamax product. The supplement also included a paragraph IV certification asserting that all the listed patents were invalid, unenforceable or would not be infringed by Teva’s commercial marketing of its proposed product. On November 6, 2001, Merck filed Civil Action No. 01-728, alleging that the filing of Teva’s supplement to the ANDA was an act of infringement under 35 U.S.C. § 271(e)(2)(A). On January 14, 2002, the Court consolidated all three cases under Civil Action No. 01-048. One of the listed patents against which Teva certified was U.S. Patent No. 4,621,-077 (“the ’077 Patent”), which had already been the subject of litigation between the parties in this Court (Civil Action No. 00-035-JJF) in connection with Teva’s application to market alendronate sodium for daily administration. The Court entered judgment in favor of Merck in that case on December 2, 2002, and an appeal from that judgment is now pending in the United States Court of Appeals for the Federal Circuit. (D.I.123-1). The parties agreed that they will be bound in this case, with regard to issues concerning the ’077 Patent, by a final decision in the prior litigation. (D.I.128). Prior to trial Merck stipulated that the only claims at issue in this litigation are claims 23 and 37 of the ’329 Patent and further stipulated that it would not allege an invention date for those claims prior to July 22, 1997. (D.I.128). Teva stipulated that if found valid and enforceable, claims 23 and 37 of the ’329 Patent would be infringed by the commercial marketing of Teva’s proposed 70 mg and 35 mg alendronate sodium products for weekly administration. (D.I. 109, Pretrial Order, Tab 1, ¶¶ 8-9). The issues of validity and enforceability of the ’329 Patent were tried before the Court from March 4-7, 2003. The Court has jurisdiction over the parties and the subject matter pursuant to 28 U.S.C. § 1338(a). Additionally, venue is appropriate under 28 U.S.C. § 1391(c) and § 1400(b). Neither jurisdiction nor venue are contested by the parties. This Opinion constitutes the Court’s Findings of Fact and Conclusions of Law with respect to the issues tried before the Court. II. The ’329 Patent and Bone Biology In General The ’329 Patent discloses less-frequent-than daily administration of bisphospho-nates (e.g., alendronate) to inhibit bone resorption. (D.I. 143 at 8). Claims 23 and 37, the only asserted claims, relate specifically to the treatment and prevention of osteoporosis by once-weekly administration of alendronate. Osteoporosis is related to processes that are imbalanced in bone, and therefore, the Court will discuss the background of bone biology as it relates to osteoporosis and the use of alen-dronate for treatment of the disease. Bone is the tissue that provides mechanical support to the body. It is made up of a protein matrix, which is overlaid with mineral to give it hardness. (Russell at 108-109; DTX 523 at 2). Two principal types of cells maintain bone: 1) osteo-clasts, which break down bone, and 2) osteoblasts, which build new bone. Id. The process of bone destruction and rebuilding is known as “remodeling.” In the bone remodeling process, osteoclasts attach to the bone surface, become activated, and erode away the bone material beneath them, leaving defects in the bone structure. The destruction of bone by osteo-clasts is called bone “resorption.” Osteob-lasts then attach to the eroded surface of these defects, lay down new bone, and then become inactive. In the normal healthy adult the remodeling process is balanced. In other words, bone is destroyed and built at the same rate. (Russell at 109-110; DTX 523 at 3-4). In osteoporosis, bone destruction and formation are no longer balanced and bone is destroyed faster than it is replaced. Therefore, osteoporosis can lead to bone that is thinner, weaker, more fragile and porous. (Russell at 110-115; DTX 523 at 7, 8). Osteoporosis is treated primarily by inhibiting bone resorption-thus restoring the balance between bone destruction and formation. Alendronate inhibits bone resorption by blocking the bone destroying effects of osteoclasts. (Russell at 116— 117). A small portion of the ingested drug makes its way to and adheres to the bone surface, where it resides until it is taken up by osteoclasts. The alendronate then inhibits the osteoclasts from resorbing bone. (Russell at 121-122; DTX 523 at 10). Paget’s disease is also a common bone disease characterized by increased bone resorption. In Paget’s disease, increased bone remodeling occurs in localized areas of the skeleton. If Paget’s disease is not detected and treated early it can lead to an increase in bone size, fractures, and deformity. (Russell at 97). Like osteoporosis, Paget’s disease is treated by inhibiting bone resorption with alendronate. (Russell at 125-126). III. Teva’s Motion in Limine to Preclude Merck From Relitigating the Factual Findings Underlying the Decision in Teva Pharmaceuticals Ltd. et al. v. Instituto Gentili Spa et al. (D.I.113). Teva filed a Motion in Limine to Preclude Merck from Relitigating the Factual Findings Underlying the Decision in Teva Pharmaceuticals Ltd et al. Istituto Gentili Spa et al., (High Court of Justice, Chancery Division, Patents Court, January 21, 2003)). (D.I.113). Accordingly, the Court will discuss the motion in limine before it delves into the issues of validity and enforceability of the ’329 Patent. Teva’s principal defense in this case is that claims 23 and 37 are invalid because the claimed invention is anticipated or would have been obvious in view of the prior art. At the same time that the parties were litigating the validity of the ’329 Patent in this Court, they were also involved in a ease in the British High Court of Justice (the “High Court”). That case was a challenge by Teva and others to the validity of the European Patent No. 998,-292 (the “ ’292 Patent”), which corresponds to the ’329 Patent, and is based on the same provisional applications filed in July 1997. Teva, by its motion, contends that the ’292 Patent covers the identical concept as the ’329 Patent: the once-weekly dosing of alendronate sodium to treat osteoporosis, using seven times the normal daily dose. The High Court conducted a full trial on the merits from November 5-8, 2002, and heard further arguments from counsel on November 12-13, 2002. The trial involved live testimony from Merck’s expert Dr. Socrates Papapoulos, who is Merck’s expert in this case. In addition, Merck offered the testimony of Dr. Yates, the principal inventor of the ’329 Patent, who also testified in this case. On January 22, 2003, Justice Jacob of the High Court found that the claimed invention was invalid because it would have been obvious to a person skilled in the art, it claims a method of treatment, and is incapable of industrial application. A. Applicable Legal Principles Teva contends that the Court should adopt the High Court’s factual findings concerning obviousness pursuant to the doctrine of collateral estoppel. Collateral estoppel is appropriate if: (1) the issue is identical to one decided in the first action; (2) the issue was actually litigated in the first action; (3) resolution of the issue was essential to a final judgment in the first action; and (4) plaintiff had a full and fair opportunity to litigate the issue in the first action. Micron Technology, Inc. v. Rambus, Inc., 189 F.Supp.2d 201, 209 (D.Del.2002) (citations omitted). Additionally, the doctrine of collateral estoppel applies in patent cases. See Blonder-Tongue Laboratories, Inc. v. University of Illinois Foundation, 402 U.S. 313, 91 S.Ct. 1434, 28 L.Ed.2d 788 (1971). B. Parties’ Contentions 1. Teva’s Contentions By its motion, Teva contends that Merck had the identical motivation in litigating' the British case as it does in the instant ease: to discredit the Lunar News (a prior art reference) and Teva’s reliance on its teachings. Moreover, Teva contends that Merck’s barristers were afforded a full and fair opportunity to cross-examine all of Teva’s witnesses and did so at length. Teva contends that the evidence was heard by Justice Jacob of the High Court, who is experienced in patents. On January 22, 2003, Justice Jacob found the ’292 Patent invalid and entered judgment against Merck. In its motion, Teva concedes that the legal standard may vary between Britain and the United States; nevertheless, Teva contends that regardless of the differences, if any, between the legal standards for determining validity, collateral estoppel should still apply to the resolution of the underlying factual issues. Specifically, Teva contends that all of the eleménts of collateral estop-pel are met in this case with regard to the High Court’s factual findings on obviousness. First, Teva contends that collateral es-toppel applies to fact findings of foreign courts. Teva argues that courts have recently recognized that parties who litigate in a foreign court should be bound by the results of that litigation to the extent that the requirements of the collateral estoppel doctrine are met. For example, Teva points to Vas-Cath, Inc. v. Mahurkar, 745 F.Supp. 517 (N.D.Ill.1990), rev’d on other grounds, 935 F.2d 1555 (Fed.Cir.1991), where the parties extensively litigated the issue of obviousness in Canada, and the district court held that the parties were bound by the fact-finding of the Canadian Court. Additionally, Teva points to Northlake Marketing & Supply, Inc. v. Glaverbel, S.A., 958 F.Supp. 373, 379 (N.D.Ill.1997) (“Northlake I”) and Northlake Marketing & Supply, Inc. v. Glaverbel, S.A., 986 F.Supp. 471, 475-76 (N.D.Ill.1997) (“Northlake II”), where the parties had previously litigated the validity of a Belgian patent that corresponded to the United States patent in suit. The district court in those cases held that the Belgian Court’s conclusions about the scope and content of prior art were binding on the parties in the United States litigation. Further, Teva directs the Court to Oneac Corp. v. Raychem Corp., 20 F.Supp.2d 1233, 1242-1243 (N.D.Ill.1998), where a corresponding European patent was litigated in the High Court and the district court held that with respect to the United States patent, it would not give preclusive effect to questions of law or mixed questions of law and fact, but it would adopt the British Court’s factual findings. Additionally, Teva points to Federal Circuit decisions that have declined to afford collateral estoppel effects to judgments in foreign cases, but distinguishes them on the basis that those decisions were predicated on what the Federal Circuit views as different standards of patentability in other countries. See, e.g., Medtronic Inc. v. Daig Corp., 789 F.2d 903 (Fed.Cir.1986)(declining to adopt German tribunal’s determination that corresponding German patent was invalid in view of different legal standards); In re Dulberg, 472 F.2d 1394 (Oust. & Pat.App.1973) (same). Second, Teva contends that the issues were the same in the British litigation; the obviousness of administering alendronate sodium once a week at a dose of about seven times the daily dose. Further, Teva argues that the issue of the scope and content of the prior art are the same in both cases; whether the Lunar News publications taught the administration of alen-dronate sodium once a week, and whether the prior art taught that the dose should approximate seven times the daily dose. In addition, Teva argues that Merck’s fear defense is an issue in both cases. Merck claims that persons skilled in the art would have rejected the Lunar News teachings because of the fear that patients would not tolerate the larger dose. Merck raised the issue in Britain, and after considering the evidence, the High Court concluded that the “fear defense fails”. For example, the High Court found that the rare instances of esophageal side effects were attributed primarily to failure to follow the dosing instructions (D.I.114, Ex. A, ¶ 65). Third, Teva argues that the same issues were actually litigated in the High Court. For instance, Teva contends, the parties fully aired all factual evidence, where both sides had qualified expert witnesses to explain the evidence to the Court. Further, Teva argues that all witnesses appeared live and were extensively cross-examined and after the trial both parties provided written submissions and appeared for extensive argument before Justice Jacob. As a result, Teva argues, Merck cannot contend that these issues were not litigated. Fourth, Teva argues that the issues were determined by a valid and final judgment. Teva points out that the judgment of the High Court was the “Approved Judgement of that Court.” It was issued on January 21, 2003 and reissued in corrected form January 22, 2003. Teva notes that Merck has appealed the judgment, but that fact does not imply that the judgment is not final for purposes of collateral estoppel. In fact, Teva argues that it is well settled that the pendency of an appeal does not diminish the preclusive effect of an appealed judgment. (D.I. 114 at 13) (quoting Rice v. Department of Treasury, 998 F.2d 997, 999 (Fed.Cir.1993)). Lastly, Teva contends that the resolution of obviousness was essential to the judgment in the High Court. Specifically, it contends that Justice Jacobs was required to and did evaluate and interpret the prior art provided by Merck’s witnesses, and that, all findings on these issues were necessary to his final judgment that the patent was invalid for obviousness. Based on this, Teva argues that the High Court’s factual findings should be given preclusive effect. 2. Merck’s Contentions In response, Merck argues that there is no transnational collateral estoppel as to the validity of a United States Patent. First, Merck contends that Teva fails to point to a single Federal Circuit case where, a foreign court’s judgment that the patent was invalid, or the factual underpinnings of such a judgment, was given collateral estoppel effect in a case litigating the validity of a United States Patent. In fact, Merck argues that the Federal Circuit and its predecessor court have rejected such attempts. For example in Medtronic Inc. v. Daig Corp., 789 F.2d 903 (Fed.Cir.1986), cert. denied, 479 U.S. 931, 107 S.Ct. 402, 93 L.Ed.2d 355 (1986), the Federal Circuit rejected the argument that it should adopt the conclusion of a German tribunal that a German counterpart was obvious and stated, “[tjhis argument is specious. The patent laws of the United States are the laws governing a determination of obviousness/nonobviousness of a United States patent in a federal court.” Id. at 907-908. Additionally, Merck contends that the predecessor to the Federal Circuit came to the same conclusion in In re Dulberg 472 F.2d 1394, 1398 (Cust. & Pat.App.1973) and In re Larsen, 49 C.C.P.A. 711, 292 F.2d 531, 533 (Cust. & Pat.App.1961), where in both cases, the court refused to consider the actions of a foreign country’s patent office with respect to the patenta-bility of the subject matter before the court. Further, Merck argues that district courts have refused to give collateral es-toppel effect to a foreign court’s judgment. For example, Merck points to Cuno, Inc. v. Pall Corp., 729 F.Supp. 234 (E.D.N.Y.1989), where the High Court found the European counterpart of the United States patent at issue to be valid and infringed, and when the plaintiff sought to have the United States district court give collateral estoppel effect to certain factual findings, the court denied the request and stated that: Even if the court were to apply collateral estoppel to certain factual findings made by the British Court — as opposed to importing its legal conclusions wholesale-it is not clear that the trial time would be significantly shortened. Furthermore, the Federal Circuit’s reluctance to give collateral estoppel effect to foreign judgments would seem to apply here to foreign findings of facts insofar as those findings involve mixed questions of fact and foreign law. Id. at 238-239. Moreover, Merck distinguishes the cases cited by Teva. First, in regard to the On-eac case, Merck points out that the court refused to give preclusive effect to questions of law or mixed questions of law and fact, and to the extent that certain factual findings were given collateral estoppel effect, it was because both parties to the suit agreed to be bound by those factual determinations. Oneac Corp., 20 F.Supp.2d at 1242-1243. Additionally, Merck points to the Vas-Cath case where the Northern District of Illinois adopted certain factual findings of a Canadian Court in regard to the validity of a patent, after parsing out the Canadian judgment, comparing the relative Canadian and United States’ laws and making its own conclusions regarding the applicability of the factual determinations in the context of the United States’ legal framework. Additionally, in the Northlake cases, Merck points out that the district court adopted only certain factual findings from a previous Belgian proceeding after careful review of those findings and contends that most importantly, the issues that were precluded limited the evidence that the patent challenger could rely on. See Northlake II, 986 F.Supp. at 475-476; Northlake I, 958 F.Supp0. at 379. Next, Merck argues that the requirements for collateral estoppel have not been met. First, Merck contends that the High Court’s factual findings regarding obviousness were not essential to the final judgment because the High Court found that the ’292 was invalid based on three grounds: 1) invalid as a method of treatment; 2) incapable of industrial application; and 3) invalid as obviousnot obviousness alone. Lastly, Merck argues that the facts and applicable legal standard is different. Specifically, Merck contends that in the United States obviousness is ultimately a question of law which rests on the following factual inquiries: 1) the scope and content of prior art; 2) the level of ordinary skill in the art; 3) the differences between the claimed invention and the pri- or art; and 4) objective considerations of nonobviousness. See Advanced Display Systems, Inc. v. Kent State Univ., 212 F.3d 1272, 1284-85 (Fed.Cir.2000). On the other hand, Merck argues, in Britain, the determination of obviousness is based on the following factual inquiries: 1) identifying the inventive concept embodied in the patent in suit; 2) assuming the mantle of the normally skilled but unimaginative addressee in the art at the priority date and impute to him what was, at that date, common general knowledge in the art; 3) identifying what, if any, differences exist between the matter cited as being made available to the public and the alleged invention; 4) determining whether, viewed without any knowledge of the alleged invention, those differences constitute steps which would have been obvious to the skilled man or whether they required any degree of invention. (D.I. 126 at 17) (citing Windsurfing International, Inc. v. Tahur Marine (Great Britain) Ltd., 1985 R.P.C. 59, 60-61 (1985 Ct. Of Appeal)). Merck contends that although these standards are similar, the United States Court is required to consider objective considerations of obviousness, while in Britain they are not. Accordingly, Merck contends that collateral estoppel is improper. C. Discussion As outlined above, the standards for determining obviousness in the United States and Britain are different. In- fact, for purposes of this motion, Teva concedes that there may be differences in the legal standards for validity between the United States and Britain. Additionally, after reviewing the “factual findings” of the High Court, the Court finds that many of the principles are mixed questions of law and fact. The cases cited demonstrate that mixed questions of law and fact should not be adopted if there are two different legal standards, as in this case. See, e.g., Oneac Corp., 20 F.Supp.2d at 1242-1243 (declining to adopt mixed questions of law and fact). Additionally, in Oneac the court only adopted factual findings from a foreign tribunal where the parties agreed to be bound by such factual findings. Id. at 1242-43. This is not the situation in the instant case because Merck opposes any adoption of the High Court’s factual findings. Also, the Court finds that Merck has successfully distinguished the Northlake cases from the instant case, where in the Northlake cases the issues that were precluded limited the evidence that the patent challenger could rely on and the adopted factual findings did not go to the validity of the patent in suit. The Court also concludes that all of the elements necessary for a finding of collateral estoppel are not present in this case. Specifically, the High Court’s factual findings relating to obviousness were not essential to the High Court’s decision because that decision was based on three separate grounds as detailed above. The Third Circuit has stated that “if a judgment of a court of first instance is based on determinations of two issues, either of which standing independently would be sufficient to support the result, the judgment is not conclusive with respect to either issue standing alone.” Arab African Int’l Bank v. Epstein, 958 F.2d 532, 535, (3d Cir.1992) (quoting Restatement (Second) of Judgments § 27, cmt. i), rev’d in part on other grounds, 10 F.3d 168 (3d Cir.1993). The Court concludes that based on this standard, the High Court’s finding of obviousness cannot be said to be essential to the final determination. There may be eases where “the balance tips in favor of preclusion because of the fullness with which the issue was litigated and decided in the first action.” Masco Corp. v. United States, 303 F.3d 1316, 1329-1330 (Fed.Cir.2002). However, the Court concludes that this is not such a case, especially in light of the fact that the Federal Circuit has cautioned courts against giving too much weight to foreign tribunals who are confronted with the same prior art. See Heidelberger Druckmaschinen AG v. Hantscho Comm. Prods., Inc., 21 F.3d 1068, 1072 (Fed.Cir.1994) (recognizing that theories and laws of pat-entability differ from country to country and stating that “[c]aution is required when applying the action of a foreign patent examiner to deciding whether the requirements of 35 U.S.C. § 103 are met under United States law, for international uniformity in theory and practice has not been achieved.”). While the Court has reviewed Justice Jacob’s factual findings in regard to obviousness, based on the aforementioned reasons, the Court declines to adopt them and will make independent findings of fact on the issue of validity. Accordingly, Teva’s motion will be denied. IY. Invalidity Once issued a patent is presumed to be valid. See 35 U.S.C. § 282. The party challenging the patent bears the burden of proving by clear and convincing evidence that the patent is invalid. See Helifix Ltd. v. Blok-Lok Ltd., 208 F.3d 1339, 1346 (Fed.Cir.2000). Clear and convincing evidence is evidence that places in the fact finder “an abiding conviction that the truth of [the] factual contentions are ‘highly probable.’ ” Colorado v. New Mexico, 467 U.S. 310, 316, 104 S.Ct. 2433, 81 L.Ed.2d 247 (1984). Defendants contend that the ’329 Patent is invalid and therefore cannot be infringed. Defendants argue invalidity on two grounds: anticipation by the July 1996 Lunar News reference under 35 U.S.C. § 102(a), and obviousness under 35 U.S.C. § 103. For the reasons set forth below, the Court concludes that the ’329 Patent is valid. A. Claim Construction The first step in any invalidity analysis is claim construction which is an issue of law. SIBIA Neurosciences, Inc. v. Cadus Pharmaceutical Corp., 225 F.3d 1349, 1355 (Fed.Cir.2000); Markman v. Westview Instruments, Inc., 52 F.3d 967, 970-71 (Fed.Cir.1995) (en banc), aff'd, 517 U.S. 370, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996). A claim term should be construed to mean “what one of ordinary skill in the art at the time of the invention would have understood the term to mean.” E.g., Markman, 52 F.3d at 986. Further, when conducting a claim construction analysis, a district court should be cognizant of the fact that claims should be construed, if possible, to uphold their validity. In re Yamamoto, 740 F.2d 1569, 1571 n. * (Fed. Cir.1984) (citations omitted). The starting point for a claim construction analysis is the claims themselves. Vitronics Corp. v. Conceptronic, Inc., 90 F.3d at 1582; see also Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305 (Fed.Cir.1999) (stating that “[t]he starting point for any claim construction must be the claims themselves.”). Thereafter, the remainder of the intrinsic evidence should be examined beginning with the specification and concluding with the prosecution history. Vitronics, 90 F.3d at 1582 (outlining this order for examination in claim construction). Generally, there is a strong presumption in favor of the ordinary meaning of claim language as understood by those of ordinary skill in the art. Bell Atl. Network Servs., Inc. v. Covad Communications Group, Inc., 262 F.3d 1258, 1268 (Fed.Cir.2001). However, it is well-settled that a patentee may act as his own lexicographer and use the specification to supply implicit or explicit meanings for claim terms. Bell Atl. Network Servs., 262 F.3d at 1268 (Fed.Cir.2001); Vitronics Corp., 90 F.3d at 1582; Markman, 52 F.3d at 980 (noting that patentee is free to be his own lexicographer, but emphasizing that any special definitions given to words must be clearly set forth in patent). “[T]he patentee’s lexicography must, appear ‘with reasonable clarity, deliberateness, and precision’ before it can affect the claim.” Renishaw PLC v. Marposs Societa’ per Azioni, 158 F.3d 1243, 1249 (Fed.Cir.1998) (quoting In re Paulsen, 30 F.3d 1475, 1480 (Fed.Cir.1994)). If the meaning of a claim term is clear from the totality of the intrinsic evidence, than the claim may be construed. If, however, the meaning of a claim term is “genuinely ambiguous” after examining the intrinsic evidence, than a court may consult extrinsic evidence. Bell & Howell Document Mgmt. Procls. Co. v. Altek Sys., 132 F.3d 701, 706 (Fed.Cir.1997). Claim terms in claims 23 and 37 of the ’329 Patent are disputed in this case. Accordingly, the Court will focus its discussion on these claims In full, claim 23 of the ’329 Patent provides, “[a] method according to claim 22 wherein said unit dosage of said bisphos-phonate comprises about 70 mg of alendro-nate monosodium trihydrate on an alen-dronic acid active basis.” (PTX 1, ’329 Patent at col. 21, lines 24-27) (emphasis added). In full, claim 37 of the ’329 Patent provides, “[a] method according to claim 36 wherein said bisphosphonate unit dosage comprises about 35 mg of alendronate mo-nosodium trihydrate, on an alendronic acid active basis.” (PTX 1, ’329 Patent at col. 22, lines 24-26) (emphasis added). Teva contends that the term “about” in claims 23 and 37 should be construed according to its ordinary meaning of “approximately.” (D.I. 147 at 3). Merck contends that the patentee in this case acted as his own lexicographer and set out the meaning of “about” in the specification where the specification explains that the term “about” accounts for the variability of weight of the active ingredient that would result from the use of different salts of alendronic acids. (D.I. 141 at 42). Thus, Merck contends that the phrase “about 70 mg” as used in claim 23 and “about 35 mg” as used in claim 37 means 70 and 35 mg respectively of the active ingredient on an alendronic acid active basis. Id. at 43. In other words, Merck contends that, regardless of the final weight of the actual active ingredient in the tablet, it contains the same number of alendronate core molecules as 70/35 mg of alendronic acid. In rebuttal, Teva contends that Merck’s proffered construction makes no sense. Teva points out that according to Merck, the word “about” is used to account for the fact that different alendronate salts have different molecular weights, and that to deliver the same amount of physiologically active compound to the bone they must be delivered at slightly different dosage strengths. (D.I. 147 at 4). Teva contends that Merck’s interpretation is nonsensical because the claim itself accounts for this phenomenon by directing that the compound be administered on the basis of a common denominator, i.e., “on an alen-dronic active basis.” Id. In other words, Teva contends that the claims require that the amount “alendronate sodium trihyd-rate” be sufficient to deliver the same amount of active material as “about 70/35 mg” of alendronic acid. Id. As a result, Teva contends, the term “about” does not perform the function which Merck assigns to it, and must be in the claim for another purpose, that is, to have its ordinary meaning of “approximately.” After reviewing the claim terms and the specification, the Court concludes that the patentee explicitly and with reasonable clarity and precision defined the term “about 70 mg” in claim 23 and “about 35 mg” to mean the equivalent of 70/35 mg of alendronic acid when taking into account molecular weight variances for its derivatives that carry accessories. Simply put, no matter what the final weight of the actual active ingredient in the tablet is, it contains the same number of alendronate core molecules as 70/35 mg of alendronic acid. The relevant portion of the ’329 Patent specification provides: Because of the mixed nomenclature currently in use by those or [sic] ordinary skill in the art, reference to a specific weight or percentage of bisphosphonate compound in the present invention is on an active weight basis unless otherwise indicated herein. For example the phrase “about 70 mg of bone resorption inhibiting bisphosphonate selected from the group consisting of alendronate, pharmaceutically acceptable salts thereof and mixtures thereof, on an alendronic acid weight basis” means that the amount of bisphosphonate compound selected is calculated based on 70 mg of alendronic acid. PTX 1, the ’329 Patent, col. 10, 65-col. 11, line 8. (emphasis added). The Court concludes that the specification clearly indicates that the terms “about 70 mg” and “about 35 mg” refer to the fact that depending on the derivative of the alendronic acid that could be used in the oral formulation, different weights will be needed in order to get the same effect as 70 or 35 mg of the seminal compound, alendronic acid. As Merck points out, the alendronate sodium in Fosamax includes an atom of sodium metal for each molecule of alendronate sodium. (D.I. 138 at 24). If a formulator was to select a different salt which includes a metal atom that is heavier than salt, e.g., a potassium or barium atom, the total amount of material in each tablet would have to increase if the amount of alendronic acid were to remain the same. By conforming the weight of the alendro-nate derivative in the claim of the ’329 Patent to the equivalent weight of the alendronic acid, a formulator can consistently know how many basic units (alen-dronic acid units) are to be used, even though the final total weight may be different. Examples 7 and 8 of the ’329 Patent reinforce this conclusion. They provide for oral formulations “containing about 35 mg” and “about 70 mg” of alendronate “on an alendronic acid active basis.” The claims at issue use the same phraseology and the ingredient tables in the examples are consistent with the premise that “about” accounts for the fact that alendro-nate derivatives have accessories that add to the weight of the molecules. Thus, in the examples “about 35 mg” turns out to be 45.68 mg of alendronate monosodium trihydrate and the “about 70 mg” turns out to be 91.35 mg of alendronate monosodium trihydrate. See PTX 1, the ’329 Patent col. 19 lines 13-15, col. 19, lines 44-M6, col. 19 lines 20-21, col. 19 lines 51-52. Although the Court finds that Dr. Russell, is competent in the area of bisphos-phonates, it does not find his opinion as to the definition of the phrases “about 70/35 mg” in the ’329 Patent persuasive. During cross examination on this issue, Dr. Russell testified as follows: Q. Now is it true that when you deal with the claims in this case, the claims recite 70 and 35; correct? That is 70 mg a week and 35? A. The claims say about 70 and about Q. And what does “about” mean to you? A. Well about to me depends how precise a definition we want. But for purposes of how close the 40 and 80 are to about 35 and 70, I’ve given you my opinion on that, that for practical purposes, those would be the same, they would be indistinguishable in their effects, given everything else we know about the properties of these drugs. Q. But the claim itself, what the claim really means, is 70, not 80; correct? A. It says about 70 and about 35. Q. Did you read the patent, Dr. Russell, the entire body of the patent? A. Yes, I have. Q. So in the patent, does it tell you what about 70 means? A. There is a reference somewhere to about in the patent as I recall, but I’d need to be directed to where it was. Q. Why don’t you go to the first, in the patent, which is Defendant’s Exhibit 1 and Plaintiffs Exhibit 1, at column 11, lines-about 1 through 9. It says here in the definitional context exactly what about 70 milligrams means; correct? A. It well, there’s almost an intrinsic contradiction in this, because the definition here is talking about 70, and then referring to whatever salt form is used being referenced to the alendronie acid itself, yes. Q. But in the patent it gives you a precise reference and says when we say about 70 milligrams of a bone resorption inhibiting bisphosphonate, what we mean is that amount of a bisphosphonate that will deliver an equivalent amount, the equivalent of 70 milligrams of alen-dronic acid; correct? A. Yes. I have difficulty with this statement because the reason if it’s that precise at 70, why does it use the phrase about? Q. But they gave you that exact definition; correct? A. It’s a curious use of the English language. Q. I understand, but it is what it says, and perhaps the person wanted to say if it’s a certain salt one, you might use 71, and if it’s a certain salt 2, you might use 73. Isn’t that what’s indicated in this? A. Possibly. Q. But that’s what the definition says; right? A. That is the definition as it’s described in the patent. Russell at 337-339. (emphasis added). Although Dr. Russell opined that the explicit definition of the disputed claim terms in the specification was “a curious use of the English Language,” he testified that Merck’s proffered construction is the definition as it is described in the patent. The Court finds Dr. Russell’s interpretation unpersuasive, especially in light of the fact that patentees may give special meanings to claim terms either explicitly or implicitly in patent specifications. Further, with regard to Teva’s claim that there is no function to Merck’s proffered consl notion, the Court finds this argument unpersuasive given the clear directive in the specification to construe the term “about 70/35 mg” to mean the equivalent of 70/35 mg of alendronie acid when taking into account molecular weight variances for its derivatives and the fact that depending on the derivative of alendronie acid used in the oral formulation, different weights will be needed in order to get the same effect as 70 or 35 mg of alendronic acid. See Bell Atl. Network Servs., 262 F.3d at 1268 (noting that the specification must express a clear intent to redefine a claim term). Accordingly, the Court wall accept Merck’s proffered construction and construe the disputed claim terms “about 70/35 mg” to mean the equivalent of 70/35 mg of alen-dronic acid when taking into account molecular weight variances for its derivatives that carry accessories. B. Anticipation Anticipation is determined through a comparison of the claim language with a single prior art reference. See Wesley Jessen Corp. v. Bausch & Bomb, Inc., 209 F.Supp.2d 348, 391 (D.Del. 2002). Anticipation under 35 U.S.C. § 102 requires that every element of the claim be found either expressly or inherently “in a single prior art reference.” In re Robertson, 169 F.3d 743, 745 (Fed.Cir.1999). Thus, if the prior art reference does not expressly state an element of the claim, “that reference may still anticipate if that element is ‘inherent’ in its disclosure.” Id. Inherency is established if the evidence makes “clear that the missing descriptive matter is necessarily present in the thing described in the reference and, and that it would be so recognized by persons of ordinary skill.” Continental Can Co. v. Monsanto Co., 948 F.2d 1264, 1268 (Fed.Cir.1991). Although inherency cannot be established through probabilities, recognition by a person of ordinary skill in the art before the critical date of the patent is not required to show inherent anticipation. Schering Corp. v. Geneva Pharms., Inc., 339 F.3d 1373, 1377 (Fed.Cir.2003) (rejecting the contention that inherent anticipation requires recognition in the prior art before the critical date); In re Robertson, 169 F.3d at 745 (noting that inherent anticipation cannot be demonstrated through probabilities). 1. The Parties’ Contentions Teva contends that a July 1996 Lunar News article expressly anticipates claims 23 and 37 of the ’329 Patent. Teva points out that since Merck has stipulated that it does not assert an invention date before July, 22, 1997, the July 1996 Lunar News is prior art under 35 U.S.C. § 102(a). (D.I. 143 at 19). Further, Teva points out that although it has the burden of proving invalidity by clear and convincing evidence, that burden is more easily met in this situation because Merck failed to provide the PTO with the July 1996 Lunar News. -Teva contends that the July 1996 Lunar News discloses every element of claims 23 and 37 of the ’329 Patent. Teva points out that claim 23 defines a method of treating osteoporosis which comprises of oral administration of “about 70 mg” alendronate monosodium trihydrate, on an active alen-dronic acid basis, once-weekly. Similarly, Teva argues the July 1996 Lunar News discloses the same elements where it discusses the use of bisphosphonates, including alendronate, “in dealing with osteoporosis,” which means the treatment and prevention of osteoporosis. (D.I. 143 at 21; Russell at 137). Further, Teva contends that the July 1996 Lunar News also specifies that the alendronate therapy it is discussing includes “oral” alendronate therapy, and that the term “alendronate” refers to “Fosamax by Merck.” Teva also contends that the active ingredient of Fos-amax was well known to be alendronate monosodium trihydrate, and the dosage strength of Fosamax was known to be reported on an alendronic acid basis. (D.I. 143 at 21; DTX 394; Russell at 138-39). Teva also points out that the article specifies that the drug can be administered on a weekly basis at a dose of 80 mg where it states that, “... oral alendronate potentially could be given in a 40 or 80 mg dose once/week.” (D.I. 143 at 21)(quoting DTX 418 at 23). Teva directs the Court to Dr. Russell’s testimony where he opines that to a person skilled in the art, 80 mg of alendronate once per week is clinically indistinguishable from 70 mg once a week, and is therefore “about 70 mg.” (D.I. 143 at 21; Russell at 138). Teva also contends that Merck itself viewed 80 mg and -70 mg as the same weekly dose. (D.I. 143 at 21; DTX 147 at MK0158265). Thus, Teva contends the July 1996 Lunar News Article discloses every element of claim 23: treatment of osteoporosis by the administration of about 70 mg monosodium trihydrate on an alendronic acid basis once-weekly. (D.I. 143 at 22). Teva further contends that the July 1996 Lunar News anticipates claim 37 of the ’329 Patent. Claim 37 claims a method for preventing osteoporosis in a human being comprising of orally administering about 35 mg of alendronate sodium on an alendronic acid basis as a unit dosage according to a continuous schedule having a dosage interval of once-weekly. (D.I. 143 at 22; DTX 1). Teva points out that the only difference between the two claims is that claim 23 is directed to “treatment” of osteoporosis with a 70 mg weekly dose, and claim 37 is directed to “prevention” with a 35 mg weekly dose. Teva reiterates the contention that the July 1996 Lunar News deals with both the treatment and prevention of osteoporosis and discloses the use of a 40 mg once-weekly oral dose. (D.I. 143 at 22). Teva again directs the Court to Dr. Russell’s testimony where he testified that to a person skilled in the art, a 40 mg dose of alendronate once per week is clinically indistinguishable from 35 mg once per week and is therefore “about 35 mg.” (D.I. 143 at 22; Russell at 140; DTX 147 at MK0158265). As a result, Teva contends, that the July 1996 Lunar News discloses every element of claim 37: prevention of osteoporosis by oral administration of about 35 mg alendronate mono-sodium trihydrate on an alendronic acid basis once weekly. (D.I. 143 at 22). Teva contends that Merck’s “fear defense” is irrelevant to anticipation. First, Teva points out that claims 23 and 37 do not require that once-weekly administration of alendronate meet any standard of safety or tolerability. (D.I. 143 at 23). Even if they did, Teva argues, such a requirement would not avoid anticipation because the property of tolerability is inherent in the method disclosed in prior art. Further, Teva argues that the concept of “teaching away” from an invention is inapplicable in an anticipation analysis, and therefore, the Court should not consider it. (D.I. 143 at 24). Based on this, Teva contends that claims 23 and 37 are anticipated by the July 1996 Lunar News, and are therefore, invalid. In reply, Merck contends that the July 1996 Lunar News fails to anticipate claims 23 and 37 of the ’329 Patent. Merck points out that the claims require the use of 70 or 35 mg of alendronate sodium on an alendronic acid active basis and even if one were to read the July 1996 Lunar News suggestion that “[e]ven alendronate potentially could be given in a 40 or 80 mg dose once/week” as referring to the amount on an alendronic acid active basis, 80 mg is not the same as 70 mg and 40 mg is not the same as 35 mg. Merck argues that the unambiguous weight requirement for alendronate in claims 23 and 37 is not met by the Lunar News ’ suggestion of 80 or 40 mg, and therefore, it fails to anticipate claims 23 and 37. (D.I. 138 at 27). Further, Merck argues that the July 1996 Lunar News is not enabling, and therefore, cannot anticipate. Specifically, Merck contends that in order for a disclosure to be enabling it must allow one of skill in the art to practice the invention, and the July 1996 Lunar News falls short of this standard because it fails to address the expectation by physicians in the field during 1996-1997 that alendronate sodium at doses over 20 mg would not be well-tolerated in the prevention and treatment of osteoporosis. Merck points to Dr. Fen-nerty’s testimony to establish that a knowledgeable gastroenterologist during the applicable period would have been “extraordinarily concerned” about suggesting 40 or 80 mg of alendronate to treat osteoporosis. (D.I. 138 at 28; Fennerty at 270-271). Further, Merck argues that Dr. Papa-poulos, Merck’s expert with extensive bis-phosphonate and clinical osteoporosis experience, corroborates this sentiment. (D.I. 138 at 28). Merck argues that given the state of the medical knowledge at the time, a physician would not administer those high dosages when managing osteoporosis, and as a result, the July 1996 Lunar News fails to anticipate claims 23 and 37 of the ’329 Patent. 2. Whether the July 1996 Lunar News Anticipates the ’329 Patent After a review of the record evidence, the Court concludes that claims 23 and 37 of the ’329 Patent are not anticipated under 35 U.S.C. § 102(a). Specifically, the Court concludes that Teva has failed to prove by clear and convincing evidence that the July 1996 Lunar News expressly or inherently discloses the dosage amounts for alendronate in claims 23 and 37. As a threshold matter and contrary to Teva’s contentions, it has to prove invalidity by clear and convincing evidence. See American Hoist & Derrick Co. v. Sowa & Sons, Inc., 725 F.2d 1350, 1360 (Fed.Cir.1984) (citations omitted) (stating that when a challenger produces prior art not before the PTO “the standard of proof does not change; it must be by clear and convincing evidence or its equivalent.”) With this standard in mind, the Court will consider the parties’ contentions with regard to anticipation. The Lunar corporation was a manufacturer of bone densitometry equipment, which is a diagnostic tool for osteoporosis. (Russell at 129). The Lunar News was a quarterly newsletter distributed by the Lunar Corporation to its customers. (Mazess Dep. at 55-56; Russell at 129). It was authored by Dr. Richard Mazess , the former President of the Lunar Corporation. The July 1996 edition contained a section entitled, “Update Bisphosphonate.” (PTX 29 at 23). The section discusses bisphosphonates as a treatment for osteoporosis. Id. Specifically, in reference to the use of alendronate for treatment of osteoporosis, it states that “[s]ome United States physicians are reluctant to treat because of: a) side effects; b) difficulty of dosing; and (c) high costs ($700/year).” (PTX 19 at 23). To address the difficulty of dosing and high costs the article suggests: The difficulties with oral bisphospho-nates may favor their episodic (once/ week) or cyclical (one week each month) administration. Even oral alendronate potentially could be given in a 40 or 80 mg dose once/week to avoid dosing problems and reduce costs. PTX 29 at 23. Teva contends that the July 1996 Lunar News article discloses all of the elements in claim 23 of the ’329 Patent. Specifically, Teva argues that the July 1996 Lunar News discloses the following elements: 1) A method of treating osteoporosis in a human; 2) orally administering; 3) about 70 mg; 4) of alendronate monosodium trihydrate; 5) on an alen-dronic acid active basis; 6) as a unit dosage; and 7) according to a continuous schedule having a dosing interval once-weekly. (D.I. 143 at 23). Merck asserts that the July 1996 Lunar News article does not anticipate claim 23 because it fails to reference 70 mg of alendronate sodium on an alendronic acid active basis as required by claim 23. (D.I. 141 at 44). After reviewing the July 1996 Lunar News in light of the ’329 Patent, and the Court’s construction of the claim terms, the Court is not persuaded that Teva has demonstrated by clear and convincing evidence that claims 23 and 37 of the ’329 Patent are anticipated by the July 1996 Lunar News. The July 1996 Lunar Neivs fails to reference 70 mg of alendronate sodium on an alendronic acid basis as required by the claim. Instead it references an 80 mg dose of oral alendronate. Thus, it does not expressly disclose “about 70 mg” of alendronate sodium “on an alen-dronic acid basis.” Likewise, the Court is not persuaded that Teva has demonstrated inherency. Although Dr. Russell testified that 80 mg and “about 70 mg” are the same for all practical purposes because they have the same effect on patients, he did not testify that this element was “necessarily present” in the July 1996 Lunar News reference or that its disclosure was sufficient to show that this element was the natural result flowing from the operation as taught. In fact, in the Court’s view, Dr. Russell’s testimony was insufficient on this issue, and was, at best, con-elusory. For example, although Dr. Russell testified that 80 mg and 70 mg are the same for all practical purposes because they would have the same effect, the Court recognizes that in rendering his opinion Dr. Russell did not take into account the Court’s construction of the term “about 70 mg”. (Russell at 137-139). Further, the Court notes that Dr. Russell provided no evidence to support his conclusion that 70 and 80 mg were equivalent. In fact, Dr. Papapoulos testified on cross-examination that one would need to test the 80 and 70 mg doses before concluding with any certainty that they are the same and the regulations regarding the filing of an ANDA recognize that any change in the dosage of a drug would require additional data. (Papapoulos at 676-678; 21 U.S.C. § 355(j)(2); 21 C.F.R. § 314.93). Dr. Russell, provided no such data. Based on this, the Court concludes that Teva has failed to demonstrate that the July 1996 Lunar News inherently or expressly disclosed the element of “about 70 mg” of alendronate sodium “on an alendronic acid active basis” as required by claim 23 of the ’329 Patent. Similarly, the Court concludes that the July 1996 Lunar News fails to disclose “about 35 mg” as required by claim 37 of the ’329 Patent. Specifically, the July 1996 Lunar News fails to reference “35 mg” of alendronate sodium “on an alen-dronic acid active basis” as required by the claim. Although it references “40 mg”, in light of the Court’s claim construction of “about 35 mg” to mean the equivalent of 35 mg of alendronic acid when taking into account molecular weight variances for its derivatives that carry accessories, the Court concludes that the July 1996 Lunar News reference does not expressly disclose “about 35 mg” as required by claim 37. Likewise, the Court concludes that Teva’s inherency argument as to claim 37 must also fail. Dr. Russell testified that a 40 mg dose is about the same as a 35 mg for all practical purposes. (Russell art 140-141). However, the Court finds Dr. Russell’s opinion on this issue to be conclusory because he provides no evidence, statistical tests or data to support this assertion. Further, Dr. Russell did not testify that this element was “necessarily present” in the July 1996 Lunar News reference or that its disclosure was sufficient to show that this element was the natural result flowing from the operation as taught. Based on this, the Court finds that the evidence is insufficient to show that each element of claims 23 and 37 of the ’329 Patent were present in the prior art reference expressly or inherently. Accordingly, the Court concludes that Teva has failed to establish by clear and convincing evidence that the ’329 Patent was anticipated by the July 1996 Lunar News. Because the Court concludes that claims 23 and 37 of the ’329 Patent were not anticipated by the July 1996 Lunar News, the Court will not address the parties’ contentions concerning enablement of the prior art. C. Obviousness Teva contends that the ’329 Patent is invalid, under 35 U.S.C. § 103, as obvious. In pertinent part, 35 U.S.C. § 103 provides that a patent may not be obtained “if the differences between the subject matter sought to be patented and prior art are such that the subject matter as a whole would have been obvious to a person having ordinary skill in the art ...” 35 U.S.C. § 103. The obviousness determination is a question of law which is based on several underlying factual inquiries. See Richardson-Vicks Inc. v. Upjohn Co., 122 F.3d 1476, 1479 (Fed.Cir.1997). The underlying factual inquiries require consideration of the four “Graham” factors which are: (1) the scope and content of the prior art; (2) the differences between the claims and the prior art; (3) the level of ordinary skill in the pertinent art; and (4) any secondary considerations of nonobviousness such as commercial success, long felt but unsolved need, failure of others, and acquiescence of others in the industry that the patent is valid. See Graham v. John Deere Co. of Kansas City, 383 U.S. 1, 17-18, 86 S.Ct. 684, 15 L.Ed.2d 545 (1996). Additionally, as with anticipation, the burden of demonstrating obviousness is with the challenger and invalidity must be proven by clear and convincing evidence. C.R. Bard, Inc. v. M3 Systems, 157 F.3d 1340, 1351 (Fed.Cir.1998). 1. The Parties’ Contentions Teva contends that the ’329 Patent is invalid as obvious because both the April 1996 and July 1996 editions of Lunar News explicitly disclose the weekly administration of alendronate for osteoporosis and a person skilled in the art would have understood in July 1997 that the weekly dose for treatment and prevention of osteoporosis should be “about 70 mg” and “about 35 mg” respectively, and that these doses are explicitly set out in the July 1996 Lunar News. Teva argues that not only did the Lunar News disclose the concept of once-weekly dosing and provide the appropriate dose, a person of ordinary skill would have predicted the Lunar News teaching to be effective. (D.I. 143 at 26). Further, Teva contends that there was a motivation to employ once-weekly dosing because of the inconvenience of the dosing regimen which consisted of taking the tablet before eating, remaining upright for a half an hour and taking the tablet with a full glass of water. Id. at 27. Teva points out that the April 1996 and July 1996 editions of Lunar News explicitly stated the motivation to administer alendronate weekly; to improve patient convenience and compliance with the dosing instructions. Id. Thus, Teva argues that the pri- or art that claimed the invention also disclosed the motivation to make it. Id. Teva contends that a person of skill in the art would not have'been deterred from once-weekly dosing because of the fear of increased gastrointestinal side effects. Id. As to this point Teva argues that the early reports of esophagitis would not have deterred a person of skill in the art from once-weekly dosing because the early reports showed that these events were rare, occurring in one out of every ten thousand patients taking 10 mg of alendronate daily, and that these effects were for the most part reversible with proper treatment. Id. at 28; Markowitz at 436-37; 451. Teva also points out that in March 1996, five months after the launch of 10 mg daily alendronate tablet, ten million patients had been prescribed the tablet and fifty cases of severe esophagitis had been reported to Merck, and Merck took no action until it learned that a letter written by a well-known bone-specialist discussing two such cases was circulating within the' Mayo Clinic Health System. (D.I. 143 at 29; Hirsch Dep. at 54-56). When it finally took action, Teva argues, Merck’s investigation concluded that the pill esophagitis cases were caused primarily by the failure of patients to adhere to the dosing instructions. (D.I. 143 at 29; Markowitz at 442; Hirsch Dep. at 66; 82-84).. Teva also points out that in March 1996, Merck disseminated a “Dear Doctor” letter, informing physicians about the infrequent cases of esophagitis, stating that in a “large majority” of cases patients appeared to have not complied with the dosing instructions, and advocating “strict compliance” with those instructions. (D.I. 143 at 30; DTX 34). Merck later reported on the severe esophagitis cases in the October 1996 De Groen et al. article in the New England Journal of Medicine. (PTX 91). The De Groen paper reported that 51 patients experienced adverse effects classified as “serious” or “severe” out of the 470,000 patients worldwide who had received prescriptions for alendronate to treat osteoporosis up to that time. (D.I. 143 at 30). Teva directs the Court to its gastroenterology expert, Dr. David Mar-kowitz, who testified that the extremely low incidence of these effects, and the description of the cases, led gastroenterol-ogists to conclude at the time that the likely cause of the problem was “pill eso-phagitis.” (D.I. 143 at 30; Markowitz 435, 438). Teva argues that the evidence presented at trial leads to the conclusion that once-weekly administration would have been expected to decrease the incidence of severe esophagitis cases because it would: 1) improve patient compliance with the dosing instructions (Russell at 195-96; Markowitz at 485-86; Fennerty at 311); and 2) decrease the frequency of administration, thereby decreasing the chances of the tablet “sticking” in the esophagus (Russell at 196-197; Markowitz at 443). Teva also asserts that the evidence presented at trial does not support a dose-response relationship between alendronate and gastrointestinal effects that would have deterred a person of ordinary skill in the art from once-weekly dosing. (D.I. 143 at 32). For example, Teva argues that the results of the Chestnut study related to daily and not weekly dosing and demonstrated that 90% of postmenopausal women with osteoporosis tolerated the 40 mg daily dose. Id. at 34. Also, Teva contends that Dr. Fennerty’s testimony regarding a dose-related relationship was discredited by Merck’s pre-litigation behavior and directs the Court to the testimony of Dr. Markowitz who testified that his contemporaneous investigations indicated that severe events were extremely rare with alen-dronate and that overall the drug was well tolerated. Id. at 35. In addition, Teva contends that before this litigation, Merck admitted that prior art data available in July 1997 from Pa-get’s patients showed that once weekly dosing would be well-tolerated. For example, Teva directs the Court to a May 1997 “Tactical PAC” review seeking management approval to go forward with the once-weekly dosing program where it stated that “the 40 and 80 mg doses were well-tolerated even when given on a daily basis.” (D.I. 143 at 39, DTX 147 at MK0158265). Further, Teva points out that Merck, in a formal submission to the FDA maintained that data from Paget’s disease provided an expectation that once-weekly doses would be well tolerated. (D.