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`Page 1 of 14
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`395 F.3d 1364 (2005)
`
`MERCK & CO., INC., Plaintiff-Appellee,
`v.
`TEVA PHARMACEUTICALS USA, INC., Defendant-Appellant.
`
`No. 04-1005.
`
`United States Court of Appeals, Federal Circuit.
`
`Decided: January 28, 2005.
`
`1365
`
`*1365 John F. Lynch, Howrey Simon Arnold & White, LLP, of Houston, Texas, argued for plaintiff-appellee. With him
`on the brief were Nicolas G. Barzoukas and Richard L. Stanley. Of counsel on the brief were Paul D. Matukaitis,
`Edward W. Murray and Gerard M. Devlin, Merck & Co., Inc., of Rahway, New Jersey.
`
`James Galbraith, Kenyon & Kenyon, of New York, New York, argued for defendant-appellant. With him on the brief
`were Maria Luisa Palmese and William G. James, II.
`
`Before RADER, GAJARSA, and PROST, Circuit Judges.
`
`GAJARSA, Circuit Judge.
`
`1366
`
`Teva Pharmaceuticals USA, Inc. ("Teva") appeals the final judgment of the United States District Court of Delaware,
`which, after a bench trial, found Merck & Co.'s ("Merck") U.S. Patent No. 5,994,329 (issued Nov. 30, 1999) ("the '329
`patent") *1366 not invalid as anticipated or obvious. The district court further found the '329 patent to be enforceable,
`and the ' 329 patent claims 23 and 37 constructively infringed by Teva's Abbreviated New Drug Application ("ANDA")
`under 35 U.S.C. § 271(e)(2)(A) of the Hatch-Waxman Act. Merck & Co., Inc. v. Teva Pharms. USA, Inc., 288
`F.Supp.2d 601 (D.Del.2003) ("Merck"); Merck & Co., Inc. v. Teva Pharms. USA, Inc., No. 01-CV-0048, Order (D.Del.
`Sept. 24, 2003) (Final Judgment Order Pursuant to Fed.R.Civ.P. 54(b)) ("Final Judgment Order").[1]
`
`We disagree with the district court's construction of the claim term "about" in claims 23 and 37 of the '329 patent.
`Because we further hold claims 23 and 37 obvious in light of the prior art, we vacate the judgment of the district court
`and hold the claims invalid and not infringed.
`
`I. BACKGROUND
`
`A. '329 Patent
`
`Merck owns the '329 patent. The '329 patent, entitled "Method for Inhibiting Bone Resorption," teaches a method of
`treating and preventing osteoporosis through less-than-daily administration of bisphosphonate compounds. '329
`patent, col. 1, ll. 15-25. The patent was filed on August 14, 1998, and Merck stipulated at trial that it would not allege
`an invention date prior to July 22, 1997 for the claims at issue. Merck, 288 F.Supp.2d at 606.
`
`Bisphosphonates are a family of chemical compounds that are known to selectively inhibit the bone destruction
`process that contributes to osteoporosis and other bone diseases. '329 patent, col. 1, ll. 45-50. Bisphosphonates
`include, among other compounds, alendronate, risedronate, tiludronate, pamidronate, ibandronate, zolendronate, and
`etidronate. Id. at col. 1, ll. 54-65; col. 2, ll. 28-31. At issue in this case are once-weekly dosages of alendronate
`monosodium trihydrate.
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`ARGENTUM Exhibit 1187
`Argentum Pharmaceuticals LLC v. Research Corporation Technologies, Inc.
`IPR2016-00204
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`00001
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`Bisphosphonates are not readily absorbed by the gastrointestinal ("GI") tract. The medications thus require rigorous
`dosing instructions: a patient must take the medicine on an empty stomach and remain upright and fasting for thirty
`minutes after ingestion. '329 patent, col. 2, ll. 3-24. In addition, the compounds are known to have adverse GI side
`effects that physicians believed to be related, in part, to (a) irritation to the patient's esophagus, or (b) the size of the
`dose. Id. at col. 2, ll. 23-46.
`
`Before the '329 patent issued, standard osteoporosis treatments consisted of small daily doses of bisphosphonates to
`avoid GI complications. Id. at col. 1, ll. 54-61; col. 2, ll. 34-35, 44-46. According to the patent, however, the adverse GI
`side-effects resulting from repetitive irritation to the GI tract were the primary concern in the field. Id. at col. 2, ll. 65-67;
`col. 3, l. 57 — col. 4, l. 13. The inventors trumpeted the reduced-frequency dosing schedule disclosed in the '329
`patent as decreasing the irritating effect of the compounds, as well as increasing patient compliance with the rigorous
`dosing instructions. Id. at col. 3, ll. 57-64; col. 4, ll. 14-23.
`
`This case involves dependent claims 23 and 37 of the '329 patent. At trial, the parties agreed to cast the text of these
`claims in independent form, incorporating all the dependent limitations:
`
`23. A method for treating osteoporosis in human comprising orally administering about 70 mg of
`alendronate monosodium trihydrate, on an alendronic acid basis, as a unit dosage according to a
`continuous schedule having a dosing interval of once-weekly.
`
`1367
`
`*1367 37. A method for preventing osteoporosis in human comprising orally administering about 35 mg
`of alendronate monosodium trihydrate, on an alendronic acid basis, as a unit dosage according to a
`continuous schedule having a dosing interval of once-weekly.
`
`'329 patent, col. 21, ll. 24-27 (claim 23) (emphasis added); col. 22, ll. 24-26 (claim 37) (emphasis added). We note that
`the only differences between claim 23 and claim 37 are (1) the dosage amount of alendronate monosodium trihydrate
`(70 mg or 35 mg) and (2) whether the method is directed to treating or preventing osteoporosis.
`
`Merck has Food and Drug Administration ("FDA") approval to market both a once-weekly and a relatively diminished
`daily dose of alendronate monosodium trihydrate, which it does under the trade name Fosamax. Merck, 288
`F.Supp.2d at 605.
`
`B. Litigation
`
`In late 2000, Teva amended an existing ANDA and sought FDA approval to market generic versions of Merck's once-
`weekly Fosamax supplement in 35 mg and 70 mg quantities.[2] Merck, 288 F.Supp.2d at 605-06; Teva Br. at 4. Merck
`subsequently filed suit against Teva under 35 U.S.C. § 271(e)(2)(A), alleging Teva's ANDA filing was an act of
`infringement.[3]
`
`According to the trial court, Merck acted as its own lexicographer and through the specification redefined the ordinary
`meaning of "about" in claims 23 and 37 — which both parties agree has the ordinary meaning "approximately" — to
`something quite different. Merck, 288 F.Supp.2d at 612-16. Thus, the district court concluded the terms "about 35 mg"
`in claim 37 and "about 70 mg" in claim 23 mean exactly 35 (or 70) mg of alendronic acid.[4]
`
`Relying on this construction of "about," the district court dismissed Teva's allegations that the claims at issue were (1)
`anticipated by a July 1996 Lunar News article or (2) rendered obvious by an April 1996 Lunar News article combined
`with the July 1996 article.[5] The trial court found both articles qualified as prior art publications under 35 U.S.C. § 102
`(a). Merck, 288 F.Supp.2d at 618-19. The *1368 April 1996 article in Lunar News recommends weekly dosages of
`alendronate to improve patient compliance:
`
`1368
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`[O]ne of the difficulties with alendronate is its low oral bioavailability. When taken with water in a fasting
`state, only about 0.8% of the oral dose is bioavailable. Even coffee or juice reduces this by 60%, and a
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`meal reduces it by >85%. Alendronate must be taken, after an overnight fast, 30-60 minutes before
`breakfast. Subjects should remain seated or standing; a very small group of patients have reported
`some upper gastrointestinal distress if this is not done. This regime may be difficult for the elderly [to]
`maintain chronically. An intermittent treatment program (for example, once per week, or one week
`every three months), with higher oral dosing, needs to be tested.
`
`Update: Bisphosphonate, Lunar News, Apr. 1996, at 31 (emphasis added).
`
`The July 1996 Lunar News article further emphasizes the need for a once-weekly dose of Fosamax because "[s]ome
`United States physicians are reluctant to treat [patients with Fosamax] because of: a) side effects; b) difficulty of
`dosing; and c) high costs ($700/year)." The author suggests:
`
`The difficulties with oral bisphosphonates 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.[6]
`
`Update: Bisphosphonate, Lunar News, July 1996, at 23 (emphasis added).
`
`Regarding anticipation, the trial court held the July 1996 article does not "expressly or inherently disclose the dosage
`amounts for alendronate in claims 23 and 37" because there was no evidence that 40 mg and 80 mg of alendronate
`contains "the same number of alendronate core molecules" as found in 35 mg and 70 mg, respectively, of alendronic
`acid. Merck, 288 F.Supp.2d at 618-20.
`
`As for obviousness, the district court concluded the suggestion of weekly treatment was not "clinically useful or
`obvious in July 1997 because of the known dose-related gastrointestinal side effects" associated with the daily
`formulation of Fosamax. Merck, 288 F.Supp.2d at 628. Although it is undisputed that a once-weekly dosage was
`known to be efficacious, the court determined that the Lunar News articles could not overcome doctors' concerns
`associated with higher dosages because the Lunar News articles were not published in peer-reviewed journals or
`authored by one skilled in the art. Merck, 288 F.Supp.2d at 628-29.
`
`Finding the '329 patent not invalid as anticipated or obvious, the district court delayed the effective date of the FDA
`approval of Teva's ANDA until the '329 patent expires and enjoined commercial sale of Teva's generic treatment. Final
`Judgment Order at 1. This appeal followed. We have jurisdiction under 28 U.S.C. § 1295(a)(1).
`
`1369
`
`*1369 II. DISCUSSION
`
`A. Standard of Review
`
`On appeal from a bench trial, this court reviews the district court's conclusions of law de novo and findings of fact for
`clear error. Golden Blount, Inc. v. Robert H. Peterson Co., 365 F.3d 1054, 1058 (Fed.Cir.2004); Brown & Williamson
`Tobacco Corp. v. Philip Morris Inc., 229 F.3d 1120, 1123 (Fed.Cir.2000). A finding is clearly erroneous when, despite
`some supporting evidence, "the reviewing court on the entire evidence is left with the definite and firm conviction that a
`mistake has been committed." United States v. United States Gypsum Co., 333 U.S. 364, 395, 68 S.Ct. 525, 92 L.Ed.
`746 (1948).
`
`The court reviews claim construction, a question of law, de novo. Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448,
`1456 (Fed.Cir.1998) (en banc). Obviousness is a question of law based on underlying factual determinations.
`Richardson-Vicks, Inc. v. Upjohn Co., 122 F.3d 1476, 1479 (Fed.Cir.1997). The court reviews an obviousness ruling
`de novo, but reviews the underlying factual findings for clear error. Graham v. John Deere Co., 383 U.S. 1, 17, 86
`S.Ct. 684, 15 L.Ed.2d 545 (1966); Golden Blount, 365 F.3d at 1058. The underlying factual determinations include (1)
`the scope and content of the prior art, (2) the level of ordinary skill in the art, (3) the differences between the claimed
`invention and the prior art, and (4) objective indicia of nonobviousness. Graham, 383 U.S. at 17-18, 86 S.Ct. 684.
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`B. Claim Construction
`
`In finding that Merck acted as its own lexicographer, the district court relied on the following passage from the
`specification:
`
`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.
`
`'329 patent, col. 10, l. 65 — col. 11, l. 8 (emphasis added). According to the district court's opinion, the patentee uses
`the phrase "about 35 [or 70] mg" to account for variations in the molecular weight of the different derivatives of
`alendronic acid and to deliver exactly 35 (or 70) mg of alendronic acid. Merck, 288 F.Supp.2d at 613. For example, the
`court noted that alendronate monosodium trihydrate, which is used in Fosamax, requires an atom of sodium for each
`molecule. Id. at 613-14. If a heavier metal were chosen, such as potassium, the weight of the derivative compound
`would have to increase to deliver exactly the same number of molecules of the active alendronate compound found in
`35 [or 70] mg of alendronic acid. Id. at 614. The district court thus construed the term "about 35 [or 70] mg" to mean
`the amount of the derivative compound that gives exactly 35 [or 70] mg of the active compound.
`
`1370
`
`We reverse the district court's construction of "about" and hold that such term should be given its ordinary meaning of
`"approximately."[7] To properly construe *1370 a claim term, a court first considers the intrinsic evidence, starting with
`the language of the claims. Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed.Cir.1996). Generally claim
`terms should be construed consistently with their ordinary and customary meanings, as determined by those of
`ordinary skill in the art. Brookhill-Wilk 1, LLC v. Intuitive Surgical, Inc., 334 F.3d 1294, 1298 (Fed.Cir.2003). While in
`some cases there is a presumption that favors the ordinary meaning of a term, Tex. Digital Sys. v. Telegenix Inc., 308
`F.3d 1193, 1202 (Fed.Cir.2002), the court must first examine the specification to determine whether the patentee
`acted as his own lexicographer of a term that already has an ordinary meaning to a person of skill in the art. See, e.g.,
`Renishaw PLC v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250 (Fed.Cir.1998); Brookhill-Wilk, 334 F.3d at 1299.
`
`When a patentee acts as his own lexicographer in redefining the meaning of particular claim terms away from their
`ordinary meaning, he must clearly express that intent in the written description. See, e.g., Bell Atl. Network Servs. v.
`Covad Communications Group, Inc., 262 F.3d 1258, 1268 (Fed.Cir.2001). We have repeatedly emphasized that the
`statement in the specification must have sufficient clarity to put one reasonably skilled in the art on notice that the
`inventor intended to redefine the claim term. Id.; see also Elekta Instrument S.A. v. O.U.R. Sci. Int'l, Inc., 214 F.3d
`1302, 1307 (Fed.Cir.2000) ("Absent an express intent to impart a novel meaning, claim terms take on their ordinary
`meaning."); Renishaw, 158 F.3d at 1249 ("The patentee's lexicography must, of course, appear `with reasonable
`clarity, deliberateness, and precision' before it can affect the claim.") (quoting In re Paulsen, 30 F.3d 1475, 1480
`(Fed.Cir.1994)); Union Carbide Chems. & Plastics Tech. Corp. v. Shell Oil Co., 308 F.3d 1167, 1177-78 (Fed.Cir.2002)
`(stating that the "presumption in favor of the claim term's ordinary meaning is overcome, however, if a different
`meaning is clearly and deliberately set forth in the intrinsic evidence"). In the present case, the passage cited by the
`district court from the specification for Merck's definition of "about" is ambiguous. It fails to redefine "about" to mean
`"exactly" in clear enough terms to justify such a counterintuitive definition of "about."
`
`1371
`
`The phrase's ambiguity arises from the fact that it can easily be read as Teva *1371 does — as a way of explaining
`what is meant by the use of the phrase "alendronate acid active basis" rather than as a way of radically redefining
`what is meant by "about." The district court construed the phrase "about 70 [or 35] mg" to mean that one should
`administer approximately 70 (or 35) mg of the derivative compound, such that the end result is that the patient is
`administered exactly 70 (or 35) mg of alendronic acid. In other words, the district court determined that the quantity
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`specified in the claims (35 or 70 mg) modifies the amount of the derivative compound rather than the active
`compound. Under such a construction, the term "about" informs one of ordinary skill in the art to select whatever
`quantity of the derivative compound necessary to give exactly 35 (or 70) mg of alendronic acid; for alendronate
`monosodium trihydrate, the word "about" thus meant that 45.68 mg (or 91.35 mg) of that compound should be
`delivered — the amount necessary to give exactly 35 (or 70) mg of alendronic acid.
`
`Unlike the limiting definition of "about" adopted by the district court, Teva's interpretation of the paragraph in question
`would mean that "70 [or 35] mg" refers to the amount of the active compound to be administered rather than the
`amount of the derivative compound. The term "about" in the claims would then serve to modify the quantity of the
`active compound in a way consistent with its normal definition of "approximately." Under this construction, the
`modifying phrase "about 70 [or 35] mg" would refer to approximately 70 (or 35) mg of alendronic acid.[8]
`
`The claim construction urged by Merck and adopted by the district court reads the sentence of the passage underlined
`above out of context. In the sentence before the highlighted sentence, the patentee informs those of ordinary skill in
`the art that, when the patent refers to a certain amount of a bisphosphonate compound, it is actually instructing them
`to administer a certain amount of the active component of the compound rather than the compound itself, i.e., that one
`should calculate the amount dispensed on an "active weight basis." This preceding sentence thus acts to specify a
`common denominator to be used for all derivatives of alendronic acid. The underlined sentence merely gives a specific
`example — that of an alendronate derivative — to show what is meant by using the phrase "active weight basis."
`
`Given that the passage that Merck relies on is amenable to a second (and more reasonable) interpretation, we hold
`Merck did not clearly set out its own definition of "about" with "reasonable clarity, deliberateness, and precision," and
`thus failed to act as its own lexicographer. In re Paulsen, 30 F.3d at 1480.
`
`As further support for this conclusion, we note that other parts of the specification also suggest that "about" should be
`given its ordinary meaning of "approximately." The specification repeatedly describes a range of acceptable dosage
`amounts, with the patentee emphasizing that unit dosages will vary. For example, the specification suggests that a
`once-weekly dosage amount could contain anywhere from about 17.5 mg to about 70 mg of any alendronate
`compound on an alendronate acid active basis, with about 35 mg and about 70 mg being only two examples of a unit
`dosage:
`
`1372
`
`*1372 For once-weekly dosing, an oral unit dosage comprises from about 17.5 mg to about 70 mg of
`the alendronate compound, on an alendronic acid active weight basis. Examples of weekly oral
`dosages include a unit dosage which is useful for osteoporosis prevention comprising about 35 mg of
`the alendronate compound, and a unit dosage which is useful for treating osteoporosis comprising
`about 70 mg of the alendronate compound.
`
`'329 patent, col. 12, ll. 56-63 (emphasis added). In addition to the above passage, at another point in the specification
`the range for the normal unit dosage is further widened to "about 8.75 to about 140 mg." '329 patent, col. 12, ll. 52-55
`(stating that "a unit dosage typically comprises from about 8.75 mg to about 140 mg of an alendronate compound on
`an alendronic acid active weight basis"). The specification thus suggests the patentee contemplated a range of
`dosages, further compromising Merck's proposition that it acted as its own lexicographer in defining "about" to mean
`"exactly."[9]
`
`Finally, our construction of "about" eliminates the problem pointed out by Teva that the district court's construction of
`the term "about" renders other parts of the claim superfluous. As Teva notes, the specification uses both the term
`"about" and "on an alendronic acid basis" at least 15 times to describe a dosage strength. If, as Merck urges, "about
`35 [or 70] mg" means exactly 35 (or 70) mg of alendronic acid, then the oft-repeated phrase "on an alendronic acid
`active basis" would be unnecessary since such an understanding would be clear simply by using the term "about." A
`claim construction that gives meaning to all the terms of the claim is preferred over one that does not do so. Elekta,
`214 F.3d at 1307 (construing claim to avoid rendering the 30 degree claim limitation superfluous); Gen. Am. Transp.
`Corp. v. Cryo-Trans, Inc., 93 F.3d 766, 770 (Fed.Cir.1996) (rejecting the district court's claim construction because it
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`rendered superfluous the claim requirement for openings adjacent to the end walls). By construing "about" to mean its
`accepted and ordinary meaning of "approximately," the phrase "alendronic acid basis" is no longer excess verbiage,
`but is instead necessary because it is the noun that "about 35 [or 70] mg" modifies.
`
`Because the patentee did not clearly redefine "about" in the specification, and because the district court construed the
`claim term in a manner inconsistent with the specification, we reverse the district court's claim construction. We thus
`hold that the term "about" should be given its ordinary and accepted meaning of "approximately."
`
`C. Invalidity
`
`In light of the corrected claim construction we find reversible error in the district court's obviousness analysis. A patent
`claim is invalid "if the differences between the subject matter sought to be patented and the prior art are such that the
`subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary
`skill in the art to which said subject matter pertains." 35 U.S.C. § 103(a) (2000). The ultimate issue of obviousness
`turns on four factual determinations: (1) the scope and content of the prior art, (2) the level of ordinary skill in the art,
`(3) the differences between the claimed invention and the prior art, and (4) *1373 objective indicia of nonobviousness.
`Graham v. John Deere Co., 383 U.S. 1, 17-18, 86 S.Ct. 684, 15 L.Ed.2d 545 (1966). As explained below, we find clear
`error in the trial court's findings on these underlying facts.[10] On reviewing these factual bases, we conclude the district
`court also erred in refusing to invalidate claims 23 and 37 for obviousness in view of the 1996 Lunar News articles.
`
`1373
`
`The central issue concerns the differences between the aspects of the invention claimed at claims 23 and 37, and the
`teachings of the Lunar News articles. As the district court necessarily recognized, there are more similarities than
`differences. These claims, and the July 1996 article, both teach administering alendronate once a week instead of
`once a day. These claims read in light of the specification, and the July 1996 article, both indicate — and it has been
`conceded as known in the art at the time[11] — that for treating or preventing osteoporosis a once-weekly dosage at
`seven times the daily dose would be as effective as seven daily doses. The '329 patent, and both the April and July
`1996 articles, explain the motivation for a once-weekly dose as increasing patient compliance, by making it easier to
`take the drug (and incur the inconvenience of the rigorous dosing regimen less frequently). Although the claims teach
`70 or 35 mg doses rather than the 80 or 40 mg doses disclosed in the July 1996 article, Dr. Arthur C. Santora — one
`of the co-inventors on the '329 patent — admitted against Merck's interest that a once-weekly 40 mg dose would be as
`effective as seven daily 5 mg doses, and a once-weekly 80 mg dose would be as effective as seven daily 10 mg
`doses, in preventing or treating osteoporosis. There was no great leap required of those skilled in the art to go from 40
`or 80 mg once a week, the pills available at the time to treat patients with Paget's disease, to a 35 or 70 mg pill once a
`week. The district court's conclusion that the claims are not obvious cannot rest on any of these similarities between
`the claimed invention and the two Lunar News articles.
`
`The district court distinguished the two Lunar News articles on grounds that they failed to explain how the once-weekly
`dosing overcame concerns in the art with adverse GI side effects. Merck, 288 F.Supp.2d at 628-29. We are left with
`the firm conviction that this distinction is misplaced. As noted, the district court found those in the art had identified two
`types of adverse GI problems with alendronate. The first, and most significant, involved esophageal injury or repetitive
`irritation of the esophagus. The district court, reviewing the October 1996 article by DeGroen in the New England
`Journal of Medicine, expressly recognized the literature taught that complications related to alendronate were due to
`"prolonged contact of the drug with the esophagus." Merck, 288 F.Supp.2d at 627. Confronted with this problem,
`Merck revised its dosing instructions and sent the clarifying materials to prescribing physicians in a March 1996 "Dear
`Doctor" letter. After Merck sent this letter, the reported incidence of GI distress fell to almost nothing even as the
`number of patients being prescribed Fosamax doubled by October 1996. Although the '329 patent focuses on this
`adverse GI side-effect, it provides no additional motivation to overcome this problem beyond the motivation described
`in the two articles. The '329 patent, both articles, and the prevailing knowledge of those skilled *1374 in the art,
`recognized that to the extent "dosing problems" were related to repetitive irritation of the esophagus (from patients
`getting pills stuck in their throats), taking fewer pills each week could reduce the attending GI problems.[12] Thus, the
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`district court clearly erred in finding any significant difference between the claimed invention and the two articles as to
`this type of GI problem.
`
`The district court found a second adverse GI side-effect related to the size of the dose, which Merck argued gave rise
`to "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, 288 F.Supp.2d at 624; see also id. at 622-
`23, 627-30 (discussing Chesnut study). Neither the '329 patent nor the Lunar News articles explain how a higher once-
`weekly dosing regimen would avoid this set of dose-related adverse side effects. The '329 patent sets forth no human
`clinical or laboratory data showing the safety and tolerability of the treatment methods claimed by the patent. The only
`data provided in the '329 patent was generated in beagles, an experiment discredited at trial and disregarded by the
`district court in its decision. So while the district court may be correct in finding the Lunar News articles may have
`invited skepticism based on concerns for dose-related GI problems, the claimed invention adds nothing beyond the
`teachings of those articles. Thus, the district court clearly erred in finding any difference between the claimed invention
`and the articles on this point.
`
`The district court's only remaining distinction between the claimed invention and the two Lunar News articles goes to
`the probative value of the articles. The trial court wrote that it "[was] not persuaded that the two Lunar News articles,
`not published in peer-reviewed journals or authored by one skilled in the art, either alone or in combination, overcame
`the serious side effect concerns associated with higher dosage units of alendronate sodium." Merck, 288 F.Supp.2d at
`629. Although these indicia of reliability — whether a study is peer-reviewed, and the credentials of the author —
`properly go to weight when the trial court has not excluded evidence as unreliable and irrelevant, the district court's
`reliance on these factors to distinguish Merck's claimed invention is, again, misplaced. First, as noted above, these
`factors provide no relevant distinction between the articles and the claimed invention because the '329 patent also fails
`to explain how its higher dosing would overcome these dose-related side-effects. Second, as explained below the
`district court's finding the author of the Lunar News articles not skilled in the relevant art is inconsistent with the court's
`own definition of the relevant art. Thus, the extent to which the district court discounts the probative value of the two
`articles based on the credentials of the author calls for closer scrutiny and *1375 casts doubt on the findings that
`depend on this reasoning.
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`1375
`
`In short, the district court clearly erred in distinguishing the claimed invention from the two Lunar News articles offered
`as section 103 prior art. Contrary to the district court's findings, these articles support the conclusion that Merck's
`claims 23 and 37 are invalid as obvious.
`
`For similar reasons we find the district court's characterization of the scope and content of the prior art favors
`invalidating claims 23 and 37 as obvious. The district court described its larger task as identifying "a showing of the
`teaching or motivation to combine prior art references." Merck, 288 F.Supp.2d at 625 (quoting In re Gartside, 203 F.3d
`1305, 1319 (Fed.Cir.2000)). But as shown above, in this case the Lunar News articles contain the relevant teaching of
`the weekly dosing claimed in the '329 patent. The "specific combination" of elements in claims 23 and 37 differs from
`the disclosure in the Lunar News articles only in terms of a minor difference in the dosage; without this difference, the
`Lunar News articles would anticipate claims 23 and 37 under section 102. For the Lunar News articles to render claims
`23 and 37 obvious, the district court need only have found a suggestion or motivation to modify the dosages from
`those in the articles to those in the claims. See, e.g., SIBIA Neurosciences, Inc. v. Cadus Pharm. Corp., 225 F.3d
`1349, 1356 (Fed.Cir.2000). But as noted above, Merck's own inventors admit the difference in dosing amount is
`obvious. If anything, concern over dosing amount suggests lowering the weekly dosage — from 80 to 70 mg, and from
`40 to 35 mg, just as Merck did. The district court thus clearly erred to the extent it found lacking any motivation to
`combine existing knowledge with the Lunar News articles to reach the claimed invention.
`
`The district court failed to ascertain the required motivation to combine references to achieve the claimed invention,
`and it ignored the plain teachings of the Lunar News articles. As the court stated, "the issue is when viewing the
`mosaic of prior art, whether those of ordinary skill in the art would have had the motivation to formulate a once-weekly
`seven-fold daily dose of alendronate, despite safety concerns." Merck, 288 F.Supp.2d at 626.
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`http://scholar.google.com/scholar_case?q=395+f.3d+1364&hl=en&as_sdt=2006&case=16...
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`Merck & Co. v. Teva Pharmaceuticals USA, 395 F. 3d 1364 - Court of Appeals, Federal ...
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`The Lunar News articles had clearly suggested the once-weekly dosing. They did so, as noted above, and as
`described in the '329 patent, to avoid or minimize problems related to dosing frequency. And as shown above, the
`district court itself found this particular set of problems were of greatest concern in the art.