`
`Merck & Co. v. Teva Pharmaceuticals USA, 395 F. 3d 1364 Court of Appeals, Federal Circuit 2005 Google Scholar
`
`395 F.3d 1364 (2005)
`
`MERCK & CO., INC., PlaintiffAppellee,
`v.
`TEVA PHARMACEUTICALS USA, INC., DefendantAppellant.
`
`No. 041005.
`
`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 plaintiffappellee. 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 defendantappellant. 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 HatchWaxman 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. 01CV0048, 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 lessthandaily administration of bisphosphonate
`compounds. '329 patent, col. 1, ll. 1525. 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.
`
`https://scholar.google.com/scholar_case?q=merck+%26+co+v+teva+&hl=en&as_sdt=2006&case=16422293572234260019&scilh=0
`
`1/15
`
`WATSON LABORATORIES, INC. , IPR2017-01621, Ex. 1121, p. 1 of 15
`
`
`
`5/17/2017
`
`Merck & Co. v. Teva Pharmaceuticals USA, 395 F. 3d 1364 Court of Appeals, Federal Circuit 2005 Google Scholar
`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. 4550.
`Bisphosphonates include, among other compounds, alendronate, risedronate, tiludronate, pamidronate,
`ibandronate, zolendronate, and etidronate. Id. at col. 1, ll. 5465; col. 2, ll. 2831. At issue in this case are
`onceweekly dosages of alendronate monosodium trihydrate.
`
`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. 324. 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. 2346.
`
`Before the '329 patent issued, standard osteoporosis treatments consisted of small daily doses of
`bisphosphonates to avoid GI complications. Id. at col. 1, ll. 5461; col. 2, ll. 3435, 4446. According to the
`patent, however, the adverse GI sideeffects resulting from repetitive irritation to the GI tract were the primary
`concern in the field. Id. at col. 2, ll. 6567; 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. 5764; col. 4, ll.
`1423.
`
`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 onceweekly.
`
`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 onceweekly.
`
`'329 patent, col. 21, ll. 2427 (claim 23) (emphasis added); col. 22, ll. 2426 (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 onceweekly 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 onceweekly 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]
`
`https://scholar.google.com/scholar_case?q=merck+%26+co+v+teva+&hl=en&as_sdt=2006&case=16422293572234260019&scilh=0
`
`2/15
`
`WATSON LABORATORIES, INC. , IPR2017-01621, Ex. 1121, p. 2 of 15
`
`
`
`5/17/2017
`
`Merck & Co. v. Teva Pharmaceuticals USA, 395 F. 3d 1364 Court of Appeals, Federal Circuit 2005 Google Scholar
`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 61216. 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 61819. The *1368 April 1996 article in Lunar
`News recommends weekly dosages of alendronate to improve patient compliance:
`
`1368
`
`[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 meal reduces it by >85%. Alendronate must be taken, after an overnight fast, 3060
`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 onceweekly 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 61820.
`
`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 doserelated gastrointestinal side effects" associated with the daily
`formulation of Fosamax. Merck, 288 F.Supp.2d at 628. Although it is undisputed that a onceweekly 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 62829.
`
`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).
`
`https://scholar.google.com/scholar_case?q=merck+%26+co+v+teva+&hl=en&as_sdt=2006&case=16422293572234260019&scilh=0
`
`3/15
`
`WATSON LABORATORIES, INC. , IPR2017-01621, Ex. 1121, p. 3 of 15
`
`
`
`5/17/2017
`1369
`
`Merck & Co. v. Teva Pharmaceuticals USA, 395 F. 3d 1364 Court of Appeals, Federal Circuit 2005 Google Scholar
`
`*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. RichardsonVicks, 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 1718, 86 S.Ct. 684.
`
`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 61314. 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
`
`https://scholar.google.com/scholar_case?q=merck+%26+co+v+teva+&hl=en&as_sdt=2006&case=16422293572234260019&scilh=0
`
`4/15
`
`WATSON LABORATORIES, INC. , IPR2017-01621, Ex. 1121, p. 4 of 15
`
`
`
`5/17/2017
`
`Merck & Co. v. Teva Pharmaceuticals USA, 395 F. 3d 1364 Court of Appeals, Federal Circuit 2005 Google Scholar
`(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. BrookhillWilk 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); BrookhillWilk, 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, 117778 (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 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
`
`https://scholar.google.com/scholar_case?q=merck+%26+co+v+teva+&hl=en&as_sdt=2006&case=16422293572234260019&scilh=0
`
`5/15
`
`WATSON LABORATORIES, INC. , IPR2017-01621, Ex. 1121, p. 5 of 15
`
`
`
`5/17/2017
`
`Merck & Co. v. Teva Pharmaceuticals USA, 395 F. 3d 1364 Court of Appeals, Federal Circuit 2005 Google Scholar
`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 onceweekly 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 onceweekly 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. 5663 (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. 5255 (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. CryoTrans, Inc., 93 F.3d 766, 770
`(Fed.Cir.1996) (rejecting the district court's claim construction because it 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
`
`https://scholar.google.com/scholar_case?q=merck+%26+co+v+teva+&hl=en&as_sdt=2006&case=16422293572234260019&scilh=0
`
`6/15
`
`WATSON LABORATORIES, INC. , IPR2017-01621, Ex. 1121, p. 6 of 15
`
`
`
`5/17/2017
`
`1373
`
`Merck & Co. v. Teva Pharmaceuticals USA, 395 F. 3d 1364 Court of Appeals, Federal Circuit 2005 Google Scholar
`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, 1718, 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.
`
`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 onceweekly 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 onceweekly 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 coinventors on the '329
`patent — admitted against Merck's interest that a onceweekly 40 mg dose would be as effective as seven
`daily 5 mg doses, and a onceweekly 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
`onceweekly 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 sideeffect, 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 district court clearly erred in finding any significant difference between the claimed
`invention and the two articles as to this type of GI problem.
`
`1374
`
`https://scholar.google.com/scholar_case?q=merck+%26+co+v+teva+&hl=en&as_sdt=2006&case=16422293572234260019&scilh=0
`
`7/15
`
`WATSON LABORATORIES, INC. , IPR2017-01621, Ex. 1121, p. 7 of 15
`
`
`
`5/17/2017
`
`Merck & Co. v. Teva Pharmaceuticals USA, 395 F. 3d 1364 Court of Appeals, Federal Circuit 2005 Google Scholar
`The district court found a second adverse GI sideeffect related to the size of the dose, which Merck argued
`gave rise to "the expectation by physicians in the field during 19961997 that alendronate sodium at doses
`over 20 mg would not be welltolerated in the prevention and treatment of osteoporosis." Merck, 288
`F.Supp.2d at 624; see also id. at 62223, 62730 (discussing Chesnut study). Neither the '329 patent nor the
`Lunar News articles explain how a higher onceweekly dosing regimen would avoid this set of doserelated
`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 doserelated 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 peerreviewed 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 doserelated sideeffects. 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.
`
`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.
`
`https://scholar.google.com/scholar_case?q=merck+%26+co+v+teva+&hl=en&as_sdt=2006&case=16422293572234260019&scilh=0
`
`8/15
`
`WATSON LABORATORIES, INC. , IPR2017-01621, Ex. 1121, p. 8 of 15
`
`
`
`5/17/2017
`
`Merck & Co. v. Teva Pharmaceuticals USA, 395 F. 3d 1364 Court of Appeals, Federal Circuit 2005 Google Scholar
`The distric