Patent Docs

Adapt Pharma Operations Ltd. v. Teva Pharmaceuticals USA, Inc. (Fed. Cir. 2022)

By Kevin E. Noonan --

In a crowded pharmaceutical art, the deficiencies thereof being so patent that the FDA encouraged industry to address and correct them, concerning a formulation developed to address the opioid crisis raging earlier in this century (see "Empire of Pain"), when is a resulting formulation obvious over that prior art and in view of the objective indicia of nonobviousness?  This was the question facing the Federal Circuit in Adapt Pharma Operations Ltd. v. Teva Pharmaceuticals USA, Inc., the panel majority affirming a District Court decision that the claimed invention was indeed obvious.

The suit arose over Teva's submission of an ANDA for a generic version of Adapt's Narcan® product having a Paragraph IV certification over the Adapt's Orange Book Listed patents.  Adapt asserted U.S. Patent Nos. 9,468,747; 9,561,177; 9,629,965; and 9,775,838 in this litigation, which are directed to methods for treating opioid addiction by intranasal administration of naloxone (using a revised formulation of Adapt's Narcan® medication for preventing opioid overdoses).  The use of naloxone was well-known in the art at the time the patents-in-suit were filed, and there were several alternative pharmaceutical products used for this purpose.  In addition to intravenous Narcan® administration, the art also recognized intranasal administration routes using an FDA-approved atomization device (termed MAD in the opinion).  In addition, the opinion notes that Narcan® doses of 2 mg, 8 mg, and 16 mg were known in the art to be effectively administered intranasally.  These administration routes and methods had the disadvantage of being amenable for use only to trained medical personnel (for the intravenous injection route) and for requiring assembly of the MAD device which even then could deliver too much fluid in the nose.

The trial was limited to a subset of the claims of the asserted patents, specifically "claims 7 and 9 of the '747 patent; claim 4 of the '177 patent; claims 21, 24, and 25 of the '965 patent; and claims 2, 24, 33, and 38 of the '838 patent."  The District Court considered dependent claim 9 of the '747 patent to be representative, but the Federal Circuit, understanding the issues on appeal to relate to claims 1 and 2, reproduced these claims in the opinion:

1.  A method of treatment of opioid overdose or a symptom thereof, comprising nasally administering to a patient in need thereof a dose of naloxone hydrochloride using a single-use, pre-primed device adapted for nasal delivery of a pharmaceutical composition to a patient by one actuation of said device into one nostril of said patient, having a single reservoir comprising a pharmaceutical composition which is an aqueous solution of about 100 μL comprising:
    about 4 mg naloxone hydrochloride or a hydrate thereof;
    between about 0.2 mg and about 1.2 mg of an isotonicity agent;
    between about 0.005 mg and about 0.015 mg of a compound which is at least one of a preservative, a cationic surfactant, and a permeation enhancer;
    between about 0.1 mg and about 0.5 mg of a stabilizing agent; and
    an amount of an acid sufficient to achieve a pH of 3.5-5.5.

2.  The method as recited in claim 1 wherein: the isotonicity agent is NaCl;
the preservative is benzalkonium chloride; the stabilizing agent is disodium edetate; and the acid is hydrochloric acid.

(where italicized limitations are relevant to the outcome).

The District Court found that the asserted claims were invalid as being obvious over the disclosures of either of two sets of prior art references:  PCT Pub. No. WO 2000/62757 in view of U.S. Patent No. 5,866,154 and a scientific reference (designated Kerr 2009) directed to a clinical trial of intranasal versus intramuscular naloxone treatment for heroin overdose (termed "the Davies combination"); or PCT Pub. No. WO 2012/15317 in view of a first scientific review of nasal drug delivery devices and a second scientific review article on nasal spray formulations (termed the "Strang combination").  According to the Federal Circuit opinion, the '757 PCT application sets forth detailed drawings and disclosure of spray applicators for intranasal administration and particularly naloxone, wherein administration "can be carried out by an unskilled person, rapidly and with a good chance of successfully reviving a patient suffering from opioid over-dosage."  Naloxone formulations for use with the disclosed applicators can include isotonic salt solutions (specifically 0.9% NaCl) and have a "slightly acidic" pH (with pH 6.5 being exemplary).  The reference disclosed that such formulations could also include preservatives including benzalkonium chloride (BZK).  The Kerr 2009 reference disclosed specifically that intranasal of naloxone was beneficial, inter alia to reduce the risk of needlesticks in intravenous administration, and provided a comparison between administering 2 mg/mL naloxone intranasally with intramuscular naloxone injections.  The '154 patent provided evidence that including EDTA enabled naloxone formulations to be sterilized without significant degradation.

The second set of references considered by the District Court, the Strang combination, included various naloxone formulations for intranasal administration in the '317 PCT application, including 4 mg/mL concentrations of the drug in aqueous saline solution and a pH of 5.5, administered in small (100 µL) volumes.  This reference was considered in combination with a first review article regarding drug formulations for nasal naloxone administration and the effects of various excipients, including benzalkonium chloride as a preservative, EDTA as a chelating agent, and sodium chloride as a tonicity agent, having an optimal pH of between 4.5 and 6.5; and a second review article disclosing various delivery devices.  In particular, the latter article advised that drugs like naloxone are advantageously administered using single- or double-dose devices.

The parties having stipulated to infringement, the District Court entered judgment that the asserted claims were invalid and this appeal followed.

The Federal Circuit affirmed, in an opinion by Judge Stoll joined by Judge Prost; Judge Newman dissented.  Adapt based its appeal on three of the District Court's factual findings:

(1) its finding that a skilled artisan would have been motivated to combine the prior art references to arrive at the claimed invention; (2) its finding that the prior art, as a whole, does not teach away from the claimed invention; and (3) its findings related to Adapt's proffered objective indicia of nonobviousness.

With regard to the motivation to combine question, the majority expressly disagreed with Adapt's argument that the District Court erred in 'fail[ing] to articulate a reason why a skilled artisan would have been motivated to combine the prior art references to arrive at the claimed invention."  According to the opinion, the District Court's reasoning, that the skilled worker would have been motivated to "(1) formulate an intranasal naloxone product that would improve upon the MAD Kit; (2) select the claimed excipients—sodium chloride, BZK, EDTA, and hydrochloric acid for adjusting the pH—and [a prior art] device for intranasal delivery; (3) select a 4 mg dose of naloxone; and, accordingly, (4) combine the prior art references themselves" was supported by substantial evidence (the Federal Circuit noted that "the district court issued a nearly 100-page, comprehensive opinion setting forth its findings of fact and conclusions of law . . . , as well as making specific credibility determinations as to each of the witnesses that testified").  That motivation was based on the shortcomings of the prior art being sufficiently "well-known" that the FDA had encouraged industry to develop improved intranasal delivery methods (which had prompted co-plaintiff Opiant's predecessor Lightlake to develop the invention encompassed in the patents-in-suit).  These deficiencies were further supported by the prior art references Teva asserted against Adapt's patents and by expert testimony at trial.  The appropriate motivation extended, in the majority's view, to the components of the claimed formulation, based on testimony from both parties' experts and specific reference in the cited art to each claimed excipient and formuation conditions (i.e., pH).  Similarly, the majority found support in the art and evidence for the 4 mg dose.  Taken together, the majority found substantial evidence that the skilled worker would have been properly and sufficiently motivated to combine these features and elements (as part of the "interrelated teachings") to arrive at the invention claimed in the patents-in-suit, considering the Davies or Strang combination of references.

Next, the majority addressed Adapt's argument that the prior art, as a whole, taught away from the claimed invention, in particular a reference that taught against BZK as a preservative.  This reference was not relied upon otherwise and, the majority noted, was published after the earliest priority date of the patents-in-suit.  Expert testimony countered this argument at trial based on the higher (8.5-fold) BZK concentration taught in the reference, which testimony the District Court credited.  This was not error, according to the majority, and agreed the teachings of a single reference would not satisfy the teaching away standard, which depends on the rubric that an obviousness determination is made over the prior art "as a whole," citing Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006) (emphasis in opinion), further asserting that "[t]he district court, sitting as the fact finder, was entitled to consider the teachings of the prior art as a whole in finding that the prior art did not teach away from the claimed invention."

Adapt's final argument, regarding the objective indicia of nonobviousness was no more availing.  Adapt's argument on the order in which the District Court made its determinations (finding the claims to be obvious before considering evidence for the objective indicia) was not supported by In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Pat. Litig., 676 F.3d 1063, 1075–76, 1079 (Fed. Cir. 2012), in the majority's view.  That decision had been predicated on the District Court not considering all the evidence relating to the obviousness question, whereas here the District Court had not so err (indeed, the majority cited KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007), for the principle that the order in which the obviousness analysis is performed is not controlling).  The majority then considered the District Court's findings on unexpected results, copying by others, industry skepticism, and long-felt but unmet need, and failure of others (again, noting the extensiveness, over twenty pages, of the District Court's analysis in its opinion).  The majority agreed with the District Court's holding that the evidence adduced at trial did not support Adapt's contentions that the District Court had erred in not finding these objective indicia to have overcome its holding that the asserted claims were obvious (although the majority did criticize the District Court's performance of the analysis regarding long-felt need, being focused "almost entirely" of the prior art MAD kit, but said it was harmless error).

While admitting that this was a "close case," the majority concluded that the District Court's opinion was supported by substantial evidence and affirmed on that basis.

Judge Newman dissented, based in large part on her assessment of the objective indicia and in particular the long-felt but unmet need and failure of others to satisfy it.  In the Judge's opinion, the prior art contained no teaching nor suggestion for the claimed invention, all the components of which were separately known.  And Judge Newman was not convinced by the evidence that there was a sufficient motivation to combine these several elements; in the Judge's view this is "a classical example of judicial hindsight, where the invention itself is the only guide to the selections from the prior art."  The majority's error was, in the Judge's view, in taking the "existence of the separate components [to] suffice[] to find obviousness of this specific [claimed] combination" when the prior art "gave no direction as to which of the many possible combination choices were likely to be successful," citing Leo Pharm. Prods., Ltd. v. Rea, 726 F.3d 1346 (Fed. Cir. 2013).  Judge Newman also considered the majority to have provided the motivation to combine the references from "the known need for a better product" and that this was error, saying that "[t]he artisan's knowledge that the available products are deficient does not render the remedy obvious when it is eventually discovered" and that "[a] motivation to improve a product does not render the successful improvement obvious."  In addition, the prior art teachings "against" using BZK were persuasive to Judge Newman as a teaching away.  Finally, unlike the majority Judge Newman found procedural error in the District Court's assessment of the objective indicia of nonobviousness after determining the claims were obvious, and that on the merits these considerations should have led the Court to a conclusion that the claims were nonobvious.

Adapt Pharma Operations Ltd. v. Teva Pharmaceuticals USA, Inc. (Fed. Cir. 2022)
Panel: Circuit Judges Newman, Prost, and Stoll
Opinion by Circuit Judge Stoll; dissenting opinion by Circuit Judge Newman

Quest Diagnostics Investments LLC v. Hirshfeld (Fed. Cir. 2021)

By Donald Zuhn –-

Earlier today, the Federal Circuit affirmed the final determination by the U.S. Patent and Trademark Office Patent Trial and Appeal Board finding claims 1, 2, and 4-14 of U.S. Patent No. 8,409,862 unpatentable as either anticipated or obvious.

The '862 patent is directed to using mass spectrometry to detect low levels of testosterone in female humans.  The '862 patent explains that while testosterone levels are much lower in females as compared to males, testosterone can be purified prior to mass spectrometry, which can improve the limit of detection.  Claims 8 and 9, which were relevant to the appeal, require the detection of testosterone at concentrations of less than 5 ng/dL or less than 1 ng/dL in the sample, respectively.

Laboratory Corporation of America Holdings had petitioned for inter partes review of the claims found by the Board to be unpatentable, arguing that claims 8 and 9 would have been obvious in view of Clarke, an abstract found on a CD from the 49th annual conference of the American Society for Mass Spectrometry (ASMS) held in May 2001, or as obvious in view of Clarke in combination with another reference (Draisci).  The opinion notes that "Clarke details a method for detecting low levels of testosterone and describes a method similar to the '862 patent—wherein testosterone is purified before mass spectrometry."  The opinion also notes that Clarke discloses the detection of testosterone down to 50 pg/mL, which is equivalent to 5 ng/dL.

On appeal, Quest argued that the Board erred with respect to two of its findings:  first, that Clarke was valid prior art as a printed publication, and second, that claims 8 and 9 would have been obvious in light of Clarke or Clarke in combination with Draisci.  Regarding the first determination, the Board noted that the ASMS sent the CD containing Clarke (and approximately 1,600 other abstracts) to thousands of ASMS members, and that the CD was available in the University of Wisconsin-Madison library before the priority date of the '862 patent.  The Board also noted that the CD permitted users to search abstracts using certain keywords.  Regarding the second determination, the Board concluded that it would have been obvious to reach detection limits below 5 ng/dL and 1 ng/dL based on the teachings of Clarke or Clarke with Draisci, finding that a skilled artisan would have been motivated to achieve a lower level of detection and would have reached these levels by optimizing several experimental parameters (in particular, by increasing the volume of the sample and modernizing the equipment).

With regard to Clarke, Quest argued that this reference was not a printed publication because it was not publicly accessible.  In particular, Quest pointed out that Clarke was on a CD with approximately 1,600 other abstracts and that the CD provided minimal indexing, which made Clarke "an obscure, inaccessible reference."  The Federal Circuit, however, disagreed, stating that "although Clarke was surrounded by hundreds of other abstracts, the ASMS distributed the CD to the specific people most motivated to search the CD and find Clarke" (emphasis in opinion).  The Federal Circuit also noted that the CD allowed for some keyword searching using several mass spectrometry-related keywords, even if the keyword "testosterone" could not be searched.  The Federal Circuit therefore concluded that substantial evidence supported the Board's finding that Clarke was publicly available and thus prior art.

With regard to the Board's finding of obviousness with respect to claims 8 and 9, Quest argued that there was no motivation to modify Clarke to increase sensitivity, that there was no reasonable expectation of success in doing so, and that there was a documented failure of others.  The Federal Circuit first found that substantial evidence supported the Board's conclusion that there was a motivation to improve the sensitivity of methods measuring testosterone.  Quest had specifically argued that 5 ng/dL and 1 ng/dL of testosterone are below the clinically relevant range of testosterone, but the Court was unpersuaded that this would have discouraged the development of more sensitive methods.  The Court next found that substantial evidence supported the Board's finding that a skilled artisan would have had a reasonable expectation of success of achieving a lower level of detection, noting that the Board had recognized a number of parameters, including increasing the sample volume, that a skilled artisan could have modified to reach 5 ng/dL or 1 ng/dL detection.  Finally, the Court was unpersuaded by Quest's argument that Kushnir et al., 52(1) CLIN. CHEM. 120–28 (2006), demonstrated a failure of others to reach detection levels of 5 ng/dL or 1 ng/dL without derivatizing testosterone.  "Given the deferential standard of review, as well as the differences in Kushnir's detection method relative to the claims at issue," the Board "decline[d] to say that the Board erred in determining that Kushnir fails to establish nonobviousness."  The Federal Circuit therefore found that substantial evidence supported the facts underlying the Board's conclusion that claims 8 and 9 would have been obvious in view of Clarke.

Finding that substantial evidence supported both of the Board's findings that were challenged by Quest, the Federal Circuit affirmed the Board's finding that claims 1, 2, and 4–14 of the '862 patent were unpatentable as either obvious or anticipated.

Quest Diagnostics Investments LLC v. Hirshfeld (Fed. Cir. 2021)
Nonprecedential disposition
Panel: Chief Judge Moore and Circuit Judges Clevenger and Chen
Opinion by Circuit Judge Chen

Teva Pharmaceuticals USA, Inc. v. Corcept Therapeutics, Inc. (Fed. Cir. 2021)

By Kevin E. Noonan --

There are some cases where the Federal Circuit makes its decision based on the eternal verities of patent law (insofar as there are any eternal verities in patent law).  One such decision arose earlier this month when the Federal Circuit affirmed a determination of non-obviousness by the Patent Trial and Appeal Board in an inter partes review proceeding, that opinion captioned Teva Pharmaceuticals USA, Inc. v. Corcept Therapeutics, Inc.

The case arose incident to ANDA litigation between the parties involving Corcept's Korlym product comprising the active pharmaceutical ingredient mifepristone for treating Cushing's Syndrome.  The drug had been recognized since the 1980's as an antiprogestin compound, but its relevant effect in vivo turned out to be as a glucocorticoid reception antagonist, which suggested its use against Cushing's (which was known to be caused by excessive levels of cortisol).  Corcept obtained FDA approval for the drug contingent on its performance of a post-marketing study under the provisions of 21 U.S.C. § 355(o)(3), one of which was to conduct "[a] drug-drug interaction clinical trial to determine a quantitative estimate of the change in exposure of mifepristone following co-administration of ketoconazole (a strong CYP3A4 inhibitor)."  The agency provided a description of the basis for this study, which included information such as ignorance in the art regarding the "degree of change" in exposure to mifepristone in the presence of drugs like ketoconazole and the potential safety risk that could arise.  Important to the issues before the Court was Korlym's approved label, which recommended a starting dose of 300 mg/day that could be increased in increments to 1200 mg/day, and a caveat that administration of the drug should be limited to 300 ng/day in the presence of strong CYP3A inhibitors.

Corcept performed the required study and obtained patent protection on the resulting treatment method, U.S. Patent No. 10,195,214; claim 1 is representative:

A method of treating Cushing's syndrome in a patient who is taking an original once-daily dose of 1200 mg or 900 mg per day of mifepristone, comprising the steps of:
    reducing the original once-daily dose to an adjusted once-daily dose of 600 mg mifepristone,
    administering the adjusted once-daily dose of 600 mg mifepristone and a strong CYP3A inhibitor to the patient,
    wherein said strong CYP3A inhibitor is selected from the group consisting of ketoconazole, itraconazole, nefazodone, ritonavir, nelfmavir, indinavir, boceprevir, clarithromycin, conivaptan, lopinavir, posaconazole, saquinavir, telaprevir, cobicistat, troleandomycin, tipranivir, paritaprevir, and voriconazole.

The basis for Teva's IPR challenge was that this claim was obvious over Korlym's label in combination with the FDA study memorandum (which the opinion refers to as "Lee"), further and optionally in combination with FDA guidance documents on drug-drug interactions.

The Board found that Teva had not satisfied its burden of showing obviousness by a preponderance of the evidence, specifically a showing that "a skilled artisan would have had a reasonable expectation of success for safe co-administration of more than 300 mg of mifepristone with a strong CYP3A inhibitor."  The Board's decision also specifically discredited Teva's expert's declaration and testimony to the contrary.  This appeal followed.

The Federal Circuit affirmed, in a decision by Chief Judge Moore joined by Judges Newman and Reyna.  The opinion sets forth the bases for Teva's appeal as first, that the Board required "precise predictability" from the prior art in achieving the claimed invention (instead of a reasonable expectation of success) and second, that the issue involved "range" precedents that the Board did not apply (for recent examples, see Biogen Int'l GmbH v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2021), and Indivior UK Ltd. v. Dr. Reddy's Laboratories S.A. (Fed. Cir. 2021)).  As can be her wont, the Chief Judge summarized the panel's opinion in the simple phrase "[w]e do not agree" with either of these arguments.

With regard to the "reasonable expectation of success" argument, the opinion notes that the existence of the expectation is a question of fact requiring substantial evidence (although noting that the ultimate obviousness determination is a question of law subject to de novo review).  The issue, according to the Federal Circuit, was whether the skilled artisan would have had a reasonable expectation of success in achieving the invention as claimed with regard to the specific mifepristone dose (600 mg/day) in combination with a strong CYP3A inhibitor.  What the skilled worker would have lacked, according to the panel, was such a reasonable expectation that administering more than 300 mg/day in the presence of a strong CYP3A inhibitor would be safe.  Indeed, the Board went so far as to say the skilled worker would have had "no expectation" of such success in view of the cited art (keeping in mind the statements in Lee regarding the safety of the combination of mifepristone and a strong CYP3A inhibitor being unknown).  The Federal Circuit found these circumstances to be dispositive on this issue, citing Honeywell Int'l Inc. v. Mexichem Amanco Holding S.A. DE C.V., 865 F.3d 1348, 1356 (Fed. Cir. 2017), for the principle that where there is no expectation of success there can be no reasonable expectation of success.  The opinion specifically addressed Teva's expert's testimony, regarding what the Court considered contradictory statements prior to IPR institution ("it was reasonably likely that 600 mg [per day of mifepristone] would be well tolerated and therapeutically effective") and afterwards (wherein the expert stated "unequivocally" that "a skilled artisan 'would have no expectation as to whether the co-administration of 600 mg of mifepristone with ketoconazole would be safe'").

Next considering Teva's range argument, the panel set forth its basis for rejecting the argument, that "Teva had failed to prove the general working conditions disclosed in the prior art encompass the claimed invention."  This is based on the Court's precedent that "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," citing E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018).  The "general working conditions" under consideration in the Court's range cases involved instances where "prior art ranges and claimed ranges either overlap or are close enough such that one skilled in the art would have expected them to have the same properties," citing, inter alia, Valeant Pharms. Int'l, Inc. v. Mylan Pharms. Inc., 955 F.3d 25, 32 (Fed. Cir. 2020).  Instead of a range the Board found, the prior art here recited a particular dose (300 mg/day), a conclusion the Federal Circuit held was supported by substantial evidence including the Korlym label and certain industry publications not specifically referenced in the opinion that voiced consistent limitations on mifepristone doses in the presence of strong CYP3A inhibitors.  Relying on the Board's findings on reasonable expectation of success the panel rejected Teva's argument that prior art monotherapy (i.e., mifepristone doses in the absence of strong CYP3A inhibitors) supported their obviousness argument on the basis that the skilled worker would have had no expectation of success regarding combination therapy based on these monotherapies.

As for those eternal verities, the ones applied by the Federal Circuit here were the requirement for a showing that the skilled worker would have had a reasonable expectation of success in achieving the claimed invention in view of the asserted prior art, and that decisions of the Board on questions of fact supported by substantial evidence are difficult if not almost impossible for the Federal Circuit to overturn (see, for example, Qiagen North America Holdings Inc. v. Handylab, Inc. (Fed. Cir. 2021); Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co., Eli Lilly & Co. v. Teva Pharmaceuticals Int'l GmbH, and Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co. (Fed. Cir. 2021); Trustees of Columbia University v. Illumina, Inc. (Fed. Cir. 2021); and In re Fulton (Fed. Cir. 2021), but see, Chemours Company FC, LLC v. Daikin Industries, Ltd. (Fed. Cir. 2021)).  In this way the Court's decision was unremarkable except as an example of these fundamental principles.

Teva Pharmaceuticals USA, Inc. v. Corcept Therapeutics, Inc. (Fed. Cir. 2021)
Panel:  Chief Judge Moore and Circuit Judges Newman and Reyna
Opinion by Chief Judge Moore

Horizon Medicines LLC v. Alkem Laboratories Ltd. (Fed. Cir. 2021)

By Kevin E. Noonan --

Joint inventorship has been called "one of the muddiest concepts in the muddy metaphysics of patent law" because the "exact parameters of what constitutes joint inventorship are quite difficult to define."  Mueller Brass Co. v. Reading Indus., 352 F. Supp. 1357, 1372 (E.D. Pa. 1972), aff'd, 487 F.3d 1395 (3d Cir. 1983).  The consequences of an improper (or improvident) determination of inventorship (and the sometime difficulties that can arise when a change of inventorship is delayed until a patent is being asserted at trial) is illustrated in the Federal Circuit's recent non-precedential decision in Horizon Medicines LLC v. Alkem Laboratories Ltd.

The matter arose in ANDA litigation over Horizon's DUEXIS^® product, an NSAID formulation used for administration to rheumatoid arthritis and osteoarthritis patients.  According to the opinion, the prior art recognized that chronic use of NSAIDs at dosages useful for pain relief and inflammation (such as ibuprofen, a "non-selective" NSAID) produced stomach ulcers.  (In a footnote the opinion sets forth a distinction between non-selective NSAIDs, which inhibit both known forms of cyclooxygenase (COX), and "selective" NSAIDs, which only recognize the COX species that are not present in the mucus lining of the stomach and thus are not associated with stomach ulcers.)  However, selective NSAIDs were found to be disadvantageous due to cardiovascular complications associated with their use.  Horizon's claimed non-selective NSAID formulations avoided the ulcer-producing effects of non-selective NSAID administration by co-formulation with famotidine.  In ANDA litigation Horizon asserted U.S. Patent Nos. 8,067,033 and 8,067,451; claim 1 of each patent was set forth in the opinion as being representative:

'033 patent:

1.  A pharmaceutical composition comprising
    a first portion that comprises 800 mg ibuprofen and a second portion that comprises 26.6 mg famotidine,
    wherein the surface area of direct physical contact between ibuprofen and famotidine does not exceed 130 mm²,
    wherein no more than about 1% sulfamide is present when the composition is stored at 40°C and 75% relative humidity for a period of one month,
    wherein the composition is formulated so that release of both the ibuprofen and the famotidine occurs rapidly at about the same time,
    wherein none of the composition, the famotidine, and the ibuprofen is enterically coated or formulated for sustained or delayed release, and
    wherein the composition is for use according to a TID (three times per day) administration schedule for reducing the risk of developing ibuprofen-induced ulcers in a human patient requiring ibuprofen for an ibuprofen-responsive condition.

'451 patent:

1.  An oral dosage in tablet form comprising
    a first portion that comprises 800 mg ibuprofen and a second portion that comprises 26.6 mg famotidine,
    wherein a barrier layer comprising hydroxyl propyl methyl cellulose 2910, polyoxyethylene glycol 400, polysorbate 80, and titanium dioxide surrounds the second portion completely separating it from the first portion . . .

Relevant to the District Court's determinations, use of the combination of a non-selective NSAID and famotidine was known in the art to reduce stomach ulceration upon prolonged use.  The opinion explains that this advantageous combination was also known to degrade due to chemical incompatibility between these two compounds.  The claimed formulations achieved their greater stability by minimizing the surface area of direct physical contact between the incompatible ingredients; as set forth in the opinion the product contained "a famotidine core, an ibuprofen shell, and an Opadry® White barrier layer in between."

The District Court found the asserted claims (claims 1, 8, 11, and 14) of the '033 patent to be invalid for obviousness and the asserted claims (claims 1–3 and 8–10) of the '451 patent not to be infringed.  Horizon appealed.

The Federal Circuit affirmed the District Court's invalidity and non-infringement determinations in an opinion by Judge Dyk joined by Judges O'Malley and Hughes.  The District Court's obviousness determination was based on U.S. Patent Application Pub. No. 2007/0043096 A1, which Horizon argued was not properly prior art and thus the District Court had committed legal error in considering it to be so.  Because the patents-in-suit and the cited prior art patent application were filed prior to enactment of the Leahy-Smith America Invents Act, the District Court and Federal Circuit applied the novelty provisions of the 1952 Patent Act in finding the '096 application to be prior art.  The '033 patent names Inventor Tidmarsh while the '096 application names Tidmarsh and a second inventor, Golombik.  (In a footnote the Federal Circuit explains there were additional inventors named in each but that their status did not need to be resolved because resolution of the Tidmarsh/Golombik inventorship status was outcome determinative.)  At trial Horizon moved under 35 U.S.C. § 256 to add Golombik as an inventor on the '033 patent, a motion the district court denied.  Horizon's argument on appeal was that if Tidmarsh and Golombik had invented formulations comprising 800 mg ibuprofen and 26.6 mg famotidine (as set forth in the '096 application) then both inventors perforce were also inventors of the invention described and claimed in the '033 patent (which recites formulations comprising 800 mg ibuprofen and 26.6 mg famotidine).  The Federal Circuit rejected this argument.  The opinion notes that generally "the inventors named in an issued patent are presumed to be correct" and this presumption can be overcome only in the face of clear and convincing evidence, citing Caterpillar Inc. v. Sturman Indus., Inc., 387 F.3d 1358, 1377 (Fed. Cir. 2004).  Mere inventor testimony is not enough to overcome this presumption, according to the Court, and "some form of corroboration must be shown"; see EmeraChem Holdings, LLC v. Volkswagen Grp. of Am., Inc., 859 F.3d 1341, 1346 (Fed. Cir. 2017) (similar considerations provide the rationale for like requirements in interferences; see, Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1171 (Fed. Cir. 2006)).  Moreover, the opinion states that "[o]ur cases are clear that inventing something in an earlier patent or patent application does not automatically make one an inventor of patents that incorporate the earlier invention," citing Eli Lilly and Co. v. Aradigm Corp., 376 F.3d 1352, 1358, 1362 (Fed. Cir. 2004).  The Court was unpersuaded by Horizon's reliance on Pannu v. Iolab Corp., 155 F.3d 1344 (Fed. Cir. 1998), to the effect that Tidmarsh and Golombik were engaged in a "collaborative enterprise," on the grounds that unlike in Pannu "[t]he only support for Golombik's contribution to the '033 patent is testimony by Tidmarsh and Golombik."  The Federal Circuit found no clear error by the District Court based on the totality of the evidence, including putative inventor testimony (which the District Court had characterized as "non-specific," "convenient, uncorroborated, and not very credible").

The Federal Circuit also rejected Horizon's non-obviousness arguments taking the '096 application as proper prior art.  These arguments were grounded on whether the skilled worker would have had a reasonable expectation of success in achieving formulations having the stability of the claimed formulations.  This expectation arose, according to the District Court as affirmed by the Federal Circuit, from another prior art reference that disclosed using the same "tablet-in-tablet" formulation claimed in the '033 patent to achieve increased stability for combinations of drugs "similar to ibuprofen and famotidine" (as supported by expert witness testimony).  The Federal Circuit found no clear error in these District Court determinations either.

And the Federal Circuit dismissed consideration of Horizon's arguments regarding non-infringement of the '033 patent as moot in view of their affirmance of the invalidity of the '033 patent's asserted claims.

Regarding the '451 patent, Horizon argued that the District Court erred in construing the term "comprising" as recited in the claim with regard to the barrier layer limitation to mean "consisting essentially of."  The Federal Circuit rejected this argument, first, because the panel held that Horizon had not established harmful error in its briefing, and second, "the prosecution history of the '451 patent supports the district court's construction."  Specifically, the opinion points to "multiple exchanges with the Examiner" where Horizon made amendments to overcome rejections over the prior art that purportedly "focus[ed] on an embodiment of the invention that uses Opadry® White (YS-1-7003) as a barrier layer."  In view of this history the panel found no clear error in the District Court's construction nor the factual basis for its finding of non-infringement.

Horizon Medicines LLC v. Alkem Laboratories Ltd. (Fed. Cir. 2021)
Nonprecedential disposition
Panel: Circuit Judges Dyk, O'Malley, and Hughes
Opinion by Circuit Judge Dyk

Qiagen North America Holdings Inc. v. Handylab, Inc. (Fed. Cir. 2021)

By Kevin E. Noonan --

The inter partes review (IPR) provisions of the Leahy-Smith America Invents Act have been castigated by many for the propensity of the Patent Trial and Appeal Board (PTAB) to find claims challenged in these proceedings to be anticipated or obvious (albeit this outcome has been less frequent for technologies in chemical and life sciences patents).  Perhaps one reason for this less predictable negative outcome in these technologies is the countervailing (to some extent) deference the Federal Circuit has been compelled to give Patent and Trademark Office decisions on factual questions (see Dickinson v. Zurko), and the reliance of anticipation and obviousness rejections on the facts adduced by the parties in IPRs.  These considerations came into play recently in the Federal Circuit's non-precedential opinion in Qiagen North America Holdings Inc. v. Handylab, Inc., affirming the PTAB's Final Written Decision (FWD) finding that the claims challenged in the proceeding were non-obvious.

The IPRs at issue challenged the claims of Handylab's U.S. Patent No. 7,998,708 and U.S. Patent No. 8,323,900, which are directed to microfluidic systems for amplifying polynucleotides in parallel, i.e., a high throughput screening system for performing reactions like the polymerase chain reaction (PCR) on several samples at the same time.  Claim 1 of the '708 patent was reproduced in the opinion as representative of the challenged claims:

1.  An apparatus, comprising:
    a multi-lane microfluidic cartridge, each lane comprising a PCR reaction zone;
    a receiving bay configured to receive the microfluidic cartridge;
    each PCR reaction zone comprising a separately controllable heat source thermally coupled thereto, wherein the heat source maintains a substantially uniform temperature throughout the PCR reaction zone and thermal cycles the PCR reaction zone to carry out PCR on a polynucleotide-containing sample in the PCR reaction zone;
    a detector configured to detect the presence of an amplification product in the respective PCR reaction zone; and
    a processor coupled to the detector and the heat source, configured to control heating of one or more PCR reaction zones by the heat sources.

Petitioner Qiagen asserted U.S. Patent No. 6,509,186 in asking the PTAB to find the challenged claims obvious.  That reference, according to the opinion, disclosed "a thermal cycler which permits simultaneous treatment of multiple individual samples in independent thermal protocols, so as to implement large numbers of DNA experiments simultaneously in a short time."  Importantly, the Federal Circuit characterized the '186 patent teachings as disclosing a standalone "multi-chamber thermal cycler chip" having thermally isolated chambers.  Qiagen contended that this reference in combination with U.S. Patent Publication No. 2004/0037739 A1 or U.S. Patent Publication No. 2004/0151629 would render the '708 claims obvious, and the '186 patent in combination with the '739 application or U.S. Patent Publication No. 2002/0055,167 would render obvious the challenged claims of the '900 patent.

The Board's claim construction was relevant to its determination, wherein the phrase "multi-lane microfluidic cartridge" was construed to mean "a microfluidic cartridge comprising a plurality of sample lanes, each sample lane comprising a separate sample inlet and microfluidic network."  Under this construction the Board found Petitioner Qiagen had failed to establish obviousness for any of the challenged claims by a preponderance of the evidence on two independent bases.  First, the Board held that the '186 patent did not teach a multilane microfluidic cartridge, because the '186 cartridge was configured having all lanes in fluid communication with a single sample inlet comprising a common reservoir.  None of the other references asserted by Qiagen remedied this deficiency according to the Board's FWD.  The second basis for the Board's non-obviousness determination was that the skilled worker would not have been motivated to combine the prior art references with any reasonable expectation of success, the Petition (in the Board's view) providing only "a single conclusory statement" in this regard.  The Board was convinced by Handylab's expert who testified that developing a microfluidic device as claimed was "a very complex endeavor that presented [numerous] challenges."  Finally, there was an evidentiary dispute wherein the Board refused to consider a Qiagen Exhibit because it was not submitted with the Petition.  This appeal followed.

The Federal Circuit affirmed, in an opinion by Judge Clevenger, joined by Judges Taranto and Chen.  The opinion begins with the Court's determination regarding the Board's conclusion that the skilled worker would not have had a reasonable expectation of success in combining the asserted references to achieve the claimed invention.  The panel found substantial evidence supporting the Board's conclusion; indeed, the Court's finding in this regard was sufficient for the panel not to reach any of the other issues in the appeal.

First, however, the Court considered whether the Board had properly refused to consider the unsubmitted Exhibit (because this decision impacts the scope of the evidence considered by the Board in reaching its conclusion).  Applying an abuse of discretion standard, the panel considered whether Qiagen had satisfied the requirements need to show an abuse of discretion, which according to the opinion only arises if the decision:

(1) is clearly unreasonable, arbitrary, or fanciful; (2) is based on an erroneous conclusion of law; (3) rests on clearly erroneous fact findings; or (4) follows from a record that contains no evidence on which the Board could rationally base its decision,

citing VidStream LLC v. Twitter, Inc., 981 F.3d 1060, 1064 (Fed. Cir. 2020), quoting Shu-Hui Chen v. Bouchard, 347 F.3d 1299, 1307 (Fed. Cir. 2003).  Under the statutes and regulations governing IPRs, the opinion asserts, a petition must set forth "the evidence that supports the grounds for the challenge to each claim, including [copies of] printed publications that the petitioner relies upon in support of the petition," citing 35 U.S.C. § 312(a)(3), 37 C.F.R. § 42.22(a)(2) and 37 C.F.R. § 42.104(b)(5).  The panel opines that Qiagen could have submitted the absent exhibit but did not, nor did the petition "address the general state of the art of the relevant field" (Qiagen contending it was not necessary).  Under these circumstances the Federal Circuit held that there was no abuse of discretion in the Board refusing to consider the missing exhibit, particularly in view of the "expedited nature" of IPRs operating under a one-year limit for the Board to render a decision, citing Henny Penny Corp. v. Frymaster LLC, 938 F.3d 1324, 1330 (Fed. Cir. 2019), and the PTO's PTAB Consolidated Patent Trial Practice Guide (Nov. 21, 2019).  The panel rejected Qiagen's argument that the Board should have considered the missing exhibit on rebuttal because the exhibit was not relevant to the rebuttal arguments Qiagen made (relating to the asserted published applications) but rather asserted the missing exhibit to address the disclosure of the '186 patent reference.

Having determined that the scope of evidence properly relied upon by the Board in making its non-obviousness determination to be (primarily) each parties' expert witness testimony, the panel held that there was substantial evidence supporting the Board's holding, including that "Qiagen's Petitions contained only 'a single reference to reasonable expectation of success, in a conclusory statement that "a POSA would have been motivated to combine the multiplexing PCR unit of [the '186 patent] with a conventional integrated machine such as in [the cited published patent applications]'" with a high expectation of success.'"  The testimony of Qiagen's witness did not remedy this lack of evidence on the point, the Board holding that the expert's testimony was "similarly conclusory" (to be fair, perhaps because by denying entry of the missing exhibit into evidence Qiagen's expert did not have a basis to make such statements in his testimony).  The Board also relied on positive evidence in the form of Handylab's expert, who provided the basis for the Board's determination that "the development of microfluidic PCR devices was not routine and predictable by March 2006, but rather a very complex endeavor that presented challenges with regard to uniform heating, detection of small volume reactions, contamination, design and configuration of a microfluidic network, and functionally interfacing the reaction instrument with control machinery," that basis being inter alia supported by citation to "numerous contemporary publications in the field."  Moreover, the opinion asserts, "Qiagen provide[d] no basis for overruling the Board's credibility determinations."  Coupled with what the panel concluded was "substantial evidence" the Federal Circuit held that the Board's conclusion regarding the complexity of developing microfluidic PCR devices supported the Board's determination that Qiagen had not shown that the skilled worker would have had a reasonable expectation of success for Qiagen to have shown the challenged claims were obvious by a preponderance of the evidence.

Qiagen North America Holdings Inc. v. Handylab, Inc. (Fed. Cir. 2021)
Nonprecedential disposition
Panel: Circuit Judges Taranto, Clevenger, and Chen
Opinion by Circuit Judge Clevenger

Snyders Heart Valve LLC v. St. Jude Medical, LLC (Fed. Cir. 2021)

By Kevin E. Noonan --

The Supreme Court's decision in United States v. Arthrex, Inc., 141 S. Ct. 1970 (2021), at the end of its last term resulted in many cases with pending certiorari petitions that were based on Appointment Clause challenges to be remanded to the Federal Circuit, and many (if not most) of those were remanded back to the Patent Trial and Appeal Board.  The decision handed down by the Federal Circuit on Tuesday in Snyders Heart Valve LLC v. St. Jude Medical, LLC is an exception, the Court considering the appeal on the merits and reversing the Board's determination that St. Jude had shown by a preponderance of the evidence that challenged claims 1–3, 8, 9, 22, 23, 31–35, 37–39, and 45 of U.S. Patent No. 6,821,297 were invalid as being either anticipated by U.S. Patent No. 5,855,601 to Bessler or obvious over the '601 patent "in combination with other prior art references."

This is the second appeal of several IPRs between the parties; in an earlier case, St. Jude Medical, LLC v. Snyders Heart Valve LLC (Fed. Cir. 2020), the Board found Snyders' U.S. Patent No. 6,540,782, directed to an artificial heart valve and systems for introducing the valve, to be neither anticipated over U.S. Patent No. 5,957,949 nor rendered obvious over a combination of the '949 patent with U.S. Patent No. 4,339,831 to Johnson and U.S. Patent No. 5,413,599 to Imachi.  The Federal Circuit affirmed this decision.  In the same appeal, the Federal Circuit reversed the Board's finding that certain of the challenged claims of the '782 patent were anticipated by the Bessler '601 patent based on erroneous claim construction.

In this case, the Court proceeded to a decision on the merits because "all parties agree[d] that Snyders ha[d] waived its Appointments Clause challenge and that remand to the Patent Office for Director review is not proper."  But the parties differed, with Snyder asking the Court to reverse based on its decision in the earlier appeal and St. Jude asking that the case be remanded to the Board for its reconsideration in the first instance in view of the intervening Federal Circuit decision.

The Court agreed with Snyders and rendered a decision reversing the PTAB on the same basis that the Board's unpatentability decision was reversed in the earlier appeal, in a decision by Judge O'Malley joined by Judges Newman and Taranto (this was the same panel that heard the earlier appeal; there, Judge Taranto wrote the unanimous opinion).  The panel reiterated in brief their reasons for reversing the Board in its earlier decision, which bears at least a synopsis here.  According to that earlier opinion, the '782 patent disclosed and claimed an artificial heart valve that can be administered using a catheter (thereby forgoing open heart surgery) and can be placed without removing the patient's damaged valve.  The opinion asserted that the claimed artificial valve has three components: "a valve element, a frame, and a band."  System claims for introducing the valve recite components for installing the artificial valve comprising "a holder, a manipulator, and an ejector."

Claim 1 of the '782 patent is representative of the artificial heart valve claims at issue:

1.  An artificial valve for repairing a damaged heart valve having a plurality of cusps separating an upstream region from a downstream region, said artificial valve comprising:
a flexibly resilient frame sized and shaped for insertion in a position between the upstream region and the downstream region, the frame having a plurality of peripheral anchors for anchoring the frame in the position between the upstream and the downstream region and a central portion located between the plurality of peripheral anchors;
    a band attached to the frame limiting spacing between adjacent anchors of said plurality of peripheral anchors; and
    a flexible valve element attached to the central portion of the frame and adjacent the band, said valve element being substantially free of connections to the frame except at the central portion of the frame and adjacent the band, said valve element having an upstream side facing said upstream region when the frame is anchored in the position between the upstream region and the downstream region and a downstream side opposite the upstream side facing said downstream region when the frame is anchored in the position between the upstream region and the downstream region, said valve element moving in response to a difference between fluid pressure in said upstream region and fluid pressure in said downstream region between an open position in which the element permits downstream flow between said upstream region and said downstream region and a closed position in which the element blocks flow reversal from said downstream region to said upstream region, wherein the valve element moves to the open position when fluid pressure in said upstream region is greater than fluid pressure in said downstream region to permit downstream flow from said upstream region to said downstream region and the valve element moves to the closed position when fluid pressure in said downstream region is greater than fluid pressure in said upstream region to prevent flow reversal from said downstream region to said upstream region [relevant claim limitations in italics].

Relevant to the Court's decision in this appeal, and with regard to the Board's decision on the second IPR challenging claims of the '782 patent, the Federal Circuit found error in the Board's construction of the term "how the frame is sized and shaped," which Snyders had argued was incorrect because "it covers frames sized and shaped for installation with the native valve removed, rather than only with the troubled native valve remaining in place."  With regard to this limitation, the Board had found that "'[t]he claim language does not require the frame be sized and shaped for insertion into a damaged heart valve,' but 'only that the frame is sized and shaped for insertion in a position between the upstream region and the downstream region.'"  This was error in the panel's view because the Board did not consider the further disclosure in the '601 patent that the native valve was required to be replaced, which the challenged '782 patent claims expressly did not require.  The panel opinion found support for the argument that structural features of the claimed artificial valve were consistent with this lack of a requirement for native valve removal in the plain meaning of the claim language, as well as express disclosure to that effect in the '782 specification.  Specifically, the specification disclosed that "the frame is sized and shaped for insertion between the plurality of cusps C of the damaged heart valve in a position between an upstream region and a downstream region" (emphasis in opinion).  The significance for the Court was that this language indicated that the term "sized and shaped" "is not meant to refer only to placement in a position between the upstream and downstream regions, but also to fitting between the cusps of the intact native valve."  This interpretation is consistent, according to the opinion, with further disclosure in the '782 specification of the benefit of not needing to remove the native heart valve as an improvement over the prior art and in particular the deficiencies in the '601 patent in this regard.  Because the '601 patent did not meet the "size and shape" limitation as construed by the Federal Circuit, the panel reversed the Board's determination that the '782 patent claims were invalid for anticipation.

In this appeal, the Court rejected St. Jude's argument for remand that there were differences between the '782 and '297 patents relevant to the Court's decision.  The opinion states that "[t]he claims and written descriptions in the two patents are the same in all relevant respects" and accordingly the Court's construction of the "sized and shaped" limitation in the claims of the '782 patent govern proper construction of the claims of the '297 patent at issue here.  Even though the Court recognized that the written descriptions in the two specifications are not identical the Court asserted that "all portions of the '782 written description which we found 'resolve[] the interpretive question' of the proper construction of the 'sized and shaped' limitation appear in the '297 patent's written description."  The Court dismissed St. Jude's other obviousness arguments as being "vague" or that they did not overcome Snyders' arguments to the contrary based on the structure of the replacement valves or that the arguments were directed to limitations other than the "sized and shaped" limitation that the Court considered dispositive.  The panel concluded that:

[A]s in [the panel's earlier decision], our rejection of the Board's claim construction of 'sized and shaped for insertion' precludes an unpatentability finding as to the challenged claims of the '297 patent.  St. Jude relied only on its now rejected claim construction argument before the Board.  It never disputed Snyders' assertion that Bessler requires removal of the native valve before insertion of its valve.  Thus, St. Jude has not preserved any argument on which it might prevail.

On this basis the Federal Circuit reversed the Board invalidity findings.

Snyders Heart Valve LLC v. St. Jude Medical, LLC (Fed. Cir. 2021)
Nonprecedential disposition
Panel: Circuit Judges Newman, O'Malley, and Taranto
Opinion by Circuit Judge O'Malley

C.R. Bard, Inc. v. Medline Industries, Inc. (Fed. Cir. 2021)

By Kevin E. Noonan --

In a nonprecedential decision, the Federal Circuit gave a mixture of success and failure to the parties in four separate inter partes review decisions by the Patent Trial and Appeal Board, in C.R. Bard, Inc. v. Medline Industries, Inc.

The case arose in IPRs instituted in response to a challenge by Bard involving three Medline Patents:  U.S. Patent No. 9,745,088 (wherein claims 1, 2, 6–10, 16–19, 25–58, 60–74, 76–90, and 92 were challenged); U.S. Patent No. 9,808,596 (claims 7–16 and 21–22 challenged); and U.S. Patent No. 9,795,761 (claims 1–19 and 22–25 challenged).  The claims are directed to trays designed to store urinary catheterization tools, which include a lubricant syringe, an inflation syringe, and a fluid receptable.  They are useful in avoiding catheter-Associated Urinary Tract Infections (CAUTI), inter alia, by providing an organized, sterilized surface for the components used in catheterization according to a standardized protocol; a tray according to the invention is illustrated as Figure 7 of the '088 patent:

The opinion sets forth the aspects of the invention claimed in the patents challenged in each IPR:

• claims 1, 25, and 45 are representative of the '088 patent.  Claims 1 and 25 are generally directed to a tray with two syringes positioned at different heights.  Claim 45 is directed to a tray with two syringes in one compartment;

• claims 7 and 9 are representative of the '596 patent.  Claim 7 is directed to a tray with a fluid receptacle positioned between the base and the catheter.  Claim 9 is directed to a tray with a compartment configured to receive lubricant; [and]

• claim 10 is representative of the '761 patent and is directed to a tray with a lubricating jelly application chamber.

Bard challenged the claims of these patents for being obvious over four prior art references, each of which were (not surprisingly) directed to medical kits or trays:

• U.S. Patent No. 7,278,987 (Solazzo) disclosed a tray as set forth in Figures 2 and 8 below;

The relevant features are the two compartments in Figure 8 holding respectively an inflation syringe and a Foley catheter and tube of lubricant, the compartments separated by a divider that can be removed.  Also, as illustrated in Figure 2, the bottom of the container has "deep" and "shallow" sections.

• U.S. Patent No. 3,329,261 (issued July 4, 1967 to Serany) disclosed a catheterization package containing components stored in their "proper order of use" to "assure that a sterile field may be maintained as the components are removed."

• U.S. Patent No. 3,166,189 (issued January 19, 1965 to Disston) disclosed a catheterization tray which, like Serany, has the components "arranged in such order and position as to be most conveniently available when the container is opened."

• Japanese Patent No. 2007-229520 to Imai disclosed an epidural anesthesia tray containing three syringes in a single compartment.

The Board's decisions, that the cited art did not establish by a preponderance of the evidence that the challenged claims were obvious, is synopsized in a table in the opinion:

None of the PTAB's opinion discussed either party's arguments regarding secondary considerations (or objective indicia) of non-obviousness and the opinions addressed similar arguments that the Court considered in this single appeal.

The Federal Circuit affirmed-in-part, vacated-in-part and remanded, in an opinion by Judge Lourie, joined by Judges Bryson and Chen.  Bard argued that the Board erred and urged the Court to reverse the decisions without remand and without consideration of secondary considerations, while Medline argued that the decision should be affirmed on the grounds that the references were incompatible with one another (grounds the Board did not consider in any of the IPR proceedings, and regarding which Medline conceded at oral argument they were collaterally estopped from advocating on appeal).

The opinion took the Board decision on each patent in turn.  Regarding the '088 patent, Claim 45 was representative:

A medical procedure kit, comprising:
    a single layer tray having a first compartment for receiving syringes and a second compartment for receiving a medical assembly;
    a first syringe and a second syringe disposed within the first compartment;
    the medical assembly disposed in the second compartment, wherein the medical assembly comprises a coiled tubing coupled between a fluid drain bag and a Foley catheter;
    at least one layer of wrap material enclosing the single layer tray within one or more folds of the at least one layer of wrap material; and
    an outer packaging disposed about both the single layer tray and the at least one layer of wrap material.

(wherein the italicized limitations were relevant to the appeal).  The basis for the Board's non-obviousness determination was that it was not obvious to store two syringes in one compartment in view of the prior art.  The rationale for Bard's argument was that the Solazzo reference disclosed two syringes but was silent as to the location of one of them, and that it would have been obvious to put both in one compartment consistent with the disclosure that the components in the prior art tray were arranged "in logical step-by-step order."  This conclusion was also supported according to Bard by the disclosure in Disston that components should be arranged in an order that they are "most conveniently available" upon use.

The panel asserts that they agree with Bard on this issue, on the ground that there were only two alternatives (putting the two syringes together or separately) and the skilled artisan could have availed herself of the option of putting the syringes together.  "When two equally viable options are available, as here, then, without more, either one would seem to have been obvious" according to the Court's opinion.  The opinion criticizes the Board's application of the law as being "rigidly focused" on the disclosures of each prior art reference without taking into account the "creativity[] and common sense" of a person of ordinary skill in the art, citing KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415, 417 (2007), and Randall Mfg. v. Rea, 733 F.3d 1355, 1362 (Fed. Cir. 2013).  On this basis, the Court vacated the Board's decision regarding claims 45–58, 60–74, 76–90, and 92 of the '088 patent and remanded for further considerations.

The opinion next considered the Board's obviousness determination regarding claims 1 and 25 of the '088 patent; claim 1 recites:

A medical procedure kit, comprising:
    a tray having a compartment for receiving a medical assembly;
    a first syringe and a second syringe disposed within the tray;
    at least one layer of wrap material enclosing the tray within one or more folds of the at least one layer of wrap material; and
    an outer packaging disposed about both the tray and the at least one layer of wrap material, wherein:
    the first syringe and the second syringe are ordered within the tray in accordance with their use during a catheterization procedure; and
    the tray comprises a surface defining at least two compartments, the at least two compartments comprising a first compartment to support the first syringe and the second syringe; and
    the first compartment comprising a base member that defines a mnemonic device indicating which of the first syringe or the second syringe should be used first in the catheterization procedure.

(wherein the italicized limitations were relevant to the appeal).  The mnemonic device, according to Medline, relates to arrangement of syringes at different heights in the claimed tray, on the basis that a practitioner would "intuitively" use the syringe closest to the top of the tray first.  The Board rejected Bard's argument that Solazzo taught such an embodiment on the grounds that the Solazzo reference did not disclose a "contour and shape" associated with positioning the lubricating syringe at an elevated height.  But the Court agreed with Bard on this issue, again finding an overly rigid analysis of obviousness by the Board.  The opinion sets forth the disclosure in Solazzo consistent with the claimed positioning of the syringes (the first containing lubricant, the second mediating inflation of a balloon attached to the catheter to keep it in place).  This disclosure was supported by the teachings in the Serany reference that components in the tray be arranged "in proper order of use," according to the opinion.  In the Court's opinion, "a skilled artisan would have been motivated to design a compartment with a bottom portion that would elevate one syringe above another, without the aid of other items" in view of the cited prior art.  Regarding claim 25, which did not disclose the mnemonic device, the Board erred for not properly considering the teachings of the Imai reference regarding arranging syringes at different heights.  According to the panel, "[g]iven the prior art disclosures and the finite number of predictable options, a skilled artisan would have been motivated to stack the syringes by height according to their order of use."  On these grounds, the Court vacated the Board's decision with regard to claims 1, 2, 6–10, 16–19, and 25–44 of the '088 patent.

The Court next considered the Board's decision of non-obviousness for challenged claims 7 and 9 of the '596 patent, wherein representative claim 7 recites:

A catheterization kit comprising: a single level container defining a first compartment bounded by a first compartment base member and at least a first portion of a perimeter wall, the single level container defining a second compartment bounded, at least in part, by a second compartment base member and at least a second portion of the perimeter wall; a first syringe disposed within the first compartment of the single level container, the first syringe containing an inflation fluid; a second syringe disposed within the first compartment of the single level container, the second syringe containing a lubricating jelly; and a coiled medical device disposed within the second compartment of the single level container, the coiled medical device including a Foley catheter, a fluid receptacle, and a tube coupling the Foley catheter to the fluid receptacle, the Foley catheter and the fluid receptacle positioned within the second compartment such that the fluid receptacle is between the second compartment base member and the Foley catheter.

(wherein the italicized limitation was relevant to the appeal).  Once again the panel agreed with Bard that the Board erred in not concluding that the claims were obvious based on "(1) undisputed testimony that practitioners access the catheter before the fluid receptacle during a catheterization procedure, (2) Serany's disclosure that a fluid receptacle can be stored together with the catheter, and (3) Serany's disclosure that 'all the components [are] arranged in logical step-by-step order.'"  The opinion characterizes the Board's decision as "impos[ing] anticipation-like requirements on the prior art in determining obviousness."  Regarding claim 9, the relevant additional limitation is that the first compartment is "configured to receive the lubricating jelly from the second syringe to lubricate a tip of the Foley catheter when the tip is placed into the first compartment" as shown in use:

For a change, the panel agreed with Medline on this issue, agreeing that the Board had substantial evidence for concluding that this claim was non-obvious because the relevant compartment was "too deep to store lubricant and facilitate catheter lubrication."  This evidence included "expert testimony that compartment 27's depth would render it unsuitable to store lubricant for the catheter" and "that, because a doctor needs to measure the urine, "[h]aving lubrication" in the urine compartment could "ruin[]" the measurement."  Bard's arguments, that "any chamber [of the claimed tray] regardless of size and shape" is "configured for receiving lubricating jelly and facilitating the lubrication of the tip of a catheter" was inconsistent with the disclosures in the prior art and that the issue was not one of proper vel non claim construction.  Accordingly, the Court vacated the portion of the Board's decision of non-obviousness regarding challenged claims 7, 8, and 11–13 of the '596 patent and affirmed that decision regarding challenged claims 9, 10, 14–16, 21, and 22.

The last Board decision review by the Court related to the challenged claims of the '761 patent, wherein the opinion recites claim 10 as representative:

A Foley catheter container, comprising: a single layer tray comprising a surface defining at least two compartments separated by a barrier, the at least two compartments comprising: a first compartment comprising a first compartment base member, the first compartment to accommodate a first syringe and a second syringe; a second compartment comprising a second compartment base member; the Foley catheter, situated in the second compartment; the barrier separating the first compartment from the second compartment; the first compartment base member situated at a different height within the tray than the second compartment base member; the first compartment defining a lubricating jelly application chamber to lubricate the Foley catheter when passed from the second compartment into the first compartment of the single layer tray; further comprising a patient aid comprising post-procedure information, disposed on a first portion of the patient aid, for caring for the Foley catheter applied to a patient.

(wherein the italicized limitation was relevant to the appeal).  The Court's opinion was based on Bard's arguments with regard to the divider between compartments taught in the Solazzo reference and illustrate in the opinion by this Figure:

The opinion characterizes Bard's arguments as being similar to those the challenger asserted regarding claim 9 of the '596 patent, and similarly agreed with Medline that substantial evidence supported the Board's non-obviousness determination.  On the other hand, the panel agreed with Bard that the Board erred with regard to the Board's conclusions regarding the presence of two syringes in one compartment positioned at different heights (for the same reasons set forth in the opinion for challenged claims in other patents at issue) but held that error to be harmless in view of "the deficiency of the prior art concerning the lubricating chamber limitation [being] supported by substantial evidence and hence sufficient to establish nonobviousness."  The Court thus affirmed the Board's non-obviousness determination regarding challenged claims 1–19 and 22–25 of the '761 patent."

Finally, with regard to the secondary considerations issue, the Court remanded these arguments to the Board (subject to whether Medline should be collaterally estopped on remand from making "certain secondary considerations arguments").

C.R. Bard, Inc. v. Medline Industries, Inc. (Fed. Cir. 2021)
Nonprecedential disposition
Panel: Circuit Judges Lourie, Bryson, and Chen
Opinion By Circuit Judge Lourie

The Federal Circuit Addresses Commercial Success

By Michael Borella --

In academic settings, objective indicia of non-obviousness are sometimes presented as a common way of rebutting contentions that a claimed invention is obvious.  These indicia, set forth in Graham v. John Deere Co. and reiterated in KSR Int'l Co. v. Teleflex, Inc., include commercial success, long felt but unsolved needs, unexpected results, copying by others, industry praise, and failure of others.  While aesthetically pleasing from a procedural point of view, secondary considerations are notoriously difficult to successfully apply outside of law school exams.

This difficulty is largely due to the requirements that:  (1) the evidence actually exists, (2) the patentee is able to locate this evidence, and (3) the patentee can establish a nexus between the evidence and the claimed invention.  A commercial success rebuttal might involve providing sales or market share figures for a product before and after a patented new feature is released, where the latter is notably higher than the former, as well as support for the notion that this commercial success is actually a result of the patented new feature.  Industry reviews or expert testimony might be required.  And still, this evidence can be rebutted with further evidence that the commercial success was actually caused by other forces than what is claimed.

Intuitively, this all makes sense.  If one is going to argue that a claimed invention is non-obvious because it was commercially successful, the product or service that enjoyed this commercial success should have done so due to the innovative features of the claims.  Commercial success cannot be used in this fashion when it was caused by some extraneous factor, such as a major competitor leaving the market or going out of business.

Having said all of that, it is fairly rare for a patentee to win on a commercial success argument.  Recent inter partes review (IPR) final written decisions from the PTAB show how easy it is for commercial success arguments to fail.  Samsung Electronics Co., Ltd v. Cellect, LLC, No. 2020-00475 (PTAB Aug. 17, 2021) (patent owner's licensing of a product, where the patent owner's contentions do not specify which entities took a license to the patent or for what reason the licenses were taken, does not establish a nexus); Microsoft Corp. and HP Inc. v. Synkloud Technologies, LLC, No. 2020-00316 (PTAB Jun. 14, 2021) (patent owner's claim chart between the claimed invention and allegedly successful products was too high level and non-specific to establish a nexus); Red Diamond, Inc. v. Southern Visions, LLP, 2019-01671 (PTAB Mar. 31, 2021) (patent owner did not establish commercial success merely by providing sales data and contending that its market share was "high").

Successful rebuttals require specific allegations regarding both the nexus and the commercial success, which often have to be backed up by sales / market data and explained in one or more expert declarations.  Due to the time and cost of preparing such evidence, these allegations are rarely made before USPTO examiners.

Commercial success arguments remain a trap for the unwary.  Nonetheless, two recent Federal Circuit decisions that came down on two consecutive days add a little color to the landscape.

In Chemours Company FC, LLC v. Daikan Industries, Ltd, patent owner Chemours appealed a PTAB decision finding its claims obvious over its allegations of commercial success.  The Court described the relevant law as:

In general, evidence supporting objective indicia of nonobviousness must be shown to have a nexus to the claimed invention.  In the obviousness analysis, the claimed invention is, admittedly, a combination of elements that were known individually in the prior art.  Evidence of commercial success, therefore, can be linked to an inventive combination of known elements to show a sufficient nexus.

The PTAB, focusing on individual claim limitations, found that Chemours failed to establish a nexus on this basis.  The Court disagreed, however, stating that "the separate disclosure of individual limitations, where the invention is a unique combination of three interdependent properties, does not negate a nexus," and that "[c]oncluding otherwise would mean that nexus could never exist where the claimed invention is a unique combination of known elements from the prior art."

Chemours also argued that the PTAB improperly required market share data to establish a finding of commercial success, where sales data alone could be sufficient.  The Court agreed here as well, observing that:

When a patentee can demonstrate commercial success, usually shown by significant sales in a relevant market, and that the successful product is the invention disclosed and claimed in the patent, it is presumed that the commercial success is due to the patented invention.  However, market share data, though potentially useful, is not required to show commercial success.

This holding does not contradict that of Red Diamond above, as the PTAB "is certainly entitled to weigh evidence and find, if appropriate, that Chemours's gross sales data were insufficient to show commercial success without market share data."  Consequently, the Court reversed the PTAB's decision regarding commercial success.

In Oren Techs., LLC v Proppant Express Investments LLC, patent holder Oren also appealed a PTAB decision finding its claims obvious over its allegations of commercial success.  Regarding the procedural requirements of establishing a nexus, the Court wrote:

For objective evidence of secondary considerations to be accorded substantial weight, its proponent must establish a nexus between the evidence and the merits of the claimed invention.  That is, objective evidence of non-obviousness must be commensurate in scope with the claims which the evidence is offered to support.  There can be a presumption of nexus for objective considerations when the patentee shows that the asserted objective evidence is tied to a specific product and that product is the invention disclosed and claimed in the patent.  The presumption can apply even when the product has additional, unclaimed features.  Once established, this presumption of nexus is rebuttable with evidence showing the objective evidence is due to extraneous factors other than the patented invention.

Oren provided a mapping of its commercial product to the claims of its patent, and this mapping was sufficient to conclude that the product was what was being claimed.  Proppant argued that a broader version of the product with more features was responsible for any commercial success.  This argument was enough for the PTAB to conclude that the commercial success was primarily a result of the non-claimed features.

The Court disagreed, however, stating that the PTAB ignored evidence that the claimed features were also an important factor driving the commercial success of the broader product.  Oren provided licensing data and market analysis evidence that this was the case.  Since "it is not necessary that the patented invention be solely responsible for the commercial success, in order for this factor to be given weight appropriate to the evidence, along with other pertinent factors," the Court remanded the case to the PTAB for further consideration of the evidence.

Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co., Eli Lilly & Co. v. Teva Pharmaceuticals Int'l GmbH, and Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co. (Fed. Cir. 2021)

By Kevin E. Noonan --

The Federal Circuit issued three decisions on Monday relating to Eli Lilly & Co's. challenge in separate inter partes review proceedings on obviousness grounds of nine patents licensed by Teva Pharmaceuticals Int'l, with disparate results.

The patents were related to humanized monoclonal antibodies immunologically specific for calcitonin gene-related peptide (CGRP), for treatment of "all forms of vascular headache, including migraines"; each party marketed a product for this purpose (Teva's AJOVY® and Lilly's Emgality®).  The appeals clustered separate but related IPR proceedings that the Board had combined for oral argument.  In the first of these (as considered here), Eli Lilly & Co. v. Teva Pharmaceuticals Int'l GmbH, Lilly appealed the Board's decision that it had failed to show that challenged claims 1, 3, 4, 8–17, 19, 20, and 24–31 of U.S. Patent No. 8,586,045, claims 1–18 of U.S. Patent No. 9,884,907, and claims 1–18 of U.S. Patent No. 9,884,908 were obvious.  Representative claims from each patent are:

The '045 patent:

1.  A method for reducing incidence of or treating at least one vasomotor symptom in an individual, comprising administering to the individual an effective amount of an anti-CGRP antagonist anti-body, wherein said anti-CGRP antagonist antibody is a human monoclonal antibody or a humanized monoclonal antibody.

The '907 patent:

1.  A method for treating headache in an individual, comprising:
    administering to the individual an effective amount of a humanized monoclonal anti-Calcitonin Gene-Related Peptide (CGRP) antagonist antibody, comprising:
    two human IgG heavy chains, each heavy chain comprising three complementarity determining regions (CDRs) and four framework regions, wherein portions of the two heavy chains together form an Fc region; and
    two light chains, each light chain comprising three CDRs and four framework regions;
    wherein the CDRs impart to the antibody specific binding to a CGRP consisting of amino acid residues 1 to 37 of SEQ ID NO:15 or SEQ ID NO:43.

The '908 patent:

1.  A method for treating headache in an individual, comprising:
    administering to the individual an effective amount of a humanized monoclonal anti-Calcitonin Gene-Related Peptide (CGRP) antagonist antibody, comprising:
    two human IgG heavy chains, each heavy chain comprising three complementarity determining regions (CDRs) and four framework regions, wherein portions of the two heavy chains together form an Fc region; and
    two light chains, each light chain comprising three CDRs and four framework regions;
    wherein the CDRs impart to the antibody specific binding to a CGRP consisting of amino acid residues 1 to 37 of SEQ ID NO:15 or SEQ ID NO: 43, and wherein the antibody binds to the CGRP with a binding affinity (KD) of about 10 nM or less as measured by surface plasmon resonance at 37^o C.

Lilly asserted three prior art references in support of its obviousness challenge:

• Olesen et al., "Calcitonin Gene-Related Peptide Receptor Antagonist BIBN 4096 BS for the Acute Treatment of Migraine," N. ENG. J. MED. 350: 1104–10 (2004), which taught treatment of migraine with CGRP receptor antagonist.

• Tan et al., "Calcitonin gene-related peptide as an endogenous vasodilator: immunoblockade studies in vivo with an anti-calcitonin gene-related peptide monoclonal antibody and its Fab' fragment," 89 CLINICAL SCI. 6: 565–73 (1995), which taught using full-length anti-CGRP mAb to block CGRP binding to its receptor in rats.

• U.S. Patent No. 6,180,370, which is a general reference teaching use of "recombinant DNA and monoclonal antibody technologies for developing novel therapeutic agents."

The Board rendered its decision that Lilly failed to show the challenged claims were obvious over this art.  This decision depended in part of its claim construction wherein the preambles of each of the challenged claims constituted a "statement of intended purpose" and were limiting to that extent, which thus raised in Lilly the burden of showing that the skilled worker would have had a reasonable expectation of success in achieving this intended purpose.  In a bit of circular reasoning, the Board construed the claim term "effective amount" to be the amount that would achieve this preamble purpose of a beneficial result but not a clinical result (i.e., of treating migraine).

The Board found the cited art taught each and every one of the limitations recited in the claims, and the skilled artisan would have been motivated to combine the teachings in the cited art and that safety concerns would not have deterred, discouraged, or taught away from pursuing" the invention.  But Lilly failed to show a reasonable expectation of success in the Board's opinion, including that the blood-brain barrier "raised uncertainty, unpredictability, and skepticism in using full-length anti-CGRP antibodies" therapeutically.  This was enough to defeat obviousness for these method claims, which the panel stated was consistent with Honeywell International Inc. v. Mexichem Amanco Holdings S.A. DE C.V., 865 F.3d 1348, 1356 (Fed. Cir. 2017), and were analogous to Novartis Pharmaceuticals Corp. v. West-Ward Pharmaceuticals International Ltd., 923 F.3d 1051 (Fed. Cir. 2019).

The Federal Circuit affirmed in a decision (as all three decisions were) by Judge Lourie joined by Judges Bryson and O'Malley.  On appeal, Lilly raised two arguments.  First, that the Board's claim construction was in error for interpreting the preambles to require a beneficial result that was related to the construction of "effective amount."  Second, Lilly argued the Board's standard for reasonable expectation of success was improperly high.

With regard to claim construction, the panel agreed with Teva that the Board properly construed the preambles to be limiting.  Specific to the facts in each case, as it must be under Storage Tech. Corp. v. Cisco Sys., Inc., 329 F.3d 823, 831 (Fed. Cir. 2003), here the panel held that in this case, the claims were directed to methods for achieving a particular purpose, i.e., "treating or reducing the incidence of vasomotor symptoms, and the method comprises a single step of administering an effective amount of a composition, namely, a humanized anti-CGRP antagonist antibody."  The panel recognized the contrast between method claims such as these and composition of matter or apparatus claims, which are directed to what the claimed invention is rather than what it does, citing Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1468 (Fed. Cir 1990); Cochlear Bone Anchored Solutions AB v. Oticon Med. AB, 958 F.3d 1348, 1355 (Fed. Cir. 2020); Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 320 F.3d 1339, 1345 (Fed. Cir. 2003); and Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333 (Fed. Cir. 2003).  The Board's construction with regard to the limiting nature of the preambles satisfied the "essence of the claimed invention" requirement and thus was proper.  Recitation of the affirmative limitation of an "effective amount" raised the question of an "effective amount" to do what according to the opinion, which is to achieve the purpose recited in the preamble (the opinion calls this "the only metric by which one practicing the claim could determine whether the amount administered is an 'effective amount'").  The specification defined this amount to be "an amount sufficient to effect beneficial or desired results" and further the specification contained "extensive discussions of such treatment in every section of the patent[]," according to the opinion.  Under these circumstances the panel held that the preamble thus gives "life and meaning" to the claimed methods and is thus properly construed to be limiting.  And the panel further recognized that the preamble also provides antecedent basis for reciting "an individual" in the affirmative limitations recited in the claim, distinguishing Cochlear because that was an apparatus claim and method claims were at issue here.

Turning to reasonable expectation of success, the panel pointed out that the Board's finding of sufficient motivation to combine does not necessarily satisfy the reasonable expectation of success standard, citing Procter & Gamble Co. v. Teva Pharms. USA, Inc., 566 F.3d 989, 994 (Fed. Cir. 2009), and in particular Novartis Pharmaceuticals Corp. v. West-Ward Pharmaceuticals International Ltd., 923 F.3d 1051 (Fed. Cir. 2019).  The Court found the claims here to be analogous to those in WestWard, where despite there being motivation to combine, the biology involved was sufficiently uncertain and unpredictable for there to be no reasonable expectation of success.  Because the limitations in the preamble were properly construed by the Board to require successful methods of treatment, these limitations informed the expectation of success argument as to what is expected and what constitutes success according to the Court.

This understanding by the Board as supported by definition in specification according to the opinion:

As is understood by those skilled in the art, individuals may vary in terms of their response to treatment, and, as such, for example, a "method of reducing incidence of headache in an individual" reflects administering the anti-CGRP antagonist antibody based on a reasonable expectation that such administration may likely cause such a reduction in incidence in that particular individual.

The expectation was not based on a requirement for clinical data (which Lilly argued) and not supported by "isolated, out-of-context statements plucked from dozens of pages of the Board's factual findings" by Lilly.  As in the Court's decision in Sanofi v. Watson Labs. Inc., 875 F.3d 636, 647 (Fed. Cir. 2017), the panel "decline[d] to infer a demand for data from the Board's observation that references did not include those data."  The substantial evidence standard merited the panel's deference to the Board's conclusion that Lilly had not shown a reasonable expectation of success for the challenged method claims.

The Court also rejected Lilly's challenge of error based on considerations of the blood-brain barrier and whether there was uncertainty regarding the capacity for the claimed antibodies to traverse this natural barrier.  Lilly argued that the prior art showed some evidence for migraine relief in the absence of crossing the blood-brain barrier, and thus that any basis by the Board for finding no reasonable expectation of success on this basis as error.  The Court focused on the uncertainty of whether the antibody therapeutic used in the claimed method would actually cross the blood-brain barrier or would need to do so to provide a beneficial effect.  The Court held that Lilly bore the burden of establishing a reasonable expectation of success which under the facts considered by the Board it did not do.

The second appeal, Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co., was directed to the Board's finding that claims to anti-CGRP monoclonal antibodies were obvious.  The claims challenged by Lilly in these IPRs were claims 1–7 and 15–20 of U.S. Patent No. 9,340,614, claims 1–6 and 14–19 of U.S. Patent No. 9,266,951, and claims 1–5 of U.S. Patent No. 9,890,210.  The following claims are representative:

The '614 patent:

1.  A human or humanized monoclonal anti-CGRP antagonist antibody that preferentially binds to human α-CGRP as compared to amylin.

The '951 patent:

1.  A human or humanized monoclonal anti-CGRP antagonist antibody that (1) binds human α-CGRP and (2) inhibits cyclic adenosine monophosphate (cAMP) activation in cells.

The '210 patent:

1.  A humanized monoclonal anti-Calcitonin Gene-Related Peptide (CGRP) antagonist anti-body, comprising:
    two human IgG heavy chains, each heavy chain comprising three complementarity determining regions (CDRs) and four framework regions, wherein portions of the two heavy chains together form an Fc region; and
    two light chains, each light chain comprising three CDRs and four framework regions;
    wherein the CDRs impart to the antibody specific binding to a CGRP consisting of amino acid residues 1 to 37 of SEQ ID NO:15 or SEQ ID NO:43.

Lilly asserted these prior art references in support of its obviousness challenge in these IPRs:

• Tan et al., "Calcitonin gene-related peptide as an endogenous vasodilator: immunoblockade studies in vivo with an anti-calcitonin gene-related peptide monoclonal antibody and its Fab' fragment," 89 CLINICAL SCI. 6: 565–73 (1995), which taught using full-length anti-CGRP mAb to block CGRP binding to its receptor in rats.

• Wimalawansa, "Calcitonin Gene-Related Pep-tide and its Receptors: Molecular Genetics, Physiology, Pathophysiology, and Therapeutic Potentials," 17 ENDOCRINE REVIEWS 5: 533–85 (1996), which is a review article regarding CGRP, its structure and effects, as well as possible uses for agonists and antagonists.

• U.S. Patent No. 6,180,370, which is a general reference teaching use of "recombinant DNA and monoclonal antibody technologies for developing novel therapeutic agents."

The Board found the skilled worker would have both a reason to combine these teachings to achieve the claimed invention and have had a reasonable expectation of success in finding the claims obvious.  The Board based its decision on the existence of anti-CGRP mAbs from other species, which would have provided sufficient motivation for the skilled worker to make humanized counterparts, and for the reasonable expectation of success that the claims recited no limitations regarding safety or efficacy for any intended purpose (in this way differing from the method claims the Board found not to be obvious over the same or related art as discussed above).  On this basis, the Board rejected Teva's argument that Lilly had a burden of establishing a reasonable expectation from the cited art for treating any disease or condition.

(In a side note, Teva had challenged the Board's decision based on the purported unconstitutionality of the APJs under the Court's decision in Arthrex, Inc. v. Smith & Nephew, Inc., 941 F.3d 1320 (Fed. Cir. 2019).  After the Supreme Court's decision in United States v. Arthrex, Inc., 141 S. Ct. 1970 (2021), during the pendency of this appeal, the panel gave Teva the choice of a hearing on the merits of the appeal or request for an immediate remand to the Board for resolution of the Arthrex question.  Teva chose this appeal on the merits, and the Federal Circuit's opinion followed.)

The Federal Circuit affirmed, in an opinion by Judge Lourie joined by Judges Bryson and O'Malley.  The panel rejected Teva's argument that the Board erred in finding a motivation and basis for the skilled worker to combine the cited art that differed from what Lilly had argued in this regard.  The difference, Teva maintained, was that under Lilly's purported argument there would need to be a therapeutic aim implicating safety and efficacy for the claimed anti-CGRP antibodies while in the Board's consideration it did not.  The Federal Circuit agreed with the Board that this was not a case where the Board "deviate[d] from the grounds in the petition and raise its own obviousness theory," citing Sirona Dental Sys. GmbH v. Institut Straumann AG, 892 F.3d 1349, 1356 (Fed. Cir. 2018).  In a nuanced argument, the panel found that the Board's appreciation of the motivation to make the claimed antibodies was to make humanized antibodies for treating human disease, based on "[c]ommon sense and scientific reality."  But the needed motivation was to make the antibodies not to use the antibodies to treat disease.  For the panel, "the relevant inquiry—which the Board extensively analyzed—is whether those [safety and efficacy] concerns would have dissuaded a skilled artisan from making the claimed antibodies to study their therapeutic potential in the first place."  That not being the case, the panel held that the Board had properly considered and was convinced by Lilly's evidence for a motivation to combine sufficient to support the Board's obviousness determination.  The panel noted that the Board had not disregarded Teva's arguments regarding safety and efficacy, according to the opinion; rather, it had considered the evidence in making a factual finding supported by substantial evidence to which the Court was obligated to defer.

Teva also argued more specifically that the Board had relied upon "unsupported interpretations of isolated statements in the prior art to find a motivation to study or use humanized anti-CGRP antibodies."  The panel noted that Lilly provided evidence, including expert testimony, to the contrary.  But the basis for the Court's rejection of Teva's arguments is that "[b]ut what a piece of prior art teaches presents a question of fact that is reviewed for substantial evidence," citing In re Warsaw Orthopedic, Inc., 832 F.3d 1327, 1332 (Fed. Cir. 2016), and In re Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000).  Under this deferential review, the panel held that the Board did not err in finding a reasoned basis for the skilled worker to combine the references.

The panel also considered and rejected Teva's arguments that the Board's determination that Teva's evidence for secondary considerations (or objective indicia) of non-obviousness failed due to a lack of nexus between the evidence and the claimed invention.  This evidence was related to both Teva's own (AJOVY®) and Lilly's (Emgality®) anti-CGRP mAb products with regard to "industry-wide acclaim, satisfied a long-felt need, achieved unexpected results, faced industry skepticism, and achieved commercial success" (i.e., almost all the secondary considerations), as well as licenses with third parties for its products falling within the scope of the claims.  With regard to the Board's lack-of-nexus determination, the panel acknowledged the presumption that a nexus exists if tied to a specific product "that is the invention disclosed and claimed," under Fox Factory, Inc. v. SRAM, LLC, 944 F.3d 1366 (Fed. Cir. 2019).  However, under certain circumstances there can be unclaimed features of such a commercial product along a continuum that can affect the nexus determination under this precedent.  Although the Court found that the "rule" the Board distilled from the Court's precedent was flawed and error, the panel held that the Board nevertheless conducted the proper nexus assessment in finding Teva was not entitled to the nexus presumption that can attach to a successful commercial product and that its error was thus harmless.  That assessment was consistent with the Court's rubrics set forth in Immunex Corp. v. Sandoz Inc., 964 F.3d 1049, 1067–68 (Fed. Cir. 2020), in the distinctions the panel appreciates between this invention and the one in Immunex.  In that case, the antibodies were disclosed and claimed based on structure whereas here they are claimed with regard to their function.  The Court cited its decision in Amgen Inc. v. Sanofi, 987 F.3d 1080, 1087 (Fed. Cir. 2021) (acknowledging in a footnote that the Amgen decision was rooted in Section 112 considerations), that antibodies claimed by function can be broad (or overbroad) because they do not define antibodies falling within the scope of the claims by structural limitations.  As a result, the panel opined that "[a] claim to 'anything that works' hardly has a nexus to any particular product."  Once again, the panel found that the Board's factual determinations were sufficient to support by substantial evidence its determination that there was a lack of nexus here between the parties' commercial products and the claimed invention.

The panel also rejected Teva's arguments that the third party licenses were sufficient to show the required nexus.  This decision rested on those licenses encompassing 188 patents (including the ones at issue here) and that the royalty obligations did not depend on whether these patents were invalidated or not.

The final decision, Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co., was the only non-precedential decision and was directed to the Board's determination that the challenged claims of Teva's U.S. Patents 9,346,881, 9,890,211, and 8,597,649 were obvious.  In a summary opinion by Judge Lourie joined by Judges Bryson and O'Malley, the Court affirmed the Board's obviousness determination, substituting any detailed explication of the Board's decision and the panel's own rationale by stating:

In the two consolidated appeals, the parties made substantively identical arguments, mostly copied and pasted verbatim from one case to the other.  Teva included the following footnote in its opening brief:

In a second decision issued the same day, the Board also held unpatentable the challenged claims of three related composition patents.  That decision, which is materially identical in reasoning, is the subject of Teva's companion appeal no. 20-1747.  Teva's arguments in the two appeals are the same . . . [emphasis in opinion].

Lilly, not disagreeing with this sentiment, the panel asserted that "[d]uring the combined oral argument in the two consolidated appeals, neither party argued that any one of the six appeals should be decided differently from the others."  Accordingly, the Court based this opinion on its opinion affirming the Board's obviousness determination in Teva's other appeal of rejection of its monoclonal antibody claims for being obvious.

Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co. (Fed. Cir. 2021)
Panel: Circuit Judges Lourie, Bryson, and O'Malley
Opinion by Circuit Judge Lourie

Eli Lilly & Co. v. Teva Pharmaceuticals Int'l GmbH (Fed. Cir. 2021)
Panel: Circuit Judges Lourie, Bryson, and O'Malley
Opinion by Circuit Judge Lourie

Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co. (Fed. Cir. 2021)
Panel: Circuit Judges Lourie, Bryson, and O'Malley
Opinion by Circuit Judge Lourie

Chemours Company FC, LLC v. Daikin Industries, Ltd. (Fed. Cir. 2021)

By Kevin E. Noonan --

The Federal Circuit, and the Court of Customs and Patent Appeals before it, generally reviewed decisions by the Patent and Trademark Office under the same standard applied to district court decisions, whether the factual basis for the decision was "clearly erroneous" (questions of law were, and are, decided de novo), acting as a check on the administrative agency's interpretations of its precedent and Congress's statutory mandates.  That changed when the Supreme Court decided, in Dickinson v. Zurko (1999), pursuant to the provisions of the Administrative Procedures Act (5 U.S.C. §§ 551 et seq.) and specifically 5 U.S.C. § 706, that factual determinations should be upheld if supported by substantial evidence.  This change in standard of review became even more important after enactment of the post-grant review procedures in the Leahy-Smith America Invents Act, and in particular the inter partes review (IPR) provisions (35 U.S.C. §§ 311 et seq.) with regard to obviousness determinations under 35 U.S.C. § 103.  This is because while obviousness is a legal determination, it is based on factual determinations that have been much more likely to pass muster under substantial evidence review and has led the Federal Circuit generally to affirm decisions by the Patent Trial and Appeal Board (PTAB) on that basis.  Not so in Chemours Company FC, LLC v. Daikin Industries, Ltd., decided last week, which showed perhaps the limits of deference the Court is willing to entertain in reviewing PTAB obviousness determinations.

The case arose over Daikin's challenge of two Chemour patents, U.S. Patent Nos. 7,122,609 and 8,076,431.  The technology was directed to extrusion coating of communications cables involving pulling said cables through melted polymers for form insulation.  Chemour's patents disclosed "a polymer with unique properties such that it can be formed at high extrusion speeds while still producing a high-quality coating on the communication cables" and specifically performing extrusion at 30±3g/10 min characterized as "a high melt flow rate."  The opinion recites Claim 1 of the '609 patent as being representative:

1.  A partially-crystalline copolymer comprising tetrafluoroethylene, hexafluoropropylene in an amount corresponding to a hexafluoropropylene index (HFPl) of from about 2.8 to 5.3, said copolymer being polymerized and isolated in the absence of added alkali metal salt, having a melt flow rate of within the range of about 30±3 g/10 min, and having no more than about 50 unstable endgroups/10⁶ carbon atoms.

The Board found all claims in both patents to be obvious over the disclosure of U.S. Patent No 6,541,588.  The basis for the determination was that the '588 patent teaches that cables can be insulated at speeds similar to the range recited in the '609 patent claims (in one example being 24 g/10 min, which is close to the lower limit of Chemour's range, 27 g/10 min).  Significantly, the '588 patent also teaches that it is important to maintain "a very narrow molecular weight distribution" in the polymer (which in a footnote the Court explains means "[a] polymer with a narrower molecular weight distribution has more polymer chains that are of similar lengths, while a broad molecular weight distribution fluorinated ethylene propylene ("FEP") has more variation in polymer chain lengths").  The Board found that "a skilled artisan would have been motivated to increase the melt flow rate of [the '588 patent]'s preferred embodiment to within the claimed range in order to coat wires faster."  Notwithstanding the narrow range teaching regarding polymer molecular weight in the '588 patent, the Board further found that "it is not clear on this fully developed record why the skilled artisan would have been motivated to maintain such a narrow molecular weight distribution when seeking to achieve even higher coating speeds" and that the '588 patent specification "lacked specificity" regarding the metes and bounds of "narrow" and "broad" molecular weight ranges.  This was enough for the Board to opine that "this purported discovery would not have prevented the skilled artisan, at the time of the invention of the '609 patent, from considering other techniques—such as broadening the polymer's molecular weight distribution—to achieve higher coating speeds . . . ."  Based on these factual determinations, the PTAB held the claims in the '609 and '431 patents were obvious, and Chemour appealed.

The Federal Circuit reversed, in an opinion by Judge Reyna joined by Judge Newman; Judge Dyk concurred with majority that the Board's decision was erroneous but not with reversal of the judgment.  The majority's opinion was based on its conclusion that while it was permissible for the Board "to inform itself of the state of the art at the time of the invention," "the Board appears to have ignored the express disclosure in [the '588 patent] that teaches away from the claimed invention and relied on teachings from other references that were not concerned with the particular problems  [the '588 patent]  sought to solve.  In other words, the Board did not adequately grapple with why a skilled artisan would find it obvious to increase [the '588 patent]'s melt flow rate to the claimed range while retaining its critical "very narrow molecular-weight distribution."  Regarding the motivation to increase the melt flow rate to be within the range recited in the '609 and '431 patents, the opinion states the Board did not support with substantial evidence "why a POSA would be motivated to increase [the '588 patent]'s melt flow rate to the claimed range, when doing so would necessarily involve altering the inventive concept of a narrow molecular weight distribution polymer."  The majority perceived that the '588 patent taught away from broadening the molecular weight range to achieve the higher melt flow rates.  The '588 patent itself recited "numerous examples of processing techniques that are typically used to increase melt flow rate, which [the '588 patent] cautions should not be used due to the risk of obtaining a broader molecular weight distribution" (emphasis in opinion).  The majority agreed with Chemour that "the Board needed competent proof showing a skilled artisan would have been motivated to, and reasonably expected to be able to, increase the melt flow rate of [the '588 patent]'s polymer to the claimed range when all known methods for doing so would go against [the '588 patent]'s invention by broadening molecular weight distribution" which in the majority's view it did not.

The majority also opined on the Board's erroneous application of the objective indicia of non-obviousness; Judge Dyk joined his brethren in this portion of the opinion.  The issue involved the commercial success flavor of objective non-obviousness, where the panel held the Board erred for finding an insufficient nexus between said success and the patents at issue.  Chemour's argument on appeal on this issue was twofold: first, that the PTAB found no nexus on a limitation-by-limitation basis, and that the Board required Chemour to show market share data to establish commercial success.  The panel agreed with Chemour's first argument, stating that "the separate disclosure of individual limitations, where the invention is a unique combination of three interdependent properties, does not negate a nexus" because "[c]oncluding otherwise would mean that nexus could never exist where the claimed invention is a unique combination of known elements from the prior art," citing WBIP, LLC v. Kohler Co., 829 F.3d 1317, 1332 (Fed. Cir. 2016).  With regard to Chemour's market data argument, the panel agreed that a showing of "significant sales in the relevant market" of a product "disclosed and claimed in the patent" provides a presumption "that the commercial success is due to the patented invention," citing J.T. Eaton & Co. v. Atl. Paste & Glue Co., 106 F.3d 1563, 1571 (Fed. Cir. 1997).  Market share data, "though potentially useful," is not required to satisfy the standard of commercial success according to the Court.

Finally, the panel assessed Chemour's argument that the PTAB erred in its finding that the patents-at-issue were so-called "blocking patents" that would have prevented competitors from entering the relevant market (and thus provide an alternative explanation for the purported commercial success; (see "Acorda Therapeutics, Inc. v. Roxane Laboratories, Inc. (Fed. Cir. 2018)").  The panel held that the Board erred in its determination, stating without analysis or explanation that the challenged patent, which covers the claimed invention at issue, cannot act as a blocking patent.

As a side note, the panel declined to consider Chemour's argument that the Board's decision was in violation of the Appointments Clause, after the Supreme Court's decision in U.S. v. Arthrex.

The basis for Judge Dyk's partial dissent was his disagreement with his colleagues that the '588 patent "taught away" from the claimed invention.  Specifically, the Judge thought the polymer disclosed in the '588 patent was "nearly identical" to the polymer recited in the patents-at-issue.  The only difference in Judge Dyk's apprehension of the claimed invention with the '588 patent is the extrusion rate, which is similar between the challenged claims and the reference.  In his view, the '588 patent disclosed that even though "a narrow molecular weight distribution performs better" it also acknowledged "the feasibility of using a broad molecular weight distribution to create polymers for high speed extrusion coating of wires."  This, in the Judge's opinion, was not a teaching away and "[t]he majority's approach impermissibly expands the teaching away doctrine such that it encompasses a reference's mere preference for a particular alternative."  Judge Dyk also believes that the distinction between narrow and broad molecular weight ranges was insufficiently disclosed in the '588 patent to support the majority's opinion.  Accordingly, Judge Dyk would remand for a determination of obviousness in view of the proper consideration of the secondary indicia as set forth in the majority opinion.

Chemours Company FC, LLC v. Daikin Industries, Ltd. (Fed. Cir. 2021)
Panel: Circuit Judges Newman, Dyk, and Reyna
Opinion by Circuit Judge Reyna; opinion concurring in part and dissenting in part by Circuit Judge Dyk

Becton, Dickinson & Co. v. Baxter Corp. Englewood (Fed. Cir. 2021)

By Kevin E. Noonan --

In Becton, Dickinson & Co. v. Baxter Corp. Englewood, the Federal Circuit overturned a decision by the Patent Trial and Appeal Board (PTAB) in an inter partes review that claims in the challenged patent were not invalid for obviousness.

The patent at issue, U.S. Patent No. 8,554,579, is directed to telemedicine methods and particularly to methods for preparing patient-specific doses of pharmaceuticals.  Claim 8 was considered representative by the Court:

8.  A system for preparing and managing patient-specific dose orders that have been entered into a first system, comprising:
                        . . .
    a dose preparation station for preparing a plurality of doses based on received dose orders, the dose preparation station being in bi-directional communication with the order processing server and
    having an interface for providing an operator with a protocol associated with each received drug order and specifying a set of drug preparation steps to fill the drug order, the dose preparation station including an interactive screen that includes prompts that can be highlighted by an operator to receive additional information relative to one particular step and includes areas for entering an input;
    . . . and wherein each of the steps must be verified as being properly completed before the operator can continue with the other steps of drug preparation process, the captured image displaying a result of a discrete isolated event performed in accordance with one drug preparation step, wherein verifying the steps includes reviewing all of the discrete images in the data record . . . .

The claim terms at issue, both of which are recited in representative claim 8, are "highlighting" and various forms of the concept of "verification," as indicate in the claim as set forth above.  Becton, Dickinson asserted three prior art references in support of its IPR challenge sounding in obviousness:  U.S. Patent No. 8,374,887 ("Alexander"), U.S. Patent No. 6,581,798 ("Liff"), and U.S. Patent Publication No. 2005/0080651 ("Morrison").  The Board had found that the skilled artisan would have been motivated to combine the Alexander and Liff references, and even the combination of all the references.  Similarly, the Board found Baxter's evidence of secondary considerations to be weak, according to the Federal Circuit's opinion.  Nevertheless, the Board found that the Alexander reference, taken alone, did not render obvious the "verification" limitation, or that the combination of the references did not render obvious the "highlighting" limitation of the challenged '579 patent claims.

The Federal Circuit reversed the Board's determinations, in an opinion written by Judge Dyk, joined by Judges Prost and Clevenger.  The panel first addressed the "verification" limitation.  According to the Court, the Board's application of its construction was not supported by substantial evidence.  Specifically, the Court held that the Board erred in concluding that the primary reference, Alexander, only disclosed that the remote pharmacist may verify but not that she must verify "each and every step before the operator is allowed to proceed."  The opinion states that in the panel's view "'may' does not mean 'occasionally,' but rather that one 'may' choose to systematically check each step."  This is significant because the Court found that in the context of the prior art Alexander specification "[t]here is no significant difference between that teaching of Alexander and the '579 patent's verification requirement, which the Board construed as requiring that 'the system will not allow the operator to proceed to the next step until the prior step has been verified.'"  The Court rejected Baxter's arguments to the contrary that unverified prescription filling was within the scope of the Alexander teaching (which argument was based on deposition testimony of Becton's expert), nor that use of the term "the system" in the Alexander process implicated a mechanical "hard stop" to the prescribing function, the Court stating that "[n]othing in the construction requires a mechanical stop as opposed to requiring authorization from a pharmacist to continue."  Accordingly, the panel held that the Board's determination to the contrary was not supported by substantial evidence.

With regard to the "highlighting" limitation the opinion notes that this limitation is tied to embodiments having "an interactive screen that includes prompts that can be highlighted by an operator to receive additional in-formation relative to one particular step," as illustrated by Figure 10 of the '579 patent:

The Court's understanding of the Board's construction of this term was that "the only missing element of this limitation [in the Alexander reference] is the ability to highlight prompts to receive more information concerning drug preparation steps."  And this feature was disclosed in the Liff reference in the panel's assessment (albeit in the physical rather than the virtual, computer realm; as stated in the opinion the system disclosed in the Liff reference comprises "a cabinet adapted to store a variety of prepackaged pharmaceuticals in a plurality of bins for filling patient prescriptions"; the Liff system was illustrated by Figure 14F of that patent:

The Board had characterized its non-obviousness determination based on the highlighting limitation to be a "close case"; the Court disagreed.  To the panel, the Liff patent's teachings regarding highlighting for one purpose (i.e., patient characteristics) clearly would not have precluded the skilled worker from applying the highlighting function to another feature (e.g., information regarding the prescription order).  In the panel's view, their decision was predicated on the Supreme Court's teachings in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007), that "[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results."  In addition, the panel relied on KRS for the principle that "[a] person of ordinary skill is also a person of ordinary creativity, not an automaton" with regard to the question of whether the "additional information that might be relevant" was limited to what the Liff reference expressly disclosed.

In an interesting aside, the Court considered the issue of whether the Alexander reference was properly prior art under 35 U.S.C. § 102(e), because all claims in that patent were subsequently cancelled in an IPR.  Baxter argued that this eliminated the statutory requirement that the reference be "granted" and hence § 102(e) no longer applied.  The panel rejected that interpretation of the statute, saying that the Alexander reference satisfied the statutory terms because "the grant[] had occurred" and that the statute did not require the patent be currently valid to qualify as prior art.

Finally, the panel addressed Baxter's secondary considerations evidence, agreeing with the Board that it was "weak" and did not rebut the prima facie case.

The Court's invalidation outcome is rare with regard to an obviousness determination by the PTAB because it is equally rare that the Board does not amass sufficient evidence to be considered substantial and thus is not entitled to deference under Dickerson v. Zurko.  But where, as here, an IPR petitioner can demonstrate sufficient paucity of factual basis supporting the PTAB's non-obviousness determination, the outcome is unsurprising no matter how infrequent it may be in practice.

Becton, Dickinson & Co. v. Baxter Corp. Englewood (Fed. Cir. 2021)
Panel: Circuit Judges Prost, Clevenger, and Dyk
Opinion by Circuit Judge Dyk

Raytheon Technologies Corp. v. General Electric Co. (Fed. Cir. 2021)

By Michael Borella --

The legal concept of obviousness is tricky.  A claimed invention is found obvious if the prior art teaches or suggests all claim limitations and one of ordinary skill in the art would have been motivated to combine the relevant teachings of the references.  The inherent subjectivity of such an analysis can lead to reasonable people disagreeing on whether an invention is ultimately patentable.  But it does not end there -- like an onion, obviousness has layers.[1]  Normally, whether the references themselves provide enabling disclosure is not relevant.  Except when it is.

Raytheon is the owner of U.S. Patent No. 9,695,751, which was challenged by General Electric (GE) in an inter partes review before the Patent Trial and Appeal Board (PTAB).  Of note are claims 1-3 of the patent, shown in part below.

1.  A gas turbine engine comprising:
    a fan including a plurality of fan blades . . . ;
    a compressor section;
    a combustor in fluid communication with the compressor section;
    a turbine section in fluid communication with the combustor, the turbine section including a fan drive turbine and a second turbine . . . ; and
    a speed change system configured to be driven by the fan drive turbine to rotate the fan about the axis; and
    a power density at Sea Level Takeoff greater than or equal to 1.5 lbf/in³ and less than or equal to 5.5 lbf/in³ and defined as thrust in lbf measured by a volume of the turbine section in in³ measured between an inlet of a first turbine vane in said second turbine to an exit of a last rotating airfoil stage in said fan drive turbine.

2.  The gas turbine engine as recited in claim 1, wherein the fan drive turbine has from three to six stages.

3.  The gas turbine engine as recited in claim 2, wherein said number of fan blades is less than 18 and the second turbine has two stages.

In the words of the court, "[t]he '751 patent generally claims a geared gas turbine engine with two turbines and a specific number of fan blades and turbine rotors and/or stages."  Further, the "key distinguishing feature of the claims is the recitation of a power density range that the patent describes as being 'much higher than in the prior art.'"  Here, power density is defined as sea-level-takeoff (SLTO) thrust divided by the engine turbine volume.

During the proceeding, Raytheon disclaimed claims 1 and 2 (among others), leaving claim 3 as representative.  GE's obviousness contentions for claim 3 relied only on a single reference, a non-patent literature document by Knip.

Knip is "a 1987 NASA technical memorandum that envisions superior performance characteristics for an imagined advanced turbofan engine incorporating all composite materials."  It is undisputed that such an engine could not be built in 1987 and still cannot be built today.  But such speculation allowed Knip "to assume aggressive performance parameters for an advanced engine, including then-unachievable pressure ratios and turbine temperatures."  Nonetheless, Knip does not disclose SLTO thrust, turbine volume, or power density for this hypothetical engine.  GE asserted that "because power density is a result-effective variable, even if Knip did not disclose a turbine section volume and/or SLTO thrust that resulted in a power density within the claimed range, it would have nevertheless been obvious to a skilled artisan to modify the thrust and/or turbine volume for Knip's engine to optimize the power density."

Before the PTAB, Raytheon argued that "GE's expert employed a flawed methodology in deriving the power density of Knip's advanced engine from the parameters that Knip disclosed," and that Knip's disclosure failed to enable a skilled artisan to make the claimed invention.  GE countered by stating that "the issue of whether Knip enabled its advanced engine was irrelevant to the question whether a skilled artisan reviewing Knip could make the '751 Patent's engine (using any already available materials) without undue experimentation."  Note the subtle difference in the points being made -- Raytheon is alleging that Knip does not enable one to make the invention of the '751 patent, while GE is addressing whether Knip enables one to make Knip's own engine.

In any event, the PTAB ultimately found Knip enabling because it allowed "a skilled artisan to "determine a power density as defined in claim 1, and within the range proscribed in claim 1."  As a result, the PTAB concluded that Knip rendered the claims obvious.

On review, the Federal Circuit set forth the delicate interactions between obviousness and enablement.  Writing for the Court, Judge Chen noted that "[i]n general, a prior art reference asserted under § 103 does not necessarily have to enable its own disclosure, i.e., be 'self-enabling,' to be relevant to the obviousness inquiry."  To that point, "a reference that does not provide an enabling disclosure for a particular claim limitation may nonetheless furnish the motivation to combine, and be combined with, another reference in which that limitation is enabled."  Further, "such a reference may be used to supply claim elements enabled by other prior art or evidence of record."

Thus, the point at issue in this case was whether a skilled artisan could have made the claimed invention regardless of whether the cited references are self-enabling.  Of particular relevance to single-reference obviousness contentions such as one made by GE, is that "a standalone § 103 reference must enable the portions of its disclosure being relied upon."

The Court found that the PTAB erred by focusing on whether Knip enabled determination of a power density.  The PTAB should have considered "whether Knip enabled a skilled artisan to make and use the claimed invention."  The PTAB's conclusion of obviousness could have been supported "if GE had presented other evidence to establish that a skilled artisan could have made the claimed turbofan engine with the recited power density."  But that did not happen.  Therefore, according to the Court, "Knip's self-enablement (or lack thereof) is not only relevant to the enablement analysis, in this case it is dispositive."

The Court also found GE's use of expert testimony to be lacking, because its expert constructed "a computer model simulation of Knip's imagined engine" rather than the actual engine.  In contrast, Raytheon's expert presented unrebutted evidence of non-enablement -- the "unavailability of the revolutionary composite material contemplated by Knip."  Raytheon also "submitted evidence that the exceptional temperature and pressure parameters cited in Knip had not been achieved through other means as of the priority date."

Moreover, GE argued that a skilled artisan could achieve the claimed power density by optimizing Knip's engine.  But the Court rejected this notion, stating that "[i]f a skilled artisan cannot make Knip's engine, a skilled artisan necessarily cannot optimize its power density."

For these reasons, the Court reversed the PTAB's finding of claim 3 to be obvious.

This case is interesting, though it presents an avenue for arguing for non-obviousness that is unlikely to be available in practice very often.  Here, the Knip reference was admittedly speculative, and gaps between Knip's speculation and reality matched up with the gaps in GE's arguments.  By adding in other references or reasoning, the outcome may have differed.  Perhaps the holding here is best summarized by Judge Chen writing "if an obviousness case is based on a non-self-enabled reference, and no other prior art reference or evidence would have enabled a skilled artisan to make the claimed invention, then the invention cannot be said to have been obvious."

[1] Also like an onion, obviousness as a legal principle has the ability to make one involuntarily cry.

Raytheon Technologies Corp. v. General Electric Co. (Fed. Cir. 2021)
Panel: Circuit Judges Lourie, Chen, and Hughes
Opinion by Circuit Judge Chen

 

Takeda Pharmaceutical Co. v. Torrent Pharmaceuticals Ltd. (Fed. Cir. 2021)

By Kevin E. Noonan --

In a terse, non-precedential opinion, the Federal Circuit affirmed a district court's judgment that Defendants Torrent Pharmaceuticals and Indoco Remedies Ltd. had failed to prove that the claims asserted by Plaintiff/patentee Takeda were obvious, either under the statute or the judicially created doctrine of obviousness-type double patenting, in Takeda Pharmaceutical Co. v. Torrent Pharmaceuticals Ltd.

The case arose in ANDA litigation over Takeda's allegations that Defendants would infringe claims 4 and 12 of Orange Book-listed U.S. Patent No. 7,807,689:

4.  A compound of the formula

or pharmaceutically acceptable salts thereof.

12.  A compound of the formula

wherein the compound is present as a benzoate salt.

These claims cover the active ingredient for Takeda's alogliptin benzoate formulations, marketed under the brand names Nesina®, Kazano®, and Oseni® for treatment of Type II diabetes.  Defendants' challenges were based on factual determinations by the District Court, including testimony from three experts; based on this evidence the District Court found that Defendants had not established invalidity on either statutory (over the cited art) or obviousness-type double patenting grounds.

Not surprisingly the Federal Circuit affirmed, in an opinion by Judge Chen joined by Judges Mayer and Dyk.  The Court recognized Defendants' arguments to be grounded in whether a skilled worker would have had a reasonable expectation of success, in the context of what the opinion characterized as "the undisputed factual finding" that "in the relevant art of pharmaceutical development, very small changes in molecular structure can have dramatic effects on the properties of the molecule" and "the more distantly related two chemical structures are, the less probable it will be that they have the same biological effect."  Regarding obviousness-type double patenting, Defendants asserted Takeda's co-owned U.S. Patent No. 7,723,344 as disclosing a "lead compound" (termed F162 in the opinion) that upon further development would have rendered the alogliptin compound obvious.  This contention was that the structural differences between these compounds (replacement of a pyrimidinone scaffold with uracil) would have been obvious in view of two scientific references, which Defendants argued taught "scaffold replacement techniques" and that uracil lowered blood glucose in animal studies, respectively.  The opinion rejected this argument on the grounds that "[c]ollectively, these references, along with other evidence of record, do not demonstrate that uracil was known to possess DPP-IV inhibitory activity or other characteristics desirable in a scaffold for DPP-IV inhibition as of the relevant priority date" and accordingly that there was no clear error in the District Court's determination that Defendants failed to establish invalidity on obviousness-type double patenting grounds over this art.

Defendants' second argument in favor of obviousness-type double patenting is that the skilled worker would have been motivated to replace a fluoro-olefin substituents in F162 by an amide in alogliptin, based on the skilled worker recognizing these substituents as isosteres.  The District Court had found that the skilled worker would not have been motivated to make this substitution, which the Federal Circuit held was not clear error because Defendants had not cited any art that provided this motivation and there were "myriad more conservative and predictable modifications that were available for transforming F162 into a 'novel' compound" (and Takeda had elicited an admission from Defendants' expert at trial that he did not know of any prior art disclosing this specific modification.

Turning to obviousness under 35 U.S.C. § 103, Defendants asserted art purportedly teaching substitution of a xanthine scaffold moiety for the uracil moiety in alogliptin.  The Federal Circuit agreed that the District Court did not err in concluding that Defendants had not shown that the skilled worker could reasonably expected this substitution to be successful.  This was because "the interchangeability references on which Indoco relies do not pertain to DPP-IV inhibitors or diabetes [thereby failing any expectation that the substituted compound would be operative], nor do they, or any other prior art of record, teach substituting an existing xanthine scaffold for uracil (thereby failing to establish the viability of the substitution on structural grounds]."

The opinion concludes by considering Defendants' argument that the District Court erred as to the level of skill of the ordinarily skilled worker.  This question arose with regard to whether the skilled person should have "specific experience developing DPP-IV inhibitors and/or type II diabetes drugs," and was relevant to the weight the District Court gave to the testimony of Takeda's expert who lacked such experience.  The Federal Circuit found this distinction immaterial because the District Court considered the prior art from both perspectives (i.e., a skilled artisan with and without such expertise) and found Defendants had not shown Takeda's asserted claims to be obvious ("[g]iven the substantive gaps in establishing motivation and reasonable expectation of success identified above, the record supports the district court's conclusion that it would have reached the same outcome under either definition of a skilled artisan").  Moreover, the opinion states that Defendants failed to show that applying the standard to the skilled artisan issue they espouse would have made any difference.   Accordingly, the Federal Circuit affirmed the District Court's finding against Defendants.

Takeda Pharmaceutical Co. v. Torrent Pharmaceuticals Ltd. (Fed. Cir. 2021)
Nonprecedential disposition
Panel: Circuit Judges Dyk, Mayer, and Chen
Opinion by Circuit Judge Chen

Trustees of Columbia University v. Illumina, Inc. (Fed. Cir. 2021)

By Kevin E. Noonan --

While much has been written about the effect of the post-grant review provisions of the Leahy-Smith America Invents Act (2012) in invalidating U.S. patents, the change in the law most responsible for how easy it has become to invalidate patents is arguably the Supreme Court's decision in Dickinson v. Zurko (1999).  That decision, which applied the provisions of the Administrative Procedures Act (1948) to judicial review of U.S. Patent and Trademark Office determinations mandated that disgruntled patentees and patent applicants show that factual decisions by the Office are not supported by substantial evidence in order to overturn these decisions.  These considerations extend even to questions of law like obviousness, which are based on factual determinations. And this difficulty was ultimately the reason Columbia University did not prevail in its attempt to overturn the Patent Trial and Appeal Board's judgment in an inter partes review proceeding that invalidated challenged patent claims for obviousness in Trustees of Columbia University v. Illumina, Inc.

The appeal arose from five IPRs involving U.S Patent Nos. 9,718,852; 9,719,139; 9,708,358; 9,725,480; and 9,868,985.  The claims were directed to methods for "sequencing by synthesis" (SBS) (methods of nucleic acid sequencing) and recited, in separate patents, analogues of the nucleotide bases adenine, guanine, cytosine, and thymidine.  These derivatives were modified by having a unique detectable label conjugated to the base by a cleavable linker and further using a small, cleavable chemical moiety to block or cap the 3' hydroxyl on the deoxyribose sugar comprising the nucleotide to prevent extension of a polymerize nucleic acid chain:

where "Y" is a cleavable linker, "Tag" is the detectable label, and "OR" is the cleavable chemical moiety in this adenine embodiment of the claimed invention; analogous embodiments for guanine, cytosine, and thymidine were provided in particular challenged patents.  In the practice of the claimed methods, these species were added to a reaction mixture comprising a polymerase capable of incorporating the modified base into a growing nucleic acid strand, synthesis permitted to occur with detection of the specific detectable tags, and then cleavage of the blocking moiety and the tag with the next cycle of polymerization permitted to occur.  These steps comprised a cycle of the sequencing by synthesis (SBS) reaction and could be used inter alia in automated sequencing regimes.

The relevant limitations of the claims involved "the use of a capping group that is 'small,' and not a 'ketone group,' 'a methoxy group, or an ester group.'"  The four references used by the PTAB to hold these claims obvious included use of an allyl group which satisfies these characteristics.  The references were:  "(1) Tsien et al., WO 91/06678 (May 16, 1991) ("Tsien"), (2) James M. Prober et al., A System for Rapid DNA Sequencing with Fluorescent Chain-Terminating Dideoxynucleotides, 238 SCIENCE 336–41 (Oct. 16, 1987) ("Prober"), (3) Michael L. Metzker et al., Termination of DNA synthesis by novel 3′- modified-deoxy-ribonucleoside 5'-triphosphates, 22 NUCLEIC ACIDS RESEARCH 4259–67 (1994) ("Metzker"), and (4) Dower et al., U.S. Patent 5,547,839, Aug. 20, 1996 ("Dower")."  The Tsien and Dower references taught SBS methods, Tsien using allyl capping groups, and the Dower patent teaching "small" capping groups, which can include allyl groups.  The Metzker reference, which provided one basis for Columbia's argument that the challenged claims were not obvious, disclosed a DNA sequencing method "equivalent to SBS" but taught that allyl capping groups provided incomplete activity.  The Board found that the claims to nucleotide analogues were obvious over the combination of the Tsien and Prober references or the combination of the Metzker, Prober, and Dower references (although the Federal Circuit's opinion states that the Prober reference was directed to "limitations not at issue in this appeal" and provided no further explication of that reference's relevance).

The basis for the Board's first determination of obviousness is that the Tsien reference disclosed the use of allyl capping groups in SBS methods.  The Metzker reference was applied in the alternative for the same teaching, the Board disagreeing with Columbia's position that the incomplete termination teachings of Metzker taught away from Tsien's teaching that allyl capping groups could be used for SBS methods as well as concluding that "a person of ordinary skill would have understood that Metzker's experiment could be further improved by 'increasing [nucleotide] concentration or reaction time.'"  The Board's conclusions were not unanimous, however, with one member of the panel dissenting on the grounds that the teachings of the Metzker reference would have "discouraged" the skilled worker from pursuing SBS methods using modified nucleotides having allyl-capped residues.

The Federal Circuit affirmed, in an opinion by Judge Lourie joined by Judges O'Malley and Reyna.  The panel rejected in turn the three arguments asserted by Columbia.  First, Columbia contended that the Board erred in its interpretation of the Metzker reference's teachings, and failed to recognize that those teachings would have constituted a "teaching away" by informing that skilled person that allyl capping groups were not efficient enough for successful SBS (because, according to the opinion's characterization of Columbia's argument, "SBS requires efficient incorporation of nucleotides").  The panel held that the Board's conclusions regarding the Metzker reference's teachings were supported by substantial evidence, and that teaching away must be shown by "'clear discouragement' from implementing a technical feature," citing Univ. of Md. Biotechnology Inst. v. Presens Precision Sensing GmbH, 711 F. App'x. 1007, 1011 (Fed. Cir. 2017) (quoting In re Ethicon, Inc., 844 F.3d 1344, 1351 (Fed. Cir. 2017)).  In the Court's view, Columbia did not meet this threshold based on three facts.  First, the Tsien reference taught successful SBS methods using nucleotides having allyl capping groups.  Second, the Board "carefully evaluated Metzker and found that it confirms rather than negates Tsien's teachings."  With regard to whether the SBS methods were successful enough, the panel was content with the Board's determination that Metzker did not describe SBS methods using allyl-capped nucleotide analogues as failures.  And third, while the art taught SBS methods using alternative capping groups the existence of "better" alternatives does not negate "inferior" alternatives in the prior art from supporting an obviousness determination.

Columbia's second argument, that the skilled worker would not have had a reasonable expectation of success in achieving SBS using analogue nucleotides comprising allyl-capped moieties, was equally unavailing.  The panel's basis for rejecting this argument was that a "reasonable expectation of success" does not require "the best of all possible results."  (And in a wonderful aphorism, the opinion notes that "[s]uccess may not have only one definition."  Words to live by indeed.)  Once again, the Court held that the Board's findings on the reasonable expectation of success issue was supported by substantial evidence.  These findings include as a side note that Illumina had in a separate reexamination made the argument that the Tsien reference would not have provided a reasonable expectation of success for SBS methods, which the Board and the Court rejected because in that reexamination the priority date (which affected what was known by the person of skill in the art) was 1994 rather than, as here, October 2000.  With regard to the application of the inefficient termination by allyl capping moieties in Metzker, the panel agreed with the Board that the skilled worker "would have known that 'increasing concentration [of nucleotides] or reaction time could help incorporation efficiency.'"  Despite the necessarily speculative nature of that finding the Court held that the Board was entitled to rely on Illumina's expert to support it.  And the panel refused the invitation it perceived Columbia was making that it "reweigh" the evidence to come to a different conclusion.

Finally, Columbia's own specification provided support for the Board's reasoning that the skilled worker would expect (reasonably) that nucleotide analogues comprising allyl capping moieties could be used in SBS methods.  As has frequently been the case in adverse decisions in other contexts (see Ariosa Diagnostics, Inc. v. Sequenom, Inc., for example), disclosure intended to render claims as unlimited as possible here were used to support their invalidity.  Indeed, Columbia's patent cited the Metzker reference "as evidence that allyl groups can be 'used to cap the 3′-OH group using well-established synthetic procedures'" (emphasis in opinion) as well as other positive statements about this reference.  And the opinion cited PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1362 (Fed. Cir. 2007), for the proposition that "[a]dmissions in the specification regarding the prior art are binding on the patentee for purposes of a later inquiry into obviousness" (itself a quote from Constant v. Advanced Micro-Devices, Inc., 848 F.2d 1560, 1570 (Fed. Cir. 1988)).  The opinion asserts that "[i]n sum . . . Columbia has not pointed to any flaw in the Board's analysis."  In the Court's view, the Board was given "two alternative theories" of whether (or not) the skilled artisan would have had a reasonable expectation of success in using detectably labeled nucleotide analogues comprising allyl capping groups in SBS methods and substantial evidence supported their conclusion.

As for Columbia's third argument, that the Metzker teachings (as flawed as Columbia contended they were) were limited to adenine analogues, and did not support obviousness of challenged patents relating to guanine, cytosine, or thymidine analogues, the panel summarily rejected it, stating that the Board had considered the evidence to support application of these references in its obviousness rejections for these patents as well, and substantial evidence supported the Board's conclusions.

The message is clear:  a patentee (or applicant) facing the Board's invalidation (or rejection) based on obviousness will find it very difficult to overturn unless the factual basis upon which the Board rests its obviousness conclusion is not supported by substantial evidence.  This reality suggests that the fight must be had before the Board, with as much contrary evidence as possible of whatever form or type supports a conclusion of non-obviousness.  Because cases like this one strongly suggest that it is unlikely that there will be another opportunity to prevail before the Federal Circuit.  

Trustees of Columbia University v. Illumina, Inc. (Fed. Cir. 2021)
Nonprecedential disposition
Panel: Circuit Judges Lourie, O'Malley, and Reyna
Opinion by Circuit Judge Lourie