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`Entered: February 10, 2016
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________________
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`PRAXAIR DISTRIBUTION, INC.
`Petitioner
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`v.
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`MALLINCKRODT HOSPITAL PRODUCTS IP LTD.,
`Patent Owner
`_______________________
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`Case IPR2015-00529
`U.S. Patent No. 8,846,112 B2
`_______________________
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`Before LORA M. GREEN, TINA E. HULSE, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
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`
`
`PATENT OWNER’S SUR-REPLY TO PRAXAIR DISTRIBUTION, INC.’S
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 8,846,112
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`Case IPR2015-00529
`U.S. Patent No. 8,849,112
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`TABLE OF CONTENTS
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`I.
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`II.
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`Introduction ...................................................................................................... 1
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`The Construction of “Pharmaceutically Acceptable Nitric Oxide
`Gas” Is Undisputed .......................................................................................... 1
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`III. The “Providing . . . Information” Elements Of Claims 1-11 Are
`Entitled To Patentable Weight ......................................................................... 2
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`A.
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`B.
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`AstraZeneca Is Inapposite ..................................................................... 3
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`King Is Also Inapposite ......................................................................... 5
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`IV. Claims 1-11 Of The ’112 Patent Are Not Directed To An
`Inherent Property Of Nitric Oxide ................................................................... 9
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`V.
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`The Objective Indicia Of Non-Obviousness Are Compelling ...................... 10
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`VI. Conclusion ..................................................................................................... 10
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`i
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`Case IPR2015-00529
`U.S. Patent No. 8,849,112
`I.
`INTRODUCTION1
`Petitioner’s arguments assume that claims 1-11 of the ’112 Patent are
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`directed only to the provision of prior art nitric oxide gas. They are not; the
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`claimed methods require providing pharmaceutically acceptable nitric oxide gas,
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`along with critical information to effectuate new methods of using the drug—a
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`safer treatment that helps avoid serious adverse events in at-risk patient
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`populations. As set forth in the specification, these new methods would not exist
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`without the claimed information. The providing information claim element is
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`entitled to patentable weight because it is inextricably intertwined with the
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`implementation—and function—of the claimed methods. The Board should affirm
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`the claims’ validity.
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`II. THE CONSTRUCTION OF “PHARMACEUTICALLY
`ACCEPTABLE NITRIC OXIDE GAS” IS UNDISPUTED
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`Petitioner neither disputes Patent Owner’s construction of “pharmaceutically
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`acceptable nitric oxide gas” nor proposes an alternative. The only expert testimony
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`comes from Patent Owner’s expert. (See Ex. 2020 at 30-31; Ex. 1057 at 64:4-21.)
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`The Board should adopt Patent Owner’s uncontested construction: “suitably safe
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`1 Patent Owner sought, and was granted, leave to file a 10 page sur-reply to
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`respond to arguments first raised in Petitioner’s Reply.
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`1
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`Case IPR2015-00529
`U.S. Patent No. 8,849,112
`for pharmaceutical use.” (See Resp. at 21-23.)2,3
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`III. THE “PROVIDING . . . INFORMATION” ELEMENTS OF CLAIMS
`1-11 ARE ENTITLED TO PATENTABLE WEIGHT
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`Petitioner contends that the “providing . . . information” elements cannot be
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`functionally related to the claimed methods for two reasons: (1) per AstraZeneca
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`LP v. Apotex, Inc., 633 F.3d 1042 (Fed. Cir. 2010), “instructions for use do not
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`create a new or unobvious drug or change the drug’s ability to treat [a disease]”;
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`and (2) per King Pharm., Inc. v. Eon Labs, Inc., 616 F.3d 1267 (Fed. Cir. 2010),
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`“[i]nformation regarding how to administer [a pharmaceutically acceptable drug]
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`does not change the method of obtaining and supplying that [drug].” (Reply at 8,
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`2 Petitioner’s suggestion that the “preamble is not limiting,” (Reply at 6 n.3), is
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`wrong; Patent Owner relied on the preamble to overcome prior art and it is
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`therefore limiting as a matter of law. (See Resp. at 19-20.)
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`3 Petitioner’s suggestion that this construction may be impermissible because it
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`could “var[y] over time” (Reply at 6-7 n.4) is incorrect. See Mass. Inst. of Tech. &
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`Elecs. for Imaging, Inc. v. Abacus Software, 462 F.3d 1344, 1353 (Fed. Cir. 2006)
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`(meaning of claim terms set at time of filing). Such terms are common. See, e.g.,
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`Apotex Inc. v. Alcon Pharm., Ltd., No. IPR2013-00012, 2013 WL 5970130, at *4
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`(P.T.A.B. Mar. 19, 2013) (defining “pharmaceutically acceptable vehicle” to
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`include composition that can be “safely” used).
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`2
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`Case IPR2015-00529
`U.S. Patent No. 8,849,112
`10.)4 Neither point has merit.
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`A. AstraZeneca Is Inapposite
`Petitioner’s reliance on AstraZeneca is misplaced. There, the Federal
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`Circuit found instructions contained in an FDA-required label to be functionally
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`unrelated to a claimed drug product, 633 F.3d at 1048, 1063, reasoning that “[t]he
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`instructions in no way function with the drug to create a new, unobvious product,”
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`because “[r]emoving the instructions from the claimed kit does not change the
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`ability of the drug to treat respiratory diseases.” Id. at 1065. Petitioner’s argument
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`parrots this language, but ignores the claims at issue here: “Patent Owner’s revised
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`instructions for use do not create a new or unobvious drug or change the drug’s
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`ability to treat hypoxic respiratory failure.” (Reply at 8.)5
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`4 All emphases are added unless indicated otherwise.
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`5 AstraZeneca did not hold printed instruction for a drug to be per se unpatentable;
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`it merely found that the required functional relationship was absent. All limitations
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`of a claim, including printed matter, must be considered—“the board cannot
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`dissect a claim, excise the printed matter from it, and declare the remaining portion
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`of the mutilated claim to be unpatentable.” In re Gulack, 703 F.2d 1381, 1385 &
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`n.8 (Fed. Cir. 1983) (explaining that its predecessor court grew “notably weary of
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`reiterating th[e] point . . . that printed matter may well constitute structural
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`limitations upon which patentability can be predicated.”).
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`3
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`U.S. Patent No. 8,849,112
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`The challenged claims, however, are not product claims as in AstraZeneca.
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`They claim new, non-obvious methods for providing a drug product to be used in a
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`safer manner. That is not a distinction without difference. While information does
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`not transform a drug product into a new product, it can transform a method into a
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`new, unobvious method.
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`Petitioner also relies on AstraZeneca’s statement that “FDA regulations
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`require a label containing information needed for the safe and effective use of any
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`drug,” which “is a requirement for FDA approval, not patentability.” 633 F.3d at
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`1065. But the claims in AstraZeneca did not contain a claim element—like the
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`“pharmaceutically acceptable” term in the claims at issue—that functionally links
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`the required safety of the drug to the claimed invention. (See Resp. at 31-33
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`(discussing relevant expert testimony).)6
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` Put simply, the information in
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`6 Contrary to Petitioner’s contentions (Reply at 13-14), expert testimony is relevant
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`to this determination. See, e.g., In re Distefano, 808 F.3d 845, 848 (Fed. Cir. 2015)
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`(printed matter analysis includes “factual findings” reviewed for “substantial
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`evidence”). Dr. Rosenthal answered the relevant factual question here. (See Ex.
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`1057 at 60:1-61:3 (“I understand that pharmaceutically acceptable nitric oxide gas
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`requires the provision of information that’s described in the ’112 patent.”); see also
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`Resp. at 31-33.)
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`4
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`U.S. Patent No. 8,849,112
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`AstraZeneca was, at best, functionally tied to FDA approval, but here it is
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`inextricably and functionally intertwined with the recited “pharmaceutically
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`acceptable” claim limitation (in addition to otherwise directly effectuating a new
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`method of using nitric oxide as described above).7 (See Resp. at 23-27.)
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`B. King Is Also Inapposite
`Petitioner’s reliance on King is similarly misplaced. Petitioner relies on
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`King to argue a lack of functional relationship because providing “[i]nformation
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`regarding how to administer [pharmaceutically acceptable nitric oxide] does not
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`change the method of obtaining and supplying that gas.” (Reply at 10.) That
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`suggestion is without merit. The drug at issue in King was normally consumed
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`with food. 616 F.3d at 1277-79. The Federal Circuit reasoned that claim language
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`informing patients of the additional benefits of doing so was not functionally
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`related to the methods, and could not impart patentability. Id. The Court
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`explained that “[i]rrespective of whether the patient is informed about the benefits,
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`the actual method, taking [the drug] with food, is the same.” 616 F.3d at 1279.
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`7 This language is absent from claims 12-22, for which Patent Owner has not
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`asserted the “providing . . . information” elements to be functionally related to the
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`methods. That difference should not be ignored. See Schumer v. Lab. Comput.
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`Sys., Inc., 308 F.3d 1304, 1316 (Fed. Cir. 2002) (“When determining the validity
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`of the claims of a patent, each claim must be separately considered.”).
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`5
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`U.S. Patent No. 8,849,112
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`That is not the case here. Unlike in King, the information the claims require
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`transforms the ordinary methods: the information is “sufficient” to cause
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`physicians to alter the methods of using nitric oxide to avoid potentially life-
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`threatening adverse events. (See Ex. 1001 at cls. 1-11.) The written description
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`discusses the required functional effect of altering nitric oxide treatment methods
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`to exclude at-risk patients and provides an example of how such information
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`empirically transformed treatment. (See, e.g., id. at 12:48-58.) The prosecution
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`history further confirms that a number of adverse events occurred without the
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`information and that the frequency of such events dropped significantly after the
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`information changed the exclusion criteria. (See, e.g., Ex. 1056 at 667.)
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`Claim 1 expressly requires that the information provided be “sufficient to
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`cause a medical provider considering inhaled nitric oxide treatment [for certain
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`contraindicated patients] . . . to elect to avoid treating one or more of [those]
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`patients” to avoid the risk of a serious side effect. (Ex. 1001 at cl. 1.) The claims
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`ensure a changed method—the information must be of the sort that is “sufficient”
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`to cause physicians to not treat at-risk patients (or, at a minimum, alter the
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`treatment plan to carefully weigh the risks of doing so, see, e.g., cls. 3-4). Several
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`dependent claims expressly require administration of nitric oxide altered by the
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`provided information: (i) Claim 3 requires receiving information and one patient
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`(not-at-risk) receiving nitric oxide treatment while another at-risk patient may not;
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`6
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`U.S. Patent No. 8,849,112
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`(ii) Claim 4 requires that at least one patient who has LVD is nevertheless
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`administered pharmaceutically acceptable nitric oxide gas; and (iii) Claim 9
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`requires discontinuing nitric oxide
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`treatment “in accordance with
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`the
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`recommendation” provided. (Id. at cls. 3, 4, 9.)
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`Petitioner has no substantive response. Its invocation of King relies on
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`mischaracterizing the claims as being limited to simply supplying nitric oxide—
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`which ignores the novel functional (and essential) effect of the provided
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`information on the administration of nitric oxide. (See Reply at 10.) Petitioner
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`never addresses the “sufficient to cause” requirement in claim 1. (Id.) For claims
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`3 and 4, Petitioner admits there are administration steps, but oddly states that they
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`are irrelevant because “[a] doctor may choose to treat or not treat a patient based
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`on her own skill and experience” (whether or not a doctor—or anyone for that
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`matter—chooses to practice a claimed method is entirely irrelevant to invalidity).
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`(Reply at 10 n.5.) And Petitioner fails to address claim 9 at all, waiving any right
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`to dispute the patentability of that claim.
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` At bottom, Petitioner ignores the critical fact that the “providing . . .
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`information” limitation is functionally intertwined with the claimed methods and
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`transforms the ordinary, prior art methods of supplying and using nitric oxide into
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`new, unobvious ones that better ensures patient safety. Because of that functional
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`relationship, the limitation should be afforded patentable weight under King.
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`7
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`U.S. Patent No. 8,849,112
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`That conclusion is confirmed by In re Huai-Hung Kao, 639 F.3d 1057,
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`1072-73 (Fed. Cir. 2011). The claimed method there required (i) administering a
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`painkiller and (ii) “providing information” about a correlation between renal
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`impairment and bioavailability of that painkiller. Id. at 1064. The Court held that
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`the “providing information” step was due no patentable weight because it had no
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`functional relationship to administering the painkiller. Id. at 1073. “Just as in
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`King,” the informing step did not “‘transform[ ] the process of taking the drug.’”
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`Id. at 1072-73 (quoting King, 616 F.3d at 1279). The converse is true here. As
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`discussed, the “providing . . . information” steps in the subject claims transform the
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`process of administering nitric oxide. (See, e.g., Ex. 1001 at cls. 1, 3, 4, 9.) The
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`specification confirms that the information is of the sort that empirically resulted in
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`such a change. (Ex. 1001 at 12:48-58.) Thus, the “providing . . . information”
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`limitations are therefore functionally related to the underlying method and deserve
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`patentable weight.
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`Indeed, the functional importance of the provided information to the claimed
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`invention here is no different from the inseparable nature of the printed digits to
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`the endless band in Gulack, 703 F.2d at 1383-87, or the essential nature of the
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`deliberately false volumetric measurements to the measuring devices in In re
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`Miller, 418 F.2d 1392, 1396 (C.C.P.A. 1969). Eliminating the printed digits in
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`Gulack or the volumetric indicia in Miller would have fundamentally altered the
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`8
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`U.S. Patent No. 8,849,112
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`function of the inventions in those cases. The same is true here—withholding the
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`provided information would eliminate the novel safer method of using nitric oxide
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`otherwise effectuated by that information.
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`IV. CLAIMS 1-11 OF THE ’112 PATENT ARE NOT DIRECTED TO AN
`INHERENT PROPERTY OF NITRIC OXIDE
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`Petitioner suggests that the challenged claims are invalid because they
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`merely “acknowledge[] an inherent property of nitric oxide.” (Reply at 11-12.)
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`The Board’s refusal to institute IPRs on the four related patents, which recognized
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`the novelty of the disclosed inventions, precludes this argument. See Nos.
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`IPR2015-00522, -00524, -00525, -00526 Paper 12. And none of Petitioner’s cases
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`involve method claims directed to the provision of information or administration
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`based on information that was previously unknown, and are thus inapposite.
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`Indeed, Petitioner only asserts that “recognizing previously unknown qualities of a
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`product is not inventive.” (Reply at 12.) But new methods can be patented. See,
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`e.g., In re Ngai, 367 F.3d 1336, 1338-39 (Fed. Cir. 2004); Prometheus Labs., Inc.
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`v. Roxane Labs., Inc., 805 F.3d 1092, 1098 (Fed. Cir. 2015) (“[A] particular
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`treatment may be effective with respect to one subset of patients and ineffective
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`(and even harmful) to another subset of patients. Singling out a particular subset of
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`patients for treatment . . . may reflect a new and useful invention that is patent
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`eligible despite the existence of prior art or a prior art patent disclosing the
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`9
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`U.S. Patent No. 8,849,112
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`treatment method to patients generally.”) (internal citation omitted).
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`V. THE OBJECTIVE INDICIA OF NON-OBVIOUSNESS ARE
`COMPELLING
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`Petitioner asserts that the INOT22 study—which the PTAB found to be
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`“compelling” with respect to the related patents—should be disregarded.
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`Petitioner supports this conclusion with only attorney argument that “[t]he
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`INOT22 study does not even relate to the challenged claims.” (Reply at 21.) The
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`record proves otherwise; Dr. Rosenthal having provided unrebutted testimony that
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`based on the results of the INOT22 study, the prescribing information for
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`INOmax® (which is approved for the treatment of neonates) was amended to
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`include the requisite warnings regarding patients with LVD. (Ex. 2020 ¶ 65; see
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`also Ex. 1001 at 9:51-56.)8 Dr. Rosenthal thus established the nexus between the
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`INOT22 study and neonatal patients, such as those in claims 1-11.
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`VI. CONCLUSION
`For the reasons set forth above, Patent Owner respectfully submits that the
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`Board should confirm the validity of the subject claims.
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`Dated: February 10, 2016
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`Respectfully submitted,
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`/Robert Steinberg/ (Reg. No. 33,144)
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`8 Dr. Rosenthal disagreed that information from a certain patient population is per
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`se irrelevant to another patient population. (Ex. 1057 at 136:23-140:21.)
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`10
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`CERTIFICATE OF SERVICE
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`Pursuant to 37 C.F.R. § 42.6(e), I certify that on this 10th day of
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`February, 2016, true and correct copies of the foregoing PATENT OWNER’S
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`SUR-REPLY TO PRAXAIR DISTRIBUTION, INC.’S PETITION FOR
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`INTER PARTES REVIEW OF U.S. PATENT NO. 8,846,112 were served by
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`electronic mail on Petitioner’s lead and backup counsel at the following email
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`addresses:
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`sanjay.murthy@klgates.com
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`benjamin.weed@klgates.com
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`sara.kerrane@klgates.com
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`michael.abernathy@klgates.com
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`margaux.nair@klgates.com
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`maria.doukas@klgates.com
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`Praxair-Ikaria@klgates.com
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`By: /Robert Steinberg/
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`Robert Steinberg (Reg. No. 33,144)
`bob.steinberg@lw.com
`Latham & Watkins LLP
`355 South Grand Avenue
`Los Angeles, CA 90071-1560
`213.485.1234; 213.891.8763 (Fax)