Appeals from the United States Patent and Trademark Office,
Patent Trial and Appeal Board in No. IPR2015-00529.
William R. Peterson, Morgan, Lewis & Bockius LLP,
Houston, TX, argued for appellant. Also represented by Sanjay
K. Murthy, Michael J. Abernathy, Maria Doukas, Chicago, IL;
Julie S. Goldemberg, Philadelphia, PA.
Kenneth G. Schuler, Latham & Watkins LLP, Chicago, IL,
argued for cross-appellant. Also represented by David K.
Callahan, Marc Nathan Zubick; Gabriel Bell, Inge Osman,
Jonathan M. Strang, Washington, DC; Robert Steinberg, Los
Prost, Chief Judge, Newman and Lourie, Circuit Judges.
Lourie, Circuit Judge.
Distribution, Inc. ("Praxair") appeals from the
inter partes review decision of the United States
Patent and Trademark Office Patent Trial and Appeal Board
("the Board") holding claim 9 of U.S. Patent 8,
846, 112 (the "'112 patent") not unpatentable
as obvious under 35 U.S.C. § 103 (2006). Praxair
Distrib., Inc. v. Mallinckrodt Hosp. Prods. IP Ltd., No.
IPR2015-00529, 2016 WL 3648375 (P.T.A.B. July 7, 2016)
("Decision"). Mallinckrodt Hospital
Products IP Ltd. ("Mallinckrodt") cross-appeals
from the same decision holding, inter alia, claims
1-8 and 10-11 unpatentable as obvious. Because we conclude
that the Board did not err in its conclusions as to claims
1-8 and 10-11, but did err with respect to claim 9, we affirm
the Board's decision in part and reverse it in part.
owns the '112 patent, which is directed to methods of
distributing nitric oxide gas cylinders for pharmaceutical
applications. Inhaled nitric oxide is approved by the U.S.
Food and Drug Administration ("FDA") for treating
neonates with hypoxic respiratory failure, '112 patent
col. 1 ll. 21-25, a condition where oxygen levels in the
blood are too low. Nitric oxide functions to dilate blood
vessels in the lungs and can thereby improve blood
oxygenation. Id. col. 3 ll. 34-56. Mallinckrodt
exclusively supplies inhaled nitric oxide in the United
States for pharmaceutical use under the brand name
nitric oxide may cause harmful side effects. For example, the
specification of the '112 patent describes a clinical
study, INOT22, which identified patients with preexisting
left ventricular dysfunction ("LVD") as having an
increased risk of serious adverse events ("SAEs"),
which include pulmonary edema ("PE"), when
administered nitric oxide. Id. col. 14 ll. 17-25.
Patients with preexisting LVD are characterized by having a
pulmonary capillary wedge pressure ("PCWP") greater
than 20 mm Hg. Id. col. 1 ll. 56-61. Accordingly,
after identifying the relationship between preexisting LVD
and SAEs in patients administered nitric oxide, the INOT22
protocol was updated to exclude from the study patients
having PCWP greater than 20 mm Hg. Id. col. 14 ll.
19-21. The specification of the '112 patent, however,
advises only that "[t]he benefit/risk of using [inhaled
nitric oxide] in patients with clinically significant LVD
should be evaluated on a case by case basis, "
id. col. 14 ll. 21-25, and further proposes amending
the INOmax prescribing information to include "a
precaution for patients with LVD, " id. col. 9
claims of the '112 patent generally require supplying a
medical provider with a cylinder of nitric oxide gas and
providing the medical provider with certain prescribing
information relating to the harmful side effects of nitric
oxide for certain patients identified in the INOT22 study.
Claim 1 is illustrative and reads as follows:
1. A method of providing pharmaceutically acceptable nitric
oxide gas, the method comprising: obtaining a cylinder
containing compressed nitric oxide gas in the form of a
gaseous blend of nitric oxide and nitrogen;
supplying the cylinder containing compressed nitric oxide gas
to a medical provider responsible for treating neonates who
have hypoxic respiratory failure, including some who do not
have left ventricular dysfunction;
providing to the medical provider (i) information that a
recommended dose of inhaled nitric oxide gas for treatment of
neonates with hypoxic respiratory failure is 20 ppm nitric
and (ii) information that, in patients with preexisting left
ventricular dysfunction, inhaled nitric oxide may increase
pulmonary capillary wedge pressure (PCWP), leading to
pulmonary edema, the information of (ii) being sufficient to
cause a medical provider considering inhaled nitric oxide
treatment for a plurality of neonatal patients who (a) are
suffering from a condition for which inhaled nitric oxide is
indicated, and (b) have pre-existing left ventricular
dysfunction, to elect to avoid treating one or more of the
plurality of patients with inhaled nitric oxide in order to
avoid putting the one or more patients at risk of pulmonary
Id. col. 14 ll. 28-52. We refer to the last two
claim limitations of claim 1 collectively as the
"providing information" limitation.
dependent claims add additional steps directing what a
recipient of the provided information should do with it.
Claim 3 depends from claim 1 and requires determining that a
neonatal patient has preexisting LVD and then
"evaluating the potential benefit of treating the
[neonatal patient] with 20 ppm inhaled nitric oxide vs. the
potential risk that inhaled nitric oxide could cause an
increase in PCWP leading to pulmonary edema" (the
"evaluating" limitation). Id. col. 14 ll.
57-66. Claim 9 depends from independent claim 7. Claim 7
concludes with a "recommendation that, if pulmonary
edema occurs in a patient who has pre-existing [LVD] and is
treated with inhaled nitric oxide, the treatment with inhaled
nitric oxide should be discontinued" (the
"recommendation" limitation). Id. col. 15
ll. 60-63. Claim 9 then reads:
9. The method of claim 7, further comprising:
performing at least one diagnostic process to identify a
neonatal patient who has hypoxic respiratory failure and is a
candidate for inhaled nitric oxide treatment;
determining prior to treatment with inhaled nitric oxide that
the neonatal patient has pre-existing left ventricular
treating the neonatal patient with 20 ppm inhaled nitric
oxide, whereupon the neonatal patient experiences pulmonary
in accordance with the recommendation of [claim 7],
discontinuing the treatment with inhaled nitric oxide due
to the neonatal patient's pulmonary edema.
Id. col. 16 ll. 2-13 (emphases added).
petitioned for inter partes review of claims 1- 19
of the '112 patent, which the Board instituted. The Board
held that claims 1-8 and 10-19 would have been obvious over
the INOmax Label,  Bernasconi,  Loh,  and Goyal.
Decision, 2016 WL 3648375, at *22. But the Board
concluded that claim 9 was not unpatentable as obvious over
those same references. Id. at *19.
present appeal involves several disputes over the Board's
claim constructions and obviousness analysis. The Board found
that a person of ordinary skill was at least a physician with
experience treating pediatric heart and lung disease and
administering vasodilators, and found "that the overall
level of skill in the art is high." Id. at *4.
In construing the claims, the Board applied the printed
matter doctrine. The Board interpreted the providing
information, evaluating, and recommendation claim limitations
to be either printed matter or purely mental steps not
entitled to patentable weight, as those limitations lacked a
functional relationship to the other claim limitations except
in claim 9. Id. at *9-10. For claim 9, however, the
Board interpreted "in accordance with" to mean
"based on, or as a result of" the recommendation to
discontinue nitric oxide treatment from claim 7, thereby
establishing a functional relationship to the recommendation
limitation. Id. at *11.
Board also construed "pharmaceutically acceptable nitric
oxide gas" in the preambles of claims 1 and 7 as
"nitric oxide gas that is suitable for pharmaceutical
use, " and rejected Mallinckrodt's proposed
construction of "pharmaceutically acceptable" that
would require considering information provided in the label
of the supplied product. Id. at *6-7.
to patentability, the Board found that the cited prior art
collectively taught each limitation of claims 1-8 and 10-19
that did have patentable weight, and that a person of
ordinary skill in the art would have been motivated to
combine the INOmax Label, Bernasconi, Loh, and Goyal
references. Id. at *14-18. The Board therefore held
claims 1-8 and 10-19 unpatentable for obviousness.
Id. However, the Board did not so conclude with
respect to claim 9. The only reference considered by the
Board regarding claim 9 was Bernasconi. Id. at *19.
Bernasconi disclosed administering nitric oxide to new-borns
with hypoxic respiratory failure at the FDA-recommended dose
of 20 ppm. Bernasconi also discussed several reports of
"negative effects of inhaled [nitric oxide] in patients
with [LVD], " including "rapid left heart failure
and pulmonary oedema." J.A. 249. Accordingly, Bernasconi
emphasized "the need for careful observation and
intensive monitoring during [nitric oxide] inhalation in
patients with left ventricular failure." Id.
Board found that Bernasconi did not teach or suggest
discontinuing nitric oxide treatment when a patient with LVD
experiences a pulmonary edema, but rather, "contrary to
the claim language, " contemplated administering nitric
oxide to patients with LVD as long as they were carefully
monitored. Decision, 2016 WL 3648375, at *19.
Furthermore, the Board found "compelling"
Mallinckrodt's argument based on secondary
considerations, namely that "if it were obvious to a
person of ordinary skill in the art to exclude children with
LVD from treatment with [nitric oxide], the experts in the
field who designed the [INOT22] study would have excluded
those children from the original protocol." Id.
As a result, the Board held that Praxair did not prove by a
preponderance of the evidence that claim 9 was unpatentable
as obvious. Id.
timely appealed from the Board's decision as to claim 9,
and Mallinckrodt cross-appealed from the same decision as to
claims 1-8 and 10-11. We have jurisdiction under 28 U.S.C.
review of a Board decision is limited. In re Baxter
Int'l, Inc. 678 F.3d 1357, 1361 (Fed. Cir. 2012). We
review the Board's legal determinations de novo,
In re Elsner, 381 F.3d 1125, 1127 (Fed. Cir. 2004),
but we review the Board's factual findings underlying
those determinations for substantial evidence, In re
Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000). A
finding is supported by substantial evidence if a reasonable
mind might accept the evidence as adequate to support the
finding. Consol. Edison Co. v. NLRB, 305 U.S. 197,
is a question of law with underlying factual issues,
including the scope and content of the prior art, differences
between the prior art and the claims at issue, the level of
ordinary skill, and relevant evidence of secondary
considerations. Graham v. John Deere Co., 383 U.S.
1, 17-18 (1966). Claim construction is also a question of law
that may involve underlying factual inquiries. Teva
Pharm. USA, Inc. v. Sandoz, Inc., 135 S.Ct. 831, 841
(2015). We review the Board's claim construction based
solely on intrinsic evidence de novo, while we
review subsidiary factual findings regarding extrinsic
evidence for substantial evidence. HTC Corp. v. Cellular
Commc'ns Equip., LLC, 877 F.3d 1361, 1367 (Fed. Cir.
Claims 1-8 and 10
it underlies the ultimate obviousness issue, we first address
Mallinckrodt's cross-appeal challenging the Board's
application of the printed matter doctrine to claims 1-8 and
Mallinckrodt argues that the Board erred in applying the
printed matter doctrine during claim construction rather than
when it assessed patentability. Mallinckrodt also argues that
the Board substantively misapplied the printed matter
doctrine by extending it to encompass mental steps.
Furthermore, Mallinckrodt contends that the Board erred in
construing the term "pharmaceutically acceptable, "
and that the broadest reasonable interpretation of the term
supplies a functional relationship between any claimed
printed matter and the other limitations of the claims of the