Merck & Cie v. Gnosis S.P.A.

United States Court of Appeals
for the Federal Circuit
______________________
MERCK & CIE,
Appellant
v.
GNOSIS S.P.A., GNOSIS BIORESEARCH S.A.,
GNOSIS U.S.A., INC.,
Appellees
______________________
2014-1779
______________________
Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. IPR2013-
00117.
______________________
Decided: December 17, 2015
______________________
THOMAS J. PARKER, Alston & Bird LLP, New York,
NY, argued for appellant. Also represented by JITENDRA
MALIK, Durham, NC; KIRK T. BRADLEY, Charlotte, NC
JOSEPH CWIK, Amin Talati & Upadhye, LLC, Chicago,
IL, argued for appellee. Also represented by JONATHAN
JACOB KRIT, Amin Talati, LLC, Chicago, IL.
______________________
Before NEWMAN, PLAGER, and HUGHES, Circuit Judges.
2 MERCK & CIE v. GNOSIS S.P.A.
Opinion for the court filed by Circuit Judge HUGHES.
Dissenting opinion filed by Circuit Judge NEWMAN.
HUGHES, Circuit Judge.
Merck & Cie appeals from the Patent Trial and Ap-
peal Board’s decision that the contested claims of its
patent are invalid for obviousness. Merck argues that the
prior art taught away from the claimed method, and that
objective indicia of non-obviousness further support the
patentability of the claims. Because the Board’s factual
findings to the contrary were supported by substantial
evidence and because we agree with the Board’s ultimate
conclusion of obviousness, we affirm.
I
A
Merck owns U.S. Patent No. 6,011,040. At the re-
quest of Gnosis S.p.A., Gnosis Bioresearch S.A., and
Gnosis U.S.A. (collectively, Gnosis) the Board instituted
inter partes review of claims 1–3, 5, 6, 8, 9, 11–15, and
19–22 of the ’040 patent. Merck filed a response and a
motion to cancel claims 1–3, 5, 6, and 13, which the Board
granted. Accordingly, the Board only reviewed the pa-
tentability of dependent claims 8, 9, 11, 12, 14, 15, and
19–22.
The ’040 patent relates to methods of using folates to
lower levels of homocysteine in the human body. ’040
patent, col. 1 ll. 10–14. Homocysteine is an amino acid
that, when present in excessive quantities, can cause
severe cardiovascular, ocular, neurological, and skeletal
disorders. Id. at col. 1 ll. 60–62. One way the body regu-
lates homocysteine levels is through a metabolic process
called the methionine cycle, in which homocysteine is
converted to methionine. A common cause of elevated
homocysteine levels, or hyperhomocysteinemia, is a
deficiency of the enzymes and other compounds used in
MERCK & CIE v. GNOSIS S.P.A. 3
the methionine cycle to dispose of homocysteine. Id. at
col. 1 l. 45.
One such compound is 5-methyl-tetrahydrofolic acid
(5-MTHF). 5-MTHF is a reduced folate, meaning it is less
oxidized than folic acid. 5-MTHF occurs naturally in
foods, and is also produced when folic acid is metabolized
in the body. The methionine cycle uses 5-MTHF and
vitamin B12 to convert homocysteine to methionine.
There are two stereoisomers of 5-MTHF relevant
here. Stereoisomers are compounds with the same chemi-
cal formula, but with different three-dimensional orienta-
tions. The “natural” stereoisomer of 5-MTHF is 5-methyl-
(6S)-tetrahydrofolic acid or L-5-MTHF. The “unnatural”
stereoisomer is 5-methyl-(6R)-tetrahydrofolic acid or D-5-
MTHF, and is a mirror image of L-5-MTHF.
Claims 8 and 9 of the ’040 patent recite a method of
“preventing or treating disease associated with increased
levels of homocysteine . . . comprising administering at
least one tetrahydrofolate in natural stereoisomeric form,”
wherein the tetrahydrofolate is L-5-MTHF or a salt
thereof. ’040 patent, col. 5 ll. 26–31, 56–57, col. 6 ll. 1–3.
Claims 11 and 12 further require that the increased
levels of homocysteine are associated with a deficiency of
methylene tetrahydrofolate reductase, an enzyme that
helps generate L-5-MTHF for the methionine cycle. Id. at
col. 6 ll. 7–17. In claims 14 and 15, the deficiency specifi-
cally involves thermolabile (i.e. easily affected by heat)
methylene tetrahydrofolate reductase. Id. at col. 6 ll. 23–
33.
Claim 21 limits the method in claim 11 to require ad-
ministration of L-5-MTHF “in combination with at least
one pharmaceutically compatible active substance or at
least one pharmaceutically compatible adjuvant sub-
stance,” and claim 22 specifies that the pharmaceutically
compatible active substance “comprises at least one B-
4 MERCK & CIE v. GNOSIS S.P.A.
vitamin.” Id. at col. 6 ll. 49–56. Claims 19 and 20 apply
the same “pharmaceutically compatible active substance”
limitations to the method in claim 5, in which the admin-
istered tetrahydrofolate is one of a list of compounds that
includes L-5-MTHF. Id. at col. 5 ll. 36–41.
B
The Board found that all of the contested claims were
obvious in light of three prior art references: European
Patent App. No. 0 595 005 (Serfontein); U.S. Patent No.
5,194,611 (Marazza); and Johan Ubbink et al., Vitamin B-
12, Vitamin B-6, and Folate Nutritional Status in Men
with Hyperhomocysteinemia, 57 Am. J. Clinical Nutrition,
47, 47–53 (1993) (Ubbink).
Serfontein discloses “a pharmaceutical preparation for
lowering levels of homocysteine . . . in a patient.” Serfon-
tein, at 4 ll. 37–39. Serfontein teaches that elevated
levels of homocysteine are linked to numerous clinical
defects, including cardiovascular problems such as preco-
cious occlusive vascular disease; and abnormalities in the
eyes, skeletal system, and central nervous system.
Serfontein also explains that high levels of homocysteine
are often associated with folate deficiencies, and are
sometimes caused by hereditary enzyme deficiencies.
Thus, to treat high levels of homocysteine, Serfontein
discloses a preparation that includes “folate or a suitable
active metabolite of folate,” along with vitamins B6 and
B12. Id. at ll. 37–42.
Although Serfontein does not specify what constitutes
a “suitable active metabolite of folate,” Marazza identifies
L-5-MTHF as a “natural metabolite” that may be used “as
at least one active compound” in a treatment for folate
deficiency. Marazza, col. 1 ll. 25–28. Marazza explains
that commercially available forms of 5-MTHF at the time
were mixtures of L-5-MTHF and its enantiomer
D-5-MTHF. Id. at col. 2 ll. 3–6. It then discusses previ-
ous studies suggesting that the unnatural enantiomer
MERCK & CIE v. GNOSIS S.P.A. 5
D-5-MTHF may interfere with the transport of folate
through the cell membranes in humans. Id. at col. 2 ll.
16–20. To address this issue, Marazza teaches a process
by which a mixture of these 5-MTHF stereoisomers may
be separated into pure L-5-MTHF and D-5-MTHF forms.
Id. at col. 3 ll. 32–36.
Ubbink is a study of folate levels in men with elevated
levels of homocysteine. Ubbink affirms that “[n]umerous
studies have indicated that elevated plasma homocysteine
concentrations are associated with increased risk for
premature vascular disease.” J.A. 836. It also states that
the reasons for hyperhomocysteinemia include enzyme
defects such as “cystathionine-β-synthase deficiency, or
possession of a thermolabile variant of methylenetetrahy-
drofolate reductase, an enzyme required in the remethyla-
tion of homocysteine to methionine.” J.A. 836 (citations
omitted). Ubbink describes the positive results of treating
these conditions with a vitamin supplement containing
folic acid.
The Board found that, because of the close similarity
of purpose and disclosure between Serfontein and Maraz-
za, a person of ordinary skill in the art would have been
motivated to combine the two references to arrive at a
method of treating elevated levels of homocysteine with
L-5-MTHF, as recited in claims 8, 9, 19, and 20 of the ’040
patent. Further, the Board found a person of skill would
have been motivated to use this method in the situation
disclosed in Ubbink, in which the elevated homocysteine
levels are associated with certain enzyme deficiencies.
The Board found that this combination of Serfontein,
Marazza, and Ubbink discloses the additional limitations
of claims 11, 12, 14, 15, 21, and 22.
The Board also considered objective indicia of non-
obviousness. The Board concluded that Merck failed to
demonstrate an adequate nexus between the novel fea-
tures of the ’040 patent and the evidence of commercial
6 MERCK & CIE v. GNOSIS S.P.A.
success, licensing, copying, and industry praise. It also
found that the evidence of long-felt but unmet need,
unexpected results, and industry skepticism was unper-
suasive.
Accordingly, the Board concluded that the asserted
claims of the ’040 patent would have been obvious to a
person of ordinary skill at the time of the invention. The
Board also found that Serfontein anticipates claims 8, 9,
19, and 20. And the Board construed the claims not to
exclude the administration of a mixture that includes
both L-5-MTHF and D-5-MTHF.
Merck appeals. We have jurisdiction under 28 U.S.C.
§ 1295(a)(4)(A).
II
Merck appeals the Board’s obviousness determina-
tion, anticipation finding, and claim construction. Be-
cause we affirm the Board’s determinations that the
asserted claims are invalid as obvious, we need not reach
Merck’s arguments with respect to anticipation and claim
construction. 1
Obviousness is a question of law based on underlying
findings of fact. In re Kubin, 561 F.3d 1351, 1355 (Fed.
Cir. 2009). The factual findings include: “(1) the scope
and content of the prior art; (2) the differences between
the prior art and the claims at issue; (3) the level of
ordinary skill in the art at the time the invention was
made; and (4) objective evidence of nonobviousness, if
1 During oral argument, Merck agreed that even if
the Board’s claim construction is incorrect, it did not
affect the obviousness determination. See Oral Argument
at 1:47, Merck & Cie v. Gnosis S.P.A., No. 14-1779 (Apr. 7,
2015), available at http://oralarguments.cafc.uscourts.gov/
default.aspx?fl=2014-1779.mp3.
MERCK & CIE v. GNOSIS S.P.A. 7
any.” Id.; see also Graham v. John Deere Co., 383 U.S. 1,
17–18 (1966). If all elements of the claims are found in a
combination of prior art references, as is the case here,
the factfinder should further consider whether a person of
ordinary skill in the art would be motivated to combine
those references, and whether in making that combina-
tion, a person of ordinary skill would have a reasonable
expectation of success. Medichem, S.A. v. Rolabo, S.L.,
437 F.3d 1157, 1164 (Fed. Cir. 2006). In appeals of Board
decisions, these factual findings are reviewed for substan-
tial evidence. In re Gartside, 203 F.3d 1305, 1313 (Fed.
Cir. 2000); see also In re Cuozzo Speed Techs., LLC, 793
F.3d 1268, 1280 (Fed. Cir. 2015). Based on the underly-
ing factual findings, we review the Board’s ultimate
conclusion of obviousness de novo. In re Mouttet, 686 F.3d
1322, 1330–31 (Fed. Cir. 2012).
The Board’s finding of a motivation to combine
Serfontein, Marazza, and Ubbink to arrive at the claimed
method was supported by substantial evidence. So was
the Board’s finding that the proffered evidence of objective
indicia of non-obviousness lacked an adequate nexus with
the merits of the claimed invention. In light of these
factual findings, we agree with the Board’s ultimate
conclusion that the asserted claims were obvious under 35
U.S.C. § 103.
A
The record amply supports the Board’s finding of a
motivation to combine Serfontein and Marazza. Serfon-
tein explains that elevated levels of homocysteine are
often associated with folate deficiencies. Accordingly,
Serfontein discloses a method of treating elevated levels
of homocysteine using a “suitable active metabolite of
folate” and B-vitamins. While Serfontein does not specifi-
cally identify which metabolites of folate are “suitable” for
addressing folate deficiencies, Marazza does. It highlights
L-5-MTHF as a “natural metabolite” of folate in which
8 MERCK & CIE v. GNOSIS S.P.A.
there is an “increasing interest” for the treatment of folate
deficiencies. Marazza, col. 1 ll. 26–29. Thus, as the Board
found, a person of ordinary skill viewing Serfontein and
Marazza would have been motivated to use L-5-MTHF as
the “suitable active metabolite of folate” called for by the
method disclosed in Serfontein.
Merck argues that the prior art teaches away from
this combination by suggesting: (1) administering 5-
MTHF would actually increase levels of homocysteine,
(2) 5-MTHF would be too unstable for therapeutic use,
and (3) L-5-MTHF is a poor substrate for polyglutama-
tion, a process that facilitates retention and use of L-5-
MTHF in the cell. Merck cites isolated prior art disclo-
sures for support. Viewing the prior art as a whole,
however, the Board’s finding that the prior art does not
teach away from combining Serfontein and Marazza is
supported by substantial evidence.
The prior art does not unambiguously teach that ad-
ministration of 5-MTHF would increase homocysteine
levels. Merck relies on two prior art references: Harpey 1,
a journal article discussing the treatment of an infant
with chronically high levels of homocysteine; and Harpey
2, a letter to the editor of the journal with updates on that
treatment. See J.A. 1253–57. Merck argues that, based
on its expert testimony, these references show that ad-
ministration of 5-MTHF increases homocysteine levels,
because the infant’s homocysteine levels rose during
administration of 5-MTHF from 0 µmol/L to 13 µmol/L.
But this conclusion relies on the wrong starting point.
Prior to treatment, the infant’s homocysteine levels were
233 µmol/L, whereas 0 µmol/L was normal. Only after a
variety of other treatments were the infant’s levels of
homocysteine reduced to 0 µmol/L. Thus, although
switching to 5-MTHF may have correlated with a slight
increase in homocysteine, the net effect is still a reduction
of homocysteine levels. Moreover, the researchers them-
selves seemed to think that 5-MTHF controlled the in-
MERCK & CIE v. GNOSIS S.P.A. 9
fant’s homocysteine levels. If they thought otherwise,
they would have terminated treatment for that reason,
given that the infant’s symptoms from elevated homocys-
teine levels were severe. But they did not. Instead, the
stated reason for eventually withdrawing 5-MTHF was
“because of its instability.” J.A. 1257. Given this context,
substantial evidence supports the Board’s finding that a
person of ordinary skill would not understand the Harpey
references to teach that 5-MTHF would increase previous-
ly untreated homocysteine levels.
Nor does the prior art compel a finding that a person
of ordinary skill would have thought 5-MTHF was too
unstable for therapeutic use. The Harpey references,
published in 1981 and 1983 respectively, certainly suggest
5-MTHF was unstable. Harpey 1 states that “[a]lthough
[5-MTHF] would be desirable for use in therapy, it is
probably too unstable.” J.A. 1255. Harpey 2 explains
that treatment with 5-MTHF “had to be withdrawn
because of its instability.” J.A. 1257. But subsequent
references disclose that 5-MTHF is suitable for pharma-
ceutical use. A study published in 1986 explains that
although prior “[s]tudies of MTHF . . . were hampered by
its chemical instability[,] [a] new and stable preparation
of MTHF has become available for clinical trials.” J.A.
1243 (Reggev reference); see also J.A. 3188 (Pattini refer-
ence discussing 1988 study in which 5-MTHF was admin-
istered to cross-country skiers daily); J.A. 840 (Godfrey
reference reporting 1990 study in which 5-MTHF was
administered to treat psychiatric disorders). And in 1990,
the Marazza reference clearly identified L-5-MTHF as a
suitable compound for treating folate deficiency. Maraz-
za, col. 1 ll. 25–28. Because the prior art must be consid-
ered as a whole, Medichem, 437 F.3d at 1166, the Board’s
finding that a person of ordinary skill would not have
thought that 5-MTHF was too unstable for pharmaceuti-
cal use is supported by substantial evidence.
10 MERCK & CIE v. GNOSIS S.P.A.
Finally, although some prior art references suggest
that L-5-MTHF is a poor substrate for polyglutamation,
others disclose that L-5-MTHF is nonetheless effective for
treatment of elevated homocysteine levels. Merck argues
that because L-5-MTHF was understood to have a poor
capacity for polyglutamation, a process that helps retain
folates in the cell, a person of ordinary skill at the time
would have thought that L-5-MTHF does not accumulate
within the cell, where the conversion of homocysteine to
methionine occurs. According to Merck, a person of skill
would therefore would have been discouraged from using
L-5-MTHF to lower homocysteine levels.
This argument, however, ignores other prior art dis-
closing that 5-MTHF does, in fact, accumulate in the cell.
The Wagner reference states that at least 20% of 5-MTHF
was retained within the cell in that study, as Merck
conceded before the Board. J.A. 512, 2068. And another
reference, Regland, teaches that 5-MTHF was the “drug of
choice” because “MTHF is the form of folate that is taken
up by the cells.” J.A. 851. Accordingly, the prior art as a
whole supports the Board’s conclusion that a person of
ordinary skill would not have avoided L-5-MTHF because
it does not accumulate within the cells.
Merck further argues that L-5-MTHF’s poor capacity
for polyglutamation makes it a less effective substrate for
the enzymes involved in converting homocysteine to
methionine. Merck seizes on a prior art statement that
“[m]etabolism of folates to polyglutamates [i.e. polygluta-
mation] is required for their biological activity because
polyglutamate forms are much more effective substrates
for folate-dependent enzymes than are the monogluta-
mate derivatives.” J.A. 1313 (declaration of Dr. Gregory
(quoting article by Dr. Shane)). Merck also points to an
isolated statement in the Wagner reference that “under
the conditions of the present study, isolated [liver cells]
did not significantly metabolize [5-MTHF].” J.A. 2070.
MERCK & CIE v. GNOSIS S.P.A. 11
Again, other prior art references show that 5-MTHF
would nonetheless be effective for lowering homocysteine
levels. The Ueland reference discloses, and Merck agrees,
that folic acid is an effective means of decreasing homo-
cysteine levels. And according to Ueland, folic acid ac-
complishes this reduction by “increas[ing] the
intracellular pool of [5-MTHF] which in turn may serve as
a methyl-donor in the [methionine cycle].” J.A. 801.
Merck failed to present credible evidence that 5-MTHF
derived from folic acid is any more capable of polygluta-
mation in the cell or any more effective as a substrate for
folate-dependent enzymes than natural L-5-MTHF ad-
ministered directly. Indeed, a 1989 reference concludes
that directly administered 5-MTHF is actually more
efficient than folic acid: “In some cells, the concentration
of folic acid required to generate adequate concentrations
of intracellular folates is 100-200 times that of reduced
folates such as [5-MTHF] . . . .” J.A. 1275. And other
references disclose that 5-MTHF is effective for treating
symptoms associated with folate deficiency. See Marazza,
col. 1 ll. 25–28; J.A. 840 (Godfrey reference); J.A. 844
(Regland reference). In view of these references, a person
of skill in the art would have had reason to use L-5-MTHF
instead of folic acid, notwithstanding prior suggestions
that L-5-MTHF has a poor capacity for polyglutamation.
Accordingly, the record amply supports the Board’s find-
ing that a person of ordinary skill would not understand
the prior art to teach away from using 5-MTHF based on
its capacity for polyglutamation.
Serfontein specifically calls for a “suitable active me-
tabolite of folate” to help lower homocysteine levels, and
Marazza provides that L-5-MTHF is one such metabolite.
The Board properly concluded that any doubt about the
suitability of L-5-MTHF was overcome by the weight of
the prior art. We therefore conclude that substantial
evidence supports the Board’s finding that a person of
ordinary skill would have been motivated to use
12 MERCK & CIE v. GNOSIS S.P.A.
L-5-MTHF to treat elevated levels of homocysteine in the
manner recited in claims 8, 9, 19, and 20 of the ’040
patent.
The Board’s additional finding of a motivation to use
the method disclosed in Serfontein and Marazza to treat
elevated homocysteine levels associated with certain
enzyme deficiencies, as disclosed in Ubbink, is also sup-
ported by substantial evidence. Merck’s sole argument
against this finding is that Ubbink used folic acid, not
reduced folates such as L-5-MTHF, to treat elevated
levels of homocysteine associated with certain enzyme
deficiencies. As the Board found, however, this distinc-
tion would not have undermined a person of ordinary
skill’s motivation to combine. Ubbink involved a deficien-
cy in the enzyme methylenetetrahydrofolate reductase.
According to the prior art, this enzyme is important
because it helps produce 5-MTHF for the methionine
cycle. J.A. 786 (Ueland reference). A deficiency in this
enzyme, therefore, reduces the amount of 5-MTHF avail-
able for converting homocysteine to methionine. Id. In
Ubbink, patients with this deficiency were treated using
folic acid, which reduces homocysteine levels by increas-
ing the intracellular pool of 5-MTHF. J.A. 801 (Ueland
reference). As mentioned above, a person of skill would
have known that administering 5-MTHF directly would
accomplish a similar result. See J.A. 1275 (study suggest-
ing 100-200 times more folic acid would be needed to
match the results of directly administered 5-MTHF);
Marazza, col. 1 ll. 25–28 (describing 5-MTHF as a popular
supplement for the treatment of folate deficiency). Thus,
the record supports the Board’s finding that the method of
using L-5-MTHF disclosed in Serfontein and Marazza was
a natural alternative to using folic acid when elevated
homocysteine levels are associated with enzyme deficien-
cies, as disclosed in Ubbink. The resulting combination
discloses each limitation of claims 11, 12, 14, 15, 21, and
22.
MERCK & CIE v. GNOSIS S.P.A. 13
In a final challenge to the Board’s decision, Merck
complains that the Board never made an express finding
that a person of ordinary skill would have a reasonable
expectation of success in combining Serfontein and
Marazza, or in further combining Serfontein, Marazza,
and Ubbink. Under KSR International Co. v. Teleflex
Inc., 550 U.S. 398, 418, (2007), a factfinder’s analysis of a
reason to combine known elements in the art “should be
made explicit.” But KSR does not require an explicit
statement of a reasonable expectation of success in every
case. Cf. id. at 419 (cautioning against confining the
obviousness analysis using formalistic rules). Here, the
Board addressed Merck’s arguments against a reasonable
expectation of success in the context of its teaching away
arguments. By rejecting Merck’s argument that the prior
art taught away from combining Serfontein, Marazza, and
Ubbink, the Board impliedly found a reasonable expecta-
tion of success. We decline to overturn the Board’s deci-
sion for failure to state expressly that a person of ordinary
skill would have had a reasonable expectation of success.
Merck fails to establish that the Board’s factual
determinations are not supported by substantial evidence.
In light of those findings, we agree with the Board that
the prior art and expert testimony present strong evi-
dence of obviousness.
B
Objective indicia of nonobviousness can serve as an
important check against hindsight bias and “must always
when present be considered.” In re Cyclobenzaprine
Hydrochloride Extended-Release Capsule Patent Litig.,
676 F.3d 1063, 1075–76 (Fed. Cir. 2012) (quoting
Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1538–39
(Fed. Cir. 1983)). Even when present, however, objective
indicia “do not necessarily control the obviousness deter-
mination.” Bristol-Myers Squibb Co. v. Teva Pharm.
USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014).
14 MERCK & CIE v. GNOSIS S.P.A.
“For objective evidence of secondary considerations to
be accorded substantial weight, its proponents must
establish a nexus between the evidence and the merits of
the claimed invention.” In re Huai-Hung Kao, 639 F.3d
1057, 1068 (Fed. Cir. 2011) (quoting Wyers v. Master Lock
Co., 616 F.3d 1231, 1246 (Fed. Cir. 2010)). Where objec-
tive indicia “result[ ] from something other than what is
both claimed and novel in the claim, there is no nexus to
the merits of the claimed invention.” Id. “To the extent
that the patentee demonstrates the required nexus, his
objective evidence of nonobviousness will be accorded
more or less weight.” In re GPAC Inc., 57 F.3d 1573, 1580
(Fed. Cir. 1995).
Here, the Board properly considered Merck’s evidence
regarding objective indicia of nonobviousness, but found
that the nexus between the merits of the invention and
the evidence of commercial success, licensing, copying,
and industry praise was weak. The Board also found the
evidence of long-felt but unmet need was unpersuasive.
The Board therefore afforded the evidence of objective
considerations little weight. We conclude that these
factual findings are supported by substantial evidence.
Merck’s evidence of commercial success relates to sev-
eral products manufactured and sold by Merck’s licensee,
Pamlab (the Pamlab products). The Metanx®, Cerefo-
lin®, CerefolinNAC®, Néevo®, and NéevoDHA® products
contain L-5-MTHF in addition to other active ingredients.
In the Deplin® product, the only active ingredient is L-5-
MTHF. Deplin® is intended for use as a supplemental
treatment of major depressive disorder (MDD) or schizo-
phrenia.
As the Board found, the “mixed” products—Metanx®,
Cerefolin®, CerefolinNAC®, Néevo®, and NéevoDHA®—
have material features beyond those disclosed and
claimed in the ’040 patent. While the asserted claims
most closely related to these products recites a method of
MERCK & CIE v. GNOSIS S.P.A. 15
treating elevated homocysteine levels using a mixture of
L-5-MTHF and “at least one B-vitamin,” see ’040 patent,
col. 6 ll. 46–48 (claim 19); id. at ll. 54–55 (claim 21), these
products go further and contain a specific combination of
specific forms of B-vitamins and other active ingredients.
For example, the Cerefolin® product combines L-5-MTHF
with specific quantities of riboflavin (vitamin B2), cyano-
cobalamin (a form of vitamin B12), and pyridoxine hydro-
chloride (a form of vitamin B6). Merck failed to establish
that the commercial success of these products was due to
the claimed method—using L-5-MTHF and “at least one
B-vitamin”—as opposed to the specific formulations in the
mixed products. Indeed, a Pamlab executive stated that
the success of two of these products was due to the
“unique combination” of their ingredients. J.A. 1855–56;
see also J.A. 1542 (expert stating that effectiveness of
Metanx® “was likely due to the synergistic interactions of
its components”). Thus, the Board’s finding that this
evidence of commercial success should be afforded little
weight was supported by substantial evidence.
The alleged nexus between the asserted claims and
the Deplin® product was also tenuous. “If commercial
success is due to an element in the prior art, no nexus
exists.” Tokai Corp. v. Easton Enters., Inc., 632 F.3d
1358, 1369 (Fed. Cir. 2011). The Board identified two
prior art references disclosing compounds containing
5-MTHF that were used to treat depression associated
with folate deficiencies, just like the Deplin® product.
The Godfrey reference describes a study in which admin-
istering 5-MTHF improved the recovery of patients with
major depression or schizophrenia and a folate deficiency.
Similarly, the LeGrazie reference discloses the use of 5-
MTHF to treat a subject with “organic mental disturb-
ances with depression of mood.” J.A. 750. Thus, substan-
tial evidence supports the Board’s finding that the use of
5-MTHF for treating major depressive disorder and
schizophrenia was known in the prior art, and therefore
16 MERCK & CIE v. GNOSIS S.P.A.
Merck could not show a sufficient nexus between the
commercial success of the Deplin® products and the novel
features in the asserted claims.
Merck’s evidence of copying and industry praise was
based on the same Pamlab products. Like the evidence of
commercial success, Merck failed to show an adequate
nexus between these objective indicia and the novel
features of the asserted claims. Thus, substantial evi-
dence supports the Board’s finding that evidence copying
and industry praise is entitled to little weight.
Merck’s evidence of licensing is similarly unavailing.
Although Merck successfully licensed the ’040 patent to
Pamlab, the licensing agreement also covered several
other patents. One of those patents claims the stable
form of L-5-MTHF used in Pamlab’s products more pre-
cisely than the ’040 patent. See U.S. Patent No.
6,441,168. A Pamlab executive explained that Pamlab
desired this stable form “[b]ecause of its uniqueness and
its novel properties,” J.A. 3879, and touted the ingredient
as “[o]ne particular differentiator that makes our product
unique,” J.A. 1848. It is therefore difficult to determine
the extent to which the licensing agreement was a result
of the novel features in the ’040 patent, as opposed to the
other patents involved. In light of this ambiguity, the
Board’s finding that the evidence of licensing should not
be afforded much weight was reasonable.
Finally, Merck alleges that the ’040 patent resolved a
long-felt but unmet need for a supplemental therapy for
treating MDD. As mentioned, however, substantial
evidence supports the Board’s finding that the prior art
disclosed the use of 5-MTHF to treat depression associat-
ed with folate deficiencies, such as MDD. Merck’s argu-
ment that the ’040 patent met a long-felt need for MDD
treatment, therefore, is not sufficiently connected with the
novel elements of the asserted claims.
MERCK & CIE v. GNOSIS S.P.A. 17
Although another factfinder may have reasonably
evaluated Merck’s evidence of objective indicia of non-
obviousness differently in the first instance, the Board’s
conclusion that this evidence was not persuasively tied to
the novel features of the asserted claims is supported by
substantial evidence. In light of this finding, we agree
with the Board that these objective indicia carry little
weight.
III
The Board found persuasive evidence that the claimed
method of treating elevated levels of homocysteine would
have been obvious to a person of skill in light of the prior
art, particularly Serfontein, Marazza, and Ubbink. And
the Board found that Merck’s evidence of objective indicia
of non-obviousness was not closely tied to the allegedly
novel features of the claimed invention. These findings
were supported by substantial evidence and, on balance,
provide strong evidence of obviousness. We therefore
agree with the Board’s ultimate legal conclusion that
claims 8, 9, 11, 12, 14, 15, and 19–22 of the ’040 patent
are invalid under 35 U.S.C. § 103.
AFFIRMED
United States Court of Appeals
for the Federal Circuit
______________________
MERCK & CIE,
Appellant
v.
GNOSIS S.P.A., GNOSIS BIORESEARCH S.A.,
GNOSIS U.S.A., INC.,
Appellees
______________________
2014-1779
______________________
Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. IPR2013-
00117.
______________________
NEWMAN, Circuit Judge, dissenting.
This appeal is from a decision of the Patent Trial and
Appeal Board (“PTAB”), on Inter Partes Review in ac-
cordance with the America Invents Act. The PTAB held
the claims of the patent in suit invalid. My concern is
with the court’s implementation of this new statute, lest
its legislative purpose be unfulfilled.
The America Invents Act (“AIA”) is the fruit of eight
years of study, as legislators and other concerned persons
considered how to revive industrial innovation in the
United States. Loss of an effective patent incentive was
believed to have contributed to diminished technologic
advance and consequent losses in economic growth. See
2 MERCK & CIE v. GNOSIS S.P.A.
157 Cong. Rec. S948-49 (daily ed. Feb. 28, 2011) (state-
ment of Sen. Leahy) (“High quality patents are the key to
our economic growth.”); 157 Cong. Rec. H4423 (daily ed.
June 22, 2011) (statement of Rep. Smith) (“The current
patent system is outdated and dragged down by frivolous
lawsuits and uncertainty regarding patent ownership.
Unwarranted lawsuits that typically cost $5 million to
defend prevent legitimate inventors and industrious
companies from creating products and generating jobs.”);
153 Cong. Rec. HE773 (daily ed. Apr. 18, 2007) (statement
of Rep. Berman) (introducing a predecessor bill) (“These
studies offer a number of recommendations for increasing
patent quality and ensuring that patent protection pro-
motes—rather than inhibits—economic growth and
scientific progress.”).
It was believed that the PTO was granting patents too
easily, and that the courts were not consistently deciding
patentability issues. To attempt to remedy these defi-
ciencies, the America Invents Act created a new adjudica-
tive tribunal (the Patent Trial and Appeal Board or
PTAB) within the Patent and Trademark Office, and
established new procedures including changes in the
burdens of proof, limiting the path of judicial review, and
providing for finality and strict time limits. The purpose
is to restore an effective and balanced system of patents,
whereby valid patents may reliably be confirmed and
invalid patents efficiently invalidated.
This appeal raises questions of implementation of the
statutory plan, for the judicial role includes assuring that
the statutory assignment is fulfilled. The Supreme Court
has stated:
Reviewing courts are not obliged to stand aside
and rubberstamp their affirmance of administra-
tive decisions that they deem inconsistent with a
statutory mandate or that frustrate the congres-
sional policy underlying a statute. Such review is
MERCK & CIE v. GNOSIS S.P.A. 3
always properly within the judicial province, and
courts would abdicate their responsibility if they
did not fully review such administrative decisions.
N.L.R.B. v. Brown, 380 U.S. 278, 291–92 (1965).
The realignments of burdens and standards of proof
established by the America Invents Act are part of the
legislative balance, whose target is correctness and effi-
ciency. My concern is that the PTAB and this court have
departed from explicit and implicit provisions of the
statute. When that departure is rectified, the result is
changed. Thus I must, respectfully, dissent.
The Burden of Proof in the PTAB
The America Invents Act requires that the burden of
proving invalidity of an issued patent is on the petitioner
for post-grant review. 35 U.S.C. § 316(e). The Act estab-
lished the standard of proof of invalidity to be applied by
the PTAB, requiring that invalidity be proved by a pre-
ponderance of the evidence, and eliminating any defer-
ence to the prior examination and grant of the patent. As
an important aspect of the legislation, the Act did not
adopt the judicial standard of requiring clear and convinc-
ing evidence to establish invalidity.
Although the placement of the burden of proof of inva-
lidity is on the petitioner, the petitioner now may prove
invalidity by no more than a preponderance of the evi-
dence. 35 U.S.C. § 316(e).
The AIA established a powerful incentive to challenge
patent validity in the PTAB instead of the district court,
for the attacker faces a lower standard of proving invalidi-
ty in the PTAB. However, the correct law must be ap-
plied, and disputed facts found and reviewed on the
entirety of the evidence, as the preponderance standard
requires.
4 MERCK & CIE v. GNOSIS S.P.A.
The Burden of Proof in the Federal Circuit and
Finality
Another important aspect of the America Invents Act
is the provision for finality and estoppel after the PTAB
decision and any appeal to the Federal Circuit. The Act
does not permit subsequent review of the PTAB’s validi-
ty/invalidity decision in any other tribunal, whether by
appeal or direct review or as a defense or offense in litiga-
tion. The AIA provides that a petitioner (or real party in
interest or privy of the petitioner)
may not assert either in a civil action . . . [or] . . .
before the International Trade Commission . . .
that the claim is invalid on any ground that the
petitioner raised or reasonably could have raised
during that post-grant review.
35 U.S.C. § 315(e)(2). This change from present law was
long-debated, and is directed to the goals of correctness,
uniformity, finality, and expedition.
Thus it is incorrect for this court, as the only review-
ing tribunal, to review the PTAB decision under the
highly deferential “substantial evidence” standard. Our
obligation is to assure that the legislative purpose is met,
through application of the statute in accordance with its
purpose. See Calvert Cliffs’ Coordinating Comm., Inc. v.
U. S. Atomic Energy Comm’n, 449 F.2d 1109, 1111 (D.C.
Cir. 1971) (“Our duty, in short, is to see that important
legislative purposes, heralded in the halls of Congress, are
not lost or misdirected in the vast hallways of the federal
bureaucracy.”). This court’s resort to deferential “sub-
stantial evidence” review is at odds with the benefits that
Congress intended.
The substantial evidence standard determines wheth-
er the decision could reasonably have been made, not
whether it was correctly made. See 3 Steven Alan Chil-
dress & Martha S. Davis, Federal Standards of Review §
MERCK & CIE v. GNOSIS S.P.A. 5
15.04 (4th ed. 2010). The substantial evidence standard
originated with appeals of jury verdicts, in recognition of
the role of credibility at trial. Id. “Substantial evidence”
was incorporated into the Administrative Procedure Act
in recognition of the expertise of specialized agencies. Id.
Here, however, a new system was created to respond to
the belief that the agency was making mistakes. See, e.g.,
157 Cong. Rec. S1326 (daily ed. March 7, 2011) (state-
ment of Sen. Sessions) (“This will allow invalid patents
that were mistakenly issued by the PTO to be fixed early
in their life, before they disrupt an entire industry or
result in expensive litigation.”); 153 Cong. Rec. H10276
(daily ed. Sept. 7, 2007) (statement of Rep. Goodlatte,
commenting on a predecessor bill to the AIA) (“The PTO,
like any other large government agency, makes mistakes.
H.R. 1908 creates a post-grant opposition procedure to
allow the private sector to challenge a patent just after it
is approved to provide an additional check on the issuance
of bogus patents.”). This new system is directed at cor-
recting mistakes. Deferential review by the Federal
Circuit falls short of the legislative purpose of providing
optimum determination of patent validity.
The Federal Circuit is the only review body for these
new agency proceedings, for the America Invents Act
displaced the alternative path of challenge to PTO deci-
sions in the district court. Thus the PTAB’s adjudications
must be reviewed for correct application of the standard of
proof established by the America Invents Act. In 35
U.S.C. § 316(e):
In an inter partes review instituted under this
chapter, the petitioner shall have the burden of
proving a proposition of unpatentability by a pre-
ponderance of the evidence.
On appeal to the Federal Circuit, our assignment is to
determine whether the PTAB ruling is correct in law and
supported by a preponderance of the evidence. The panel
6 MERCK & CIE v. GNOSIS S.P.A.
majority errs in importing into these proceedings the
Administrative Procedure Act standard that applies to
initial patent examination decisions, Maj. Op. at 7, citing
In re Gartside, 203 F.3d 1305, 1313 (Fed. Cir. 2000) (PTO
decisions sustained if supported by substantial evidence).
Appellate review of agency rulings on the preponder-
ance standard, accompanied by finality, is not the general
APA rule, but has been adopted by statute in other special
situations. For example, under the Service Contract Act,
“[i]f supported by a preponderance of the evidence, the
[agency’s] findings are conclusive in any court of the
United States.” 41 U.S.C. § 6507(e) (formerly 41 U.S.C.
§ 39). The regional circuits have interpreted the prepon-
derance standard to require review for “clear error” on
appeal. See Dantran, Inc. v. U.S. Dep’t of Labor, 171 F.3d
58, 71 (1st Cir. 1999) (rejecting “substantial evidence”
review standard); see also Amcor, Inc. v. Brock, 780 F.2d
897, 901 (11th Cir. 1986) (“determination by the adminis-
trator . . . must be affirmed unless it is not supported by a
preponderance of the evidence.”).
Such close appellate scrutiny is critical to the legisla-
tive balance of the America Invents Act, whose purpose is
to reach an expeditious and reliable determination on
which inventors and industry innovators and competitors
can rely. The Federal Circuit’s adoption of deferential
“substantial evidence” review strays from this purpose. If
Congress intended that deferential review would apply to
PTAB determinations in which “substantial evidence” is
“something less than the weight of the evidence,” Consolo
v. Fed. Mar. Comm’n, 383 U.S. 607, 620 (1966), explicit
assignment of this standard would reasonably have been
expected.
For example, the majority decides that “substantial
evidence” supports the PTAB’s finding of a motivation to
combine the information in the Serfontein and the Maraz-
za references, as I discuss infra. The PTAB cited no
MERCK & CIE v. GNOSIS S.P.A. 7
source for this finding, other than “[t]he close similarity of
purpose and disclosure between these references.” PTAB
Op. at 23. The panel majority, looking for “substantial
evidence” supporting the PTAB, does not discuss the
evidence weighing against this finding, such as the known
side effects of the L-5-MTHF isomer, its instability, the
equivocal clinical observations, and Merck’s and the
University’s commercial success, as well as the long-felt
need, failure of others, industry praise, licensing, and
copying. Deferential review on a standard that looks at
only one side of the evidence is less likely to uncover
errors in the balance and burden of proof.
Application of the Correct Appellate Standard
The patent claims the use of a specific tetrahydro-
folate stereoisomer, L-5-methyltetrahydrofolate (L-5-
MTHF) to treat elevated homocysteine, including a genet-
ic disorder called homocysteinuria, a debilitating affliction
that the Serfontein reference (European Patent No.
0595005 (EP’005)) describes as “an inborn error of metab-
olism which is either caused by an enzyme defect in the
transsulfuration pathway or a similar defect in the 5-
methyl tetrahydrofolate dependent remethylation of
homocysteine to methionine.” EP’005 at 3, ll. 20–22.
The PTAB found that Serfontein concerns the generic
class of “folate or a suitable active metabolite of folate or a
substance which releases folate in vivo.” PTAB Op. at 23.
Serfontein states that “it is known that vitamin B6,
vitamin B12 and folate play a role in regulating the
methionine-homocysteine pathway and controlling levels
of homocysteine,” EP’005 at 3, ll. 54–56, and that “[a]t the
same time, deficiencies (individually) of each of these
vitamins have also been known to be associated with
increased homocysteine levels.” EP’005 at 3, ll. 31–32.
This description does not mention the L-5-MTHF isomer,
or that this specific stereoisomer is effective in treating
elevated homocysteine.
8 MERCK & CIE v. GNOSIS S.P.A.
Serfontein recognized an “association” between folate
deficiency and increased homocysteine, but did not sug-
gest that L-5-MTHF is useful to treat elevated homocyste-
ine, with or without B vitamins. The PTAB recognized
this gap in Serfontein, and held that Marazza, U.S. Pa-
tent No. 5,194,611 (“the ’611 Patent”), filled the gap.
Marazza states that L-5-MTHF is “the predominant
circulating form of reduced folates in mammals,” and
“[t]here exists an increasing interest for the application of
this natural metabolite as at least one active compound in
a therapeutical agent, for example as vitamin in folate
deficiency states.” ’611 Patent, col. 3, ll. 23–29.
However, Marazza does not link the L-5-MTHF iso-
mer to treatment of elevated homocysteine, or suggest
this use. And Serfontein only states that elevated homo-
cysteine levels are “associated with” folate deficiency. EP
’005, col. 3, ll. 31-32. Missing is a teaching or suggestion
in either of these references that L-5-MTHF could be
effectively used to treat elevated homocysteine with a
reasonable expectation of success. Several other refer-
ences in the record discuss folate biochemistry and report
various scientific investigations, yet amid extensive and
extremely close prior art, no reference suggests the meth-
od described in this patent. 1
The PTAB erred in concluding that “one reading
Serfontein would have considered 5-methyl-(6S)-
tetrahydrofolic acid (L-5-MTHF) a viable choice, as ex-
pressly taught in Marazza, for a suitable active metabo-
lite of folate in Serfontein’s method.” PTAB Op. at 25.
1 It has been suggested that the claims are unduly
broad. This breadth is challenged in the concurrent inter
partes review of U.S. Patent No. 7,172,778, where an
additional reference is discussed.
MERCK & CIE v. GNOSIS S.P.A. 9
Marazza does not teach that L-5-MTHF is suitable to
treat elevated homocysteine, but only that it is an “active”
folate for treating folate deficiency. Amid the uncertain
predictability of biological response, this background does
not provide a reasonable likelihood of successful treat-
ment with any selected stereoisomer. Only hindsight
provides such prophesy.
The evidence of record does not support the PTAB’s
apparent assumption that any folate would be effective
against elevated homocysteine. No reference teaches that
L-5-MTHF has this activity. A prima facie case cannot be
based on the inventor’s successful investigations.
The PTAB states that “Serfontein calls for a ‘suitably
active metabolite of folate’ in preparations used to correct
folate deficiency and treat diseases associated with ele-
vated levels of homocysteine.” PTAB Op. at 23. This
statement appears to enlarge Serfontein, who uses folate
for “lowering levels of homocysteine or . . . counteracting
the harmful effects associated with homocysteine.”
EP’005 at 2, ll. 1–3.
The PTAB states that “Marazza specifically identifies
chirally-pure L-5-MTHF as an active metabolite of folate
suitable for use as a therapeutic agent in folate deficient
states.” PTAB Op. at 23. The PTAB combines the Serfon-
tein and Marazza references because “the close similarity
of purpose and disclosure between these references would
have provided sufficient rationale for one of ordinary skill
in the art to have combined the teachings therein.” PTAB
Op. at 23. However, there is no suggestion to select and
make such combination with a reasonable expectation of
success in treating elevated homocysteine. The only
source of this concept is hindsight reconstruction using
the teachings of these inventors.
10 MERCK & CIE v. GNOSIS S.P.A.
The Evidence does not Establish a Reasonable Like-
lihood of Success
My colleagues find that “the PTAB impliedly found a
reasonable expectation of success,” observing that the
PTAB did not accept Merck’s argument that the refer-
ences “taught away” from Merck’s use. It is undisputed
that no reference taught Merck’s use. There was evidence
of instability and failures using the L-5-MTHF isomer in
folate treatments. No reference contains a suggestion to
use L-5-MTHF or expectation of success. Even Marazza
states only that there was “an increasing interest” in L-5-
MTHF. ’611 Patent, col.1, l.25.
The Court in KSR International Co. v. Teleflex Inc.,
550 U.S. 398, 421 (2007), in discussing the “obvious to try”
standard of obviousness, cautioned that something would
be “obvious to try” if “there are a finite number of identi-
fied, predictable solutions” with “anticipated success.”
“The obviousness inquiry entails consideration of whether
a person of ordinary skill in the art ‘would have been
motivated to combine the teachings of the prior art refer-
ences to achieve the claimed invention, and . . . would
have had a reasonable expectation of success in doing so.’”
Insite Vision Inc. v. Sandoz, Inc., 783 F.3d 853, 859 (Fed.
Cir. 2015) (quoting Procter & Gamble Co. v. Teva Pharms.
USA, Inc., 566 F.3d 989, 994 (Fed. Cir. 2009)) (elisions in
original). Here, the purported “reasonable expectation of
success” came from the hindsight knowledge of these
inventors’ success.
The references are not uniform, as the panel majority
acknowledges. Merck provided references showing that
experiments administering L-5-MTHF to human subjects
were abandoned or not conducted because the compound
was too unstable. Merck also provided references describ-
ing experiments that show that 5-MTHF is not metabo-
lized by hepatocytes grown in culture. Other references
suggest that reduced folates such as L-5-MTHF are less
MERCK & CIE v. GNOSIS S.P.A. 11
bioavailable than folic acid. PTAB Op. at 20. These
references support the position that adverse effects, or no
clear benefit, would reasonably be predicted for L-5-
MTHF.
In contrast, Gnosis provided references suggesting
that lower concentrations of reduced folates could produce
the same intracellular concentrations as folic acid. PTAB
Op. at 20-21. Whether or not these inconsistent teachings
are viewed as “teaching away” they do not teach toward a
reasonable likelihood of success. The panel majority errs
in law, in stating that “the PTAB impliedly found a rea-
sonable expectation of success” based on the PTAB’s
finding of no “teaching away.” Such “implication” resides
only in the backward-looking eye of the beholder.
Objective Indicia of Non-obviousness
Indicia such as commercial success “may often be the
most probative and cogent evidence [of non-obviousness]
in the record,” Procter & Gamble Co. v. Teva Pharm. USA,
Inc., 566 F.3d 989, 998 (Fed. Cir. 2009) (modification in
original) (quoting Stratoflex, Inc. v. Aeroquip Corp., 713
F.2d 1530, 1538 (Fed. Cir. 1983)). Such considerations
are a foil to judicial hindsight. In re Cyclobenzaprine
Hydrochloride Extended-Release Capsule Patent Litig.,
676 F.3d 1063, 1075–76 (Fed. Cir. 2012) (“The objective
considerations, when considered with the balance of the
obviousness evidence in the record, guard as a check
against hindsight bias.”).
Here there was a crowded field of science, and the re-
sponse of the marketplace, in an area of recognized need,
is evidence that the assertedly obvious discovery by these
inventors was not obvious, for it eluded many scientists in
the field.
My colleagues respond to Merck’s evidence of com-
mercial success, industry praise, copying, and licensing,
by stating that “[e]ven when present, however, objective
12 MERCK & CIE v. GNOSIS S.P.A.
indicia ‘do not necessarily control the obviousness deter-
mination.’” Maj. Op. at 13. However, the law is not that
the objective indicia must “control” the result, but that
these indicia must be considered, for whatever weight the
evidence warrants. The value and need for an invention,
and failure of others to solve a known problem, is relevant
evidence.
The PTAB discounted Merck’s evidence of commercial
success, observing that the commercial products con-
tained vitamins in addition to L-5-MTHF. I doubt that
this squabble is about the sale of vitamins; there is no
suggestion, anywhere in the record before us, that these
products were sold and purchased for any purpose other
than for the L-5-MTHF to treat homocysteineurea, with
or without beneficial B vitamins as in claim 22. See In re
GPAC, 57 F.3d at 1580 (Fed. Cir. 1995) (“A prima facie
case of nexus is generally made out when the patentee
shows both that there is commercial success, and that the
thing (product or method) that is commercially successful
is the invention disclosed and claimed in the patent.”).
Here there was no argument that consumers purchased
the L-5-MTHF product to obtain other ingredients.
The panel majority acknowledges that “although an-
other factfinder may have reasonably evaluated Merck’s
evidence of objective indicia of non-obviousness differently
in the first instance, the Board’s conclusion . . . is sup-
ported by substantial evidence.” Maj. Op. at 17. This is
another illustration of the flaw in this court’s using the
substantial evidence standard, for the question before us
is whether the preponderance of the evidence supports the
PTAB’s decision.
CONCLUSION
The America Invents Act is a remedy for the present
regime of uncertainty and unreliability of patents. Our
obligation is to assure that the correct law is applied, that
MERCK & CIE v. GNOSIS S.P.A. 13
the burdens are correctly placed, and that the statutory
standard of proof is met.
The PTAB is not an examining body, but an adjudica-
tory body, an objective arbiter between opposing parties.
On questions that are close, as here illustrated, the
standard of review can affect the result. My colleagues
err in applying deferential review, instead of assuring
that the PTAB’s factual findings are supported by the
preponderance of the evidence, as the statue requires.
From the court’s departure from the criteria of the
America Invents Act, and from the incorrect result that
ensues in this case, I respectfully dissent.