Novartis Pharmaceuticals v. Accord Healthcare Inc. ( 2022 )

Case: 21-1070 Document: 41 Page: 1 Filed: 01/03/2022
United States Court of Appeals
for the Federal Circuit
______________________
NOVARTIS PHARMACEUTICALS CORPORATION,
Plaintiff-Appellee
v.
ACCORD HEALTHCARE, INC., AUROBINDO
PHARMA LTD., AUROBINDO PHARMA USA, INC.,
DR. REDDY’S LABORATORIES, INC., DR. REDDY’S
LABORATORIES, LTD., EMCURE
PHARMACEUTICALS LTD., HERITAGE
PHARMACEUTICALS INC., GLENMARK
PHARMACEUTICALS INC., USA, GLENMARK
PHARMACEUTICALS LIMITED, HETERO USA,
INC., HETERO LABS LIMITED UNIT-V, HETERO
LABS LIMITED, MYLAN PHARMACEUTICALS,
INC., PRINSTON PHARMACEUTICAL INC.,
STRIDES GLOBAL PHARMA PRIVATE LIMITED,
STRIDES PHARMA, INC., TORRENT PHARMA
INC., TORRENT PHARMACEUTICALS LTD.,
ZYDUS PHARMACEUTICALS (USA) INC., CADILA
HEALTHCARE LTD., APOTEX INC., APOTEX
CORP., SUN PHARMACEUTICAL INDUSTRIES,
LTD., SUN PHARMACEUTICAL INDUSTRIES INC.,
SUN PHARMA GLOBAL FZE,
Defendants
HEC PHARM CO., LTD., HEC PHARM USA INC.,
Defendants-Appellants
______________________
2021-1070
______________________
Case: 21-1070 Document: 41 Page: 2 Filed: 01/03/2022
2 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
Appeal from the United States District Court for the
District of Delaware in No. 1:18-cv-01043-KAJ, Circuit
Judge Kent A. Jordan.
______________________
Decided: January 3, 2021
______________________
JANE M. LOVE, Gibson, Dunn & Crutcher LLP, New
York, NY, argued for plaintiff-appellee. Also represented
by PAUL E. TORCHIA, ROBERT TRENCHARD.
PAUL SKIERMONT, Skiermont Derby LLP, Dallas, TX,
argued for defendants-appellants. Also represented by
SARAH ELIZABETH SPIRES; MIEKE K. MALMBERG, Los Ange-
les, CA.
______________________
Before MOORE, Chief Judge, LINN and O’MALLEY, Circuit
Judges.
Opinion for the court filed by Circuit Judge O’MALLEY.
Dissenting opinion filed by Chief Judge MOORE
O’MALLEY, Circuit Judge.
HEC Pharm Co., Ltd. and HEC Pharm USA Inc. (col-
lectively, “HEC”) appeal from a district court bench trial in
which the court found that a patent assigned to Novartis
Pharmaceuticals Corp. (“Novartis”), U.S. Patent
No. 9,187,405 (“the ’405 patent”), is not invalid and that
HEC’s Abbreviated New Drug Application (“ANDA”) in-
fringes. HEC argues that the district court erred in finding
that the ’405 claims do not fail the written description re-
quirement of 35 U.S.C. § 112(a). Because we do not discern
any clear error in the district court’s decision, we affirm.
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NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 3
I. BACKGROUND
Novartis markets a 0.5 mg daily dose of fingolimod hy-
drochloride under the brand name Gilenya. The medica-
tion is used to treat relapsing remitting multiple sclerosis
(“RRMS”), a form of multiple sclerosis (“MS”). MS is a de-
bilitating immune-mediated demyelinating disease in
which the immune system attacks the myelin coating the
nerves in the central nervous system. Most MS patients
initially present as RRMS patients, but many eventually
develop a secondary progressive form of MS, causing them
to experience growing disability. There is currently no cure
for MS. The disease is managed by reducing or preventing
relapses and thereby slowing disability.
HEC filed an ANDA seeking approval to market a ge-
neric version of Gilenya. Novartis sued, alleging that
HEC’s ANDA infringes all claims of the ’405 patent. 1
A. The ’405 Patent
The ’405 patent claims methods to treat RRMS with
fingolimod (also known as FTY720 and 2-amino-2-[2-(4-oc-
tylphenyl)ethyl]propane-1,3-diol in the ’405 patent) or a
fingolimod salt, such as fingolimod hydrochloride (also
known as Compound A in the ’405 patent), at a daily dosage
of 0.5 mg without an immediately preceding loading dose.
’405 patent col. 12 ll. 49–55.
A loading dose is a higher than daily dose “usually
given ‘as the first dose.’” J.A. 27 (¶ 63) (quoting J.A. 23125
(Tr. 547:12–18) and citing J.A. 23344 (Tr. 766:4–6)). Both
parties’ experts agreed with this definition. J.A. 23125
(547:12–18) (HEC’s expert, Dr. Hoffman, testifying that “a
1 Novartis sued several other defendants who had
also filed ANDA applications. The cases as to those other
defendants all settled or were stayed prior to trial, which
proceeded only as to HEC.
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4 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
loading dose is a higher-than-therapeutic level dose, usu-
ally given . . . as the first dose in order to get therapeutic
levels up quickly . . . and it’s usually for more acute situa-
tions”); J.A. 23344 (Tr. 766:4–6) (Novartis’s expert, Dr.
Steinman, agreeing that “a loading dose is a higher-than-
daily dose”). It is undisputed that loading doses were well-
known in the medical field generally and in the prior art.
And the experts in this case agree that loading doses are
used for some medicaments used in connection with MS.
The ’405 patent has six claims. Claim 1 of the ’405 pa-
tent recites:
A method for reducing or preventing or alleviating
relapses in Relapsing-Remitting multiple sclerosis
in a subject in need thereof, comprising orally ad-
ministering to said subject 2-amino-2-[2-(4-oc-
tylphenyl)ethyl]propane-1,3-diol, in free form or in
a pharmaceutically acceptable salt form, at a daily
dosage of 0.5 mg, absent an immediately preceding
loading dose regimen.
Claims 3 and 5 are similar but are directed to a
“method of treating” RRMS and a “method of slowing pro-
gression of” RRMS, respectively, rather than a “method for
reducing or preventing or alleviating relapses in” RRMS.
Id. col. 12 ll. 59–64, col. 13 ll. 1–6. Claims 2, 4, and 6 are
dependent claims that limit the methods of claims 1, 3, and
5, respectively, to administration of 2-amino-2-[2-(4-oc-
tylphenyl)ethyl]propane-1,3-diol hydrochloride, i.e., fin-
golimod hydrochloride. Id. col. 12 ll. 56–58, col. 12 ll.
65–67, col. 13 ll. 7–9.
The ’405 patent was filed on April 21, 2014. It claims
priority to a British patent application that was filed on
June 27, 2006. The parties, for the most part, focus their
discussion on the specification of the ’405 patent, despite
HEC’s argument that the inventors did not possess the in-
vention as of the 2006 priority date. HEC’s argument that
the 2006 application does not contain adequate written
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description of the ’405 claims requires reference to the 2006
application itself. Thus, we find it necessary to look to the
specification of the 2006 priority application, despite the
parties’ failure to fully explain the contents of that applica-
tion. Although the specifications are different from each
other, they are, in all aspects relevant to this appeal, sub-
stantively similar.
The specifications of the ’405 patent and the 2006 pri-
ority application both describe the use of a class of S1P re-
ceptor modulators, including fingolimod, to treat or prevent
“neo-angiogenesis associated with a demyelinating disease,
e.g. multiple sclerosis.” ’405 patent col. 1 ll. 5–8; J.A.
23751. The specifications each identify fingolimod hydro-
chloride (Compound A) as a particularly preferred com-
pound within the class of S1P receptor modulators. ’405
patent col. 8 ll. 17–30; J.A. 23759–60.
Both specifications describe the results of an Experi-
mental Autoimmune Encephalomyelitis (“EAE”) experi-
ment. ’405 patent col. 10 ll. 32–col. 11 ll. 2; J.A. 23762–63.
In the EAE experiment, a disease that mimics RRMS was
induced in Lewis rats. 2 The rats suffered acute disease
within 11 days after immunization, with almost complete
remission around day 16 and relapse around day 26. The
specifications report that an S1P receptor modulator, e.g.,
Compound A (fingolimod hydrochloride) “significantly
blocks disease-associated neo-angiogenesis when adminis-
tered to the animals at a dose of from 0.1 to 20 mg/kg p.o.” 3
’405 patent col. 10 ll. 61–64; J.A. 23763. They further re-
port that disease relapse was completely inhibited in rats
to which Compound A was “administered daily at a dose of
2 Lewis rats are inbred laboratory rats used to study
disease. Inbred Rats, CHARLES RIVER,
https://www.criver.com/sites/default/files/resources/Inbre-
dRatsDatasheet.pdf (last visited November 5, 2021).
3 P.o. indicates oral administration.
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0.3 mg/kg” or “administered p.o. at 0.3 mg/kg every 2nd or
3rd day or once a week.” ’405 patent col. 10 ll. 64–col. 11 ll.
3; J.A. 23763.
Both specifications then describe a prophetic human
clinical trial (“Prophetic Trial”). 4 ’405 patent col. 11 ll.
3–38; J.A. 23763–64. The Prophetic Trial describes a trial
in which RRMS patients would receive 0.5, 1.25, or 2.5 mg
of an S1P receptor modulator, e.g., Compound A (fin-
golimod hydrochloride), per day for two to six months. ’405
patent col. 11 ll. 8–14; J.A. 23763. The specifications do not
mention a loading dose associated with the Prophetic Trial.
’405 patent col. 11 ll. 8–14; J.A. 23763.
Both specifications then describe a wide range of poten-
tial dosages, which “will vary depending upon, for example,
the compound used, the host, the mode of administration
and the severity of the condition to be treated.” ’405 patent
col. 11 ll. 20–24; J.A. 23764. Those potential dosages in-
clude a “preferred daily dosage range [of] about from 0.1 to
100 mg” and “a dose of 0.5 to 30 mg [of Compound A] every
other day or once a week.” ’405 patent col. 11 ll. 24–38; J.A.
23764.
B. The District Court Proceedings
After a four-day bench trial, the district court found
that HEC’s ANDA product would infringe claims 1–6 of the
’405 patent. The court also found that HEC had not shown
that the ’405 patent is invalid for (1) insufficient written
description for the no-loading-dose limitation and for the
4 Prophetic trials explain how a drug would be ad-
ministered and how a patient given that drug should be
monitored in a clinical trial. Prophetic trials are not clini-
cal trials that are performed; they are merely described on
paper. Prophetic trials are sometimes used in patent ap-
plications because clinical trials are expensive and time
consuming.
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claimed 0.5 mg daily dose or (2) anticipation. HEC appeals
the district court’s findings as to written description for the
0.5 mg daily dose and no-loading-dose limitations.
With respect to the written description for the claimed
0.5 mg daily dose, the district court found that a skilled ar-
tisan would understand that the inventors possessed a 0.5
mg daily dose based on one of the successful doses in the
EAE experiment results, 0.3 mg/kg weekly. The court cred-
ited the testimony of two of Novartis’s expert witnesses, Dr.
Lawrence Steinman, M.D., and Dr. William Jusko, Ph.D.,
to make the leap from a 0.3 mg/kg weekly rat dosage to a
0.5 mg daily human dosage. The court noted that the 0.5
mg daily dose is also illustrated in the Prophetic Trial. The
district court concluded that there was sufficient written
description for the 0.5 mg daily dosage limitation.
With respect to the written description for the “absent
an immediately preceding loading dose” limitation, the dis-
trict court again found sufficient written description in the
EAE model and the Prophetic Trial. Neither the Prophetic
Trial nor the EAE model recite a loading dose. The district
court found that the “Prophetic Trial describes giving a
‘daily dosage of 0.5 . . . mg’ fingolimod to treat RRMS,
started ‘initially.’” J.A. 26 (quoting ’405 patent col. 11 ll.
8–13). The court found, crediting expert testimony, that,
“[i]f a loading dose were directed, the Patent would say that
a loading dose should be administered ‘initially.’” J.A. 26
(citing J.A. 23334–35 (Tr. 756:16–757:8); J.A. 23441–42
(Tr. 863:22–864:18)). Similarly, the district court found
that the “EAE example discloses a dosing regimen which
does not involve a loading dose.” J.A. 27 (citing J.A. 23345
(Tr. 767:3–5); J.A. 22793 (Tr. 215:16–21)). Finally, the
court found that, while the patent describes alternate dos-
ing regimens, such as “intermittent dosing,” it does not de-
scribe administering those regimens with loading doses.
J.A. 27. Thus, the district court concluded, “[t]he EAE
model and the Prophetic Trial . . . indicate to a person of
ordinary skill that the claimed invention did not include
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8 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
the administration of a loading dose,” and, thus, the patent
provides sufficient written description of the negative lim-
itation. J.A. 37–38.
HEC appeals. We have jurisdiction under 28 U.S.C.
§ 1295(a)(1).
II. DISCUSSION
On appeal, HEC challenges the district court’s deci-
sions concerning the ’405 patent’s written description of the
0.5 mg daily dose limitation and the no-loading-dose nega-
tive limitation. “Whether a claim satisfies the written de-
scription requirement is a question of fact that, on appeal
from a bench trial, we review for clear error.” Allergan, Inc.
v. Sandoz Inc., 796 F.3d 1293, 1308 (Fed. Cir. 2015) (quot-
ing Alcon Rsch. Ltd. v. Barr Lab’ys, Inc., 745 F.3d 1180,
1190 (Fed. Cir. 2014)). Under the clear error standard, we
will not overturn the district court’s factual finding unless
we have a “‘definite and firm conviction’ that a mistake has
been made.” Nuvo Pharms. (Ireland) Designated Activity
Co. v. Dr. Reddy’s Lab’ys Inc., 923 F.3d 1368, 1376 (Fed.
Cir. 2019) (quoting Scanner Techs. Corp. v. ICOS Vision
Sys. Corp. N.V., 528 F.3d 1365, 1374 (Fed. Cir. 2008)).
The written description requirement is found in section
112 of the patent statute, which provides that the patent’s
specification must contain “a written description of the in-
vention, and of the manner and process of making and us-
ing it.” 5 35 U.S.C. § 112(a). A specification that
“reasonably conveys to those skilled in the art that the in-
ventor had possession of the claimed subject matter as of
the filing date” has adequate written description of the
claimed invention. Ariad Pharms., Inc. v. Eli Lilly & Co.,
598 F.3d 1336, 1351 (Fed. Cir. 2010). “[T]he test requires
an objective inquiry into the four corners of the
5 35 U.S.C. § 112(a) also contains the separate “ena-
blement” requirement, which is not at issue in this appeal.
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specification from the perspective of a person of ordinary
skill in the art.” Id.
HEC challenges the district court’s decisions concern-
ing the ’405 patent’s written description of two limitations:
the 0.5 mg daily dose limitation and the no-loading-dose
negative limitation.
Despite arguing that the inventors did not possess the
claimed subject matter in 2006, HEC bases its arguments,
not on the 2006 priority application’s written description,
but on the ’405 patent’s specification—leaving it to this
court to independently search the 2006 priority application
for written description of the claims. HEC’s confusion is
ultimately of no moment, as we find that the claims have
adequate written description support in portions of the ’405
specification which also appear in the 2006 priority appli-
cation. 6
A. Written Description for the Dosage Limitation
HEC argues that, as of the 2006 priority date, the in-
ventors did not possess a 0.5 mg daily dose of fingolimod.
It argues that, as of that date, 0.5 mg/day was considered
too low to be effective to treat RRMS. It describes Novar-
tis’s calculation of the 0.5 mg/day human dose as derived
6 Both parties wrongly assume that, if the 2006 pri-
ority application lacks sufficient written description of the
’405 patent’s claims, those claims are invalid. If the 2006
priority application lacks sufficient written description for
the ’405 patent’s claims, the ’405 patent’s claims are not
automatically rendered invalid; they are merely deprived
of the 2006 priority date. See 35 U.S.C. § 119; see also Paice
LLC v. Ford Motor Co., 881 F.3d 894, 906 (Fed. Cir. 2018)
(“For claims to be entitled to a priority date of an earlier-
filed application, the application must provide adequate
written description support for the later-claimed limita-
tions.”).
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10 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
from the lowest disclosed dose in the rat EAE model de-
scribed in the specification as “undisclosed mathematical
sleights of hand.” Appellant’s Br. 7. And it argues that the
Prophetic Trial, which lists a 0.5 mg daily dose along with
two other dosages, does not provide sufficient written de-
scription of the 0.5 mg dose. Finally, it asserts that “blaze
marks” directing a skilled artisan to the 0.5 mg daily dose
are absent from the ’405 patent.
We do not find HEC’s arguments convincing. The Pro-
phetic Trial and the EAE model provide sufficient written
description to show that, as of the priority date, the inven-
tors possessed a 0.5 daily fingolimod dosage as claimed in
the ’405 patent. The Prophetic Trial describes dosing
RRMS patients with fingolimod hydrochloride at daily dos-
ages of 0.5, 1.25, or 2.5 mg. ’405 patent col. 11 ll. 8–16. The
Prophetic Trial’s disclosure of two other dosages does not
detract from the written description of the claimed dose.
Nor do disclosures of dosage ranges in other areas of the
specification lead away from the claimed dose.
The rat EAE model describes additional information
which provides further written description for the 0.5
mg/day limitation. The EAE model describes a dosage of
0.3 mg/kg per week as effective to “fully block[] disease-as-
sociated angiogenesis and completely inhibit[] the relapse
phases.” ’405 patent col. 10 ll. 64–col. 11 ll. 2. The district
court credited the testimonies of Dr. Steinman and Dr.
Jusko to arrive at the claimed 0.5 mg/day human dosage
from the EAE experiment’s 0.3 mg/kg per week rat dosage.
Those experts both testified that a skilled artisan would
have converted the lowest daily rat dose described in the
EAE experiment (0.3 mg/kg weekly) to a daily dose (0.042
mg/kg daily). J.A. 24 (citing J.A. 23325–26 (Tr.
747:6–748:19); J.A. 23443 (Tr. 865:12–24); J.A. 23482 (Tr.
904:2–18)). The district court found, again based on expert
testimony, that a skilled artisan “would immediately rec-
ognize that 0.3 mg/kg weekly (0.042 mg/kg daily) in rats” is
approximately 60% lower “than the lowest known effective
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dose in the prior art (0.1 mg/kg daily).” J.A. 24–25 (citing
J.A. 23440–41 (Tr. 862:25–863:21)). It found that a skilled
artisan “would understand that the EAE results in the ’405
Patent therefore demonstrate that a proportionally lower
dose (again, roughly 60% lower) could be effective in hu-
mans.” J.A. 25 (citing J.A. 23443–45 (Tr. 865:4–867:4); J.A.
23480–85 (Tr. 902:17–907:8)). It further found that a
skilled artisan “would understand that the inventors trans-
lated the lowest dose that had ever been seen as effective
from their EAE experiment (0.3 mg/kg once per week) to
the 0.5 dose.” J.A. 25 (citing J.A. 23356–57 (Tr.
778:25–779:14)).
HEC attacks the expert testimony underlying the dis-
trict court’s determination that the EAE experiment de-
scribes a 0.5 mg daily human dose as “undisclosed
mathematical sleights of hand.” Appellant’s Br. 7. We dis-
agree. A “disclosure need not recite the claimed invention
in haec verba.” Ariad, 598 F.3d at 1352. The disclosure
need only “clearly allow persons of ordinary skill in the art
to recognize that the inventor invented what is claimed.”
Id. at 1351. To accept HEC’s argument would require us
to ignore the perspective of the person of ordinary skill in
the art and require literal description of every limitation,
in violation of our precedent. We find no clear error in the
district court’s reliance on expert testimony in finding de-
scription of the 0.5 mg daily human dose in the EAE exper-
iment results.
We also reject HEC’s argument that the ’405 patent
does not have necessary “blaze marks” pointing to the 0.5
mg daily dose. “Blaze marks” directing an investigator of
ordinary skill in the art to the claimed species from among
a forest of disclosed options are not necessary in this case.
In cases where the specification describes a broad genus
and the claims are directed to a single species or a narrow
subgenus, we have held that the specification must contain
“‘blaze marks’ that would lead an ordinarily skilled inves-
tigator toward such a species among a slew of competing
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12 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
possibilities.” Novozymes v. DuPont Nutrition Biosciences
APS, 723 F.3d 1336, 1349 (Fed. Cir. 2013).
“Blaze marks” are not necessary where the claimed
species is expressly described in the specification, as the
0.5 mg daily dosage is here. See, e.g., Snitzer v. Etzel, 465
F.2d 899, 902 (C.C.P.A. 1972) (finding that interference
counts directed to the activation of a glass laser with triva-
lent ytterbium ions were adequately described by a specifi-
cation listing fourteen materials which may be used as
active laser ingredients, including trivalent ytterbium, and
noting that “there would seem to be little doubt that the
literal description of a species provides the requisite legal
foundation for claiming that species”). The ’405 patent
does not contain the laundry-list-type disclosures that we
have found require guidance to direct a skilled artisan to
the claimed species—it contains the Prophetic Trial listing
three doses, 0.5, 1.25, and 2.5 mg/day. While other sections
of the specification disclose larger ranges of potential doses
for S1P receptor modulators, e.g., 0.1 to 100 mg/day doses,
those disclosures do not diminish the literal description of
the 0.5 mg/day dose in the Prophetic Trial. All described
dose ranges include the 0.5 mg/day dose. And smaller dos-
age ranges, such as 0.5–30 mg/day, are disclosed for fin-
golimod hydrochloride. Even if blaze marks were required
in this case, the Prophetic Trial and 0.5–30 mg/day dosage
range would provide a skilled artisan more than sufficient
guidance to direct them to the claimed 0.5 mg/day dose.
Much of HEC’s argument is directed to its assertion
that no one, including the inventors, knew that a 0.5
mg/day dose would be effective as of the 2006 priority date.
That argument fails for two reasons. First, efficacy is not
a requirement of the claims. The claims require only ad-
ministration of a 0.5 mg/day dose for, inter alia, treatment
purposes. The district court found that the purpose limita-
tions are adequately described, and HEC has not appealed
that finding. Thus, cases such as Nuvo Pharms., 923 F.3d
1368, in which this court found that claims directed to an
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NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 13
amount of uncoated PPI that is effective to raise the gastric
pH to at least 3.5 were not adequately described by a spec-
ification that “provides nothing more than the mere claim
that uncoated PPI might work” where skilled artisans
“would not have thought it would work,” are distinguisha-
ble. See id. at 1381. Second, as explained above, the EAE
model provides evidence that the inventors knew that a
60% lower dose would be effective.
For these reasons, we find no clear error in the district
court’s holding that the 0.5 mg/day dosage limitation is ad-
equately described. The district court’s holding is sup-
ported by the specification and ample expert testimony
interpreting that specification.
B. Written Description for the Negative Limitation
HEC argues that there is no written description of the
negative limitation because the ’405 specification contains
no recitation of a loading dose “or its potential benefits or
disadvantages at all.” Appellant’s Br. 40. It further argues
that the district court’s finding of written description of the
negative limitation within the ’405 specification contra-
dicts the district court’s finding that Kappos 2006, which is
similarly silent as to loading doses, does not anticipate the
claims. We find both arguments unavailing.
It is well established that there is no “new and height-
ened standard for negative claim limitations.” Inphi Corp.
v. Netlist, Inc., 805 F.3d 1350, 1356 (Fed. Cir. 2015). We
are aware of no case that suggests otherwise. And, while
HEC asserts that “[i]t is well-settled law that silence alone
cannot serve as a basis for” a negative limitation, Appel-
lant’s Br. 41, HEC identifies no case that actually supports
that proposition. To the contrary, we repeatedly have re-
sisted imposition of heightened written description stand-
ards for negative limitations, such as that urged by HEC.
For example, in Santarus, Inc. v. Par Pharmaceutical,
Inc., we found that claims directed to a method of
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14 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
treatment with a pharmaceutical composition containing
no sucralfate were adequately described by a specification
that explained that, although sucralfate is “possibly the
ideal agent for stress ulcer prophylaxis,” it was known to
have occasional adverse effects. 694 F.3d 1344, 1350–51
(Fed. Cir. 2012). In Santarus, as in this case, there was
expert testimony providing a person of ordinary skill’s un-
derstanding of the patent specification. See id. at 1351.
The expert testimony in Santarus showed that “a person of
ordinary skill in this field . . . would have understood from
the specification that disadvantages of sucralfate may be
avoided by the [claimed] formulation.” Id. We explained
that “[n]egative claim limitations are adequately supported
when the specification describes a reason to exclude the rel-
evant limitation.” Id. We did not hold that a specification
must describe a reason to exclude a negative limitation. A
specification that describes a reason to exclude the relevant
negative limitation is but one way in which the written de-
scription requirement may be met.
In In re Bimeda Research. & Development Ltd., we held
that a claim that excluded a specific anti-infective, acrifla-
vine, was not adequately described by a disclosure that was
inconsistent with the exclusion of acriflavine but not other
anti-infectives or antibiotics. 724 F.3d 1320, 1324 (Fed.
Cir. 2013). The claim at issue in Bimeda was directed to a
method of preventing mastitis in dairy cows by sealing the
teat canal of a cow’s mammary gland with a seal formula-
tion that excludes acriflavine. Other claims in the same
patent excluded all anti-infective agents. We noted that
the patent repeatedly distinguished the invention as able
to prevent mastitis without the use of antibiotics. Based
on the written description’s consistent description of the in-
vention’s non-antibiotic approach to preventing mastitis,
we concluded that the patent’s disclosure was “inconsistent
with a claim which excludes acriflavine, but not the pres-
ence of other antiinfectives or antibiotics.” Id. (citation and
quotation marks omitted). We did not require that the
Case: 21-1070 Document: 41 Page: 15 Filed: 01/03/2022
NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 15
specification describe a reason to exclude acriflavine spe-
cifically, but, rather, found only that a negative limitation
which is inconsistent with the disclosure is not adequately
described.
In Inphi, we confirmed that the written description re-
quirement is satisfied where “‘the essence of the original
disclosure’ conveys the necessary information—‘regardless
of how it’ conveys such information, and regardless of
whether the disclosure’s ‘words [a]re open to different in-
terpretation[s].’” 805 F.3d at 1354 (quoting In re Wright,
866 F.2d 422, 424–25 (Fed. Cir. 1989) (citation and internal
quotation marks omitted)). We explained that “Santarus
simply reflects the fact that the specification need only sat-
isfy the requirements of § 112, paragraph 1 as described in
this court’s existing jurisprudence[.]” Id. at 1356. And we
noted that the “‘reason’ required by Santarus is provided,
for instance, by properly describing alternative features of
the patented invention.” Id. (citing In re Johnson, 558 F.2d
1008, 1019 (C.C.P.A. 1977)).
In Inphi, we found that substantial evidence supported
the Patent Trial and Appeal Board’s (“Board”) finding that
a negative limitation which had been added during prose-
cution (“DDR chip selects that are not CAS, RAS, or bank
address signals”) was adequately described by an original
specification which did not expressly articulate a reason to
exclude RAS and CAS signals. We found the Board’s deci-
sion was supported by evidence of (1) standards set by the
Joint Electron Device Engineering Council, a global stand-
ard setting body for the microelectronics industry, incorpo-
rated by reference in the patent, which specify that DDR
signals, including CS, RAS, CAS, and bank address sig-
nals, are distinct from each other; (2) a table in the specifi-
cation which excludes RAS and CAS signals; and (3)
various passages from the specification, including a figure
which distinguishes chip select signals, command signals
(including RAS and CAS signals) and bank address signals.
We concluded that the specification’s disclosure of
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16 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
alternative features was sufficient to satisfy the written de-
scription standard for the negative limitation. Id. at 1357.
In Nike, Inc. v. Adidas AG, we reiterated that Santarus
did not create a heightened standard for written descrip-
tion of negative limitations. 812 F.3d 1326, 1348 (Fed. Cir.
2016), overruled on other grounds by Aqua Prods., Inc. v.
Matal, 872 F.3d 1290 (Fed. Cir. 2017). We stated that neg-
ative limitations, like all other limitations, are held to “the
customary standard for the written description require-
ment.” Id. In Nike, we found a limitation of “flat knit
edges,” which Adidas characterized as a negative limita-
tion, was adequately described by three figures in the spec-
ification depicting the claimed textile element which Nike’s
expert opined could be made using flat knitting in contrast
to another figure’s textile element which is formed using a
circular knitting machine. Id. at1348–49.
Similarly, in Erfindergemeinschaft Uropep GBR v. Eli
Lilly & Co., Judge Bryson, sitting by designation in the
Eastern District of Texas, explained that the law does not
require that the disclosure explain a negative limitation.
276 F. Supp. 3d 629, 657–58 (E.D. Tex. 2017), aff’d, 739 F.
App’x 643 (Fed. Cir. 2018). Judge Bryson explained, citing
Bimeda, that “[w]hat is prohibited is a negative limitation
that is contrary to the thrust of the invention.” Id. at 658.
He noted that “a patentee can choose to claim any particu-
lar embodiments identified in the specification and exclude
others, without explanation, as long as the claim does not
indicate to persons of skill that it covers embodiments in-
consistent with, and therefore unsupported by, the disclo-
sure.” Id.In asserting that “silence alone cannot serve as a basis
for” a negative limitation, Appellant’s Br. 41, HEC at-
tempts to create a new heightened written description
standard for negative limitations. In doing so, it ignores a
central tenet of our written description jurisprudence—
that the disclosure must be read from the perspective of a
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NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 17
person of skill in the art—as well as precedent stating that
the disclosure need not describe a limitation in haec verba.
See, e.g., All Dental Prodx, LLC v. Advantage Dental Prod.,
Inc., 309 F.3d 774, 779 (Fed. Cir. 2002) (“[T]he failure of
the specification to specifically mention a limitation that
later appears in the claims is not a fatal one when one
skilled in the art would recognize upon reading the specifi-
cation that the new language reflects what the specifica-
tion shows has been invented.” (citing Eiselstein v. Frank,
52 F.3d 1035, 1039 (Fed. Cir. 1995)); see also Ariad, 598
F.3d at 1351. In other words, context and the knowledge
of those skilled in the art matter. And, as the Supreme
Court has made clear, when assessing what the written de-
scription reveals to a skilled artisan, common sense also
matters. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421
(2007) (holding that, in an obviousness analysis, “[r]igid
preventative rules that deny factfinders recourse to com-
mon sense, however, are neither necessary under our case
law nor consistent with it”).
The dissent notes that the Manual of Patent Examin-
ing Procedure (“MPEP”) 7 states: “The mere absence of a pos-
itive recitation is not a basis for an exclusion.” MPEP
§ 2173.05(i). As the dissent puts it—“silence alone is insuffi-
cient.” Dissent at 4. Both the MPEP and the dissent are
correct in their statement of the law: the “mere absence of
a positive recitation” is not enough and “silence alone is in-
sufficient.” But the dissent, like HEC, ignores that it is
how a skilled artisan reads a disclosure that matters. Writ-
ten description may take any form, so long as a skilled ar-
tisan would read the disclosure as describing the claimed
invention.
Our case law makes clear that “[c]ompliance with the
written description requirement is essentially a fact-based
7 The MPEP is not binding on this court but may be
persuasive.
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18 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
inquiry that will ‘necessarily vary depending on the nature
of the invention claimed.’” Enzo Biochem, Inc. v. Gen-Probe
Inc., 323 F.3d 956, 963 (Fed. Cir. 2002) (quoting Vas-Cath
Inc. v. Mahurkar, 935 F.2d 1555, 1562 (Fed. Cir. 1991)).
The MPEP similarly provides for written description in
various forms. In addition to stating that the “mere ab-
sence of a positive recitation” is not enough, the MPEP also
correctly states that no specific form of disclosure is re-
quired and provides for implicit written description. MPEP
§ 2173.05(i) states that “a lack of literal basis in the speci-
fication for a negative limitation may not be sufficient to
establish a prima facie case for lack of descriptive support.”
And MPEP § 2163 states that “newly added claims or claim
limitations must be supported in the specification through
express, implicit, or inherent disclosure.” MPEP § 2163
(emphasis added). What is critical is how a person of skill
in the art would read the disclosure—not the exact words
used.
HEC and the dissent urge us to elevate form over sub-
stance by creating a new rule that a limitation which is not
expressly recited in the disclosure is never adequately de-
scribed, regardless of how a skilled artisan would read that
disclosure. As we have several times before, we reject the
invitation to create a heightened written description stand-
ard for negative limitations. As with all other limitations,
the negative limitation here must be accompanied by an
original disclosure which conveys to a person of ordinary
skill that the inventor was in possession of the claimed in-
vention. See Ariad, 598 F.3d at 1351. And, as in all other
written description challenges, HEC was required to show
by clear and convincing evidence that the negative limita-
tion was not adequately described. The district court did
not clearly err in finding that HEC failed to do so.
In determining that there is adequate written descrip-
tion of the negative limitation, the district court correctly,
and quite carefully, conducted “an objective inquiry into
the four corners of the specification from the perspective of
Case: 21-1070 Document: 41 Page: 19 Filed: 01/03/2022
NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 19
a person of ordinary skill in the art” as required by our
precedent. See Ariad, 598 F.3d at 1351. We review the
evidence cited by the district court below and discern no
clear error in the court’s analysis or conclusions.
The Prophetic Trial describes giving RRMS patients
fingolimod hydrochloride “at a daily dosage of 0.5, 1.25 or
2.5 mg p.o.” ’405 patent col. 11 ll. 8–9. It further states
that: “Initially patients receive treatment for 2 to 6
months.” Id. col. 11 ll. 13–14. Dr. Steinman, one of Novar-
tis’s expert witnesses, testified from the perspective of a
skilled artisan that, if the Prophetic Trial included a load-
ing dose, the patent would explicitly state as much:
“[T]here were two places where if there were going
to be a loading dose, you would explicitly state it.
....
So the first place one might explicitly say there
was—there was a preceding loading dose is when
you described the daily dosage, the reason being a
loading dose would occur before the first daily dose.
The second place is even more dramatic, because
they say, “Initially patients received treatment for
2 to 6 months.” So now they’re really zooming in
on Day 1, what is that treatment, it’s a daily dose
of 0.5.
So there were two perfectly logical places that if
there was going to be a loading dose, it would have
been stated.
....
That’s where you would put it if you were going to
give a loading dose.
J.A. 23343 (Tr. 765:2–25).
Similarly, Dr. Fred Lublin, Ph.D., another expert testi-
fying for Novartis, testified that a person of skill in the art
Case: 21-1070 Document: 41 Page: 20 Filed: 01/03/2022
20 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
“would have viewed the patent as a document, as a com-
plete document, that should give you all the information
you need to carry out the claims, and that information of
having a loading dose is not there, and what’s instead there
is examples of daily dose, daily dose, daily dose.” J.A.
22791 (Tr. 213:6–15). Dr. Lublin testified that a “loading
dose is a greater than normal dose that you give until you
return to a maintenance dose” and a loading dose is “not a
daily dose.” J.A. 22792 (Tr. 214:1–9). He further testified
that “[o]ne would expect in a patent that if there was going
to be a loading dose, it would be specified.” J.A. 22793 (Tr.
215:5–8). And a third expert testifying for Novartis, Dr.
Jusko, similarly testified that, from the perspective of a
person of skill in pharmacology, the Prophetic Trial has a
“specified initial regimen that does not include a loading
dose.” J.A. 23442 (Tr. 864:14–16).
The district court credited this expert testimony, as
well as the testimony from HEC’s own expert, Dr. Paul
Hoffman, M.D., who agreed that “a loading dose is a higher-
than-therapeutic level dose, usually given . . . as the first
dose.” J.A. 23125 (Tr. 547:14–18); J.A. 27. Based on that
evidence, the court concluded that the “absence of an im-
mediately preceding loading dose from the specification,
and from the Prophetic Trial, would tell a person of skill
that loading doses are excluded from the invention.” J.A.
26. We discern no clear error in that finding. The district
court further noted that the rat EAE experiment does not
describe a loading dose. J.A. 26. It again credited the tes-
timony of multiple expert witnesses who testified that the
EAE model did not include a loading dose. J.A. 26. Dr.
Jusko, in response to a question about whether there are
any loading doses in the EAE model, stated: “Not that I’m
aware of.” J.A. 22793 (Tr. 215:16–21). Dr. Steinman simi-
larly testified that no loading dose was used in the EAE
experiment. J.A. 23345 (Tr. 767:3–5). HEC’s own expert
witness, Dr. Hoffman, testified that the EAE model does
not talk about a loading dose. J.A. 23209 (Tr. 631:18–22).
Case: 21-1070 Document: 41 Page: 21 Filed: 01/03/2022
NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 21
Based on both the specification’s disclosure of the rat EAE
model and the ample expert testimony providing evidence
of how a person of ordinary skill would read that disclosure,
the district court concluded that the “EAE example dis-
closes a dosing regimen which does not involve a loading
dose.” J.A. 27. Finally, the district court noted that, while
the patent “describes alternative dosing regimens, like ‘in-
termittent dosing,’ [it] does not describe loading doses.”
J.A. 27.
The district court concluded that the “EAE model and
the Prophetic Trial . . . both indicate to a person of ordinary
skill that the claimed invention did not include the admin-
istration of a loading dose.” J.A. 37–38. We are not left
with the “definite and firm conviction” that the district
court made a mistake in coming to this conclusion. See
Nuvo Pharms., 923 F.3d at 1376 (quoting Scanner Techs.,
528 F.3d at 1374). To the contrary, the district court’s con-
clusion appears wholly correct. To arrive at the opposite
conclusion would require us to disregard the perspective of
a person of skill in the art—something our precedent
simply does not allow. See Ariad, 598 F.3d at 1351.
We also find unpersuasive HEC’s argument that the
district court’s written description decision contradicts its
determination that the ’405 patent is not anticipated by
Kappos 2006. HEC notes that neither Kappos 2006 nor the
’405 patent’s specification explicitly state that a loading
dose should not be administered. But HEC’s argument ig-
nores the differences between the two district court find-
ings and ignores the differences between the disclosures of
Kappos 2006 and the ’405 specification.
As a granted patent, the ’405 patent is presumed valid.
Thus, it is also presumed to have a complete written de-
scription. See Nat’l Recovery Techs., Inc. v. Magnetic Sep-
aration Sys, Inc., 166 F.3d 1190, 1195 (Fed. Cir. 1999)
(“The presumption of validity includes a presumption that
the patent complies with § 112.”). No such presumption
Case: 21-1070 Document: 41 Page: 22 Filed: 01/03/2022
22 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
applies to disclosures of a prior art reference that is not it-
self a granted patent, such as Kappos 2006. Further, the
perspective of a person of skill in the art is important in
both the written description and the anticipation inquiries.
And, in this case, the district court credited the testimony
of two expert witnesses, Dr. Lublin and Dr. Steinman, who
testified that a person of skill in the art would not presume
that the Kappos 2006 abstract was complete. J.A. 30 (cit-
ing J.A. 22782 (Tr. 204:12–19) (Dr. Lublin testifying that
abstracts “have to by design” leave out information describ-
ing clinical trials); J.A. 23475 (Tr. 897:1–5) (Dr. Steinman
testifying that “an abstract, like a press release, like any
kind of announcement, is inherently incomplete,” while “a
publication and a patent are presumed complete”)). Thus,
although neither the ’405 specification nor Kappos 2006 in-
clude the phrase “loading dose,” it was not clear error for
the district court to find that a skilled artisan would read
the specification as not including a loading dose and would
read Kappos 2006 as silent on the presence or absence of a
loading dose.
Differences between the ’405 patent’s specification and
Kappos 2006 justify the district court’s findings that the
specification describes the absence of a loading dose while
Kappos 2006 does not anticipate that negative limitation.
The specification includes the Prophetic Trial, which the
district court found “describes giving a ‘daily dosage of 0.5
. . . mg’ fingolimod to treat RRMS, started ‘initially.’” J.A.
26. The district court found that, “[o]n this record, starting
with a daily dose plainly implies that there is no loading
dose.” J.A. 27. Kappos 2006 consists of two paragraphs
describing a planned clinical trial and, with respect to dos-
ing, states only that “[a]pproximately 1.100 patients . . .
are being randomised in a 1:1:1 ratio to once-daily fin-
golimod 1.25 mg, fingolimod 0.5 mg, or placebo, for up to 24
months.” J.A. 24723–24. Kappos 2006 nowhere says that
the daily fingolimod dosage should be “initially” adminis-
tered. Thus, differences between Kappos 2006 and the ’405
Case: 21-1070 Document: 41 Page: 23 Filed: 01/03/2022
NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 23
patent justify the district court’s conclusions that Kappos
2006 does not anticipate the claims and the ’405 specifica-
tion adequately describes the claims.
The dissent takes umbrage with the district court’s
finding that the “Prophetic Trial describes giving a ‘daily
dosage of 0.5 . . . mg’ fingolimod to treat RRMS, started ‘in-
itially’” because the ’405 patent says “[i]nitially, patients re-
ceive treatment for 2 to 6 months.” Dissent at 6–7; J.A. 26;
’405 patent col. 11 ll. 13–14. The dissent would find that the
“word ‘initially’ is not modifying the daily dosage; it is modi-
fying the initial length of treatment in this example.” Dissent
at 6–7. The dissent, thus, would substitute its own factual
findings for those of the district court. But, if the 2–6 month
“initial” dose does not differ in any way from the previously
described daily doses, the language, used in context, must ex-
clude a loading dose. As we have already explained, the dis-
trict court did not clearly err in finding that the “Prophetic
Trial describes giving a ‘daily dosage of 0.5 . . . mg’ fin-
golimod to treat RRMS, started ‘initially.’” J.A. 26. And we
are not free to substitute our own factual findings for those of
the district court absent clear error because “a district court
judge who has presided over, and listened to, the entire pro-
ceeding has a comparatively greater opportunity to gain the
necessary ‘familiarity with specific scientific problems and
principles,’ . . . than an appeals court judge who must read a
written transcript or perhaps just those portions referenced
by the parties.” Teva Pharms. USA, Inc. v. Sandoz, Inc., 574
U.S. 318, 319 (2015) (quoting Graver Tank & Mfg. Co. v.
Linde Air Prods. Co., 339 U.S. 605, 610 (1950)).
The dissent also asserts that, on this record, the term
“daily dose” would not convey to a skilled artisan that no
loading dose should be used. Dissent at 7–8. But the dis-
trict court’s decision did not rely only on the term “daily
dose.” Rather, as noted above, the district court found that
“starting with a daily dose plainly implies that there is no
loading dose,” as a loading dose is a larger-than-daily dose.
J.A. 27 (emphasis added). We need not, and do not, go
Case: 21-1070 Document: 41 Page: 24 Filed: 01/03/2022
24 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
further than the district court to make findings about the
term “daily dose.” The dissent’s assertion to the contrary
and allegation that we “tease[] an entirely new claim limi-
tation out of an entirely common term, relegating the legal
determination of a term’s meaning to the backseat of an
expert’s post-hoc rationalization” is, frankly, baffling. See
Dissent at 8.
Written description in this case, as in all cases, is a fac-
tual issue. In deciding that the district court did not clearly
err in finding written description for the negative limita-
tion in the ’405 patent, we do not establish a new legal
standard that silence is disclosure, as the dissent asserts.
Instead, we merely hold that, on this record, the district
court did not clearly err in finding that a skilled artisan
would read the ’405 patent’s disclosure to describe the “ab-
sent an immediately preceding loading dose” negative lim-
itation.
III. CONCLUSION
For the foregoing reasons, we affirm the district court’s
decision.
AFFIRMED
Case: 21-1070 Document: 41 Page: 25 Filed: 01/03/2022
United States Court of Appeals
for the Federal Circuit
______________________
NOVARTIS PHARMACEUTICALS CORPORATION,
Plaintiff-Appellee
v.
ACCORD HEALTHCARE, INC., AUROBINDO
PHARMA LTD., AUROBINDO PHARMA USA, INC.,
DR. REDDY’S LABORATORIES, INC., DR. REDDY’S
LABORATORIES, LTD., EMCURE
PHARMACEUTICALS LTD., HERITAGE
PHARMACEUTICALS INC., GLENMARK
PHARMACEUTICALS INC., USA, GLENMARK
PHARMACEUTICALS LIMITED, HETERO USA,
INC., HETERO LABS LIMITED UNIT-V, HETERO
LABS LIMITED, MYLAN PHARMACEUTICALS,
INC., PRINSTON PHARMACEUTICAL INC.,
STRIDES GLOBAL PHARMA PRIVATE LIMITED,
STRIDES PHARMA, INC., TORRENT PHARMA
INC., TORRENT PHARMACEUTICALS LTD.,
ZYDUS PHARMACEUTICALS (USA) INC., CADILA
HEALTHCARE LTD., APOTEX INC., APOTEX
CORP., SUN PHARMACEUTICAL INDUSTRIES,
LTD., SUN PHARMACEUTICAL INDUSTRIES INC.,
SUN PHARMA GLOBAL FZE,
Defendants
HEC PHARM CO., LTD., HEC PHARM USA INC.,
Defendants-Appellants
______________________
2021-1070
______________________
Case: 21-1070 Document: 41 Page: 26 Filed: 01/03/2022
2 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
Appeal from the United States District Court for the
District of Delaware in No. 1:18-cv-01043-KAJ, Circuit
Judge Kent A. Jordan.
______________________
MOORE, Chief Judge, dissenting.
The majority dramatically expands a patentee’s ability
to add, years after filing a patent application, negative
claim limitations that have zero support in the written de-
scription. By doing so, it contradicts our well-established
precedent and nullifies the Patent Office’s guidance in the
Manual of Patent Examining Procedure (MPEP). I would
reverse the district court’s finding that there exists written
description support as it is inconsistent with our estab-
lished precedent. Silence is not disclosure.
I
“The hallmark of written description is disclosure.” Ar-
iad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351
(en banc). The description in the specification must clearly
allow a skilled artisan to recognize that the inventor in-
vented what is claimed. Id. The ’405 patent contains no
written description support for the limitation “absent an
immediately preceding loading dose regimen.” This nega-
tive limitation was added in response to an obviousness re-
jection during prosecution of the ’405 patent’s co-pending
parent application. J.A. 23892–94. Claim 1:
1. A method for reducing or preventing or alleviat-
ing relapses in Relapsing-Remitting multiple scle-
rosis in a subject in need thereof, comprising orally
administering to said subject 2-amino-2-[2-(4-oc-
tylphenyl)ethyl]propane-1,3-diol, in free form or in
a pharmaceutically acceptable salt form, at a daily
dosage of 0.5 mg, absent an immediately preceding
loading dose regimen.
Case: 21-1070 Document: 41 Page: 27 Filed: 01/03/2022
NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 3
There is no disclosure in the specification of preventing
a loading dose. Loading doses—whether to be used or not—
are never discussed. As the majority concedes, we have
long held that silence cannot support a negative limitation;
for if the specification is silent there is no evidence that the
inventor actually possessed the invention. Maj. at 17
(“Both the MPEP and the dissent are correct in their state-
ment of the law: the ‘mere absence of a positive recitation’
is not enough, and ‘silence alone is insufficient.’”). “Nega-
tive claim limitations are adequately supported when the
specification describes a reason to exclude the relevant lim-
itation,” such as by listing the disadvantages of some em-
bodiment. Santarus, Inc. v. Par Pharm., Inc., 694 F.3d
1344, 1351 (Fed. Cir. 2012). In Inphi Corp. v. Netlist, Inc.,
805 F.3d 1350, 1356 (Fed. Cir. 2015), we explained that re-
citing alternative features of the patented invention may
also suffice. 1 In Nike, Inc. v. Adidas AG, we again reiter-
ated that the specification should indicate a reason to ex-
clude. 812 F.3d 1326, 1348 (Fed. Cir. 2016). This law, our
law, does not create a heightened standard for negative
claim limitations; it simply requires some disclosure to
demonstrate that the inventor was not, as in this case, am-
bivalent about loading doses. 2
1 Erfindergemeinschaft Uropep GBR v. Eli Lilly &
Co., 276 F. Supp. 3d 629, 657–59 (E.D. Tex. 2017), con-
sistent with Inphi, holds that when a patent discloses
many alternatives, the claims are permitted to claim only
some and exclude others. The specification here does not
disclose alternatives (some with and some without loading
doses).
2 In re Bimeda Research & Development Ltd., 724
F.3d 1320, 1323–24 (Fed. Cir. 2013), does not help the ma-
jority at all. The court simply held that, when the patent
repeatedly emphasizes that the invention was “without
Case: 21-1070 Document: 41 Page: 28 Filed: 01/03/2022
4 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
Following our clear precedent, the Patent Office’s
MPEP provides the following guidance: “The mere absence
of a positive recitation is not a basis for an exclusion,” i.e.,
silence alone is insufficient. MPEP § 2173.05(i). That re-
mains true even if it would have been obvious to a skilled
artisan to exclude the undisclosed feature. Rivera v. Int’l
Trade Comm’n, 857 F.3d 1315, 1322 (Fed. Cir. 2017) (“The
knowledge of ordinary artisans may be used to inform what
is actually in the specification, but not to teach limitations
that are not in the specification, even if those limitations
would be rendered obvious by the disclosure.”).
Nowhere in the patent does it say a loading dose should
not be administered. Nowhere does it discuss alternatives
(including or not including a loading dose). Nowhere does
it give advantages or disadvantages of including a loading
dose. Indeed, it provides no reason to exclude a loading
dose. Even Novartis’ expert, Dr. Lublin, agreed:
Q: Nothing in the text of the specification of the
’405 patent discloses a rationale for the negative
limitation prohibiting an immediately preceding
loading dose, correct?
A: I don’t believe so.
J.A. 22872–73. And all the experts agreed that loading
doses are sometimes given to MS patients. See J.A. 22780
(Dr. Lublin explaining that loading doses have been used
in trials of MS drugs and with fingolimod in particular);
J.A. 22794; J.A. 23347–48 (Dr. Steinman, Novartis’ second
physician expert, acknowledging that loading doses are
used in MS treatments); J.A. 23475 (Dr. Jusko, Novartis’
pharmacology expert, testifying that fingolimod was given
to transplant patients with a loading dose, and that he
“could envision the possibility of starting with a loading
using antibiotics,” a claim which allows some antibiotics
lacks written description support. Id.Case: 21-1070 Document: 41 Page: 29 Filed: 01/03/2022
NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 5
dose”). The ’405 patent provides nothing to signal to the
public that the inventors possessed a treatment excluding
a loading dose when a loading dose was a known possibil-
ity.
The patent is silent, eerily silent. Consistent with San-
tarus, Inphi, and Nike, there needed to be some discussion
of loading doses in order to show that the inventors in fact
invented this treatment method that is not just ambivalent
to, but expressly excludes, a loading dose. This is not a
heightened written description requirement; it is simply a
written description requirement.
The district court relied on the disclosure’s silence to
support the negative loading dose limitation, reasoning
that silence “would tell a person of skill that loading doses
are excluded from the invention.” J.A. 26 ¶ 61. We have
rejected the notion that a skilled artisan’s knowledge can
speak for a mute specification. See Rivera, 857 F.3d at
1322. Here, the expert that the majority relies upon to sup-
plement a silent disclosure concludes that a loading dose is
excluded because the patent is silent on loading doses: “the
patent [i]s a document, as a complete document, that
should give you all the information you need to carry out
the claims, and that information of having a loading dose
is not there.” Maj. at 19–20 (quoting J.A. 22791). If silence
were sufficient then every later-added negative limitation
would be supported as long as the patent makes no men-
tion of it. This is a fundamental error of law.
Novartis explained its support for the no-loading-dose
limitation as follows:
Judge Linn: There is nothing in the patent that
says treatment begins with the daily dose?
Novartis: Ummm the prophetic example says
treatment begins initially and treatment is the 0.5
mg daily dose so if that begins initially it excludes
the possibility of a loading dose.
Case: 21-1070 Document: 41 Page: 30 Filed: 01/03/2022
6 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
***
Chief Judge Moore: The patent says “Initially, pa-
tients receive treatment for 2 to 6 months,” and you
believe I should construe that as initially there is
no loading dose?
Novartis: Yes, your honor a loading dose is ex-
cluded from that treatment.
Oral Argument at 35:30–37:13. The majority claims that
the Prophetic Example in the specification describes
“start[ing] ‘initially’” by “giving a ‘daily dose of 0.5 . . . mg.’”
Maj. at 7; Maj. at 22 (same). This is a false and inaccurate
quotation. The word “initially” does not precede or modify
the daily dosage sentence; it follows it three full sentences
later. To be clear, the patent does NOT say treatment be-
gins initially with a daily dose. Here is the actual quote:
20 patients with relapsing-remitting MS receive
said compound at a daily dosage of 0.5, 1.25 or 2.5
mg p.o. The general clinical state of the patient is
investigated weekly by physical and laboratory ex-
amination. Disease state and changes in disease
progression are assessed every 2 months by radio-
logical examination (MRI) and physical examina-
tion. Initially, patients receive treatment for 2 to 6
months. Thereafter, they remain on treatment for
as long as their disease does not progress and the
drug is satisfactorily tolerated.
’405 patent at 11:8–16. The word “initially” is not some
complex, scientific term in need of expert explanation. It is
basic English. The word “initially” is not modifying the
daily dosage; it is modifying the initial length of treatment
Case: 21-1070 Document: 41 Page: 31 Filed: 01/03/2022
NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 7
in this example. 3 To the extent that the district court
reached a fact finding to the contrary, it is inconsistent
with the straight-forward, quite clear language of the pa-
tent and therefore clearly erroneous. 4
Novartis also claims that the use of the term “daily dos-
age” itself would convey to a skilled artisan that no loading
dose should be used. This is not only unsupported by the
record; it is contradicted at every turn. First, the claim al-
ready said “daily dosage” before the negative limitation
was added. It was allowed only after the applicants added
the no loading dose limitation. J.A. 23903 (Examiner’s re-
jection in parent application); J.A. 23892–93 (Applicant
Response in same); see also Novartis Br. 11–12. The appli-
cants explained they added the no-loading-dose limitation
“to specify that the [daily dosage] cannot immediately fol-
low a loading dose regiment. Applicants have made these
amendments to further distinguish their claims from the
disclosure of [the prior art].” J.A. 23892. 5 If daily already
meant no loading dose, then there would have been no rea-
son for the claims to recite both a “daily dosage” and the
negative loading dose limitation. The same logic applies to
3 I note that even if the Prophetic Example were to
be understood as not having included a loading dose that
does not mean that loading doses must be prohibited (as
the claims now require).
4 Nothing about this analysis “substitute[s] . . . fac-
tual findings for those of the district court.” Maj. at 23.
Instead, it merely points out how it is clear error for the
majority, district court, and Novartis to misquote the spec-
ification.
5 Novartis stated during argument that this limita-
tion was “added to clarify that the claim does not overlap
with [the prior art].” Oral Argument at 21:34–41. This lit-
igation claim cannot be reconciled with their own prosecu-
tion statements.
Case: 21-1070 Document: 41 Page: 32 Filed: 01/03/2022
8 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
the specification, which only mentioned “daily dosage.”
This prosecution makes clear that neither the applicant
nor the examiner believed that the use of the term “daily
dosage” alone conveyed the absence of a loading dose.
There is no evidence that daily had a special meaning
in the field of pharmacology. Daily is not a complex or com-
plicated term of art that requires expert testimony to ex-
plain. The district court construed the claim term “daily
dosage of 0.5 mg” to mean “the amount of drug that some-
one takes in a given day.” J.A. 18670. Neither party ar-
gued the term excludes a loading dose. Id. And for good
reason—it has a plain meaning, and the prosecution his-
tory shows it does not implicitly exclude a loading dose.
Novartis backdoors a claim construction argument, argu-
ing that “experts understood the patent’s description of a
‘daily dose’ as exclusive of a loading dose,” Novartis Br. 46,
but it and the district court already defined daily dosage
otherwise.
Rather than defend Novartis’ reliance on the “daily
dosage” language, the majority pivots to focus on the dis-
trict court’s statement that “starting with a daily dose
plainly implies that there is no loading dose.” Maj. at 23–
24 (quoting J.A. 27). But that statement is just another
example of the district court (and now the majority) rewrit-
ing the specification with expert testimony. The patent
never says “starting with a daily dose,” and the district
court relied exclusively on expert testimony to support that
finding. See J.A. 27 (citing J.A. 23344). But “[t]he
knowledge of ordinary artisans may . . . not [be used] to
teach limitations that are not in the specification[.]” Ri-
vera, 857 F.3d at 1322. Novartis, and now the majority,
teases an entirely new claim limitation out of an entirely
common term, relegating the legal determination of a
term’s meaning to the backseat of an expert’s post-hoc ra-
tionalization.
Case: 21-1070 Document: 41 Page: 33 Filed: 01/03/2022
NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC. 9
In fact, the district court found that a nearly identical
disclosure in the prior art (Kappos 2006, a Novartis-sup-
ported study) did not anticipate because it failed to disclose
the negative loading dose limitation. Kappos disclosed a
study administering 0.5 mg fingolimod to RRMS patients
“once-daily fingolimod for up to 24 months.” J.A. 29–30
¶ 72; J.A. 24724. The district court found Kappos 2006 did
not meet the negative loading-dose limitation, reasoning
that “[t]he failure to mention a loading dose does not . . .
indicate that the dose was not present in the trial, but only
that the presence or absence of a loading dose was not men-
tioned.” J.A. 30 ¶ 74. A district court’s “internally incon-
sistent factual findings,” like those here, “are, by definition,
clearly erroneous.” In re Sentinel Mgmt. Grp., Inc., 728
F.3d 660, 670 (7th Cir. 2013); see also United States v.
AT&T, Inc., 916 F.3d 1029, 1033 (D.C. Cir. 2019) (citing,
e.g., Anderson v. City of Bessemer, N.C., 470 U.S. 564, 575
(1985)) (“A finding may be clearly erroneous when it is il-
logical or implausible, [or] rests on internally inconsistent
reasoning.”).
The majority’s attempts to distinguish Kappos 2006
from the ’405 patent fall flat. Maj. at 21–23. To be sure,
Kappos 2006 does not “say[] the daily fingolimod dosage
should be ‘initially’ administered.” Id. at 22–23. But nei-
ther does the ’405 patent. The ’405 patent uses the word
initially to describe the length of treatment, not the dosage.
And it is simply not correct that an issued patent is “pre-
sumed to have a complete written description.” Maj. at 21.
“The presumption of validity includes a presumption the
patent complies with” the written description requirement.
Nat’l Recovery Techs., Inc. v. Magnetic Separation Sys.,
Inc., 166 F.3d 1190, 1195 (Fed. Cir. 1999). But it does not
require presuming an issued patent is “complete,” which
would mean silence presumptively supports a negative lim-
itation in every case. That presumption is contrary to our
long-standing precedent, which the majority recognizes
Case: 21-1070 Document: 41 Page: 34 Filed: 01/03/2022
10 NOVARTIS PHARMACEUTICALS v. ACCORD HEALTHCARE INC.
(see Maj. at 17), and a gross expansion of the presumption
of validity.
This specification is ambivalent as to loading doses in
a field where, by all expert accounts, loading doses of fin-
golimod were sometimes used to treat MS. The inventors
do not get to claim as their invention something they did
not disclose in the patent. There are no fact findings here
to defer to—the patent is silent as to loading doses. The
district court relied upon that silence: “The absence of an
immediately preceding loading dose from the specification,
and from the Prophetic Trial, would tell a person of skill
that loading doses are excluded from the invention.”
J.A. 26 ¶ 61. This is not a finding of fact; it is a misunder-
standing of the law. An inventor cannot satisfy the written
description requirement through silence. And when the
majority concludes otherwise, it creates a conflict with our
long-standing, uniformly-applied precedent including San-
tarus, Inphi, and Nike. While the negative limitation need
not be recited in the specification in haec verba, there must
be something in the specification that conveys to a skilled
artisan that the inventor intended the exclusion: disad-
vantages, alternatives, inconsistencies, just something.
This specification is entirely silent and ambivalent about
loading doses. These inventors did not disclose treatment
that must exclude a loading dose, and the district court’s
finding to the contrary is clearly erroneous. After this case,
negative limitations are supported by a specification that
simply never mentions them.