Santarus, Inc. v. Par Pharmaceutical, Inc. , 694 F.3d 1344 ( 2012 )

United States Court of Appeals
for the Federal Circuit
__________________________
SANTARUS, INC.,
Plaintiff-Appellant,
AND
THE CURATORS OF THE UNIVERSITY OF
MISSOURI,
Plaintiff-Appellant,
v.
PAR PHARMACEUTICAL, INC.,
Defendant-Cross Appellant.
__________________________
2010-1360, -1380
__________________________
Appeals from the United States District Court for the
District of Delaware in consolidated Case Nos. 07-CV-0551
and 07-CV-0827, Chief Judge Gregory M. Sleet.
___________________________
Decided: September 4, 2012
___________________________
MORGAN CHU, Irell & Manella LLP, of Los Angeles, Cali-
fornia, argued for both plaintiffs-appellants. With him on
the brief for The Curators of the University of Missouri were
JAMISON E. LYNCH, Mayer Brown LLP, of Chicago, Illinois.
Of counsel for Santarus, Inc. were GARY N. FRISCHLING and
SANTARUS v. PAR PHARMA 2
JOSEPH M. LIPNER, Irell & Manella LLP, of Los Angeles,
California; and ANDREA C. HUTCHINSON, Mayer Brown LLP,
of Chicago, Illinois, for The Curators of the University of
Missouri.
Janine A. Carlan, Arent Fox, LLP, of Washington, DC,
argued for defendant-cross-appellant. On the brief was
Richard J. Berman. Of counsel were Timothy W. Bucknell,
Aziz Burgy, Janine A. Carlan, Joshua T. Morris, Amy E.L.
Schoenhard, and Anthony W. Shaw.
__________________________
Before RADER, Chief Judge, NEWMAN, AND MOORE, Circuit
Judges.
Opinion for the court filed PER CURIAM. Opinion concur-
ring in part and dissenting in part filed by Circuit Judge
NEWMAN.
PER CURIAM.
Appeal and cross-appeal are taken from the judgment of
the United States District Court for the District of Dela-
ware. 1 Plaintiff Santarus, Inc. is the exclusive licensee of
patents on specified formulations of benzimidazole proton
pump inhibitors (PPI) – a class of chemical compounds that
inhibit gastric acid secretion and help prevent and treat
stomach acid-related diseases and disorders. The patents
are for the inventions of Dr. Jeffrey Phillips, and are as-
signed to the University of Missouri. Santarus provides the
PPI product omeprazole in the formulations covered by the
Phillips patents, with the brand name Zegerid®.
1 Santarus, Inc. v. Par Pharm., Inc., 720 F. Supp. 2d
427 (D. Del. 2010).
3 SANTARUS v. PAR PHARMA
Defendant Par Pharmaceutical, Inc. filed an Abbrevi-
ated New Drug Application (ANDA) for FDA approval to sell
a generic counterpart of the Santarus Zegerid® products,
invoking the Hatch-Waxman Act (the Drug Price Competi-
tion and Patent Term Restoration Act of 1984), which
established a procedure called a “Paragraph IV certifica-
tion,” 21 U.S.C. § 355(j)(2)(A)(vii)(IV), whereby an entity
that seeks to market a generic counterpart of a patented
drug product or method of use, before the patent has ex-
pired, may challenge the patent before actually marketing
the drug. Thus the parties are here litigating the issues of
infringement, validity, and enforceability of the Phillips
patents.
The district court found that Par’s ANDA products in-
fringe the Phillips patents, but held all of the asserted
claims invalid on the ground of obviousness, 35 U.S.C § 103.
The court also held certain claims invalid on the ground of
inadequate written description, 35 U.S.C. § 112. On the
defense of unenforceability, the district court held that there
was not inequitable conduct by Dr. Phillips, the University
of Missouri, or their counsel in procuring the patents. Each
side appeals the rulings adverse to it, except that Par does
not appeal the finding of infringement. We conclude that
the district court erred by holding that some of the thirty-six
asserted claims would have been obvious over the prior art;
these rulings are reversed. The court’s other rulings are
affirmed.
I. THE PHILLIPS PATENTS
Proton pump inhibitors affect the action of an enzyme
within the stomach’s parietal cells, the cells within the
membrane of the stomach that secrete hydrochloric acid. It
was known that chemicals of the class of benzimidazoles
have the property of inhibiting or inactivating this proton
pump enzyme. The benzimidazoles operate by a mechanism
SANTARUS v. PAR PHARMA 4
whereby the benzimidazole PPI, upon ingestion or intrave-
nous infusion, circulates in the bloodstream, from which it
reaches and accumulates in the parietal cells and affects the
proton pump enzyme. Hydrochloric acid secretion does not
recover until the body produces a new quantity of the pro-
ton-producing enzyme. Several benzimidazoles have been
approved by the FDA for PPI use, including products having
the common names omeprazole (brand name Prilosec®),
esomeprazole (Nexium®), lansoprazole (Prevacid®), ra-
beprazole (Aciphex®), and pantoprazole (Protonix®).
Although these PPIs are effective at blocking stomach
acid production, they are extremely acid-sensitive. It was
known that unprotected PPIs in the stomach’s acidic envi-
ronment do not survive long enough to be absorbed into the
bloodstream, and thus do not reach the parietal cells. To
avoid this destruction, PPI products for oral ingestion were
provided with an acid-resistant enteric coating, whereby the
coated PPI passes safely through the stomach to the intes-
tine, where the coating dissolves and the PPI is absorbed.
Before Dr. Phillips’s invention, all PPI products that
were FDA-approved for oral administration had an enteric
coating. In contrast, the Phillips products do not have an
enteric coating. The products can be administered as liquid
suspensions of the solid uncoated PPI together with a buff-
ering agent, whereby the PPI is absorbed directly from the
stomach into the bloodstream. This formulation has the
advantages of rapid and consistent bioavailability and
increased effectiveness, as well as ease of administration to
patients unwilling or unable to swallow capsules or tablets.
The Phillips patents explain:
in their current form (capsules containing enteric-
coated granules or enteric-coated tablets), proton
pump inhibitors can be difficult or impossible to
5 SANTARUS v. PAR PHARMA
administer to patients who are either unwilling or
unable to swallow tablets or capsules, such as criti-
cally ill patients, children, the elderly, and patients
suffering from dysphagia.
U.S. Patent No. 7,399,772, col.7 l.65 - col.8 l.4. The Phillips
products “can alternatively be formulated as a powder,
tablet, suspension tablet, chewable tablet, capsule, efferves-
cent powder, effervescent tablet, pellets and granules.” Id.
col.11 ll.50-53. The Phillips patents claim specific combina-
tions of the uncoated benzimidazole PPI and buffering
agents.
Par Pharmaceutical filed ANDA documents with the
FDA, requesting permission to market the same formula-
tions as the Zegerid® PPI, and describing the Par products
as bioequivalent to the Zegerid® products marketed by
Santarus. Par asserted unenforceability of all of the claims
of the Phillips patents, and invalidity of the claims for which
Santarus charged Par with infringement: U.S. Patent No.
6,489,346 (the ’346 patent) claims 26, 37, 38, 49, 50, 58, 59,
60, 66, 68, 80, 81, 82; U.S. Patent No. 7,399,772 (the ’772
patent) claims 1, 4, 5, 8, 10, 12, 14, 15, 20, 21; U.S. Patent
No. 6,780,882 (the ’882 patent) claims 11, 12, 15, 27; U.S.
Patent No. 6,699,885 (the ’885 patent) claims 2, 9, 11, 15,
16, 17, 18, 41; and U.S. Patent No. 6,645,988 (the ’988
patent) claim 29.
Each of the Phillips patents is a continuation or con-
tinuation-in-part in a chain that originated with Patent No.
5,840,737 (the ’737 patent) based on a provisional applica-
tion filed on January 4, 1996. The ’737 patent describes the
combination of the PPI and sodium bicarbonate, and states
the broadest claim as follows:
SANTARUS v. PAR PHARMA 6
1. A method for treating gastric acid disorders by
administering to a patient a single dose of a phar-
maceutical composition of omeprazole or lansopra-
zole in a pharmaceutically acceptable carrier
consisting essentially of a bicarbonate salt of a
Group IA metal wherein said administering step
consists of providing to the patient orally a single
dose of an aqueous solution or, suspension of the
pharmaceutical composition without requiring fur-
ther administration of the bicarbonate salt of the
Group IA metal.
’737 patent claim 1.
The ’346 patent is a continuation-in-part of the ’737 pat-
ent, with an intervening abandoned application. Similar to
the ’737 patent, the ’346 patent generally claims a method
for treating an acid-caused gastrointestinal disorder com-
prising administering a solid pharmaceutical composition in
a dosage form that is not enteric coated. See, e.g., ’346
patent claim 24. The dosage consists of PPI and a buffering
agent, and the claims specify certain ranges of PPI and
buffer.
The ’988 patent is a continuation-in-part of its predeces-
sors. It includes a new Figure 5 showing the pH of gastroe-
sophageal reflux disease and discusses the scientific
mechanism of operation of the PPI. Only claim 29 is as-
serted. It recites a non-enteric coated solid oral pharmaceu-
tical dosage form comprising approximately 5-300 mg of PPI
and a buffer in an amount of 0.1-2.5 mEq per mg of PPI.
’988 patent claim 29. The dosage form also includes a
pharmaceutically-acceptable excipient, indicating that it is a
conventional dosage form such as a tablet, capsule, or
granule. Id.
7 SANTARUS v. PAR PHARMA
The other patents include additional limitations. For
example, the ’885 patent claims recite the serum concentra-
tion or blood level of PPI that is obtained within 30 minutes
after administration. See, e.g., ’885 patent claim 2. The
’882 patent claims a stable powder for suspension, having a
specified ratio of buffering agent to PPI, and a thickening
agent. The composition recited in the ’772 patent contains
no sucralfate. ’772 patent claim 1.
Par argues that every asserted claim would have been
obvious over any one of several pieces of prior art. Par also
argues that Dr. Phillips’s own ’737 patent renders obvious
those claims to which it is prior art. Finally, Par argues
that all of the patents are unenforceable for inequitable
conduct in the Patent and Trademark Office. We start with
the issue of inequitable conduct, for this defense is asserted
against all claims of all of the patents in suit.
II. INEQUITABLE CONDUCT
Par argues that all of the Phillips patents are unen-
forceable due to inequitable conduct by Dr. Phillips, the
University of Missouri, and their attorneys, on the ground
that they were tardy in informing the PTO that Dr. Phillips
had made the uncoated PPI formulation and administered it
to some hospital patients, and had informed medical col-
leagues and recorded the medication and its test results in
hospital records, before the filing date of his first patent
application. Par cites a “Critical Care Abstract” written by
Dr. Phillips at St. Vincent’s Hospital, entitled “The Effect of
Omeprazole/Sodium Bicarbonate Solution Administration
on the Accuracy of subsequent pH Measurements Through
the Nasogastric Tube.” This document reports his meas-
urements of stomach acidity for these formulations.
Par charged that this test information and report should
have been provided to the PTO during the prosecution of the
SANTARUS v. PAR PHARMA 8
first Phillips application, instead of during the prosecution
of the second, continuing application. Par did not and does
not argue that this information invalidates any patent, but
argues that the disclosure to the PTO should have occurred
during prosecution of the first-filed application, and that
failure to do so renders unenforceable all of the patents.
Dr. Phillips testified that he was unaware that his ex-
perimental administration to patients and his measurement
of the effect on stomach acidity required disclosure to the
PTO. He testified that he had believed that only sale and
public use were required to be disclosed, not experimental
development, and that he had not intentionally withheld
information or delayed its disclosure to the PTO. The
University’s patent counsel testified that when he became
aware of this test information he provided it to the PTO by
Information Disclosure Statement during prosecution of the
’346 application, which was the first continuing application,
for the first application had already issued as a patent.
Par also stated that Dr. Phillips submitted a misleading
declaration to the PTO regarding a “Carroll Abstract,”
where, in response to an examiner’s rejection, Dr. Phillips
submitted a declaration describing a test in which he
crushed enteric-coated PPI and mixed the crushed pellets
with a sodium bicarbonate solution; he declared that a
suspension did not form, and provided a photograph of the
test tube containing the crushed pellets. Par argued that
Dr. Phillips distorted the study because he did not shake or
swirl the crushed pellets with the sodium bicarbonate
solution. Par’s expert testified that in his opinion it would
take no more than five to ten minutes for the shaken sus-
pension to become homogeneous; this opinion was not
supported with evidence.
9 SANTARUS v. PAR PHARMA
The district court found that Par had shown materiality
of some of this information, and that the explanation by Dr.
Phillips of why his test information was not initially pro-
vided to the PTO “strained credibility.” However, the court
also found that “the evidence presented is not sufficient to
establish by clear and convincing evidence that Dr. Phillips
acted with an affirmative intent to deceive.” Santarus, 720
F. Supp. 2d at 461. This finding is in accord with
Therasense, Inc. v. Becton, Dickinson & Co., where this
court explained that “[t]o prevail on a claim of inequitable
conduct, the accused infringer must prove that the patentee
acted with the specific intent to deceive the PTO.” 649 F.3d
1276, 1290 (Fed. Cir. 2011) (en banc).
On this appeal Par stresses the district court’s remark
of “strained credibility” and argues that this court should
disbelieve Dr. Phillips, and that the only reasonable infer-
ence is that he and his legal representatives acted in bad
faith and with intent to deceive. Santarus responds that the
district court did not find any testimony false, and that
intent to deceive was not established. We agree with the
district court that intent to deceive was not shown by clear
and convincing evidence. The district court’s ruling that
inequitable conduct was not established is affirmed.
III. VALIDITY
The district court invalidated the asserted claims of the
’772 patent on the ground of inadequate written description
and determined that the ’772 claims are not entitled to
claim priority to the application that issued as the ’737
patent. The court also invalidated all of the asserted claims
on the ground of obviousness over any of several prior art
references. The court held that the ’737 patent rendered
obvious every claim to which it is prior art.
SANTARUS v. PAR PHARMA 10
A. WRITTEN DESCRIPTION
The written description issue relates to the inclusion of
the clause “wherein the composition contains no sucralfate”
in the claims of the ’772 patent. This limitation is present
in the sole independent claim of the ’772 patent, claim 1,
which recites:
A method for treating an acid-caused gastrointesti-
nal disorder comprising the step of administering to
a subject suffering from said disorder a solid phar-
maceutical composition comprising:
(a) about 10mg to about 40mg of non-enteric
coated omeprazole; and
(b) sodium bicarbonate in an amount of 0.2
mEq to 5 mEq per 2mg omeprazole;
wherein the composition contains no sucralfate, the
acid-caused gastrointestinal disorder is selected
from the group consisting of duodenal ulcer, gastric
ulcer, gastroesophageal reflux disease, and erosive
esophagitis, and the sodium bicarbonate is present
in the composition in an amount sufficient to sub-
stantially prevent or inhibit acid degradation of at
least some of the omeprazole by gastric acid upon
administration to the subject.
’772 patent claim 1 (emphasis added).
The district court held that it is necessary for the ’772
specification to include evidence demonstrating that sucral-
fate is “contraindicated,” in order to meet the written de-
scription requirement of § 112 ¶1. The court held that it is
inadequate that the specification states that Phillips’s
claimed composition is “advantageous” as compared with
11 SANTARUS v. PAR PHARMA
sucralfate, a product then commonly used to treat gastric
ulcers and acid reflux. As a result, the court found that
neither the priority applications, such as the application
that issued as the ’737 patent, nor the ’772 specification
support the “no sucralfate” limitation. Santarus, 720 F.
Supp. 2d at 444. For the same reasons, the court concluded
that the asserted claims of the ’772 patent are not entitled
to claim priority to the ’737 patent’s filing date. Id.
The ’772 specification states that “H2 antagonists, antac-
ids, and sucralfate . . . have certain disadvantages associ-
ated with their use . . . . Proton pump inhibitors such as
omeprazole represent an advantageous alternative to the
use of H2 antagonists, antacids, and sucralfate as a treat-
ment for complications related to stress-related mucosal
damage.” ’772 patent, col.7 II.62-65. The district court held
that this statement is insufficient to meet the written
description requirement, stating: “While this indicates that
omeprazole is preferable to sucralfate, the same statements
indicate with no less force that omeprazole is preferable to
antacids such as sodium bicarbonate. Nonetheless, sodium
bicarbonate, an antacid, is listed as the preferred carrier or
buffer in the disclosed invention. Thus it cannot be true
that the priority applications’ disclosure of the disadvan-
tages of sucralfate, by itself, implies that its use is contrain-
dicated.” Santarus, 720 F. Supp. 2d at 443-44. The district
court held that “consequently, the court finds that neither
the priority applications nor the specification of the ’772
patent support the no sucralfate limitation, for they do not
show why a person of ordinary skill in the art reading the
application would believe that sucralfate was ‘contraindi-
cated’ in the claimed composition.” Id. at 444.
The ’737 patent specification states that sucralfate,
“possibly the ideal agent for stress ulcer prophylaxis, [citing
references],” was known to have occasional adverse effects.
SANTARUS v. PAR PHARMA 12
’737 patent, col.3 ll.14-15, ll.25-27 (“[T]he only patient whose
death was attributed to stress-related upper gastrointesti-
nal bleeding was in the sucralfate arm . . . .”). Santarus
argues that it is not necessary to include in the specification
evidence of “contraindication” of sucralfate, and cites the
testimony of Dr. Gilbert Banker, an expert witness for
Santarus, who testified that a person of ordinary skill in
this field would have known the properties and effects of
sucralfate, and would have understood from the specifica-
tion that disadvantages of sucralfate may be avoided by the
Phillips formulation.
We agree. The claim limitation specifying that sucral-
fate is not administered in conjunction with the Phillips
formulation restricted the claims to this preferred use of the
Phillips formulations. This exclusion narrowed the claims,
as the patentee is entitled to do. The Manual of Patent
Examining Procedure explains that claims may state the
exclusion of alternatives. See MPEP § 2173.05(i) (“If alter-
native elements are positively recited in the specification,
they may be explicitly excluded in the claims.”). For exam-
ple, in In re Johnson, 558 F.2d 1008, 1019 (CCPA 1977), the
applicant narrowed the claims to exclude the content of a
lost interference count, and the court observed that: “It is
for the inventor to decide what bounds of protection he will
seek.”
Negative claim limitations are adequately supported
when the specification describes a reason to exclude the
relevant limitation. Such written description support need
not rise to the level of disclaimer. In fact, it is possible for
the patentee to support both the inclusion and exclusion of
the same material. The claim limitation that the Phillips
formulations contain no sucralfate is adequately supported
by statements in the specification expressly listing the
disadvantages of using sucralfate. The district court’s
13 SANTARUS v. PAR PHARMA
holding that the ’772 patent claims are invalid on written
description grounds is thus reversed. Because the lack of
written description for the “no sucralfate” limitation was the
district court’s only reason for concluding that the ’772
patent claims cannot claim priority to the application that
issued as the’737 patent, we also reverse this holding. As a
result, the ’772 patent claims are entitled to claim priority
to the ’737 patent, which thus cannot be used as prior art
against them.
B. OBVIOUSNESS – 35 U.S.C. § 103
The primary issue on appeal is whether a solid dosage
form of non-enteric coated PPI such as omeprazole would
have been obvious to one of ordinary skill in the art. A
patent is invalid for obviousness “if the differences between
the subject matter sought to be patented and the prior art
are such that the subject matter as a whole would have been
obvious at the time the invention was made to a person
having ordinary skill in the art to which said subject matter
pertains.” 35 U.S.C. § 103(a). “Obviousness is a question of
law, which we review de novo, with underlying factual
questions, which we review for clear error following a bench
trial.” Honeywell Int’l, Inc. v. United States, 609 F.3d 1292,
1297 (Fed. Cir. 2010). These underlying factual inquires
are: (1) the scope and content of the prior art; (2) the differ-
ences between the prior art and the claims at issue; (3) the
level of ordinary skill in the field of the invention; and (4)
objective considerations such as commercial success, long
felt need, and the failure of others. KSR Int’l Co., v. Tele-
flex, Inc., 550 U.S. 398, 406 (2007) (citing Graham v. John
Deere Co., 383 U.S. 1, 17-18 (1966)). Patent invalidity must
be established by clear and convincing evidence. Microsoft
Corp. v. i4i Ltd. P’ship, 131 S. Ct. 2238, 2242 (2011).
The district court held that the asserted claims would
have been obvious over several pieces of prior art. The
SANTARUS v. PAR PHARMA 14
scope and content of the prior art applicable to each as-
serted claim, however, differs depending on the claim’s
effective filing date. Due to breaks in the chain of priority,
Santarus is unable to claim an early enough priority date to
preclude use of Dr. Phillips’s own ’737 patent as prior art for
some of the asserted claims. In a thorough analysis of
priority, the district court determined that the ’737 patent is
prior art to claims 26, 37, 38, 49, 50, 66, 68, and 80-82 of the
’346 patent and the asserted claims of the ’885 patent, ’988
patent, and ’772 patent. Santarus, 720 F. Supp. 2d at
436-37. Santarus appeals the court’s priority determination
only as to the ’772 patent (and as described above, we re-
verse), and does not contend that the district court erred by
finding that the ’737 patent was prior art to the other
claims. Accordingly, Santarus waived any argument that
the ’737 patent is not prior art to the other claims. See
Advanced Magnetic Closures, Inc. v. Rome Fastener Corp.,
607 F.3d 817, 833 (Fed. Cir. 2010). The asserted claims
thus fall into one of two categories depending on whether
the ’737 patent is prior art, and our validity analysis must
proceed on this basis.
1. Claims to Which the ’737 Patent is Prior Art
The district court correctly held that the ’737 patent
would have rendered obvious all claims to which it is prior
art. Santarus, 720 F. Supp. 2d at 452. The ’737 patent is
prior art to: claims 26, 37, 38, 49, 50, 66, 68, and 80-82 of
the ’346 patent; claims 2, 9, 11, 15-18, and 41 of the ’885
patent; and claim 29 of the ’988 patent.
The ’737 patent discloses formulating omeprazole both
in conventional dosage forms (e.g., tablets, capsules, and
granules) and also as an aqueous suspension of omeprazole
with a buffering agent. For example, the ’737 patent dis-
closes treating gastrointestinal conditions by administering:
15 SANTARUS v. PAR PHARMA
A pharmaceutical composition for making a solu-
tion/suspension of omeprazole . . . includes omepra-
zole . . . and a bicarbonate salt of a Group 1A metal
in a form for convenient storage whereby when the
composition is dissolved in aqueous solution, the re-
sulting solution is suitable for enteral administra-
tion.
’737 patent at [57].
The ’737 patent discloses an example of such a suspen-
sion, which is formed by mixing enteric coated omeprazole
particles with a solution of water and sodium bicarbonate.
Id. col.8 ll.6-41. Importantly, however, the ’737 patent
teaches that the omeprazole does not need to be enterically
coated. ’737 patent col.8 ll.18-22 (“In a preferred embodi-
ment of the present invention, enterically-coated omeprazole
particles are obtained from delayed release capsules (Astra
Merck) additionally omeprazole powder can be used.” (em-
phasis added)). Even when examples use enteric coated
omeprazole, the ’737 patent teaches that the sodium bicar-
bonate suspension “dissolves the enteric coating” and em-
phasizes that “[i]t is important . . . that the enteric coated
pellets of omeprazole must be allowed to completely break-
down in the suspension vehicle or carrier prior to admini-
stration.” Id. col.8 ll.21-28. The ’737 patent also teaches
that “[t]he omeprazole or other substituted benzimidazoles
and derivatives thereof and bicarbonate can be formed into
a tablet, capsules, or granules, by methods well known to
those skilled in the art.” Id. col.10 ll.29-33. While the prior
art before the ’737 patent taught away from tablets, cap-
sules, and granules with non-enteric coated PPI, the ’737
patent expressly teaches these formulations. The ’737
patent thus discloses a solid dosage form within the mean-
ing of the asserted claims.
SANTARUS v. PAR PHARMA 16
Santarus designates claims 2 and 17 as exemplary of
the asserted claims of the ’885 patent. These claims depend
from independent claim 1, which recites:
A method of treating a gastric acid related disorder
in a subject in need thereof, comprising:
providing a solid pharmaceutical composition for
oral administration to the subject, the composition
consisting essentially of: (a) a therapeutically effec-
tive amount of at least one acid labile, substituted
benzimidazole H+, K+-ATPase proton pump inhibi-
tor; (b) at least one buffering agent in an amount of
about 0.1 mEq to about 2.5 mEq per mg proton
pump inhibitor; and (c) one or more optional phar-
maceutically acceptable excipients, wherein at least
some of the proton pump inhibitor is not enteric
coated and the solid pharmaceutical composition
has a total buffering agent to total proton pump in-
hibitor weight ratio of greater than 20:1; and
orally administering the pharmaceutical composi-
tion to the subject,
wherein upon oral administration of the pharma-
ceutical composition to the subject, an initial serum
concentration of the proton pump inhibitor greater
than about 0.1 µg/ml is obtained at any time within
about 30 minutes after administration of the compo-
sition.
’885 patent claim 1 (emphases added). Claim 2 additionally
requires an initial serum concentration “greater than about
0.15 µg/ml at any time within about 30 minutes after ad-
ministration of the composition.” Id. claim 2. Claim 17 also
requires that the buffering agent be sodium bicarbonate “in
17 SANTARUS v. PAR PHARMA
an amount from about 1000 mg to about 2000 mg.” Id.
claim 17.
Santarus makes three arguments with regard to the
’885 patent claims: (1) they require an uncoated PPI and
buffer in specific amounts and ratios not disclosed in the
prior art; (2) they achieve the desired results using only
1000 mg to 2000 mg of sodium bicarbonate; and (3) they
achieve specific blood serum concentration levels not dis-
closed in the prior art.
Santarus is incorrect that the ’737 patent fails to dis-
close non-enteric coated PPIs and buffer within the claimed
ratios. The ’737 patent discloses broad ranges for the
amounts of omeprazole and sodium bicarbonate that can be
used, which overlap with the range of ratios of buffering
agent to PPI claimed in the ’885 patent. For example, the
’737 patent teaches that the amount of sodium bicarbonate
can vary between 0.75 mEq to 1.5 mEq per 2 mg of omepra-
zole (0.375 to 0.75 mEq per mg of omeprazole). ’737 patent
col.10 ll.15-19. This falls within the range of about 0.1 mEq
to about 2.5 mEq of buffering agent per mg of PPI claimed
in the ’885 patent. Sodium bicarbonate weighs roughly 84
mg/mEq, see Santarus, 720 F. Supp. 2d at 441, and thus the
range of buffering agent taught in the ’737 patent equates to
a weight ratio of buffering agent to PPI of greater than 20:1
(i.e., 31.5-63 mg of sodium bicarbonate per mg of PPI), as
required by the claims.
The ’737 patent also discloses claim 17’s limitation that
the buffering agent be sodium bicarbonate “in an amount
from about 1000 mg to about 2000 mg.” The ’737 patent
teaches that the dosage range of non-enteric coated omepra-
zole can vary from approximately 2 mg/day to 100 mg/day.
’737 patent col.9 ll.9-13. Because the ratio of sodium bicar-
bonate to PPI disclosed in the ’737 patent ranges from 0.75
SANTARUS v. PAR PHARMA 18
mEq to 1.5 mEq per 2 mg of omeprazole, the ’737 patent
teaches a range of 0.75-75 mEq of sodium bicarbonate. This
range equates to about 63-6300 mg of sodium bicarbonate,
which overlaps with the claimed range of 1000-2000 mg.
Santarus is also incorrect that the claims reciting spe-
cific blood serum concentrations of PPI would have been
nonobvious. The initial blood serum concentration resulting
from administering a PPI dosage is an inherent property of
the formulation, and an obvious formulation cannot become
nonobvious simply by administering it to a patient and
claiming the resulting serum concentrations. See, e.g., In re
Kao, 693 F.3d 1057, 1070 (Fed. Cir. 2011) (“[The prior art’s]
express teachings render the claimed . . . formulation obvi-
ous, and the claimed [blood concentration] adds nothing of
patentable consequence.”). To hold otherwise would allow
any formulation – no matter how obvious – to become pat-
entable merely by testing and claiming an inherent prop-
erty. There is no dispute that the blood serum
concentrations claimed in the ’885 patent are expected in
light of the dosages. In fact, a publication by Pilbrant and
Cederberg entitled “Development of an oral formulation of
omeprazole” (Pilbrant) includes a blood serum chart that
indicates that the claimed levels are easily achieved within
the first thirty minutes after administration of a suspension
of non-enteric coated omeprazole buffered with sodium
bicarbonate. J.A. 1315-16.
Santarus does not designate any of the other claims to
which the ’737 patent is prior art as being exemplary, nor
does Santarus identify any other specific limitations that
are not disclosed in the prior art. We thus hold that the
district court correctly determined that claims 26, 37, 38,
49, 50, 66, 68, and 80-82 of the ’346 patent, claims 2, 9, 11,
19 SANTARUS v. PAR PHARMA
15-18, and 41 of the ’885 patent, and claim 29 of the ’988
patent would have been obvious. 2
2. Claims to Which the ’737 Patent is Not Prior Art
The ’737 patent is not prior art to claims 58-60 of the
’346 patent or to the asserted claims of the ’882 and ’772
patents. For these claims, the two most relevant pieces of
prior art are the Pilbrant reference and an article by Lam-
ers et al. entitled “Absorption of omeprazole in Zollinger-
Ellison syndrome is accelerated by alkali” (Lamers), J.A.
1464-65. The district court held that Pilbrant and Lamers
each individually render obvious every asserted claim.
Santarus, 720 F. Supp. 2d at 449.
The parties raise several issues relating to these prior
art references. They dispute whether, at the time of the
Phillips invention, the prior art taught away from the use of
non-enteric coated oral dosage forms of PPIs. The parties
also disagree as to whether Pilbrant and Lamers teach
certain limitations of the asserted claims and whether
objective evidence justifies a finding of nonobviousness.
a. Teaching Away – The Solid Oral Dosage
Limitation
A reference “teaches away” when it “suggests that the
line of development flowing from the reference’s disclosure
is unlikely to be productive of the result sought by the
applicant.” Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157,
1165 (Fed. Cir. 2006) (quoting In re Gurley, 27 F.3d 551, 553
(Fed. Cir. 1994)). Whether a prior art reference teaches
away from the claimed invention is a question of fact. Para-
Ordnance Mfg., Inc. v. SGS Imps. Int’l, Inc., 73 F.3d 1085,
1088 (Fed. Cir. 1995).
2 For the same reasons discussed in section 2.c., infra,
the district court’s fact findings regarding objective consid-
erations are not clearly erroneous.
SANTARUS v. PAR PHARMA 20
Santarus argues that the prior art, particularly Pil-
brant, taught away from the claimed invention. Specifi-
cally, Santarus contends that the dosing regimen Pilbrant
discloses for suspensions of buffered non-enteric coated
omeprazole was so complex that it would discourage a
person of ordinary skill in the art from pursuing such for-
mulations. Santarus argues that this, coupled with the fact
that Pilbrant expressly “ruled out” non-enteric coated tab-
lets, capsules, and granules, would discourage a skilled
artisan from using any non-enteric coated oral dosage forms
of PPIs.
Santarus is partly correct. Pilbrant teaches that the op-
tions for formulating omeprazole are limited because it is
minimally soluble in water but degrades rapidly in the
acidic environment of the stomach. J.A. 1313. Pilbrant
discusses four options: 1) solutions; 2) suspensions of buff-
ered non-enteric coated omeprazole; 3) conventional oral
dosage forms – tablets, capsules or granules – with non-
enteric coated PPIs; and 4) conventional oral dosage forms
with enteric-coated PPIs. J.A. 1313-14. Pilbrant states that
the fourth option, conventional dosage forms with enteric-
coated PPIs, “offers the best possibilities.” J.A. 1314.
Pilbrant explicitly “ruled out” the third option – non-enteric
coated conventional oral dosage forms such as tablets,
capsules, or granules – because they degrade too quickly in
the stomach to be absorbed in sufficient amounts to be
effective. J.A. 1313. This disclosure would discourage a
person of ordinary skill in the art from pursuing conven-
tional oral dosage forms such as tablets, capsules, or gran-
ules with non-enteric coated PPIs, and thus teaches away
from such formulations. As a result, we hold that the
district court erred by concluding that claims directed to
such conventional dosage forms would have been obvious
over Pilbrant or Lamers. We thus reverse the court’s obvi-
ousness holding with respect to claims 4, 5, 8, 10, 12, 14,
21 SANTARUS v. PAR PHARMA
and 15 of the ’772 patent, which all are directed to conven-
tional dosage forms, such as tablet or capsules, containing
non-enteric coated PPIs. 3
Santarus is incorrect, however, that the prior art taught
away from all non-enteric coated omeprazole formulations.
The district court broadly construed the claim terms “solid
pharmaceutical composition in a dosage form” and “solid
oral pharmaceutical dosage form” as “including a powder
that can be combined with an aqueous medium then orally
administered.” J.A. 300. As a result of these undisputed
constructions, many of the asserted claims cover powder
formulations for use in aqueous suspensions. The prior art
does not teach away from such powder formulations.
As the district court found, “[t]he Lamers and Pilbrant
references teach that uncoated omeprazole formulations
containing a sodium bicarbonate buffer could be used as an
alternative to enteric coating in order to protect omeprazole
from degrading in the stomach.” Santarus, 720 F. Supp. 2d
at 448-49 (emphasis added). Although Pilbrant “ruled out”
conventional dosage forms such as tablets, capsules, or
granules with non-enteric coated PPIs, it states that a
“rapidly dissolving suspension of micronized omeprazole is
the second best choice as the reference formulation.” J.A.
1315 (emphasis added). As Par’s expert testified, Pilbrant
also teaches that such buffered suspensions using non-
enteric coated omeprazole have a similar effect on gastric
acid secretion as enteric coated omeprazole without bicar-
bonate. J.A. 1316; J.A. 1130-31.
3 Claims 4 and 5 of the ’772 patent are not expressly
limited to a tablet or capsule dosage form, but require
specific pharmaceutical excipients (disintegrants and lubri-
cants) that are commonly used in conventional dosage forms
such as tablets, not in powder formulations.
SANTARUS v. PAR PHARMA 22
Pilbrant thus teaches that, although suspensions of
buffered non-enteric coated omeprazole may be the “second
best choice,” they are a viable alternative to enteric coating.
“A statement that a particular combination is not a pre-
ferred embodiment does not teach away absent clear dis-
couragement of that combination.” Syntex (U.S.A.) LLC v.
Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005). Describ-
ing a formulation as “second best” is not a “clear discour-
agement,” as is required by our precedent.
Nor do we see any merit to Santarus’s contention that
the dosing regimen Pilbrant discloses for suspensions of
buffered non-enteric coated omeprazole was so complex that
it taught away from such formulations. Pilbrant teaches
that a total of 40 mmoles of sodium bicarbonate should be
given with 250 mL of water in five divided doses after a ten-
hour overnight fast. J.A. 1315. The district court did not
clearly err by declining to find that this regimen, which
basically requires dissolving less than half a teaspoon of
sodium bicarbonate in just over a cup of water, is such a
strain on patient compliance as to teach away from using a
buffered suspension of non-enteric coated omeprazole.
Santarus, 720 F. Supp. 2d at 447-48.
Thus, Pilbrant discloses, and does not teach away from,
“a powder that can be combined with an aqueous medium
then orally administered.” For the claims that are broad
enough to include this powder (i.e., those not limited to
tablets, capsules, or granules), the solid pharmaceutical
dosage limitation is taught by Pilbrant.
b. Other Claim Limitations
The thrust of this appeal is whether the prior art dis-
closes the claimed non-enteric coated solid pharmaceutical
dosage forms. In cursory form, Santarus argues a limited
number of additional limitations that it alleges are not
23 SANTARUS v. PAR PHARMA
present in the prior art, such as the claimed amounts and
ratios of PPI and buffer. We conclude that the district court
was correct that claims 58-60 of the ’346 patent and claims
12 and 27 of the ’882 patent would have been obvious over
Pilbrant.
Santarus contends that Pilbrant and Lamers fail to
teach a dosage with PPI and buffer in the amounts and
ratios recited in claim 60 of the ’346 patent, which Santarus
designated as an exemplary claim. Claim 60 of the ’346
patent depends from claim 57, which recites:
A solid pharmaceutical composition in a dosage
form that is not enteric-coated, comprising: active
ingredients consisting essentially of:
(a) a therapeutically effective amount of a non-
enteric coated proton pump inhibitor selected
from the group consisting of omeprazole, lanso-
prazole, rabeprazole, esomeprazole, pantopra-
zole, pariprazole, and leminoprazole, or an
enantiomer, isomer, derivative, free base, or salt
thereof; and
(b) a buffering agent selected from the group
consisting of sodium bicarbonate, and calcium
carbonate, in an amount more than about 40
times the amount of the proton pump inhibitor
on a weight to weight basis in the composition.
’346 patent claim 57. Claim 60 further requires that the
buffering agent be sodium bicarbonate in an amount of at
least 800 mg. Id. claim 60.
As the district court found, Pilbrant discloses adminis-
tering approximately 3360 mg of sodium bicarbonate with
60 mg of omeprazole, a ratio of 56:1 on a weight to weight
SANTARUS v. PAR PHARMA 24
basis. See Santarus, 720 F. Supp. 2d at 447. Pilbrant thus
teaches the limitation of using an amount of buffer “more
than about 40 times the amount of proton pump inhibitor on
a weight to weight basis.” Pilbrant’s use of 3360 mg of
sodium bicarbonate also meets claim 60’s limitation of using
“at least about 800 mg” of sodium bicarbonate. Pilbrant
similarly teaches using PPI and buffering agent in the
amounts and ratios recited in claims 58-59 of the ’346
patent and claims 12 and 27 of the ’882 patent. Thus we
find no merit in the arguments related to these claims.
Exemplary claims 20 and 21 of the ’772 patent, however,
require amounts of buffering agent not disclosed in the prior
art. Claim 20 requires 2-25 mEq of sodium bicarbonate
buffer while claim 21 requires 4-25 mEq of sodium bicar-
bonate. ’772 patent claims 20, 21. Pilbrant discloses using
40 mEq (3360 mg) of sodium bicarbonate, which is signifi-
cantly more than the amount claimed in the ’772 patent.
J.A. 1315. Par appears to contend that, because Pilbrant
and Lamers both teach the claimed ratio of sodium bicar-
bonate to PPI, it would have been obvious to a person of
ordinary skill in the art to reduce the total amount of so-
dium bicarbonate buffer disclosed in those references. See,
e.g., Cross-Appellant’s Br. 19-20. Par, however, failed to
establish this by clear and convincing evidence. Pilbrant
states that the purpose of consuming sodium bicarbonate
with the omeprazole solution was to “buffer the pH of the
gastric content to neutral values.” J.A. 1315. Par points to
nothing in the prior art that indicates it was the ratio of
buffering agent to PPI, as opposed to the total amount of
buffer consumed, that was the key to preventing the stom-
ach from being too acidic. Given the prior art’s teachings
regarding protecting omeprazole from stomach acid, we hold
that it would not have been obvious to a person of ordinary
skill in the art to decrease the amount of sodium bicarbon-
ate disclosed in Lamers or Pilbrant.
25 SANTARUS v. PAR PHARMA
Likewise, the required amount of buffering agent in
claims 11 and 15 of the ’882 patent are not disclosed by
Pilbrant or Lamers. Claim 11 requires an amount of buffer-
ing agent of about 15-30 mEq. ’882 patent claim 11. Claim
15 requires about 12.5-30 mEq of sodium bicarbonate buffer.
Id. claim 15. As a result, we reverse this portion of the
district court judgment and hold that Par did not establish
by clear and convincing evidence that these claims would
have been obvious over Pilbrant or Lamers.
c. Objective Considerations
Santarus argues that the district court’s fact findings
regarding objective evidence were clearly erroneous. Santa-
rus cites the testimony of its expert Dr. Fennerty that
skepticism in the industry, unexpected results, long-felt
need, industry recognition, and commercial success support
a holding of nonobviousness. Appellant’s Br. 50-53. Santa-
rus also cites a statement by researcher Dr. George Sachs
expressing his skepticism that Zegerid® would work. Id. at
11-12. The district court, however, reviewed all of the
secondary consideration evidence and concluded that:
The evidence in the record on several relevant sec-
ondary considerations does not undermine the
court’s finding that the patent is obvious in light of
the prior art. On the contrary, the weight of the
evidence as to the relevant secondary considerations
confirms the court’s finding in this regard.
Santarus, 720 F. Supp. 2d at 453. The court expressly
found that there was no commercial success. Id. at 453-55.
For example, the court found that sales of Zegerid® were
dwarfed by those of other PPIs and “fell far short of Santa-
rus’ own expectations.” Id. at 453-54. The court also re-
jected Santarus’s arguments with respect to the other
objective factors. Id. at 455-59. For example, the district
SANTARUS v. PAR PHARMA 26
court found the statement by Dr. Sachs unpersuasive for
several reasons, including that Dr. Sachs was not a witness
at trial and thus was not subject to cross examination. Id.
at 456. The district court’s findings of fact are entitled to
deference, and Santarus failed to show that they are clearly
erroneous. See, e.g., Para-Ordnance Mfg., Inc., 73 F.3d at
1091. We thus hold that Santarus’s objective evidence is
insufficient to overcome the obviousness of the claims over
Pilbrant. We thus affirm the district court’s conclusion that
claims 12 and 27 of the ’882 patent and claims 58-60 of the
’346 patent would have been obvious over Pilbrant and
reverse the court’s holding that claims 11 and 15 of the ’882
patent claims 20 and 21 of the ’772 patent would have been
obvious.
IV. SUMMARY
In view of the foregoing, we affirm the district court’s
ruling that Par failed to establish inequitable conduct. We
also affirm the court’s determination that the following
claims would have been obvious over the prior art: claims 12
and 27 of the ’882 patent; claims 26, 37, 38, 49, 50, 58-60,
66, 68, and 80-82 of the ’346 patent; claims 2, 9, 11, 15-18,
and 41 of the ’885 patent; and claim 29 of the ’988 patent.
We reverse the district court’s ruling that the asserted
claims of the ’772 patent and claims 11 and 15 of the ’882
patent would have been obvious. We also reverse the dis-
trict court’s holding that the claims of the ’772 patent are
invalid for lack of written description. We remand for
further proceedings consistent with this opinion.
AFFIRMED-IN-PART, REVERSED-IN-PART, and
REMANDED
United States Court of Appeals
for the Federal Circuit
__________________________
SANTARUS, INC.,
Plaintiff-Appellant,
AND
THE CURATORS OF THE UNIVERSITY OF
MISSOURI,
Plaintiff-Appellant,
v.
PAR PHARMACEUTICAL, INC.,
Defendant-Cross Appellant.
__________________________
2010-1360,-1380
__________________________
Appeal from the United States District Court for the
District of Delaware in consolidated Case Nos. 07-CV-
0551 and 07-CV-0827, Chief Judge Gregory M. Sleet.
__________________________
NEWMAN, Circuit Judge, concurring in part, dissenting in
part.
I agree that inequitable conduct has not been shown.
However, the court errs in three major areas, misconstru-
ing established law. First, the court creates a new “writ-
ten description” requirement for limitations in claims, a
requirement with important consequences for patent
content and prosecution, and that will taint large num-
bers of issued patents.
SANTARUS v. PAR PHARMA 2
The panel majority also holds that the disclosure in a
parent patent is a reference against the common disclo-
sure in a continuation-in-part patent, again tainting
many properly granted patents.
The panel majority also holds that most of the claims
in suit are invalid on the ground of obviousness over
references that explicitly teach away from the inventions
in the Phillips patents. In the district court, the experts
for both sides agreed that for oral dosage of PPIs the
protective enteric coating was understood to be essential.
Only the panel majority finds that the extreme conditions
that the prior art deemed necessary for oral dosage of
uncoated PPIs, would be acceptable for patient treatment.
The court’s new rulings are contrary to statute, prece-
dent, and common sense. They simply add to the unreli-
ability of duly granted patents, in new and unacceptable
ways.
I
WRITTEN DESCRIPTION
The claims of the ’772 patent (U.S. Patent No.
7,399,772) contain the limitation that these uncoated PPI
formulations do not contain the known therapy sucralfate.
I agree that the district court clearly erred in finding that
since the specification did not contain evidence of “contra-
indication” of sucralfate, the patent failed the written
description requirement. On appellate review, correction
of this erroneous finding is all that is needed.
However, my colleagues add a gratuitous fillip, and
devise the new rule that the specification must “describe a
reason” for the claim limitation, or the claims are invalid
on written description grounds. Maj. op. at 12 (“Negative
claim limitations are adequately supported when the
specification describes a reason to exclude the relevant
3 SANTARUS v. PAR PHARMA
limitation.”). That is not correct. Negative claim limita-
tions may often be appropriately stated in claims al-
though the reason for the limitation is not set forth in the
specification.
Negative limitations to claims may arise in a variety
of circumstances. For example, a negative limitation may
be prudently placed in a claim in response to an exam-
iner’s rejection, perhaps to distinguish a reference that
was given its “broadest reasonable interpretation” for
purposes of examination. See, e.g., In re Skvorecz, 580
F.3d 1262, 1268 (Fed. Cir. 2009) (“Applicant always has
the opportunity to amend the claims during prosecution,
and broad interpretation by the examiner reduces the
possibility that the claim, once issued, will be interpreted
more broadly than is justified.” (quoting Manual of Patent
Examining Procedure (MPEP) §2111)).
A claim limitation may distinguish the prior art al-
though the reason is not in the specification. Claims are
routinely adjusted during prosecution in the Patent and
Trademark Office. As stated in In re Johnson, 558 F.2d
1008, 1018 (CCPA 1977), “applicants frequently discover
during the course of prosecution that only a part of what
they invented and originally claimed is patentable.” This
adjustment may include limitations that respond to the
prior art developed by the examiner and traversed by the
applicant. The specification need not foresee and describe
the reason for every possible examination response.
As another example of routine patent procedures,
there may be situations in which comparative data are
provided during prosecution in order to respond to an
examiner’s rejection, see MPEP §716, and the distinction
from the prior art may lead to a claim limitation. The
need for the limitation may not have been apparent when
writing the specification. For example, in In re Johnson,
SANTARUS v. PAR PHARMA 4
supra, the court held that the claims could be limited
during prosecution in order to avoid subject matter lost in
an interference; the court explained that: “It is for the
inventor to decide what bounds of protection he will seek.”
588 F.2d at 1018.
The applicant’s obligation is to describe and claim the
invention in accordance with 35 U.S.C. §112. Thereafter,
patent examination may lead to amendments to the
claims. The MPEP §2173.05(i) advises that: “If alterna-
tive elements are positively recited in the specification,
they may be explicitly excluded in the claims.” The
MPEP does not require that the reason for such exclusion
must be stated in the specification. The panel majority
creates a new and far-reaching ground of invalidity, a
ground that received no deliberation and advice from the
concerned communities.
Further, this new requirement for patent specifica-
tions is not an issue in this case, for the ’772 specification
states that sucralfate, “possibly the ideal agent for stress
ulcer prophylaxis, [citing references],” is known to have
occasional adverse effects, and that “the only patient
whose death was attributed to stress-related upper gas-
trointestinal bleeding was in the sucralfate arm.” ’772
patent, col.4 ll.1-29. Thus the reason for excluding sucral-
fate was indeed stated in the specification. Nonetheless,
the district court held that evidence of “contraindication”
of sucralfate was required.
I agree with the panel majority that the Phillips in-
vention was adequately described, and that the district
court erred in its requirement. “Compliance with the
written description requirement is essentially a fact-based
inquiry that will ‘necessarily vary depending on the
nature of the invention claimed.’” Enzo Biochem v. Gen-
Probe, Inc., 296 F.3d 1316, 1324 (Fed. Cir. 2002) (citation
5 SANTARUS v. PAR PHARMA
omitted). The panel majority is incorrect in its new
general requirement that the reason for any negative
limitation must be included in the specification, on pain of
invalidity under §112. This new ground of invalidity
ignores the factual nature of the written description
requirement, and impugns the presumption of validity of
a duly granted patent. The court’s new rule simply adds
to the uncertainty of the patent grant, to the detriment of
invention and commerce.
II
THE PARENT PATENT AS PRIOR ART
The panel majority creates another new ground of in-
validity, in holding that the common disclosure in a
parent patent is prior art to the chain of continuing
patents. The court incorrectly holds that the parent ’737
patent (U.S. Patent No. 5,840,737) that issued to Dr.
Phillips is an invalidating reference based on the common
subject matter that has priority to the parent patent’s
filing date.
The claims at issue all include subject matter dis-
closed in the ’737 patent, subject matter for which priority
was properly claimed, with no breaks in the chain of
filings. It is beyond debate that the common subject
matter in a chain of copending applications is entitled to
priority from the earliest application disclosing the com-
mon subject matter. See, e.g., Herbert F. Schwartz &
Robert J. Goldman, Patent Law & Practice §2.III.D.7.c
(6th ed. 2008) (“A continuation-in-part is entitled to the
parent’s filing date as to any subject matter in common,
but only to its own filing date as to the new matter.”);
James E. Hawes, Patent Application Practice §18:5.50
(Rel. 27, 2011) (“The parent’s filing date will apply to all
the material in the child [CIP] that was in the parent, but
the new material will not be accorded the benefit of the
SANTARUS v. PAR PHARMA 6
parent’s filing date.”); Irah H. Donner, Patent Prosecution:
Law, Practice, and Procedure 156 (7th ed. 2011) (“The CIP
application priority date is the same as that of the earlier-
filed application for subject matter common to the two
applications.”).
Ignoring this basic tenet of patent law, the panel ma-
jority uses the common subject matter from the ’737
patent to invalidate many of the claims-in-suit. The panel
majority describes this common subject matter at length,
but instead of understanding that the common subject
matter supports the claims that are entitled to the prior-
ity of that subject matter, the panel majority holds that
the common subject matter invalidates the claims to that
subject matter.
For example, the panel majority goes into detail for
the ’885 patent (U.S. Patent No. 6,699,885), ruling that
because the claims in the ’885 patent are supported by the
common subject matter in the parent ’737 patent, the
claims in the ’885 are rendered obvious by the parent ’737
patent.
Priority for the ’885 patent was properly claimed, in
accordance with 35 U.S.C. §120, as follows:
This application is a continuation-in-part of U.S.
patent application Ser. No. 09/901,942, filed on
Jul. 9, 2001, which is a continuation-in-part of
U.S. patent application Ser. No. 09/481,207, filed
on Jan. 11, 2000, now U.S. Pat. No. 6,489,346,
which is a continuation-in-part of U.S. patent ap-
plication Ser. No. 09/183,422, filed on Oct. 30,
1998, now abandoned, which is a continuation-in-
part of U.S. patent application Ser. No.
08/680,376, filed on Jul. 15, 1996, now U.S. Pat.
No. 5,840,737, which claims priority to U.S. Provi-
sional Application Ser. No. 60/009,608 filed on
7 SANTARUS v. PAR PHARMA
Jan. 4, 1996. This application claims priority to
all such previous applications, and such applica-
tions are hereby incorporated herein by reference.
’885 patent, col.1 ll.4-16. There is no break in the chain of
priority. The panel majority correctly observes that the
’737 patent describes the subject matter claimed in the
’885 patent. The ’737 patent describes the combination of
the PPI and a Group IA metal salt, as follows:
The present invention further includes a pharma-
ceutical composition for making a solu-
tion/suspension of omeprazole or other substituted
benzimidazoles and derivatives thereof, which
consists essentially of omeprazole or other substi-
tuted benzimidazoles and derivatives thereof and
a bicarbonate salt of a Group IA metal in a form
convenient for storage, whereby when the compo-
sition is placed into a aqueous solution, the com-
position dissolves yielding a solution/suspension
suitable for enteral administration to a subject.
The pharmaceutical composition is in a solid form
prior to dissolution in the aqueous solution. The
omeprazole or other substituted benzimidazoles
and derivatives thereof and bicarbonate can be
formed into a tablet, capsule, or granules, by
methods well known to those skilled in the art.
’737 patent, col.10, ll.20-33. The panel majority explains
that the ’885 subject matter is disclosed in the ’737 pat-
ent, stating: “The ’737 patent discloses broad ranges for
the amounts of omeprazole and sodium bicarbonate that
can be used, which overlap with the range of ratios of
buffering agent to PPI claimed in the ’885 patent.” Maj.
op. at 17. The panel majority states that the “’737 patent
discloses formulating omeprazole both in conventional
dosage forms (e.g., tablets, capsules, and granules) and
SANTARUS v. PAR PHARMA 8
also as an aqueous suspension of omeprazole with a
buffering agent,” as claimed in the ’885 patent. Maj. op.
at 14. The panel majority states that “the ’737 patent
teaches that the amount of sodium bicarbonate can vary
between 0.75 mEq to 1.5 mEq per 2 mg of omeprazole
(0.375 to 0.75 mEq per mg of omeprazole),” and observes
that “this falls within the range of about 0.1 mEq to about
2.5 mEq of buffering agent per mg of PPI claimed in the
’885 patent.” Maj. op. at 17.
Focusing on claim 17 of the ’885 patent, the panel ma-
jority states that: “The ’737 patent also discloses claim
17’s limitation that the buffering agent be sodium bicar-
bonate ‘in an amount from about 1000 mg to about 2000
mg’.” The panel majority points to where the ’737 disclo-
sure shows the claim 17 dosage range of uncoated ome-
prazole, and where “the ’737 patent teaches a range of
0.75-75 mEq of sodium bicarbonate, which overlaps with
the claimed range [in the ’885 patent].” Maj. op. at 17-18.
The panel majority illustrates and stresses that the
subject matter of claim 17 is within the ’737 patent’s
disclosure.
The panel majority forgets that “matter disclosed in
the parent application is entitled to the benefit of the
filing date of the parent application.” Waldemar Link,
GmbH & Co. v. Osteonics Corp., 32 F.3d 556, 558 (Fed.
Cir. 1994); see Litton Sys., Inc. v. Whirlpool Corp., 728
F.2d 1423, 1438 (Fed. Cir. 1984) (“The earlier filing date
of the parent application pertains to material in the C-I-P
application also disclosed in the prior application. 35
U.S.C. §120.”). Instead, the panel majority relies upon
the common subject matter from the ’737 patent disclo-
sure to invalidate the ’885 claims supported by that
subject matter. This is incorrect, for the common subject
matter in the ’885 patent is entitled to the ’737 filing date.
That entitlement is not lost by issuance of the ’737 patent.
9 SANTARUS v. PAR PHARMA
The common subject matter, properly carried forward in
copending continuing patents, cannot be prior art against
itself, as the majority holds.
Similarly, the ’988 patent (U.S. Patent No. 6,645,988)
states the chain of copendency, and incorporation by
reference, as follows:
This application is a continuation-in-part of U.S.
patent application Ser. No. 09/481,207 filed Jan.
11, 2000, now U.S. Pat. No. 6,489,346 which is a
continuation-in-part of U.S. patent application
Ser. No. 09/183,422 filed on Oct. 30, 1998, now
abandoned, which is a continuation-in-part of U.S.
patent application Ser. No. 08/680,376 filed on
Jul. 15, 1996, now U.S. Pat. No. 5,840,737, which
claims priority to U.S. Provisional Application
Ser. No. 60/009,608 filed on Jan. 4, 1996. This
application claims priority to all such previous
applications, and such applications are hereby in-
corporated herein by reference to the extent per-
mitted by law.
’988 patent, col.1 II.4-15. There is no break in the chain,
no flaw in the entitlement to priority for the common
subject matter in the prior copending filings.
Similarly, the ’346 patent correctly recites the chain of
co-pendency. There are no breaks in the chain:
This application is a continuation-in-part of U.S.
patent application Ser. No. 09/183,422 filed on
Oct. 30, 1998, now abandoned, which is a con-
tinuation-in-part of U.S. patent application Ser.
No. 08/680,376 filed on Jul. 15, 1996, now U.S.
Pat. No. 5,840,737, which claims priority to U.S.
Provisional Application Serial No. 60/009,608 filed
on Jan. 4, 1996. This application claims priority
SANTARUS v. PAR PHARMA 10
to all such previous applications, and such appli-
cations are hereby incorporated by reference.
’346 patent, col.1 ll.4-12.
The novel ground of invalidity here adopted was not
accepted by the PTO. During examination, the patent
examiner reviews the priority claims, as instructed by the
Manual of Patent Examining Procedure §§201.08, 201.11.
The examiner did not cite the ’737 patent against the
later applications in the chain, during either the initial
examination of the continuing applications, or on the
reexamination of the ’885 patent during this litigation.
From the court’s incorrect ruling that the ’737 patent
is a reference against its common subject matter in the
later applications in the chain of filings, I respectfully
dissent.
III
PATENTABILITY - OBVIOUSNESS
Again ignoring the presumptions and burdens of proof
for duly granted patents, the panel majority holds many
of the remaining claims in the Phillips patents invalid for
obviousness over the prior art. Although the expert
witnesses for both sides agreed that it was uniformly
understood that a protective enteric coating is essential
for oral dosage, my colleagues find it obvious to omit the
protective enteric coating.
Many scientists studying PPI degradation by stomach
acid consistently confirmed that for practical administra-
tion the PPI must be coated with a gastric acid-resistant
coating. Nonetheless, the panel majority cites these same
scientific studies of PPI degradation in the stomach, and
concludes that they render obvious the omission of the
enteric coating. My colleagues do not mention the testi-
11 SANTARUS v. PAR PHARMA
mony of experts in PPI science, that the Phillips uncoated
formulation was “weird,” “different,” “pretty surprising,”
and “got people’s attention,” in the words of Dr. Brian
Fennerty. Nor do my colleagues mention the plethora of
patents and publications that uniformly stated that the
PPI must be enteric coated. E.g., U.S. Patent No.
4,786,505 to Lovgren and Pilbrant, col.1 ll.48-51 (“In order
to obtain a pharmaceutical dosage form of omeprazole
which prevents omeprazole from contact with acidic
gastric juice, the cores must be enteric coated.”).
The panel majority cites a study of stomach acid deg-
radation of PPI led by Dr. Pilbrant, and ignores their
conclusion that for oral administration the PPI must be
enteric coated. This study by Pilbrant and Cederberg,
“Development of an oral formulation of omeprazole,” 20
Scand. J. Gastroenterology 113 (1985) (herein Pilbrant),
explains the scientists’ studies of the rate and conditions
of PPI degradation by stomach acid. Drs. Pilbrant and
Cederberg reported that the only way they obtained
adequate absorption of uncoated PPI from the stomach
was to require an initial ten hours of fasting in order to
deplete the amount of acid in the stomach, then to drink a
sodium bicarbonate solution to neutralize any remaining
acid, then to drink buffered omeprazole rinsed down with
sodium bicarbonate solution, followed by drinking three
more doses of sodium bicarbonate solution over the next
thirty minutes.
Dr. Pilbrant described various procedures whereby he
attempted to avert or slow PPI degradation by stomach
acid, and his conclusion that the rapid acid degradation
“ruled out” an uncoated “conventional oral dosage form.”
Id. at 114. Dr. Pilbrant concluded that an “enteric-coated
dosage form, which does not release the active ingredient
for dissolution and absorption until it has been trans-
ported down to the neutral reacting part of the small
SANTARUS v. PAR PHARMA 12
intestine, offers the best possibilities.” Id. Dr. Pilbrant
recognized that the complex system whereby uncoated
PPI required lengthy fasting and successive consumption
of several liquid doses, was not a practical regimen for
administration to patients, and his “efforts were, there-
fore, concentrated on developing an enteric-coated granule
formulation.” Id. at 115.
Despite these teachings, the panel majority holds that
this Pilbrant article renders obvious Dr. Phillips’ elimina-
tion of the enteric coating. My colleagues state that Dr.
Pilbrant recommended an oral uncoated suspension as
the “second best choice.” Maj. op. at 21. That is a mis-
characterization, for Dr. Pilbrant made no such recom-
mendation; he was discussing a “reference formulation”
for studies of omeprazole in animals and human subjects:
The solubility and stability properties of omepra-
zole prevent the use of water solutions as the refer-
ence formulation in animal and human studies. A
rapidly dissolving suspension of micronized ome-
prazole is the second best choice as the reference
formulation.
Pilbrant at 116 (emphases added). Dr. Pilbrant explained
why water could not be used as the reference formulation:
In animal experiments and in initial studies in
man it is highly preferable to use water solutions
of the drug in order to avoid influences of the dos-
age form on the pharmacokinetics and pharmaco-
dynamics of the drug. Omeprazole is, however,
only soluble in alkaline water solutions with
physiologically unacceptable, high-pH values.
Pilbrant at 114. The Pilbrant publication stated that a
liquid suspension of micronized omeprazole is second best
to a water solution as an experimental reference formula-
13 SANTARUS v. PAR PHARMA
tion, not, as the majority incorrectly contends, that a non-
enteric suspension is a usable “second best” to enteric
coated forms for administration to patients. Maj. op. at
21-22.
In determining obviousness, “a court must determine
whether, at the time of the invention, a person having
ordinary skill in the art would have had reason to attempt
to make the composition” and “a reasonable expectation of
success in doing so.” Procter & Gamble Co. v. Teva
Pharms. USA, Inc., 566 F.3d 989, 995 (Fed. Cir. 2009).
The presumption of validity under Ҥ 282 requires an
invalidity defense to be proved by clear and convincing
evidence.” Microsoft Corp. v. i4i Ltd., 131 S. Ct. 2238,
2242 (2011). See id. at 2245 (“[T]here is a presumption of
validity, a presumption not to be overthrown except by
clear and cogent evidence.” (quoting Radio Corp. v. Radio
Eng’g Labs., Inc., 293 U.S. 1, 3 (1934))); Sciele Pharma
Inc. v. Lupin Ltd., 684 F.3d 1253, 1260 (Fed. Cir. 2012)
(“The presumption of validity found in § 282 is reflected in
the standard of proof required to prove invalidity, clear
and convincing evidence.”).
The prior art and the expert witnesses were explicit
and uniform, that benzimidazole PPIs require an enteric
coating for practical oral administration to patients.
Proceeding contrary to the accepted scientific knowledge
is “strong evidence of nonobviousness.” W.L. Gore &
Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 1552 (Fed.
Cir. 1983). There was no evidence contrary to the position
that an enteric coating was believed to be necessary.
This is a classical example of “teaching away,” when
persons in the field of the invention “would be led in a
direction divergent from the path that was taken by the
applicant.” Ricoh Co., Ltd. v. Quanta Computer Inc., 550
F.3d 1325, 1332 (Fed. Cir. 2008). The principal reference
SANTARUS v. PAR PHARMA 14
relied on by the panel majority concluded that an “enteric-
coated dosage form, which releases omeprazole for absorp-
tion in the small intestine . . . offers the best possibilities.”
Pilbrant, at 114-15. This conclusion was repeated in a
patent of which Dr. Pilbrant is an inventor, entitled
“Pharmaceutical Preparation for Oral Use.” This patent
refers to the studies in the Pilbrant article, and states:
From what is said about the stability properties of
omeprazole [in the article], it is obvious that an
oral dosage form of omeprazole must be protected
from contact with the acid reacting gastric juice in
order to reach the small intestine without degra-
dation.
U.S. Patent No. 4,786,505, col.1 ll.35-39 (emphasis
added). Undaunted by Dr. Pilbrant’s unequivocal state-
ments, my colleagues creatively find that Pilbrant teaches
that “suspensions of buffered non-enteric coated omepra-
zole . . . are a viable alternative to enteric coating.” Maj.
op. at 22. Rather, Dr. Pilbrant reinforced the prevailing
belief that the omeprazole must be enteric coated to
prevent contact with acidic gastric juice.
The panel majority also cites an article by Lamers et
al. entitled “Absorption of omeprazole in Zollinger-Ellison
syndrome is accelerated by alkali,” published in 26 Gut
1134-35 (1985). Lamers studied the absorption into the
blood of coated and uncoated omeprazole in bicarbonate
and saline solutions, based on experiments involving
uncoated omeprazole taken with large volumes of sodium
bicarbonate solution (as did Pilbrant). Lamers stated:
“We therefore conclude that addition of alkali accelerates
absorption of omeprazole in patients with Zollinger-
Ellison syndrome.” Lamers, like Pilbrant, did not propose
that uncoated omeprazole was a viable alternative for oral
administration to patients.
15 SANTARUS v. PAR PHARMA
For years after the discovery of the benzimidazole PPI
products, an enteric coating was believed to be essential
for oral administration to patients. Pilbrant and Lamers
and others did not change that belief; they reinforced it.
The Court has cautioned against “the distortion caused by
hindsight bias” and “arguments reliant upon ex post
reasoning” in determining obviousness. KSR Int’l Co., v.
Teleflex, Inc., 550 U.S. 398, 421 (2007).
The word “must” appears throughout the literature on
enteric coating for benzimidazole PPIs, all ignored by the
panel majority. In earlier litigation concerning omepra-
zole, this court observed that “an omeprazole formulation
needs a protective enteric coating.” In re Omeprazole
Patent Litig., 483 F.3d 1364, 1367 (Fed. Cir. 2007). Al-
though sodium bicarbonate was known to stabilize PPI’s,
it was the accepted understanding that an enteric coating
was needed to avoid rapid degradation by stomach acid.
For example, U.S. Patent No. 6,136,344 to Depui, issued
in 2000, states:
It is well known that proton pump inhibitors are
susceptible to degradation/transformation in acid
reacting and neutral media. In respect of the sta-
bility properties, it is obvious that one of the ac-
tive substances being a proton pump inhibitor
must be protected from contact with acidic gastric
juice by an enteric coating layer.
’344 patent, col.1 ll.62-67.
The teachings are uniform and uncontradicted, that
the PPI must be coated. These teachings surely teach
away from elimination of the enteric coating in oral
dosing to patients. The panel majority ignores this gen-
eral knowledge and general acceptance, although it is
reiterated and uncontradicted throughout the litigation
record.
SANTARUS v. PAR PHARMA 16
The references on which the panel majority relies are
studies of the rate and mechanism of gastric acid destruc-
tion of the uncoated PPI. Before Dr. Phillips’ invention,
no uncoated PPI formulation was achieved for patient
use. The Phillips formulation eluded the experts, despite
the extensive study of PPI degradation, despite the value
and importance of PPI medications. See Unigene Labs.,
Inc. v. Apotex, Inc., 655 F.3d 1352, 1360-61 (Fed. Cir.
2011) (“The statutory criterion is whether the invention
would have been obvious to persons of ordinary skill at
the time of the invention, not whether it is sufficiently
simple to appear obvious to judges after the discovery is
finally made.”).
My colleagues’ hindsight pronouncements of obvious-
ness are based on their knowledge of Dr. Phillips’
achievement, an achievement that was deemed “weird”
and met with incredulity. Determination of obviousness
includes whether the prior art suggested, to a person of
ordinary skill in the field of the invention, that the
method “should be carried out and would have a reason-
able likelihood of success.” Rockwell Int’l Corp. v United
States, 147 F.3d 1358, 1366 (1998) (quoting In re Dow
Chem. Co., 837 F.2d 469, 473 (Fed. Cir. 1988)). The prior
art shows the uniform belief that oral administration of
uncoated PPI is not an effective therapeutic alternative.
Dr. George Sachs 1 publicly criticized the Santarus ap-
proach:
1 The record states that Dr. Sachs was awarded the
Beaumont Prize, one of the highest honors of the Ameri-
can Gastrological Association, and was described at the
trial as “the dean of PPIs.” See Altana Pharma AG v.
Teva Pharms. USA Inc., 566 F.3d 999, 1009 (Fed. Cir.
2009) (stating that Dr. Sachs “is one of the leading re-
searchers in the PPI development field”).
17 SANTARUS v. PAR PHARMA
The principle of Santarus is to give essentially, if
you like, a bicarbonate or carbonate buffer to the
omeprazole solution. And so you don’t have en-
teric coating and it comes in a gelcoat or gelcap.
We thought about that a long time ago at Astra . .
. . Man is a continuous acid secretor; the amount
of acid man makes is not really predictable and so
you’re not really able to particularly buffer the
omeprazole solution in the stomach. So as soon as
the solution starts to fall below pH 5, which would
happen with a high degree of frequency, you sim-
ply destroy the omeprazole and it will no longer
work. So I think the Santarus principle, though
well-founded – you know, in terms of the idea of
stabilizing, simply doesn’t work in man.
Trial Tr. 23:1-20; J.A. 3672; Santarus, 720 F. Supp. 2d at
456.
Dr. Phillips “proceeded contrary to the accepted wis-
dom. . . . That fact is strong evidence of nonobviousness.”
W.L. Gore, 721 F.2d at 1552 (citing United States v.
Adams, 383 U.S. 39 (1966)). See also Standard Oil Co. v.
American Cyanamid Co., 774 F.2d 448, 454 (Fed. Cir.
1985) (“A person of ordinary skill in the art is also pre-
sumed to be one who thinks along the line of conventional
wisdom in the art.”); Arkie Lures, Inc. v. Gene Laren
Tackle, Inc., 119 F.3d 953, 958 (Fed. Cir. 1997) (“conven-
tional wisdom that a combination should not be made is
evidence of unobviousness”).
Skepticism within the industry supports unobvious-
ness of the invention. See Transocean Offshore Deepwater
Drilling, Inc. v. Maersk Contractors USA, Inc., 617 F.3d
1296, 1304 (Fed. Cir. 2010) (objective evidence of nonobvi-
ousness included “evidence of industry skepticism.”). This
skepticism, reinforced in scientific commentary and
SANTARUS v. PAR PHARMA 18
conceded by the experts, leaves no doubt that an enteric
coating was believed necessary for oral PPI administra-
tion. See Depuy Spine, Inc. v. Medtronic Sofamor Danek,
Inc., 567 F.3d 1314, 1326 (Fed. Cir. 2009) (for an obvious
combination, skilled artisans must have expected that the
combination would work for its intended purpose).
The record states that the Phillips formulation pro-
vides effective absorption of the PPI directly from the
stomach into the bloodstream, that it achieves faster
control of stomach acid, improved nocturnal acid control,
dosing independent of meals, and stabilized pharmacody-
namics. The direct absorption from the stomach has the
advantages of rapid and consistent bioavailability and
increased effectiveness, as well as ease of administration
to patients unwilling or unable to swallow capsules or
tablets, as the Phillips patents explain:
[I]n their current form (capsules containing en-
teric-coated granules or enteric-coated tablets),
proton pump inhibitors can be difficult or impos-
sible to administer to patients who are either un-
willing or unable to swallow tablets or capsules,
such as critically ill patients, children, the elderly,
and patients suffering from dysphagia.
’772 Patent, col.7 l.65 - col.8 l.4.
These advantages are reflected in the Santarus sales
growth of Zegerid® from $46 million in 2006 to over $100
million in 2008. The record states that numerous compa-
nies took a license to the Phillips patents. Evidence of
“how the patented device is viewed by the interested
public: not the inventor, but persons concerned with the
product in the objective arena of the marketplace” is
“highly probative of the issue of nonobviousness.” Arkie
Lures, 119 F.3d at 957. In Ashland Oil, Inc. v. Delta
Resins & Refractories, Inc., 776 F.2d 281, 306 (Fed. Cir.
19 SANTARUS v. PAR PHARMA
1985), this court observed that: “Secondary considerations
may be the most pertinent, probative, and revealing
evidence available to the decision maker in reaching a
conclusion on the obviousness/nonobviousness issue.”
The uniform belief was that an enteric coating is nec-
essary for oral administration of PPIs to patients. De-
spite this universal skepticism, my colleagues on this
panel find Dr. Phillips’ invention obvious to them. I
respectfully dissent.