Perrigo Companyv.Brigham and Women's Hospital, Inc.

Patent Trial and Appeal Board

Apr 13, 2015

07879662 (P.T.A.B. Apr. 13, 2015)

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Patent 5,229,137

2
We have jurisdiction under 35 U.S.C. § 314, which provides that an
inter partes review may not be instituted “unless . . . there is a reasonable
likelihood that the petitioner would prevail with respect to at least 1 of the
claims challenged in the petition.” 35 U.S.C. § 314(a). Upon considering
the Petition and the Preliminary Response, we determine that Petitioner has
not shown a reasonable likelihood that it would prevail in showing the
unpatentability of claims 1–27. Accordingly, we decline to institute an inter
partes review of those claims.
A. Related Proceedings
Petitioner states that the ’137 patent is the subject of the copending
district court case, Brigham and Women’s Hospital, Inc. and Investors Bio-
Tech, L.P. v. Perrigo Company, L. Perrigo Company and CVS Caremark
Corp., Case No. 1:13-cv-11640 RWZ (D. Mass.). Pet. 1.
B. The ’137 Patent (Ex. 1001)
The ’137 patent issued on July 20, 1993, with M. Michael Wolfe as
the listed inventor. Ex. 1001. The patent expired on May 6, 2012. Pet. 10.
The patent is drawn to a pharmaceutical formulation containing an effective
amount of an antacid and a histamine H2-receptor antagonist, as well as
methods of treating episodic heartburn using an antacid and a histamine H2-
receptor antagonist. Ex. 1001, 1:63–2:2.
According to the ’137 patent, approximately seven to ten percent of
people suffer with the pain, discomfort, and/or symptoms of episodic
heartburn, while twenty-five to forty percent of people suffer on a monthly
basis. Id. at 1:13–15. The ’137 patent defines “episodic heartburn” as:
the sensation of burning under the sternum (breastbone) and is
usually associated with the ingestion of different foods.
Episodic heartburn has also been referred to as “sour stomach,”
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Patent 5,229,137

3
“indigestion,” and “waterbrash/regurgitation.” Although
different foods, such as coffee, mints, fatty foods, alcohol, and
chocolate, are usually implicated in the etiology of episodic
heartburn, these symptoms can be caused by any type of food in
certain people. Moreover, in many people, there is no inciting
agent that can be identified, rather the disorder occurs without
any known provocation.
Id. at 1:16–27.
Antacids, and less frequently, histamine H2-receptor antagonists have
been used to treat episodic heartburn, but each treatment by itself is said to
have been proven to be inadequate. Id. at 1:35–42. In addition, according to
the ’137 patent, “the simultaneous administration of antacids and histamine
H2-receptor antagonists have been discouraged based upon studies
demonstrating that antacids decrease absorption and subsequent blood levels
of histamine Hz-receptor antagonists, such as cimetidine and ranitidine.” Id.
at 1:42–47. The ’137 patent teaches that the “invention is based upon the
unexpected realization that antacids and histamine H2-receptor antagonists
can be effectively administered together or substantially together to achieve
continuous relief from pain, discomfort and/or symptoms associated with
episodic heartburn, notwithstanding current medical teachings against the
simultaneous administration of antacids and histamine H2-receptor
antagonists.” Id. at 2:2–9.
As taught by the ’137 patent, typical dosages of antacid are 30 ml (2
tablespoons) of a high potency antacid, such as Maalox Plus® or Mylanta-
II®. Id. at 4:7–10. As for the histamine H2-receptor antagonist, typical
dosages are about 200 mg to 300 mg of cimetidine or about 100 mg to 150
mg of ranitidine. Id. at 4:10–14.

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C. Illustrative Claims
Petitioner challenges claims 1–27 of the ’137 patent. Claims 1 and 13
are the independent claims, are illustrative, and are reproduced below:
1. A method of providing immediate and sustained relief from
pain, discomfort and/or symptoms associated with episodic
heartburn in a human, said method comprising:
orally administering to a human together or substantially
together an antacid in an amount effective to substantially
neutralize gastric acid and a histamine H2-receptor antagonist in
an amount effective to substantially inhibit or block gastric acid
secretion for providing the human with immediate and
sustained relief from pain, discomfort and/or symptoms
associated with episodic heartburn, the immediate and sustained
relief provided lasting longer in duration than when the human
is orally treated with only the antacid and the immediate and
sustained relief provided being faster than and lasting at least
about as long in duration as when the human is orally treated
with only the histamine H2-receptor antagonist.

13. An oral pharmaceutical medication for providing
immediate and sustained relief from pain, discomfort and/or
symptoms associated with episodic heartburn in a human, said
oral pharmaceutical medication consisting essentially of:
an antacid in an amount effective to substantially
neutralize gastric acid;
a histamine H2-receptor antagonist in an amount effective
to substantially inhibit or block gastric acid secretion; and
a pharmaceutically acceptable carrier;
said oral pharmaceutical medication providing immediate
and sustained relief from pain, discomfort and/or symptoms
associated with episodic heartburn in the human, said
immediate and sustained relief lasting longer in duration than
when the human is orally treated with only the antacid and
being faster than and lasting at least about as long in duration as
when the human is orally treated with only the histamine H2-
receptor antagonist.
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D. The Asserted Grounds of Unpatentability
Petitioner challenges the patentability of claims 1–27 of the
’794 patent on the following grounds:
References Basis Claims Challenged
Lin1 as evidenced by PDR-
1988 for Pepcid®2 and PDR-
1987 for Mylanta®-II3
§ 102(b) 13, 20–25
Schickaneder4 as evidenced by
PDR-1987 for Tagamet®,5
PDR-1987 for Zantac®,6 PDR-
1987 for Maalox® and
Maalox® Plus ,7 and PDR-
1987 for Mylanta®-II
§ 102(b) 13, 15, 16, 18, 21–23,
26, 27
Gordon8 as evidenced by PDR-
1987 for Tagamet® and PDR-
1987 for Maalox® and
Maalox® Plus
§ 102(b) 13, 15, 16, 21–23

1 J.H. Lin et al., Effects of Antacids and Food on Absorption of Famotidine,
24 BR. J. CLIN. PHARMAC. 551–553 (1987) (“Lin”) (Ex. 1040).
2 PHYSICIAN’S DESK REFERENCE 1380–81 (42nd ed. 1988) (“PDR-1988 for
Pepcid®”) (Ex. 1015).
3 PHYSICIAN’S DESK REFERENCE FOR NONPRESCRIPTION DRUGS 1982 (8th ed.
1988) (“PDR-1987 for Mylanta®-II”) (Ex. 1014).
4 Schickaneder et al. (“Schickaneder”), EP 0286781, published Oct. 19, 1988
(Ex. 1028).
5 PHYSICIAN’S DESK REFERENCE 1927–1929 (41st ed. 1987) (“PDR-1987 for
Tagamet®”) (Ex. 1011).
6 PHYSICIAN’S DESK REFERENCE 992–93 (41st ed. 1987) (“PDR-1987 for
Zantac®”) (Ex. 1012).
7 PHYSICIAN’S DESK REFERENCE FOR NONPRESCRIPTION DRUGS 673–74
(8th ed. 1987) (“PDR-1987 for Maalox® and Maalox® Plus”) (Ex. 1013).
8 Gordon et al. (“Gordon”), EP 0294933 A2, published Dec. 14,
1988(Ex. 1029).
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Patent 5,229,137

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claim “are generally given their ordinary and customary meaning” as
understood by a person of ordinary skill in the art in question at the time of
the invention. Phillips v. AWH Corp., 415 F.3d 1303, 1312–13 (Fed. Cir.
2005) (en banc) (internal citation omitted). We apply this standard to the
claims of the expired ’137 patent. See Pet. 10 (indicating that the ’137
patent is expired); Prelim. Resp. 17 (reiterating the claim construction
standard for expired patents). “In determining the meaning of the disputed
claim limitation, we look principally to the intrinsic evidence of record,
examining the claim language itself, the written description, and the
prosecution history, if in evidence.” DePuy Spine, Inc. v. Medtronic
Sofamor Danek, Inc., 469 F.3d 1005, 1014 (Fed. Cir. 2006) (citing Phillips,
415 F.3d at 1312–17). There is a “heavy presumption,” however, that a
claim term carries its ordinary and customary meaning. CCS Fitness, Inc. v.
Brunswick Corp., 288 F.3d 1359, 1366 (Fed. Cir. 2002) (citation omitted).
i. “episodic heartburn”
As noted by Petitioner, the term “episodic heartburn” is defined in the
Specification of the ’137 patent. Pet. 11. Specifically, according to the ’137
patent, “episodic heartburn” refers to
the sensation of burning under the sternum (breastbone)
usually, but not necessarily, associated with the ingestion of
different foods. Also included in this definition of “episodic
heartburn” is sour stomach, indigestion, and
waterbrash/regurgitation.
Ex. 1001, 2:40–47.
Patent Owner does not disagree with that construction, but contends
that “episodic heartburn” does not include “distinct gastric disorders, such as
‘peptic ulcer’ disease, gastric lesions, or reflux esophagitis (also known as
erosive gastroesophageal reflux disease or “GERD”), as these disorders are
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recognized as distinct from episodic heartburn and thus involve different
diagnosis and therapeutic treatments.” Prelim. Resp. 17–18. Patent Owner
notes that construction is supported by the prosecution history, and that
Petitioner’s expert, Dr. Gary M. Annunziata, “acknowledges the important
distinction between episodic heartburn and these more serious and distinct
gastric conditions.” Id. at 18 (citing Ex. 1002, 77–78, ¶ 9; Ex. 1007 ¶¶ 26–
27).
As set forth in the Declaration of Dr. William M. Steinberg (Ex. 1002,
75–81), submitted during the prosecution of the ’137 patent:
Based upon my knowledge and experience in the field of
gastroenterology, I believe, and it is my opinion, that reflux
oesophagitis and episodic heartburn are not synonymous.
Reflux oesophagitis is a gastrointestinal disorder wherein the
lining of the esophagus, confirmed by endoscopic examination,
is inflamed or ulcerated. Episodic heartburn, on the other hand,
usually occurs without regularity and the pain or discomfort
associated therewith results from, for example, sour stomach,
indigestion and/or the regurgitation of gastric contents and bile
into the esophagus. Unlike patients diagnosed with reflux
oesophagitis, the overwhelming majority of patients suffering
from episodic heartburn typically do not have inflamed or
ulcerated esophageal linings.
Ex. 1002, 77–78 ¶ 9. Dr. Annunziata states that while episodic heartburn
may be simply related to poor dietary choices, it may also be a symptom of
GERD. Ex. 1007 ¶ 26.
We construe, therefore, “episodic heartburn” as set forth in the
Specification of the ’137 patent, with the caveat that it is not coextensive
with other gastrointestinal disorders, such as peptic ulcer disease, gastric
lesions, or GERD.
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ii. “an oral pharmaceutical medication”
Composition claim 13 is drawn to “[a]n oral pharmaceutical
medication . . . consisting essentially of[ ]an antacid . . .; a histamine H2-
receptor antagonist . . .; and a pharmaceutically acceptable carrier.”
Petitioner contends that an “an oral pharmaceutical medication” should be
construed as encompassing a liquid dosage form, a solid dosage form, or a
mixture of the two. Pet. 12. Patent Owner does not disagree with
Petitioner’s construction, but contends that “an oral pharmaceutical
medication” should be construed as a unitary dosage form that contains both
the antacid and the histamine H2-receptor antagonist. Prelim. Resp. 20–21.
We agree with Patent Owner, and construe the language of claim 13 as
requiring that oral pharmaceutical be a unitary (i.e., single) dosage form that
contains both the antacid and the histamine H2-receptor antagonist.
iii. “an antacid in an amount effective to substantially neutralize gastric
acid” and “a histamine H2-receptor antagonist in an amount effective to
substantially inhibit or block gastric acid secretion”
Petitioner contends that the “effective” amount of antacid and
histamine H2-receptor antagonist is not defined in the Specification of the
’137 patent. According to Petitioner, as discussed in the Declaration of
Dr. Annunziata, the ordinary artisan would understand “effective” to be “an
amount that that is within the recommended dose provided on the product
label (e.g., per the Physicians’ Desk Reference).” Pet. 13–14 (citing Ex.
1007 ¶ 24).
Patent Owner responds that Petitioner’s analysis is “misdirected and
incomplete.” Prelim. Resp. 21. That is, Patent Owner asserts, the
combination of the antacid with the histamine H2-receptor antagonist
“cannot result in a meaningful loss of therapeutic effectiveness” of the
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histamine H2-receptor antagonist, which is a “key limitation” in the claims,
according to Patent Owner. Id.
In order to determine what is meant by an effective amount of antacid
and histamine H2-receptor antagonist, we look to the Specification of the
’137 patent. Although we recognize that limitations from the Specification
are not to be read into the claim, “[i]t is entirely proper to use the
specification to interpret what . . . [is] meant by a word or phrase in the
claim.” E.I. Du Pont de Nemours & Co. v. Phillips Petroleum Co., 849 F.2d
1430, 1433 (Fed. Cir. 1988); see also In re Morris, 127 F.3d 1048, 1054
(Fed. Cir. 1997).
As noted above in our summarization of the ’137 patent, the patent
teaches that typical dosages of antacid are 30 ml (2 tablespoons) of a high
potentcy antacid, such as Maalox Plus® or Mylanta-II®, and typical dosages
of the histamine H2-receptor antagonist, are about 200 mg to 300 mg of
cimetidine or about 100 mg to 150 mg of rantidine. Ex. 1001, 4:7–14. That
is consistent with the Examples, as in Examples I, II, III, V, VI, and VII,
patients were given 30 mls of either Maalox Plus® or Mylanta-II®. Ex
1002, 5:40–7:12.
In these examples, patients were given from 300 to 400 mg of
cimetidine, or 150 mg ranitidine. Id. Thus, we interpret an “effective”
amount of antacid in the ’137 patent to be around 30 mls of either Maalox
Plus® or Mylanta-II®, and an “effective” amount of the histamine H2-
receptor antagonist to be at least about 200 mg of cimetidine or at least about
100 mg of rantidine. That amount of an antacid would substantially
neutralize gastric acid or substantially inhibit or block gastric acid secretion.
Those amounts of antacid and histamine H2-receptor antagonist also would
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provide immediate and sustained relief lasting longer in duration than when
the human is orally treated with only the antacid, and would be faster than,
and last at least about as long in duration as, when the human is orally
treated with only the histamine H2-receptor antagonist, as required by
independent claims 1 and 13.
As set forth in the PDR-1987 for Mylanta®-II (Ex. 1014), two
teaspoons, or 10 mls of Mylanta®-II, will neutralize 50.8 mEq of acid.
Similarly, as set forth in the PDR-199014 for Maalox® and Maalox® Plus
(Ex. 1022), two teaspoonfuls, or 10 mls of Maalox® Plus, will neutralize
58.1 mEq of acid. Thus, 30 mls of Mylanta®-II would neutralize 152.4 mEq
of acid, and 30 mls of Maalox® Plus would neutralize 174.3 mEq of acid.
Thus, we interpret an “effective” amount of antacid, as used by the ’137
patent, to be a dose of antacid that would neutralize at least about 150 mEq
of acid.
Thus, we construe an amount of antacid that is “effective to
substantially neutralize gastric acid” as an amount that will neutralize at least
about 150 mEq of acid. In addition, as to the “effective” amount of
histamine H2-receptor antagonist, that would be present in amount
equivalent to at least about 200 mg of cimetidine or at least about 100 mg of
rantidine. See, e.g., Teva Pharms.USA, Inc. v. Sandoz, Inc., 135 S. Ct. 831,
835 (2015) (noting that although claim construction is a question of law,
“the construction of a term of art has ‘evidentiary underpinnings.’”).

14 We chose the PDR-1990 as that was the closest to the filing date of the
’137 patent, which was May 6, 1992 (Ex. 1001).
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iv. preamble
Patent Owner argues that the term “episodic heartburn” in the
preamble of independent claims 1 and 13 should be given patentable weight.
Prelim. Resp. 22–23. Patent Owner notes that not only is the term recited in
the preamble, but it is also recited in the body of the claims, and thus “gives
life to the claims as defining the appropriate disorder to be treated by the
claimed method and medication.” Id. at 23.
As explained by the Federal Circuit:
If the claim preamble, when read in the context of the entire
claim, recites limitations of the claim, or, if the claim preamble
is “necessary to give life, meaning, and vitality” to the claim,
then the claim preamble should be construed as if in the balance
of the claim. . . . If, however, the body of the claim fully and
intrinsically sets forth the complete invention, including all of
its limitations, and the preamble offers no distinct definition of
any of the claimed invention’s limitations, but merely states, for
example, the purpose or intended use of the invention, then the
preamble is of no significance to claim construction because it
cannot be said to constitute or explain a claim limitation.
Pitney Bowes, Inc. v. Hewlett Packard Co., 182 F.3d 1298 (Fed. Cir. 1999);
see also Seachange In’l, Inc. v. C-Cor Inc., 413 F.3d 1361, 1375–76 (Fed.
Cir. 2005) (concluding the claim preamble to be limiting where it provided
antecedent basis for terms in the claim body).
The preamble of claim 1 recites a “method of providing immediate
and sustained relief from pain, discomfort and/or symptoms associated with
episodic heartburn in a human.” The body of the claim specifies that the
antacid and histamine H2-receptor antagonist are administered to provide
“the human with immediate and sustained relief from pain, discomfort
and/or symptoms associated with episodic heartburn.” Thus, the preamble
recitation of a method of providing immediate and sustained relief from
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pain, discomfort and/or symptoms associated with episodic heartburn in a
human provides antecedent basis for the recitation in the body of the claim.
We thus construe the preamble of claim 1 as being limiting.
Similarly, the preamble of claim 13 recites an “oral pharmaceutical
medication for providing immediate and sustained relief from pain,
discomfort and/or symptoms associated with episodic heartburn in a
human.” The body of claim 13 specifies that the pharmaceutical medication
provides “immediate and sustained relief from pain, discomfort and/or
symptoms associated with episodic heartburn in a human.” Thus, as for
claim 1, the preamble provides antecedent basis for the recitation in the body
of the claim. We, thus, construe the preamble of claim 13 as limiting the
composition. As discussed above as to the construction of what constitutes
an effective amount, the preamble limits the amount of antacid and
histamine H2-receptor antagonist contained within the oral pharmaceutical
medication.
v. All Remaining Terms
We determine that, for purposes of this Decision, none of the other
terms in the challenged claims requires express construction.
B. Patentability Challenges
i. Principles of Law
a. Anticipation
In order for a prior art reference to serve as an anticipatory reference,
it must disclose every limitation of the claimed invention, either explicitly or
inherently. In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997). We must
analyze prior art references as an ordinary artisan would. See Scripps Clinic
& Res. Found. v. Genentech, Inc., 927 F.2d 1565, 1576 (Fed. Cir. 1991),
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overruled on other grounds by Abbott Labs. v. Sandoz, Inc., 566 F.3d 1282
(Fed. Cir. 2009) (stating that to anticipate, “[t]here must be no difference
between the claimed invention and the reference disclosure, as viewed by a
person of ordinary skill in the field of the invention”).
b. Obviousness
A claim is unpatentable under 35 U.S.C. § 103(a) 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. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
(2007). The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) any differences between the claimed subject matter and the prior art;
(3) the level of ordinary skill in the art; and (4) objective evidence of
nonobviousness. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966). An
invention “composed of several elements is not proved obvious merely by
demonstrating that each of its elements was, independently, known in the
prior art.” KSR, 550 U.S. at 418.
Moreover, a determination of unpatentability on the ground of
obviousness must include “articulated reasoning with some rational
underpinning to support the legal conclusion of obviousness.” In re Kahn,
441 F.3d 977, 988 (Fed. Cir. 2006). The obviousness analysis “should be
made explicit” and it “can be important to identify a reason that would have
prompted a person of ordinary skill in the relevant field to combine the
elements in the way the claimed new invention does.” KSR, 550 U.S. at 418.
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ii. Anticipation by Lin (Ex. 1040)
Petitioner asserts that claims 13 and 20–25 are unpatentable as being
anticipated by Lin (Ex. 1040) as evidenced by PDR-1988 for Pepcid® (Ex.
1015) and PDR-1987 for Mylanta®-II (Ex. 1014). Pet. 14–19. As support,
Petitioner relies on the Declaration of Dr. Annunziata (Ex. 1007), as well as
the Declaration of Dr. Anthony S. Tornay (Ex. 1009). Patent Owner
disagrees. Prelim. Resp. 39–40. We determine that Petitioner has not
established a reasonable likelihood that it would prevail in its anticipation
challenge.
a. Analysis
According to Petitioner, Lin is drawn to a study conducted to
determine the effects of a high potency antacid on the bioavailability and
disposition of an histamine H2-receptor antagonist, famotidine. Pet. 14. As
to the limitation of “[a]n oral pharmaceutical formulation,” Petitioner points
to the teaching of Lin that the famotidine was given in one 40 mg tablet. Id.
at 16. Petitioner relies on the PDR as demonstrating therapeutically relevant
dosages of the antacid and the histamine H2-receptor antagonist. Id. at 15.
Patent Owner contends that Lin does not disclose a unitary dose. Prelim.
Resp. 39.
As discussed above, independent claim 13 requires a unitary dosage
form that contains both an antacid and a histamine H2-receptor antagonist.
Lin discloses administration of famotidine alone, famotidine plus Mylanta-
II® administered concurrently, and famotidine and a standard breakfast. Ex.
1040, 551-52. We agree with Patent Owner that Lin does not teach a unitary
dosage form containing both famotidine and Mylanta-II®.
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16
Thus, we conclude that Petitioner has not shown a reasonable
likelihood that it would prevail in showing that claims 13 and 20–25 are
unpatentable as anticipated by Lin.
iii. Anticipation by Schickaneder (Ex. 1028)
Petitioner asserts that claims 13, 15, 16, 18, 21–23, 26, and 27 are
unpatentable as being anticipated by Schickaneder (Ex. 1028) as evidenced
by PDR-1987 for Tagamet® (Ex. 1011), PDR-1987 for Zantac® (Ex. 1012),
PDR-1987 for Maalox® and Maalox® Plus (Ex. 1013), and for PDR-1987
for Mylanta®-II (Ex. 1014). Pet. 19–24. As support, Petitioner relies on the
Declaration of Dr. Annunziata (Ex. 1007). Patent Owner disagrees. Prelim.
Resp. 35–36, 40. We determine that Petitioner has not established a
reasonable likelihood that it would prevail in its anticipation challenge.
a. Overview of Schickaneder (Ex. 1028)
Schickaneder “relates to a pharmaceutical preparation which
represents a combination of acid secretion inhibitors of the type consisting of
histamine H2 receptor antagonists with antacid substances, which are
capable of producing a functional cytoprotection in gastrointestinal
diseases.” Ex. 1028, 2. Schickaneder discloses that the combination of
histamine H2-receptor antagonist with an antacid provides “a surprising
reinforcement of the antiulcer action of H2 antagonists . . . , which allows a
reduction of its dose.” Id. at 3. In particular, Schickaneder teaches the use
of usual dosage of antacids of 20 to 100 mVal. Id. at 4. Schickaneder
demonstrates the antiulcer efficacy of the formulation in rats. Id. at 5–7.
b. Analysis
According to Petitioner, Schickaneder teaches “solid and liquid
pharmaceutical dosage formulations comprising an [histamine H2-receptor
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17
antagonist], with specific mention of cimetidine and ranitidine, and an
antacid.” Pet. 20. Petitioner notes that Schickaneder discloses that
formulation may be used in the treatment of gastrointestinal disorders. Id.
According to Petitioner, Schickaneder “teaches taking a ‘usual dose’ of
antacid.” Id. Thus, for the claim 13 limitation that the antacid be present “in
an amount effective to substantially neutralize gastric acid,” Petitioner notes
that Schickaneder teaches the use of “antacids with a neutralization capacity
of 30 to 80 mVal per dose.” Id. at 21–22. Petitioner cites Wetzel15 for the
proposition that 1 mVal is equal to 1 mEquivalent (“mEq”). Id. at 22 n.3.
Patent Owner responds that Petitioner has not addressed the claim
limitation that “the medication provides ‘immediate and sustained relief
from pain, discomfort and/or symptoms associated with episodic heartburn
in a human.’” Prelim. Resp. 35.
We agree with Patent Owner that Petitioner has failed to demonstrate
a reasonable likelihood that Schickaneder anticipates independent claim 13
of the ’137 patent. As noted by Patent Owner, Schickaneder teaches the use
of the composition for the treatment of ulcers. Petitioner has not established
that the amounts of antacid and histamine H2-receptor antagonist disclosed
by Schickaneder would be effective to substantially neutralize gastric acid
and substantially inhibit or block gastric acid secretion. Moreover,
Petitioner has not established that the amounts would provide immediate and
sustained relief lasting longer in duration than when the human is orally
treated with only the antacid and being faster than and lasting at least about

15 ROBERT G.WETZEL, LIMNOLOGY LAKE AND RIVER ECOSYSTEMS, 192
(3rd ed. 2001) (“Wetzel”) (Ex. 1050).
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Patent 5,229,137

18
as long in duration as when the human is orally treated with only the
histamine H2-receptor antagonist, as required by claim 13.
Moreover, as discussed above in the section on claim construction, we
construe an “effective” amount of antacid as an amount of antacid that will
neutralize at least about 150 mEq of acid. Schickaneder teaches the use of
20 to 100 mVal, or mEq per dose, i.e., an amount of antacid that would
neutralize 20 to 100 mEq of acid per dose. That difference in the amount of
acid neutralizing capability, i.e., 20–100 mEq versus at least 150 mEq,
supports our conclusion that Petitioner has not established that the amount of
antacid, combined with the amount of H2-receptor antagonist, would provide
immediate and sustained relief from pain, discomfort and/or the symptoms
associated with episodic heartburn, as required by independent claim 13.
Thus, we conclude that Petitioner has not shown a reasonable
likelihood that it would prevail in showing that claims 13, 15, 16, 18, 21–23,
26, and 27 are unpatentable as anticipated by Schickaneder.
iv. Anticipation by Gordon (Ex. 1029)
Petitioner asserts that claims 13, 15, 16, and 21–23 are unpatentable as
being anticipated by Gordon (Ex. 1029) as evidenced by PDR-1987 for
Tagamet® (Ex. 1011) and PDR-1987 for Maalox® and Maalox® Plus (Ex.
1013). Pet. 24–27. Patent Owner disagrees. Prelim. Resp. 37, 40–41. We
determine that Petitioner has not established a reasonable likelihood that it
would prevail in its anticipation challenge.
a. Overview of Gordon (Ex. 1029)
Gordon “relates to a solid pharmaceutical dosage form comprising
cimetidine and an antacid and to a method for the preparation of such a
dosage form.” Ex. 1029, 2. According to Gordon, “it is well known . . . that
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19
when cimetidine is co-administered with antacids, particularly aluminum
hydroxide and magnesium hydroxide, there is frequently a substantial
reduction in the bioavailability of the cimetidine.” Id. Gordon teaches that
the loss of bioavailability may be avoided by granulating at least part of the
antacid separately, prior to mixing with the cimetidine. Id.
In particular, Gordon teaches a solid pharmaceutical dosage,
comprising cimetidine and an antacid. Id. The cimetidine is present in a
dosage from 50 mg to 800 mg per dosage form, and the dosage form
contains between 5 mEq and 30 mEq of antacid, i.e., an amount of antacid
that neutralizes between 5 and 30 mEq of acid. Id. at 3.
b. Analysis
According to Petitioner, Gordon teaches a solid pharmaceutical
dosage form containing both an antacid and cimetidine. Pet. 24. Petitioner
notes further that Gordon teaches that the dosage form contains between 50
and 800 mg of cimetidine, and 5–30 mEq of acid. Id. at 25. Petitioner relies
on PDR-1987 for Maalox® and Maalox® Plus (Ex. 1013) to establish that
Maalox® and Maalox® Plus provide 8.2 mEq and 23.4 mEq per tablet,
respectively. Pet. 25–26.
Patent Owner contends that Gordon does not anticipate the claimed
medication as it does not teach or suggest treatment of episodic heartburn.
Prelim. Resp. 41. In particular, Patent Owner argues that PDR-1987 does
not provide “any support for inherency of the proper dose to provide ‘an
amount effective’ for ‘immediate and sustained’ relief for ‘episodic
heartburn’ for approximately 4–6 hours when taken in combination with an
antacid.” Id.
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20
We agree with Patent Owner that Petitioner has failed to demonstrate
a reasonable likelihood that Gordon anticipates independent claim 13. As
noted by Patent Owner, Petitioner has not established that the amounts of
antacid and histamine H2-receptor antagonist disclosed by Gordon would be
effective to substantially neutralize gastric acid and substantially inhibit or
block gastric acid secretion. Moreover, Petitioner has not established that
the amounts would provide immediate and sustained relief lasting longer in
duration than when the human is orally treated with only the antacid and
being faster than and lasting at least about as long in duration as when the
human is orally treated with only the histamine H2-receptor antagonist, as
required in claim 13.
Moreover, as discussed above in the section on claim construction, we
construe an “effective” amount of antacid in claim 13 as an amount of
antacid that will neutralize at least about 150 mEq of acid. Gordon teaches
the use of 5 to 30 mEq per dose, i.e., neutralizing 5 to 30 mEq of acid per
dose. That difference in the amount of acid neutralizing capability, i.e., 5–
30 mEq versus 150 mEq, supports our conclusion that Petitioner has not
established that the amount of antacid described in Gordon, combined with
the amount of H2-receptor antagonist described in the reference, would
provide immediate and sustained relief from pain, discomfort and/or the
symptoms associated with episodic heartburn, as required by independent
claim 13.
Based on the record currently before us, therefore, we conclude that
Petitioner has not shown a reasonable likelihood that it would prevail in
showing that claims 13, 15, 16, and 21–23 are unpatentable as anticipated by
Gordon.
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21
v. Anticipation/Obviousness over Bovero (Ex. 1032)
Petitioner asserts that claims 1, 4–7, 12, 13, and 20–23 are
unpatentable as being anticipated, or, in the alternative, as being rendered
obvious by Bovero (Ex. 1032) as evidenced by, or in combination with
PDR-1990 for Pepcid® (Ex. 1021), and PDR-1990 for Maalox® and
Maalox® Plus (Ex. 1022). Pet. 27–34. As support, Petitioner relies on the
Declaration of Dr. Jiunn Huei Lin (Ex. 1005). Patent Owner disagrees.
Prelim. Resp. 38–39, 41. We determine that Petitioner has not established a
reasonable likelihood that it would prevail in its anticipation and/or
obviousness challenge.
a. Overview of Bovero (Ex. 1032)
Bovero studied the use of famotidine, a histamine H2-receptor
antagonist, in the management of gastro-oesophagel reflux. Ex. 1032,
Abstract. Patients with exclusively acidic gastro-oesophagel reflux were
treated nightly with 40 mg of famotidine. Id. at 145–146. Antacid tablets
(Maalox®) tablets also were supplied to those patients, with instructions to
take as needed. Id. at 146. Endoscopy performed after the eight week
program showed complete healing of endoscopic lesions in 60% of the
subjects, with another 21% of the subjects showing improvement in the
lesions. Id. at 147. Bovero noted that the consumption of antacid decreased
progressively during treatment. Id.
b. Analysis
Petitioner cites Bovero for its teaching of the use of the H2-receptor
antagonist, famotidine, in treating subjects with GERD. Pet. 27. The
subjects were treated with 40 mg of famotidine, and were instructed to take
an antacid (Maalox®) as needed. Id. Subjects then recorded the number of
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22
antacid tablets they took, and Bovero noted that the consumption of antacid
tablets decreased during the study. Id. at 27–28.
Specifically, as to the anticipation of the step of claim 1 of orally
administering to a patient an antacid and an histamine H2-receptor
antagonist, Petitioner relies on the teaching of Bolero that subjects were
given famotidine, and were also provided with antacid tablets, with
instructions to take them as needed. Id. at 30. In the alternative, Petitioner
relies on the PDR-1990 for Pepcid® (Ex. 1021) for teaching that an antacid
may be given concomitantly with Pepcid® (famotidine) if needed. Id. at 34.
Patent Owner contends that Bovero is drawn to the treatment of
gastro-oesophagel reflux, and never mentions episodic heartburn. Prelim.
Resp. 38. Moreover, Patent Owner argues that Bovero is silent on whether
the famotidine and the antacid were taken substantially together, and it is
clear that they were never taken as a unitary dose. Id. Patent Owner argues
further that the PDR does not remedy those deficiencies, as it does not
“provide any support for the elements missing in Bovero or provide any
support for inherency of the proper dose to provide ‘an amount effective’ for
‘immediate and sustained’ relief for ʻepisodic heartburn’ taken in
combination with an antacid.” Id. at 41.
We agree with Patent Owner that Petitioner has failed to demonstrate
a reasonable likelihood that Bovero anticipates claim independent claim 1.
As noted by Patent Owner, Petitioner has not established that the amounts of
antacid and histamine H2-receptor antagonist disclosed by Bovero would be
effective to substantially neutralize gastric acid and substantially inhibit or
block gastric acid secretion, as well as provide immediate and sustained
relief lasting longer in duration than when the human is orally treated with
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23
only the antacid and being faster than and lasting at least about as long in
duration as when the human is orally treated with only the histamine H2-
receptor antagonist, as recited in claim 1. In particular, we note that Bovero
does not disclose how much Maalox® was taken by the subjects, except for
teaching that it should be taken on an as-needed basis.
Moreover, as discussed above in the section on claim construction, we
construe an effective amount of antacid as an amount of antacid that will
neutralize at least about 150 mEq of acid. Bovero teaches the use of
Maalox® on an as needed basis. The PDR-1990 for Maalox® teaches that
two tablets of Maalox® contain 19.4 mEq, and that two to four tablets
should be taken. Taking four tablets would result in 38.8 mEq, i.e.,
neutralizing less than 40 mEq of acid. That difference in the amount of acid
neutralizing capability supports our conclusion that Petitioner has not
established that the amount of antacid, combined with the amount of H2-
receptor antagonist, would provide immediate and sustained relief from pain,
discomfort and/or the symptoms associated with episodic heartburn, as
required by independent claim 1.
Petitioner relies on the same teachings and rationale as to the
anticipation and obviousness of independent claim 13. Pet. 31–32, 34.
Patent Owner contends that Bovero does not disclose a unitary dose. Prelim.
Resp. 38. As Bovero discloses administration of famotidine, as well as the
use of an antacid as needed, we agree with Patent Owner that Bovero does
not teach a unitary dosage form containing both famotidine and an antacid.
As to the obviousness rejection, Petitioner provides no reasoning or analysis
as to why the ordinary artisan would have provided the famotidine and an
antacid in a unitary dosage form.
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Patent 5,229,137

24
Thus, we conclude that Petitioner has not shown a reasonable
likelihood that it would prevail in showing that claims 1, 4–7, 12, 13, and
20–23 are unpatentable as anticipated and/or rendered obvious by Bovero.
vi. Obviousness over the Combination of Lin (Ex. 1040),
Decktor (Ex. 1035), and Gordon (Ex. 1029)
Petitioner asserts that claims 1–13 and 15–27 are unpatentable as
obvious over the combination of Lin (Ex. 1040), Decktor (Ex. 1035), and
Gordon (Ex. 1029). Pet. 35–45. As support, Petitioner relies on the
Declaration of Dr. Annunziata (Ex. 1007). Patent Owner disagrees. Prelim.
Resp. 37, 42–44. We determine that Petitioner has not established a
reasonable likelihood that it would prevail in its obviousness challenge.
a. Overview of Lin (Ex. 1040), Decktor (Ex. 1035), and
Gordon (Ex. 1029)
Lin teaches that antacids have been shown to decrease the
bioavailability of the histamine H2-receptor antagonists, cimetidine and
ranitidine, and thus it was important to study the effect of antacids on the
histamine H2-receptor antagonist, famotidine. (Ex. 1040, 551). Lin studied
the effect of an antacid on the bioavailability of famotidine. Id., Abstract.
According to Lin, “[c]o-administration of the antacid caused a small but
significant reduction in the maximum plasma concentration (Cmax) of
famotidine from 81.1 ± 54.2 to 60.8 ± 21.6 ng ml-1 (P < 0.05) and a small
decrease in the area under plasma concentration-time curve [AUC] from
443.3 ± 249.2 to 355.0 ± 125.1 ng ml-1 h (P > 0.05).” Id.
Lin teaches further that renal excretion plays a substantial role in the
secretion of famotidine. Id. at 551. Lin administered famotidine alone,
famotidine plus 10 ml of Mylanta-II®, and famotidine and a standard
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IPR2014-01560
Patent 5,229,137

26
mild to severe esophagitis, asymptomatic mucosal damage, and reflux-
associated respiratory disease or noncardiac chest pain.” Id. Decktor
teaches that the “most common symptom of gastroesophageal reflux is
heartburn.” Id. Decktor teaches that phase I therapies to treatment include
life-style modifications and maneuvers, and may include the use of antacids
for symptomatic relief. Id. at 13. Decktor teaches that phase II,
pharmacological therapy include histamine H2-receptor antagonists, such as
famotidine and ranitidine. Id. According to Decktor, such pharmacologic
therapy is appropriate for patients who remain symptomatic despite phase I
therapy. Id. at 14.
An overview of Gordon is presented above.
b. Analysis
According to Petitioner, Lin teaches the co-administration of an
antacid with famotidine. Pet. 35. Petitioner notes that Lin teaches that the
reduction in bioavailability of 10–15% seen in the famotidine with the co-
administration of the antacid “is unlikely to be clinically relevant.” Id.
Petitioner contends that although Lin “does not expressly disclose” that
histamine H2-receptor antagonists, such as famotidine, are useful in
providing sustained relief of pain, discomfort, and/or the symptoms of
episodic heartburn, Decktor teaches that the “retrograde flow of gastric acid
into the esophagus may be accompanied by heartburn.” Id. Specifically,
Decktor teaches the use of histamine H2-receptor antagonists, such as
famotidine and ranitidine, reduces the frequency and severity of heartburn,
resulting in a decrease in antacid consumption by patients. Id.
Petitioner contends that it would have been obvious to administer an
antacid and a histamine H2-receptor antagonist together, or substantially
IPR2014-01560
Patent 5,229,137

27
together, to provide sustained relief of pain, discomfort, and/or the
symptoms of episodic heartburn. Id. at 35–36. Petitioner argues that
Gordon teaches that the antacid provides for rapid relief of symptoms,
whereas the histamine H2-receptor antagonist provides for more sustained
relief. Id. at 36–37. In particular, as to the effective amount of antacid as
recited by independent claims 1 and 13, Petitioner relies the teaching of Lin
that 10 ml of Mylanta®-II was given with the 40 mg of famotidine. Id. at
38, 41.
Patent Owner responds that Lin is unreliable, as the standard
deviations for the renal clearance rates for Treatments B and C, as presented
in Table 1 of the Lin reference (Ex. 1040, 552, Table 1), are clear errors,
which Dr. Lin failed to correct in his Declaration (Ex. 1005). Prelim. Resp.
31–33. Patent Owner contends further that Lin is not relevant to the
treatment of episodic heartburn, as healthy subjects were used in the study.
Id. at 33. Moreover, Patent Owner argues that Lin’s statement that the
change in bioavailability is unlikely to be clinically relevant is unsupported.
Id. at 34–35.
As for Decktor, Patent Owner argues that while the reference teaches
that heartburn may be a symptom of gastroesophageal reflux, it does not
discuss episodic heartburn. Id. at 42. Gordon, Patent Owner asserts, also
does not discuss episodic heartburn. Id. at 43.
We agree with Patent Owner that Petitioner has failed to demonstrate
a reasonable likelihood that the combination of Lin, Decktor, and Gordon
renders independent claims 1 and 13 obvious. As noted by Patent Owner,
Petitioner has not established that the 10 ml of Mylanta®-II antacid taught
by Lin would be effective to substantially neutralize gastric acid and
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28
substantially inhibit or block gastric acid secretion, as required in claims 1
and 13. Nor has Petitioner established sufficiently that the amounts of
antacid and histamine H2-receptor antagonist taught by the references in
combination provide immediate and sustained relief lasting longer in
duration than when the human is orally treated with only the antacid and are
faster than, and last at least about as long in duration as, when the human is
orally treated with only the histamine H2-receptor antagonist, as also
required in claims 1 and 13.
Moreover, as discussed above in the section on claim construction, we
construe an “effective” amount of antacid as an amount of antacid that will
neutralize at least about 150 mEq of acid. Lin teaches the use of 10 ml of
Mylanta®-II, which Lin teaches is a high potency antacid, with an antacid
neutralizing capacity of 50.8 mEq. Ex. 1040, 551–52. Petitioner has
provided no scientific reasoning or evidence that it would have been obvious
to increase the amount of antacid. That difference in the amount of acid
neutralizing capability (50.8 mEq versus at least 150 mEq) supports our
conclusion that Petitioner has not established that the amount of antacid,
combined with the amount of H2-receptor antagonist, would provide
immediate and sustained relief from pain, discomfort and/or the symptoms
associated with episodic heartburn, as required by independent claims 1 and
13.
Thus, we conclude that Petitioner has not shown a reasonable
likelihood that it would prevail in showing that claims 1–13 and 15–27 are
rendered obvious by the combination of Lin, Decktor, and Gordon.
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vii. Obviousness over the Combination of Schickaneder (Ex. 1028),
Bovero (Ex. 1032), and PDR-1990 for Maalox® and
Maalox® Plus (Ex. 1022)
Petitioner asserts that claims 1–13 and 15–27 are unpatentable as
obvious over the combination of Schickaneder, Bovero, and PDR-1990 for
Maalox® and Maalox® Plus. Pet. 45–49. As support, Petitioner relies on
the Declaration of Dr. Annunziata (Ex. 1007), as well as the Declaration of
Dr. Lin (Ex. 1005). Patent Owner disagrees. Prelim. Resp. 36, 38–39,44–
46. We determine that Petitioner has not established a reasonable likelihood
that it would prevail in its obviousness challenge.
a. Analysis
An overview of Schickaneder and Bovero are provided above.
Petitioner relies on Schickaneder for teaching “solid and liquid
pharmaceutical dosage formulations comprising a [histamine H2-receptor
antagonist], with specific mention of cimetidine and ranitidine, and an
antacid.” Pet. 45. Petitioner notes that Schickaneder discloses that
formulation may be used in the treatment of gastrointestinal disorders. Id.
Bovero is relied upon for teaching that treatment with 40 mg of famotidine is
effective in reducing episodic heartburn in patients with acid-reflux
esophagitis. Id. Moreover, Petitioner notes that Bovero teaches that
Maalox® tablets could be taken on an as-needed basis. Id.
Petitioner contends that it would have been obvious to administer the
oral formulation of Schickaneder to humans suffering from acid-reflux
esophagitis to reduce episodic heartburn because Schickaneder teaches that
its formulation is useful in the treatment of gastrointestinal disorders. Id. at
45–46. In particular, as to the effective amount of antacid as recited by
independent claims 1 and 13, Petitioner relies on Schickaneder for its
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teaching that the oral formulation contains 20 to 100 mEq per dose. Id. at
47.
Patent Owner responds that neither Schickaneder nor Bovero
discusses the treatment of episodic heartburn. Prelim. Resp. 45. According
to Patent Owner, none of the references “provide any support for inherency
of the proper dose necessary to provide ‘an amount effective’ for ‘immediate
and sustained’ relief for ‘episodic heartburn’ for approximately 4-6 hours
when taken in combination with an antacid.” Id. In particular, Patent
Owner asserts, Schickaneder studied the effectiveness of its formulation on
ulcers, and Bovero did not track when antacids were taken, only noting that
antacid use decreased during the study. Id.
We agree with Patent Owner that Petitioner has failed to demonstrate
a reasonable likelihood that the combination of Schickaneder, Bovero, and
PDR-1990 for Maalox® and Maalox® Plus renders independent claims 1
and 13 obvious. As noted by Patent Owner, Petitioner has not established
that the 20 to 100 mEq per dose of antacid taught by Schickaneder would be
effective to substantially neutralize gastric acid and substantially inhibit or
block gastric acid secretion, as required by claims 1 and 13. Nor has
Petitioner established sufficiently that the amounts of antacid and histamine
H2-receptor antagonist taught by the references in combination provide
immediate and sustained relief lasting longer in duration than when the
human is orally treated with only the antacid and are faster than, and last at
least about as long in duration as, when the human is orally treated with only
the histamine H2-receptor antagonist, as also required by claims 1 and 13.
Moreover, as discussed above in the section on claim construction, we
construe an “effective” amount of antacid as an amount of antacid that will
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31
neutralize at least about 150 mEq of acid. Schickaneder teaches the use of
20 to 100 mVal, i.e., a neutralizing capacity of 20 to 100 mEq per dose. Ex.
1028, 4. Petitioner has provided no scientific reasoning or evidence that it
would be obvious to increase the amount of antacid in the oral formulation.
That difference in the amount of acid neutralizing capability supports our
conclusion that Petitioner has not established that the amount of antacid,
combined with the amount of H2-receptor antagonist, would provide
immediate and sustained relief from pain, discomfort and/or the symptoms
associated with episodic heartburn, as required by independent claims 1 and
13.
Thus, we conclude that Petitioner has not shown a reasonable
likelihood that it would prevail in showing that claims 1–13 and 15–27 are
rendered obvious by the combination of Schickaneder, Bovero, and PDR-
1990 for Maalox® and Maalox® Plus.
viii. Obviousness over the Combination of Lin (Ex. 1040),
Bovero (Ex. 1032), PDR-1988 for Pepcid® (Ex. 1015), and
PDR-1987 for Mylanta®-II (Ex. 1014)
Petitioner asserts that claims 1–13 and 15–25 are unpatentable as
obvious over the combination of Lin, Bovero, PDR-1988 for Pepcid®, and
PDR-1987 for Mylanta®-II. Pet. 49–45. As support, Petitioner relies on the
Declaration of Dr. Annunziata (Ex. 1007). Patent Owner disagrees. Prelim.
Resp. 31–35, 38–39, 46. We determine that Petitioner has not established a
reasonable likelihood that it would prevail in its obviousness challenge.
a. Analysis
An overview of Lin and Bovero are provided above. According to
Petitioner, Lin teaches the co-administration of an antacid with famotidine.
Pet. 49. Petitioner notes that Lin teaches that the reduction in bioavailability
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32
of 10–15% seen in the famotidine with the co-administration of the antacid
“is unlikely to be clinically relevant.” Id. Petitioner contends that although
Lin “does not expressly disclose” that co-administration of histamine H2-
receptor antagonists, such as famotidine, with an antacid can be used to
provide sustained relief of pain, discomfort, and/or the symptoms of episodic
heartburn, Bovero reports that 40 mg famotidine is effective in reducing
episodic heartburn. Id.
Petitioner contends that it would have been obvious to the ordinary
artisan to administer a histamine H2-receptor antagonists, such as
famotidine, with an antacid together or substantially together because Lin
teaches that “administration of famotidine and an antacid together does not
alter bioavailability in a clinically relevant manner, in order to provide relief
of pain, discomfort and/or symptoms associated with episodic heartburn in a
human based on the teaching in Bovero that famotidine reduces episodic
heartburn.” Id. at 50. In particular, as the effective amount of antacid as
recited by independent claims 1 and 13, Petitioner relies the teaching of Lin
that 10 ml of Mylanta®-II was given with the 40 mg of famotidine. Id. at
51, 54–55.
Patent Owner contends that none of the references “provide any
support for inherency of the proper dose that ‘necessarily’ provides ‘an
amount effective’ for ‘immediate and sustained’ relief for ‘episodic
heartburn’ for approximately 4-6 hours when taken in combination with an
antacid.” Prelim. Resp. 46. We agree for the reasons set forth above with
respect to the challenge based on the combination of Lin, Decktor, and
Gordon.
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014-0156
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31–35, 37
the challe
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etitioner h
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33
oner has n
howing th
n of Lin,
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ONCLUS
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its obviou
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onstrated
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n (Ex. 104
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014-0156
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ansanders
ansanders
34
ORDER
ing, it is h
tes review
.com
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ereby:
of U.S. Patent No. 5,229,137,