pozen and horizon/hayman institution decision for '907 patent

7/23/2019 POZEN and Horizon/Hayman institution decision for '907 patent

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[email protected] Paper 22

571-272-7822 Entered: December 8, 2015

UNITED STATES PATENT AND TRADEMARK OFFICE

____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________

COALITION FOR AFFORDABLE DRUGS VII LLC,

Petitioner,

v.

POZEN INC.,Patent Owner.

Case IPR2015-01241Patent 6,926,907 B2

Before TONI R. SCHEINER, LORA M. GREEN, and

JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION

Denying Institution of Inter Partes Review37 C.F.R. § 42.108

mailto:[email protected]





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I. INTRODUCTION

The Coalition for Affordable Drugs VII LLC (“Petitioner”) filed a

Petition (Paper 1, “Pet.”) on May 21, 2015, requesting an inter partes review

of claims 1 – 23 of U.S. Patent No. 6,926,907 B2 (Ex. 1001, “the ’907

patent”). Pozen Inc. (“Patent Owner”) filed a Preliminary Response (Paper

15, “Prelim. Resp.”) on September 18, 2015.1, 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.”

Upon consideration of the information presented in the Petition and

the Preliminary Response, we are not persuaded that Petitioner has

established a reasonable likelihood that it would prevail in its challenges to

claims 1 – 23 of the ’907 patent. Accordingly, we decline to institute an inter

partes review of those claims.

1 Patent Owner filed an unopposed Motion for Extension of Time to File

Preliminary Response. Paper 10. The motion was granted via an email from

the Board dated September 4, 2015, and the due date for the Preliminary

Response was extended until September 19, 2015.

2 Patent Owner filed a Motion to File Under Seal its Preliminary Responseand Exhibit 2011, an associated exhibit. Paper 16. Along with the Motion

to Seal, Patent Owner filed a redacted version of the Preliminary Responseto be available to the public. Paper 13.



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A. Related Proceedings

Petitioner represents it is aware of a number of judicial matters

involving the ’907 patent (e.g., AstraZeneca AB v. Dr. Reddy’s Labs. Inc.,

3:11-cv-02317 (D.N.J.)), as well as a number of judicial and administrative

matters involving patents related to the ’907 patent (e.g., Dr. Reddy’s Labs.,

Inc. v. Pozen Inc., Case IPR2015-00802 (PTAB)). Pet. 2 – 3. Patent Owner

makes a similar representation. Paper 7, 8. After filing the current Petition,

Petitioner also filed other Petitions for inter partes review involving patents

related to the ’907 patent or directed to similar subject matter, including

Case Nos. IPR2105-01344, IPR2015-01680, IPR2015-01718.

B. The Asserted Grounds of Unpatentability

Petitioner asserts the challenged claims are unpatentable on the

following grounds. Pet. 12 – 60.3

References Basis Claims Challenged

Gimet4 and Chiverton5 § 103(a)1, 7, 8, 12, 13, 22,

and 23

3 Petitioner supports its challenge with the Declaration of Leon Shargel,

Ph.D., R.Ph., executed May 25, 2015 (“Shargel Declaration”) (Ex. 1003). 4 U.S. Patent No. 5,698,225, issued December 16, 1997 to Gimet et al.

(“Gimet”) (Ex. 1004). 5 S.G. Chiverton et al., Does misoprostol given as a single large doseimprove its antisecretory effect?, 1 ALIMENT. PHARMACOL. 403 – 07 (1989)

(“Chiverton”) (Ex. 1007).



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References Basis Claims Challenged

Gimet, Goldman,6 andRemington7

§ 103(a) 1 – 5 and 7 – 23

Goldman, Remington, andAbe8

§ 103(a)1 – 5, 7 – 18, 21, and22

Goldman, Remington, and

Fitton9 § 103(a) 1, 5, and 6

C. The ’907 Patent (Ex. 1001)

The ’907 patent, titled “Pharmaceutical Compositions for the

Coordinated Delivery of NSAIDs” discloses pharmaceutical compositions

“that provide for the coordinated release of an acid inhibitor and a non-

steroidal anti-inflammatory dr ug (NSAID)” (id. at 1:11 – 14), such that there

is “a reduced likelihood of causing unwanted side effects, especially

gastrointestinal side effects, when administered as a treatment for pain” (id.

at 1:14 – 18).

6 U.S. Patent No. 5,204,118, issued April 20, 1993 to Goldman et al.

(“Goldman”) (Ex. 1005). 7 Robert E. King & Joseph D. Schwartz, Oral Solid Dosage Forms, in R EMINGTON’S PHARMACEUTICAL SCIENCES 1603 – 32 (Alfonso R. Gennaro et

al., eds.) (17th ed. 1985) (“Remington”) (Ex. 1006). 8 Kazuo Abe et al., Effect of Oral and Intramuscular Famotidine on pH and

Volume of Gastric Contents, 68 A NESTH. A NALG. 541 – 44 (1989) (“Abe”)

(Ex. 1039).9 Andrew Fitton & Lynda Wiseman, Pantoprazole — A Review of its

Pharmacological Properties and Therapeutic Use in Acid-Related Disorders, 51 DRUGS 460 – 82 (1996) (“Fitton”) (Ex. 1048).



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Specifically, the ’907 patent discloses “a pharmaceutical composition

in unit dosage form . . . contain[ing] an acid inhibitor present in an amount

effective to raise the gastric pH of a patient to at least 3.5” (id. at 3:18 – 22),

and an NSAID “in an amount effective to reduce or eliminate pain or

inflammation” (id. at 3: 40 –41). “The term ‘unit dosage form’ . . . refers to a

single entity for drug administration. For example, a single tablet or capsule

combining both an acid inhibitor and an NSAID would be a unit dosage

form.” Id. at 3:60 – 63.

A unit dosage form of the present invention preferably providesfor coordinated drug release, in a way that elevates gastric pH

and reduces the deleterious effects of the NSAID on thegastroduodenal mucosa, i.e., the acid inhibitor is released first

and the release of NSAID is delayed until after the pH in the GItract has risen. In a preferred embodiment, the unit dosage

form is a multilayer tablet, having an outer layer comprising theacid inhibitor and an inner core which comprises the NSAID.

In the most preferred form, coordinated delivery isaccomplished by having the inner core surrounded by a

polymeric barrier coating that does not dissolve unless thesurrounding medium is at a pH of at least 3.5, preferably at

least 4 and more preferably, at least 5.

Id. at 3:63 – 4:9.

“The term ‘acid inhibitor’ refers to agents that inhibit gastric acid

secretion and increase gastric pH.” Id. at 3:25 – 27. According to the ’907

patent, preferred acid inhibiters are H2-blockers, such as famotidine (id. at

3:28 –30), and “[o]ther agents that may be effectively used include proton

pump inhibitors such as . . . esomeprazole” (id. at 3:35 – 37).



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D. Illustrative Claim

Petitioner challenges claims 1 – 23 of the ’907 patent. Claim 1,

reproduced below, is illustrative.

1. A pharmaceutical composition in unit dosage[10] form

suitable for oral administration to a patient, comprising:

(a) an acid inhibitor present in an amount effective to

raise the gastric pH of said patient to at least 3.5 upon theadministration of one or more of said unit dosage forms;

(b) a non-steroidal anti-inflammatory drug (NSAID) in

an amount effective to reduce or eliminate pain or

inflammation in said patient upon administration of oneor more of said unit dosage forms;

and wherein said unit dosage form provides for coordinated

release such that:

i) said NSAID is surrounded by a coating that, upon

ingestion of said unit dosage form by said patient, prevents the release of essentially any NSAID from

said dosage form unless the pH of the surrounding

medium is 3.5 or higher;

ii) at least a portion of said acid inhibitor is not

surrounded by an enteric coating and, upon ingestionof said unit dosage form by said patient, is released

regardless of whether the pH of the surroundingmedium is below 3.5 or above 3.5.

Ex. 1001, 20:8 – 31.

10 As issued, claim 1 used the phrase “unit dose form,” but the phrase was

corrected to read “unit dosage form” by Certificate of Correction enteredDecember 25, 2007. Ex. 1028, 1.



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II. ANALYSIS

A. Claim Construction

In an inter partes review, claim terms in an unexpired patent are

interpreted according to their broadest reasonable construction in light of the

specification of the patent in which they appear. 37 C.F.R. § 42.100(b);

Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,766 (Aug. 14,

2012); In re Cuozzo Speed Techs., LLC , 793 F.3d 1268, 1275 – 79 (Fed. Cir.

2015). Under that standard, claim terms are given their ordinary and

customary meaning, as would be understood by one of ordinary skill in the

art in the context of the entire disclosure. In re Translogic Tech., Inc., 504

F.3d 1249, 1257 (Fed. Cir. 2007).

We determine that the only claim term requiring interpretation for

purposes of this decision is “acid inhibitor.”

Petitioner contends that the broadest reasonable interpretation of “acid

inhibitor” in light of the specification includes prostaglandins, H2-blockers,and proton pump inhibitors (PPIs). Pet 10 – 11.

Patent Owner contends that “the broadest reasonable interpretation of

‘acid inhibitor’ excludes prostaglandins” because “the ’907 patent plainly

distinguishes H2- blockers and PPIs, describing them as ‘acid inhibitors,’

from synthetic prostaglandins, describing them as ‘cytoprotective agents.’”

(Prelim. Resp. 8 – 9 (citing Ex. 1001, 1:40 – 44)). Patent Owner cites and

compares passages of the specification in support of this proposition as

follows:



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(Compare Ex. 1001 at 1:40-44 (“In general, more potent and

longer lasting acid inhibitors, such as proton pump inhibitors,

are thought to be more protective during chronic administrationof NSAIDs than shorter acting agents, e.g., histamine H2

receptor antagonists . . . .”) with id . at 2:45-51 (“Other attemptsto produce an NSAID therapy with less gastrointestinal toxicity

have involved the concomitant administration of a

cytoprotective agent” including ArthrotecTM which “contains

misoprostol (a cytoprotective prostaglandin) and the NSAIDdiclofenac.”).)

Prelim. Resp. 9.

Nevertheless, the specification teaches that “[t]he term ‘acid inhibitor’ refers to agents that inhibit gastric acid secretion and increase gastric pH”

(Ex. 1001, 3:25 – 27), that preferred acid inhibiters are H2-blockers, such as

famotidine (id. at 3:28 –30), and “[o]ther agents that may be effectively used

include proton pump inhibitors such as . . . esomeprazole” (id. at 3:35 – 37).

Thus, the specification describes H2-blockers and PPIs as illustrative, rather

than exclusive, acid inhibitors. Moreover, even if we assume arguendo that

the specification distinguishes the claimed invention from ArthrotecTM (a

composition comprising a combination of misoprostol and the NSAID

diclofenac) (Prelim. Resp. 8 – 9), the distinction is not unambiguously based

on the presence of misoprostol in the composition — it could just as well be

that the amount of misoprostol in the composition is insufficient to raise

gastric pH to 3.5 or more, as required by all the challenged claims.



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Accordingly, we are not persuaded that the broadest reasonable

interpretation of “acid inhibitor” excludes prostaglandins in general, or

misoprostol in particular.

B. Claims 1, 7, 8, 12, 13, 22, and 23 — Asserted

Obviousness over Gimet and Chiverton

1. Gimet (Ex. 1004)

Gimet teaches that NSAIDs have “high therapeutic value especially

for the treatment of inflammatory conditions such as . . . osteoarthritis (OA)

and rheumatoid arthritis” (id. at 1:20 –22), but “also exhibit undesirable side

effects” (id. at 1: 24). “An especially undesirable side effect of the

administration of NSAIDs is the ulcerogenic effects generally associated

with chronic use.” Id. at 1:24 – 27. “NSAID induced ulcers in the stomach

. . . generally exhibit few or no symptoms and may cause dangerous

bleeding when undetected . . . [and] [i]n some instances . . . can prove fatal.”

Id. at 1:29 – 33.

According to Gimet, “[c]ertain prostaglandins have been shown to

prevent NSAID induced ulcers.” Id. at 1:39 – 40. Misoprostol, for example,

“is a pharmaceutically acceptable prostaglandin which has been accepted for

use in the treatment of NSAID induced ulcers.” Id. at 1:45 – 47.

Gimet discloses a pharmaceutical composition comprising a tablet

having an inner core and an outer mantle coating surrounding the inner core,

designed to “counter (by inhibiting, reducing or preventing) the ulcerogenic

side effects attendant to NSAID administration.” Id. at 1:61 – 63. The inner



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core consists of an NSAID — disclofenac or piroxicam — and the outer mantel

consists of a prostaglandin — e.g., misoprostol. Ex. 1004, 1:11 – 17, 39 – 47.

Figure 2 of Gimet, reproduced below, depicts tablet 16 in cross-

section.

Figure 2 of Gimet depicts tablet 16. Tablet 16 includes an NSAID —

diclofenac or piroxicam — in inner core 18. Enteric coating 20 surrounds

core 18, and mantle 22 — consisting of a prostaglandin, e.g., misoprostol —

surrounds the coated inner core. Ex. 1004, 6:24 – 44.

The enteric coating “can be formulated from any suitable enteric

coating material,” and “aids in segregating the NSAID from the prostaglandin and in directing the dissolution of the NSAID core in the

lower G.I. tract as opposed to the stomach.” Id. at 6:29 – 30, 33 – 36.

“When the prostaglandin is misoprostol . . . [it] is present in an

amount from about 50 to about 500 mcg and preferably from about 100 to

about 200 mcg.” Id. at 6:20 – 23.

2. Chiverton (Ex. 1007)

Chiverton teaches that “[m]isoprostol is a prostaglandin E1 analogue,

currently prescribed as a q.d.s. dose regimen for the treatment of duodenal



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ulcer” (Ex. 1007, 404), and “is believed . . . [to] act[] primarily through its

antisecretory activity rather than its cytoprotective effect” (id.). However,

according to Chiverton, a study designed to determine whether the

antisecretory effect of misoprostol could be improved by administering it as

a single large dose “confirms that misoprostol is a weak, short-acting

antisecretory drug” (id. at 405), and “raises the question of whether the

positive effects on mucosal defense, induced by prostaglandins, might be

more important for duodenal ulcer healing” (id. at 406 – 07).

The results of Chiverton’s study are shown in Figures 1 and 2, and

reproduced below.



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Figures 1 and 2 of Chiverton are box whisker plots of total twenty-four hour

gastric pH and night-time gastric pH, respectively, resulting from

administration of misoprostol or placebo under various dosing regimens.11

According to Chiverton, “only the 800 µg and 600 µg h.s. doses were

significantly different from placebo” (id. at 406). Chiverton suggests that

“the weak antisecretory action of misoprostol, seen here, raises the question

of whether the positive effects on mucosal defense, induced by

prostaglandins, might be more important for duodenal ulcer healing” (id. at

406 – 07), for example, “an increase in thickness of the mucus gel layer could

perhaps be of greater importance in the prophylaxis and treatment of

NSAID-induced injury” (id. at 407).

11 In Figures 1 and 2 of Chiverton, “q.d.s.” stands for quater die sumendus,i.e., four times a day; “h.s.” stands for hora somni, i.e., at bedtime.



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3. Analysis

With respect to claim 1, Petitioner contends that “Gimet teaches a unit

dosage form suitable for administration that comprises an NSAID and an

acid inhibitor (e.g. misoprostol), wherein the NSAID is present in an

enterically-coated core and the acid inhibitor is present in a mantle coating

surrounding the enterically-coated core.” Pet. 12 (citing Ex. 1003 ¶ 64).

With respect to the claim’s requirement for “an acid inhibitor present

in an amount effective to raise the gastric pH . . . to at least 3.5 upon the

administration of one or more of said unit dosage forms,” Petitioner

contends that “Gimet in view of Chiverton discloses this limitation.” Pet.

13. That is, according to Petitioner, “[i]n considering the dosage and

therapeutic effect upon administration of the acid inhibitor (e.g.,

misoprostol) present in [Gimet’s] unit dosage form, a known method would

be to look to related literature studying the therapeutic effect of the

particular drug . . . to provide predictable results related to administering the

drug.” Id. Petitioner contends a person of ordinary skill in the art, therefore,

“would have been motivated to look to clinical studies showing results of

misoprostol on gastric acid pH such as those shown in Chiverton to provide

predictable results of an increase of gastric acid pH associated with the

administration of . . . misoprostol.” Id. Petitioner contends that Chiverton

discloses that misoprostol “‘acts primarily through its antisecretory

activity[]’” (Pet. 14 (citing Ex. 1007, 404; Ex. 1003 ¶ 71)), and “further

discloses that misoprostol can be dosed in an amount effective to raise



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gastric pH to at least 3.5[]” (id. (citing Ex. 1007, 406, Fig. 2, Table 1; Ex.

1003 ¶ 71)).

Patent Owner contends that Gimet “does not disclose a dosage form

comprising an acid inhibitor in an amount effective to raise the gastric pH of

a patient to at least 3.5.” Prelim. Resp. 14. Patent Owner further contends

that Chiverton “shows that the doses of prostaglandin taught by Gimet are

insufficient to raise the gastric pH to 3.5” (id.), and “[e]ven [Chiverton’s]

600 mcg and 800 mcg doses, doses greater than those taught by Gimet,

failed to raise the mean pH to at least 3.5” (id.). Thus, Patent Owner argues

that “neither Gimet nor Chiverton, either alone or in combination, provides

any rationale for a dosage form comprising an acid inhibitor in an amount

effective to raise the gastric pH of a patient to at least 3.5.” Id.

First, we note that the challenged claims do not require raising the

mean gastric pH to 3.5, and we agree with Petitioner that Chiverton suggests

“that misoprostol can be dosed in an amount effective to raise gastric pH to

at least 3.5.” Pet. 14. That is, we agree with Petitioner that Chiverton shows

that it may be possible to raise gastric pH to 3.5 or higher, albeit unreliably,

by administering a dose of misoprostol at the upper end or beyond the range

disclosed by Gimet. For example, see the upper “whiskers” (i.e., vertical

lines) for Chiverton’s 400 and 800 µg doses given h.s. on the box whisker

plot shown in Figure 2 of Chiverton (Ex. 1007), and Gimet’s teaching of

“about 50 to about 500 mcg” misoprostol (Ex. 1004, 6:20 – 23).



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Nevertheless, Petitioner has not explained adequately why one of

ordinary skill in the art would have had a reason to formulate Gimet’s tablet

to increase gastric (i.e., stomach12) and/or duodenal pH to at least 3.5 in the

first place, when Gimet explicitly teaches that the enteric coating on its

tablet “direct[s] the dissolution of the NSAID core in the lower G.I. tract as

opposed to the stomach.” 13 Ex. 1004, 6:34 – 36 (emphasis added). We also

note that Gimet states a preference for a lower dose of “about 100 to about

200 mcg” misoprostol (id . at 6:20 – 23), a dose that Chiverton indicates

would not raise gastric pH to 3.5 or higher (Ex. 1007, Figs. 1 and 2).

Moreover, Petitioner does not point us to any discussion of gastric pH in

12 “Gastric” is defined as “of or relating to the stomach” ( see http://beta.merriam-webster.com/medical/gastric).13 We note Petitioner’s further assertion that

[T]he POSA would know that a typical patient would have a pH

in the small intestine after exiting the stomach of greater thanabout 3.5 . . . Thus, the POSA would have a rationale and areasonable expectation of success in preparing a combination

therapy, coordinated release, unit dosage form having a delayedrelease component, for example an enterically-coated drug

(e.g., NSAID) to prevent the release of the drug from thedosage form unless the pH of the surrounding medium (e.g.,

portions of the G.I. tract after exiting the stomach) is 3.5 orhigher.

Pet. 15 (citing Ex. 1033 ¶¶ 80 – 82).

There is no dispute that Gimet discloses an enteric coating that prevents release of the NSAID before it reaches the lower G.I. tract — the

claims, however, are directed to increasing gastric pH to at least 3.5.

http://beta.merriam-webster.com/medical/gastric

http://beta.merriam-webster.com/medical/gastric



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Gimet (much less a discussion of pH as a factor in NSAID-associated

ulcerogenesis).14 Nor does Petitioner point to anything in Chiverton which

would suggest the desirability of increasing the dose of misoprostol in

Gimet’s tablets in order to raise gastric pH to at least 3.5, especially as

Chiverton suggests that “the weak antisecretory action of misoprostol . . .

raises the question of whether the positive effects on mucosal defense,

induced by prostaglandins, might be more important for duodenal ulcer

healing than has been hither to thought.” Ex. 1007, 406– 07.

Having considered the evidence and arguments presented in the

Petition, we are not persuaded that Petitioner has established a reasonable

likelihood of prevailing in its challenge to claim 1, or claims 7, 8, 12, 13, 22,

and 23, which directly or indirectly depend from claim 1, on the basis of

obviousness over Gimet and Chiverton.

14

We note the statement in Petitioner’s background discussion of the stateof the art that “since at least 1971, NSAIDs like aspirin and naproxen have

been known to increase gastric acid production and, thus, increase theincidence of gastric ulcers.” Pet. 5 (citing Ex. 1003 ¶ 30). In support of this

proposition, paragraph 30 of Exhibit 1003 (the Shargel Declaration) citesExhibit 1011 (Valerie Vella, Drug-induced peptic ulcer disease, 10 JOURNAL

OF THE MALTA COLLEGE OF PHARMACY PRACTICE 15 – 19 (2005) (“Vella”)).

However, Vella discusses various deleterious effects of NSAIDs on gastric

mucosa (attributed to, e.g., inhibition of prostaglandin synthesis, neutrophil-

mediated injury, etc. ( see Ex. 1011, 15 – 16)), but Dr. Shargel does not point

to any discussion of gastric pH as a factor in the development of NSAID-induced gastric ulcers. Thus, Vella does not support adequately the link the

link Petitioner and Dr. Shargel draw between gastric acid production andgastric ulcers.



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C. Claims 1 – 5 and 7 – 23 — Asserted Obviousness over

Gimet, Goldman, and Remington

1. Goldman (Ex. 1005)

Goldman teaches that “the symptoms of overindulgence due to

excessive or inappropriate intake of food and/or alcoholic beverage are well

known and include headache as well as indigestion, upper abdominal

discomfort, bloating, heartburn or pyrosis.” Ex. 1005, 1:28 – 32. “The

treatment of the symptoms of overindulgence often requires the co-

administration of an analgesic to relieve the headache along with an agent toreduce gastric acidity which is generally believed to cause the indigestion

and heartburn.” Id. at 2:52 – 56.

In order to “more effectively treat all the symptoms concurrently” (id.

at 2:67 – 68), Goldman discloses “a pharmaceutical composition for treating

the symptoms of overindulgence . . . [comprising] a combination of non-

steroidal anti-inflammatory drug or acetaminophen and a histamine receptor

blocker and/or a proton pump inhibitor composition” (id. at 1:10 – 16).

Goldman teaches that acceptable histamine receptor (H2) blockers include

famotidine (id.at 3:27), acceptable proton pump inhibitors (PPIs) include

omeprazole (id.), and acceptable NSAIDs include naproxen and piroxicam

(id. at 3:17 – 22).

According to Goldman, “statistical methods are used to show that on

the average, acetaminophen or non-steroidal inflammatory agents with H1

histamine and/or H2 histamine receptor blocking drugs are more efficacious”

in treating the symptoms of overindulgence. Id. at 5:51 – 65.



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Finally, Goldman discloses “chewable and liquid dosage forms” (id.

at 6:4 – 5), and further teaches that “[v]arious conventional techniques for

preparing medicament tablets or caplets can be employed as would be

known to those skilled in the art as is disclosed for example by Remington’s

Pharmaceutical Sciences.”15 Ex. 1005, 6:26 – 30.

2. Remington (Ex. 1006)

Remington discusses generally the production of oral solid dosage

forms, such as tablets and capsules, and the many considerations that

influence the choice of a particular dosage form. Ex. 1006, 1603 – 33.

Among the many dosage forms mentioned, Remington discusses various

coated tablets, including enteric-coated tablets —“compressed tablets coated

with substances that resist solution in gastric fluid but disintegrate in the

intestine.” Id . at 1604. Remington teaches that “[e]nteric coatings can be

used for tablets containing drug substances which are inactivated or

destroyed in the stomach, for those which irritate the mucosa, or as a means

of delayed release of the medication.” Id . Remington also teaches that

tablets may be coated in order to “[r]educ[e] the risk of interaction between

incompatible components . . . by using coated forms of one or more of the

offending ingredients (particularly active compounds).” Id. at 1633.

15 This is the same publication submitted as Exhibit 1006.



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3. Analysis

Petitioner contends that “[b]oth Gimet and Goldman are directed to

pharmaceutical compositions comprising an NSAID and an acid inhibitor,

and a POSA tasked with formulating an NSAID/acid inhibitor combination

therapy would have considered their collective teachings on the subject.”

Pet. 21 (citing Ex. 1003 ¶ 117). Petitioner contends:

For example, the POSA would have substituted the NSAIDs

and acid inhibitors in Gimet for other known NSAIDs and acidinhibitors in Goldman to obtain predictable results;

alternatively, it would have been obvious to try Goldman’s NSAIDs and acid inhibitors with Gimet’s tablets; alternatively,

Gimet has a teaching, suggestion, or motivation to be combinedwith Goldman. ([Ex. 1003 ¶ 117].) A POSA would have

substituted Gimet’s prostaglandin with Goldman’s H2 blockers or PPIs to obtain predictable results of inhibiting gastric acid,

particularly since Gimet discloses that “[w]hile prostaglandinsare beneficial compounds and have found therapeutic usage,

prostaglandins are generally considered highly unstable.” (Ex.1004, col. 1 ll. 51 – 53; Ex. 1003, ¶ 119.) Goldman discloses

acid inhibitors other than the unstable prostaglandins, namelyH2 blockers and PPIs, that are “more efficacious.” (Ex.1005,

col. 5 ll. 64-65; Ex. 1003, ¶ 119.)

Pet. 21.

With respect to the challenged claims’ requirement for “an acid

inhibitor present in an amount effective to raise the gastric pH . . . to at least

3.5 upon the administration of one or more of said unit dosage forms,”

Petitioner contends that “Gimet discloses this limitation.” Pet. 22.

Petitioner contends that one of ordinary skill in the art “would know that a



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typical patient would have a pH in the stomach in a range of from about 1.5

to 3.5, and the POSA would know that the typical therapeutic effect of

known acid inhibitors is to increase the gastric pH of the patient following

the administration thereof.” Pet 23 (citing Ex. 1003 ¶ 130).

Patent Owner contends, among other things, that “Gimet and

Goldman seek solutions to two entirely different problems” in that “Gimet

seeks a formulation that would reduce the gastric ulcers that are caused by

chronic NSAID use . . . [while] Goldman discloses a formulation that can be

used to alleviate the discomfort associated with overindulgence of food and

alcohol.” Prelim Resp. 16– 17 (citing Ex. 1004, 1:10 – 63; Ex. 1005 1:10 – 16).

As in the challenge discussed above, Petitioner has not explained

adequately why one of ordinary skill in the art would have had a reason to

formulate Gimet’s tablet to increase gastric (i.e., stomach) and/or duodenal

pH to at least 3.5 in the first place, when Gimet explicitly teaches that the

enteric coating on its tablet “direct[s] the dissolution of the NSAID core in

the lower G.I. tract as opposed to the stomach.” Ex. 1004, 6:34– 36

(emphasis added). Moreover, Petitioner does not point us to any discussion

of gastric pH in Gimet (much less a discussion of pH as a factor in NSAID-

associated ulcerogenesis). To the extent Petitioner contends that one of

ordinary skill in the art “would know that a typical patient would have a pH

in the stomach in a range of from about 1.5 [up] to 3.5” (Pet 23 (citing Ex.

1003 ¶ 130)), we are not persuaded that Petitioner presents adequate support

in the record for this point. For example, Chiverton (discussed above)



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shows total twenty-four hour gastric pH and night-time gastric pH values

considerably below 3.5 in healthy volunteers in the absence of misoprostol

administration. See Ex. 1007, Figures 1 and 2.

Finally, to the extent Petitioner contends that Goldman provides “a

specific teaching, suggestion, and motivation to look to conventional

techniques for preparing medicament tablets as set forth in Remington . . .

thereby providing a design incentive to prepare or improve tablets via known

techniques including enteric and non-enteric coatings to yield predictable

results” (Pet. 22 (citing Ex. 1005, 6:26– 33; Ex. 1006, 1604, 1633; Ex. 1003

¶ 122)), we are not persuaded. Remington’s generic discussion of enteric

coatings adds little or nothing of relevance to Petitioner’s proposed

combination of Gimet and Goldman. As discussed above, Gimet explicitly

discloses an enteric coating which “aids in segregating the NSAID from the

prostaglandin and in directing the dissolution of the NSAID core in the

lower G.I. tract as opposed to the stomach.” Ex. 1004, 6:29– 30, 33 – 36.



likelihood of prevailing in its challenge to claim 1, or claims 2 – 5 or 7 – 23,

directly or indirectly dependent therefrom, on the basis of obviousness over

Gimet, Goldman, and Remington.



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D. Claims 1 – 5, 7 – 18, 21, and 22 — Asserted Obviousness

over Goldman, Remington, and Abe

1. Abe (Ex. 1039)

Abe teaches that famotidine “is a new, potent, highly selective H2-

receptor antagonist.” Ex. 1039, 541. According to Abe, oral administration

of famotidine “significantly increased the gastric pH and lowered the gastric

volume” and “[t]he mean gastric pH in the famotidine-treated group[] was in

the range of 5.7 – 7.2, which indicates that this drug effectively decreased

gastric acid secretion.” Id. at 543.2. Analysis

Claims 1 – 5, 7 – 18, 21, and 22 encompass dosage forms where the acid

inhibitor is an H2-blocker, e.g., famotidine, or a PPI, e.g., omeprazole, and

the NSAID is naproxen or piroxicam.

Petitioner contends “[i]n considering the dosage and therapeutic effect

upon administration of the acid inhibitor (e.g., famotidine) present in the unit

dosage forms of Goldman, a known method would be to look to related

literature studying the therapeutic effect of the particular drug . . . to provide

predictable results related to selecting and administering the drug.” Pet. 39

(citing Ex. 1003 ¶ 274). Petitioner contends that one of ordinary skill in the

art “would have been motivated to look to clinical studies showing results of

famotidine on gastric acid pH such as those shown in Abe to provide

predictable results of an increase in gastric acid pH associated with the

administration of the known acid inhibitor, famotidine.” Id. (citing Ex. 1003

¶ 275). Petitioner further contents that “Goldman provides . . . a specific



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teaching, suggestion, and motivation to look to conventional techniques for

preparing medicament tablets as set forth in Remington . . . , thereby

providing a design incentive to prepare or improve tablets via known

techniques including enteric and non-enteric coatings to yield predictable

results.” Id . at 40 (citing Ex. 1005, 6:26 – 33; Ex. 1006, 1604; Ex. 1003

¶¶ 276).

Patent Owner contends that “[n]othing in Goldman, Remington, or

Abe teaches the significance of the coordinated release of the immediate-

release acid inhibitor and delayed-release NSAID.” Prelim. Resp. 23.

We agree that Petitioner has not established that the teachings of

Goldman, Remington, and Abe would have given one of ordinary skill in the

art a reason to formulate a tablet with the structural and functional features

required by the challenged claims. Although Goldman discloses a

combination dosage form comprising an NSAID and the H2-blocker

famotidine (discussed above), Petitioner does not point to anything in

Goldman that describes or suggests adequately why one would have

prepared a composition as claimed, where the NSAID is coated and at least

some of the H2-blocker is not enteric-coated within the dosage form, for any

reason. Moreover, although Goldman incorporates Remington’s discussion

of oral solid dosage forms by reference (Ex. 1005, 6:26 – 33), Petitioner does

not identify anything in Goldman that points to any particular dosage form

among the many disclosed by Remington. Nor does Petitioner explain



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adequately how Abe could remedy the deficiencies discussed above in

relation to Goldman and Remington.



likelihood of prevailing in its challenge to claim 1, or claims 2 – 5, 7 – 18, 21,

and 22, directly or indirectly dependent therefrom, on the basis of

obviousness over Goldman, Remington, and Abe.

E. Claims 1, 5, and 6 — Asserted Obviousness over

Goldman, Remington, and Fitton

1. Fitton (Ex. 1048)

Fitton compares the effects of oral administration of the PPIs

pantoprazole and omeprazole on gastric acidity. Ex. 1048, 467.

2. Analysis

Claims 5 depends from claim 1, and recites that the acid inhibitor is a

PPI selected from a group including omeprazole and pantoprazole, while

claim 6 recites that the acid inhibitor is pantoprazole.

Petitioner contends that Goldman discloses “a unit dosage form

suitable for oral administration that comprises an NSAID and an acid

inhibitor (e.g., a PPI such as omeprazole)” (Pet. 56), thus, one of ordinary

skill in the art, “[i]n evaluating performance of the dosage form” (id.),

“would have been motivated to look to clinical studies showing results of

omeprazole on gastric acid pH such as those shown in Fitton.” Id. (citing

Ex. 1003 ¶¶ 395 – 96). In addition, according to Petitioner, an ordinary



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artisan “would have seen comparative results . . . that provide a motivation

and reasonable expectation of success to substitute pantoprazole for

omeprazole in the formulations of Goldman.” Id. (citing Ex. 1003 ¶ 397).

Petitioner further contends that one of ordinary skill in the art “would have

been motivated to employ conventional techniques for preparing

medicament tablets as set forth in Remington.” Id. at 56 – 57 (citing Ex. 1003

¶ 398).

Patent Owner contends, among other things, that “the deficiencies in

Petitioner’s argument about Goldman and Remington, discussed above,

remain applicable to [this] Ground” (Prelim. Resp. 24), and “[t]he addition

of Fitton does not cure these deficiencies” (id.).

We agree that Petitioner has not established that the teachings of

Goldman, Remington, and Fitton would have given one of ordinary skill in

the art a reason to formulate a tablet with the structural and functional

features required by the challenged claims. As discussed above, although

Goldman discloses a combination dosage form comprising an NSAID and

the PPI acid inhibitor omeprazole (discussed above), Petitioner does not

point to anything in Goldman that describes or suggests adequately why one

would have prepared a composition as claimed, where the NSAID is coated

and at least some of the H2-blocker is not enteric-coated within the dosage

form, for any reason. Moreover, although Goldman incorporates

Remington’s discussion of oral solid dosage forms by reference (Ex. 1005,

6:26 – 33), Petitioner does not identify anything in Goldman that points to



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any particular dosage form among the many disclosed by Remington. Nor

does Petitioner explain adequately how Fitton could remedy the deficiencies

discussed above in relation to Goldman and Remington.



likelihood of prevailing in its challenge to claim 1, or claims 5 and 6,

directly or indirectly dependent therefrom, on the basis of obviousness over

Goldman, Remington, and Fitton.

F. Motion to Seal Patent Owner’s Preliminary Response (Paper 15) was accompanied by

a Motion to File Under Seal its Preliminary Response and Exhibit 2011, an

associated exhibit (Paper 16, “Motion to Seal”), and a redacted version of

the Preliminary Response (Paper 13).

As we did not rely on the material Patent Owner sought to seal, we

decline to address the merits of the Motion to Seal. Patent Owner is

authorized to file a motion to expunge any material that it seeks to keep

confidential within thirty (30) days of the date of this decision, or within

thirty (30) days of a decision on rehearing, if rehearing is requested.

III. CONCLUSION

For the foregoing reasons, we are not persuaded that the Petition

establishes a reasonable likelihood that Petitioner would prevail in showing

claims 1 – 23 of the ’907 patent are unpatentable under 35 U.S.C. § 103(a).



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IV. ORDER

Accordingly, it is

ORDERED that the Petition is denied and no inter partes review is

instituted.



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For PETITIONER:

Amy LaValle

Rodney B. CarrollJerry C. Harris [email protected]

WICK PHILLIPS GOULD & MARTIN, [email protected]@wickphillips.com

For PATENT OWNER:

Ricardo RodriguezThomas Blinka

Dennis BennettStephen Hash

Lauren L. Stevens, Ph.DMargaret Sampson

COOLEY [email protected]

[email protected] [email protected]

[email protected] [email protected]

[email protected]





















pozen and horizon/hayman institution decision for '907 patent

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