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IPR2015-01241
Patent 6,926,907
IPR2015-01241
Patent 6,926,907
TABLE OF CONTENTS
I.
Introduction....................................................................................................1
II.
B.
C.
V.
VI.
B.
C.
Background ....................................................................................................5
A.
B.
B.
C.
D.
IPR2015-01241
Patent 6,926,907
B.
Claim 1: ...............................................................................................12
1.
2.
3.
4.
5.
C.
D.
E.
IPR2015-01241
Patent 6,926,907
2.
3.
4.
ii) said coating that does not release said NSAID unless
the pH of the surrounding medium is 3.5 or higher
surrounds said core; and............................................................18
5.
F.
G.
H.
1.
2.
B.
Claim 1: ...............................................................................................22
1.
2.
iii
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Patent 6,926,907
administration of one or more of said unit dosage forms; ........22
3.
4.
5.
C.
D.
E.
F.
G.
iv
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Patent 6,926,907
H.
I.
J.
K.
L.
M.
1.
2.
3.
4.
ii) said coating that does not release said NSAID unless
the pH of the surrounding medium is 3.5 or higher
surrounds said core; and............................................................29
5.
IPR2015-01241
Patent 6,926,907
N.
2.
O.
P.
Q.
1.
The pharmaceutical composition of any one of claims 1214, wherein said acid inhibitor is a proton pump inhibitor
and .............................................................................................32
2.
The pharmaceutical composition of any one of claims 1214, wherein said acid inhibitor is a proton pump inhibitor
and .............................................................................................33
2.
R.
S.
IPR2015-01241
Patent 6,926,907
14, wherein said acid inhibitor is an H2 blocker and ...............35
2.
T.
The pharmaceutical composition of any one of claims 1214, wherein said acid inhibitor is an H2 blocker and ...............37
2.
U.
V.
W.
IX.
1.
2.
B.
Claim 1: ...............................................................................................40
1.
vii
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Patent 6,926,907
suitable for oral administration to a patient, comprising: .........40
2.
3.
4.
5.
C.
D.
E.
F.
IPR2015-01241
Patent 6,926,907
G.
H.
I.
J.
K.
L.
M.
1.
2.
3.
4.
ii) said coating that does not release said NSAID unless
the pH of the surrounding medium is 3.5 or higher
surrounds said core; and............................................................49
5.
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Patent 6,926,907
wherein said one or more layers outside of said core do not
contain NSAID and are not surrounded by an enteric coating. ..........50
N.
2.
O.
P.
Q.
R.
1.
The pharmaceutical composition of any one of claims 1214, wherein said acid inhibitor is a proton pump inhibitor
and .............................................................................................52
2.
The pharmaceutical composition of any one of claims 1214, wherein said acid inhibitor is a proton pump inhibitor
and .............................................................................................54
2.
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Patent 6,926,907
X.
S.
T.
2.
B.
Claim 1: ...............................................................................................57
1.
2.
3.
4.
5.
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Patent 6,926,907
regardless of whether the pH of the surrounding medium
is below 3.5 or above 3.5. .........................................................59
XI.
C.
D.
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TABLE OF AUTHORITIES
Statutes
35 U.S.C. 102(b) .................................................................................................4, 5
35 U.S.C. 103(a) .................................................................................................4, 5
35 U.S.C. 311-319 ................................................................................................1
Regulations
37 C.F.R. 42.8(b)(3) ...................................................................................................3
37 C.F.R. 42.10(b) ..................................................................................................3
37 C.F.R. 42.100 et seq. ..........................................................................................1
37 C.F.R. 42.104 .....................................................................................................4
37 C.F.R. 42.15(a)...................................................................................................4
37 C.F.R. 42.6(c) .....................................................................................................5
37 C.F.R. 42.63(e)...................................................................................................5
37 C.F.R. 42.8 .........................................................................................................1
37 C.F.R. 42.8(b)(1) ................................................................................................1
37 C.F.R. 42.8(b)(2) ................................................................................................2
37 C.F.R. 42.8(b)(4) ................................................................................................3
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EXHIBIT LIST
Exhibit No.
Description
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
1012
1013
1014
IPR2015-01241
Patent 6,926,907
Exhibit No.
Description
1015
1016
1017
1018
1019
1020
1021
1022
1023
1024
1025
Oct. 20, 2004 Final Office Action, File History of the 907 Patent
1026
1027
Mar. 29, 2005 Notice of Allowance and Fee(s) Due, File History of
the 907 Patent
xv
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Exhibit No.
Description
1028
1029
1030
1031
1032
1033
1034
1035
xvi
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Patent 6,926,907
Exhibit No.
Description
1036
1037
1038
1039
1040
1041
1042
1043
1044
1045
1046
IPR2015-01241
Patent 6,926,907
Exhibit No.
Description
1047
1048
1049
1050
1051
1052
1053
1054
1055
xviii
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Exhibit No.
Description
1056
1057
xix
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Patent 6,926,907
I.
Introduction
The Coalition for Affordable Drugs VII LLC (CFAD or Petitioner)
respectfully requests inter partes review of claims 1-23 of U.S. Patent No.
6,926,907 (the 907 Patent) (Ex. 1001) in accordance with 35 U.S.C. 311-319
and 37 C.F.R. 42.100 et seq. The 907 Patent is assigned to Pozen Inc.
II.
Real Party-In-Interest
IPR2015-01241
Patent 6,926,907
HOF, and HCMF act, directly or indirectly, through HCM as the general partner
and/or investment manager of Credes, HOF, and HCMF. nXnP is a paid
consultant to HCM. Erich Spangenberg is the Manager and majority member of
nXnP. IPNav is a paid consultant to nXnP. Erich Spangenberg is the Manager and
majority member of IPNav. Other than HCM and J Kyle Bass in his capacity as
the Chief Investment Officer of HCM and nXnP and Erich Spangenberg in his
capacity as the Manager/CEO of nXnP, no other person (including any investor,
limited partner, or member or any other person in any of CFAD, Credes, HOF,
HCMF, HCM, HOM, HI, nXnP, or IPNav) has authority to direct or control (i) the
timing of, filing of, content of, or any decisions or other activities relating to this
petition or (ii) any timing, future filings, content of, or any decisions or other
activities relating to the future proceedings related to this petition. All of the costs
associated with this petition are expected to be borne by HCM, CFAD, Credes,
HOF, and/or HCMF.
B.
IPR2015-01241
Patent 6,926,907
addition, CFAD is aware of the following judicial and administrative matters
involving patents related to the 907 Patent: (1) Dr. Reddys Labs., Inc. v. Pozen
Inc., IPR2015-00802 (P.T.A.B.); (2) Horizon Pharma, Inc. v. Actavis Labs. FL,
Inc., 3:15-cv-03322 (D.N.J.); (3) Horizon Pharma, Inc. v. Dr. Reddys Labs., Inc.,
3:15-cv-03324 (D.N.J.); (4) Horizon Pharma, Inc. v. Lupin Ltd., 3:15-cv-03326
(D.N.J.); and (5) Horizon Pharma, Inc., v. Mylan Pharmas., Inc. 3:15-cv-03327
(D.N.J.).
C.
Back-Up Counsel
Jerry C. Harris, Jr. (Reg. No. 66,822)
jcharris@conleyrose.com
Rodney B. Carroll (Reg. No. 39,624)
rcarroll@conleyrose.com
Postal and Hand-Delivery Address:
Conley Rose, P.C.
5601 Granite Parkway, Suite 500
Plano, Texas 75024
(972) 731-2288 (phone)
(972) 731-2289 (fax)
Per 37 C.F.R. 42.8(b)(4), CFAD may be served at the above addresses for Lead
and Back-Up Counsel. CFAD consents to electronic service by e-mail. Per 37
C.F.R. 42.10(b), a Power of Attorney accompanies this Petition.
III.
Payment of Fees
The undersigned authorizes the Office to charge the fee required by 37 C.F.R.
IPR2015-01241
Patent 6,926,907
42.15(a) for this Petition to Deposit Account No. 50-1515.
IV.
CFAD certifies that the 907 Patent is available for inter partes review and that
CFAD is not barred or estopped from requesting inter partes review challenging
claims 1-23 of the 907 Patent on the grounds identified in this Petition.
B.
Ground 1: CFAD challenges claims 1, 7, 8, 12, 13, 22, and 23 of the 907
Patent and seeks a ruling that those claims are unpatentable under 35 U.S.C.
103(a) as obvious over Gimet (Ex. 1004) in view Chiverton (Ex. 1007). Gimet
and Chiverton are available as prior art under 35 U.S.C. 102(b).
Ground 2: CFAD challenges claims 1-5 and 7-23 of the 907 Patent and seeks
a ruling that those claims are unpatentable under 35 U.S.C. 103(a) as obvious
over Gimet in view of Goldman (Ex. 1005) and in further view of Remington (Ex.
1006). Gimet, Goldman, and Remington are available as prior art under 35 U.S.C.
102(b).
Ground 3: CFAD challenges claims 1-17, 21, and 22 of the 907 Patent and
seeks a ruling that those claims are unpatentable under 35 U.S.C. 103(a) as
obvious over Goldman in view of Remington and in further view of Abe
(Ex. 1039). Goldman, Remington, and Abe are available as prior art under 35
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Patent 6,926,907
U.S.C. 102(b).
Ground 4: CFAD challenges claims 1, 5, and 6 of the 907 Patent and seeks a
ruling that those claims are unpatentable under 35 U.S.C. 103(a) as obvious over
Goldman in view of Remington and in further view Fitton (Ex. 1048). Goldman,
Remington, and Fitton are available as prior art under 35 U.S.C. 102(b).
C.
CFAD relies upon the publications cited herein in support of Grounds 1-4.
CFAD also relies upon the Declaration of Leon Shargel, Ph.D., R.Ph. (Ex. 1003)
and the documents cited therein. Filed herewith are an Exhibit List and copies of
the references per 37 C.F.R. 42.63(e) and 37 C.F.R. 42.6(c).
V.
Background
A.
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Patent 6,926,907
Acid inhibitors refer to a group of agents that reduce gastric acid secretion and
gastric acidity. (Ex. 1003, 31.) Prostaglandins, H2 blockers, and proton pump
inhibitors (PPIs) are all types of acid inhibitors. (Id.) Since at least 1973,
prostaglandins have been known to inhibit gastric acid production. (Id.) In 1996,
misoprostol, a prostaglandin, was known to inhibit gastric acid secretion and was
approved for the treatment of gastric ulcer disease induced by NSAIDs. (Id.) In
1970, it was discovered that cimetidine, an H2 blocker, inhibited gastric acid
production. (Id.) Similarly, in the early 1980s, it was discovered that picoprazole,
a PPI, inhibited gastric acid production. (Id.) Omeprazole, another PPI, and its
inhibition of gastric action production, also was discovered in the early 1980s.
(Id.) In 1987, a group led by Gunnel Sundn separated esomeprazole, which is the
enantiopure (S)-isomer of omeprazole. (Id.)
Although NSAIDs provide certain therapeutic benefits, their tendency to
increase the incidence of gastric ulcers may limit their use. (Ex. 1003, 34.) In
order to avoid such limitations, NSAIDs have been used with acid inhibitors at
least as early as 1986. (Id.) For decades before that time, doctors had
recommended that patients take over-the-counter gastric acid neutralizers like
Maalox along with NSAIDs. (Id.) The literature is replete with combination
therapies that include NSAIDs for their therapeutic effects of reducing pain and
inflammation with acid inhibitors to address the side effects of the NSAIDs. (Id.)
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Patent 6,926,907
However, administration of separate drugs causes various patient compliance
issuespatients may forget or get confused about when to take each drug or how
much to take. (See Chen (Ex. 1018); see also id.)
Acid inhibitors have been combined with NSAIDs in a single tablet at least as
early as 1986. (See, e.g., Lukacsko (Ex. 1008), col. 3 ll. 13-18; see also Ex. 1003,
36.) For example, Dupui discloses a single tablet comprising both an NSAID
and an acid inhibitor. (Dupui (Ex. 1013), col. 1 ll. 11-20, 45-54) Depui recognizes
that such single tablet is [t]he most promising solution to the problem of healing
and preventing NSAID associated upper gastrointestinal problems. (Id. at col. 1
ll. 45-54.) Furthermore, the single tablet addresses the issue of patient compliance.
(Id. at col. 2 ll. 32-41; see also Ex. 1003, 36.)
A combination of an NSAID and an acid inhibitor is just one example of what
is called a combination therapy. (Ex. 1003, 37.) Combination therapy usually
consists of two or more active ingredients combined into a single entity. (Id.)
Through marketing of patented combination drug products, the pharmaceutical
companies can increase their revenue greatly by decreasing or hindering the
consumers access to known, tested, safe, and affordable drugs. (Id.)
Vimovo is a prime example. Vimovo is a combination therapy of naproxen
and esomeprazole magnesium. (Ex. 1003, 39.) Vimovos ingredients,
naproxen and esomeprazole magnesium, are available separately as generic drug
7
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products. (Id. at 45-51) Pozens affiliates, including Horizon Pharma USA
(Horizon) and AstraZeneca AB (AstraZeneca), currently market and sell
Vimovo. Horizon admits that the active pharmaceutical ingredients (APIs) in
Vimovo have been on the market . . . for many years. (Horizon Pharma plc
2014 Irish Statutory Accounts (Ex. 1022) at 35.) For this reason, Horizon resorts
to sales tactics to convince physicians to prescribeand pharmacists to dispense
Vimovo:
Another key part of our commercial strategy is to encourage physicians to
have their patients agree to fill prescriptions through our PrescriptionsMade-Easy (PME) [mail-order] specialty pharmacy program . . . .
[P]rescriptions filled through our PME program are . . . less likely to be
subject to the efforts of traditional pharmacies to switch a physicians
intended prescription of our products to a generic or over the counter
brand.
(Ex. 1022 at 5.) Horizon admits that sales of Vimovo may suffer [i]f we are
unsuccessful in convincing physicians to complete prescriptions through our PME
program or otherwise provide prescribing instructions prohibiting the substitution
of . . . generic naproxen and branded Nexium (esomeprazole) as a substitute.
(Ex. 1022, at 17 (emphasis added).) This is a common strategy when APIs are not
themselves patent worthy. (Ex. 1003, 40.) Nonetheless, by virtue of obtaining
the 907 Patent, Pozen and its affiliates have succeeded, thus far, in extending a
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Patent 6,926,907
monopoly on a long-known combination that should be available to the public.
(Id.)
The rewards for such an extension are considerable. Indeed, on January 1,
2014, the first day Horizon sold Vimovo, Horizon increased the list price for 60
Vimovo tablets to $959.04, or $15.98 per tablet, a 597% increase. (Wall Street
Journal (Ex. 1024).) On January 1, 2015, Horizon again increased the list price for
60 tablets, this time to $1,678.32, or $27.97 per tablet. (Id.) Currently, Vimovo
can be purchased for $26.46 per tablet. (Ex. 1003, 41.) In contrast, a similar
dosage of the two APIs of Vimovoesomeprazole magnesium and naproxen
can be purchased without a prescription for under $1.00 total. (Id.) In other
words, for the same APIs, the public must pay 30-40 times more for Vimovo.
Despite this enormous pricing disparity, Horizon has announced that it may effect
further price increases for [Vimovo] in 2015 and future periods in response to
future market conditions. (Ex. 1022, at 17.)
B.
The field of the 907 Patent is pharmacology. (Ex. 1003, 52-53.) A POSA
in that field at the time of the alleged invention of the 907 Patent, presumably
June 1, 2001, would have been a pharmacist, medical doctor, or pharmaceutical
scientist having a doctor of medicine degree, a doctor of pharmacy degree, or a
Ph.D. degree, or equivalent training or degree, and at least two years of practical
IPR2015-01241
Patent 6,926,907
experience or clinical research in pharmaceutical formulations. (Id.)
Alternatively, a POSA at the time of the alleged invention would have been a
pharmacologist or pharmacokineticist having a Ph.D. degree or equivalent training
or degree and at least two years of practical experience or clinical research in
pharmacology or pharmacokinetics. (Id.)
VI.
Claim Construction
A.
Claims 1, 4, 6, 12, 14, and 21 include the phrase unit dosage form. (Ex.
1001 col. 20 ll. 9-32, 39-41, 46-49, col. 21 ll. 1-10, 14-19, 39-40.) As issued,
claim 1 uses the phrase unit dose form, but corrects that phrase to unit dosage
form in a Certificate of Correction. (Id. at col. 20 l. 9; Certificate of Correction
(Ex. 1028) at 1.) The specification defines unit dosage form as a single entity
for drug administration. (Ex. 1001 col. 3 ll. 60-61.) Thus, the broadest
reasonable interpretation of unit dosage form in light of the specification of the
907 Patent means a single entity for drug administration. (Ex. 1003, 55.)
B.
Acid Inhibitor
Claims 1, 2, 5, 12, 14, 15, and 18 use the phrase acid inhibitor. (Ex. 1001
col. 20 ll. 12, 28, 34, 43, col. 21, ll. 9, 16, 18, 29.) The specification does not
explicitly define acid inhibitor but does state, [t]he term acid inhibitor refers
to agents that inhibit gastric acid secretion and increase gastric pH. (Ex. 1001 col.
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Patent 6,926,907
3 ll. 26-28.) In the context of claims 1, 2, 5, 12, 14, 15, and 18, as well as the
specification of the 907 Patent, the broadest reasonable interpretation of acid
inhibitor means an agent that hinders, prevents, or reduces the amount of gastric
acid. (Ex. 1003, 56.) Furthermore, under the broadest reasonable interpretation
in light of the specification of the 907 Patent, the acid inhibitor would include
prostaglandins, H2 blockers, and PPIs. (Id.)
C.
Coordinated Release
Claim 1 includes the phrase coordinated release. (Ex. 1001 col. 20 ll. 20-21.)
The specification equates a coordinated release with a sequential release:
All of the dosage forms are designed for oral delivery and provide for the
coordinated release of therapeutic agents, i.e., for the sequential release of
acid inhibitor followed by analgesic.
(Id. at col. 5 ll. 16-19.) Thus, the broadest reasonable interpretation of
coordinated release in light of the specification of the 907 Patent means
sequential release. (Ex. 1003, 57.)
D.
Per 37 C.F.R. 42.100(b), all remaining terms in claims 1-23 should be given
[their] broadest reasonable construction in light of the specification.
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Patent 6,926,907
VII. Ground 1: Gimet in View of Chiverton Renders Obvious Claims 1, 7, 8,
12, 13, 22, and 23
A.
Gimet teaches a unit dosage form suitable for oral 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. (Ex. 1003, 64.) In considering
the dosage and therapeutic effect upon administration of the acid inhibitor (e.g.,
misoprostol) present in the unit dosage form, a known method would be to look to
related literature studying the therapeutic effect of the particular drug (e.g.,
misoprostol) to provide predictable results related to administering the drug. (Id.)
Thus, a POSA 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 the known acid inhibitor, misoprostol. (Id.)
B.
Claim 1:
Gimet discloses this limitation. (Ex. 1003, 66.) Specifically, Gimet discloses
[t]he invention herein is directed to a pharmaceutical composition which is a
12
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core/mantle tablet and [a] method of treating inflammation comprising orally
administering to a patient . . . . (Ex. 1004, col. 3 ll. 8-14, col. 12 ll. 41-44; Ex.
1003, 67-68.)
2.
13
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effect on gastric pH for a dosage of from about 50 to about 500 mcg of misoprostol
could be readily determined by referencing prior art clinical studies such as
Chiverton. (Ex. 1003, 73.) Chiverton discloses that [m]isoprostol is a
prostaglandin E1 analogue that acts primarily through its antisecretory activity.
(Ex. 1007, at 404; Ex. 1003, 71.) Chiverton further discloses that misoprostol
can be dosed in an amount effective to raise gastric pH to at least 3.5. (Ex. 1007,
at 406, Fig. 2, Table 1; Ex. 1003, 71.) A POSA would have known that
misoprostol is a potent inhibitor of gastric acid secretion that can maintain
gastric pH at 4.0 or higher. (Ex. 1003, 74-75.)
3.
Gimet discloses this limitation. (Ex. 1003, 76.) Specifically, Gimet discloses
[i]f the inner core is piroxicam, the piroxicam can be present in a therapeutically
acceptable amount. (Ex. 1004, col. 4 ll. 34-39; Ex. 1003, 77.) Gimet discloses
that piroxicam is an NSAID. (Ex. 1004, col. 6 ll. 26-27; Ex. 1003, 77.) Gimet
further discloses that [t]he composition . . . provides an ease of delivery of an
NSAID for its therapeutic value such as the alleviation of inflammation. (Ex.
1004, col. 12 ll. 9-14; Ex. 1003, 77.)
4.
14
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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;
Gimet discloses this limitation. (Ex. 1003, 78.) Specifically, Gimet discloses
a tablet 16 that includes an NSAID inner core 18 surrounded by an enteric coating
20, the latter of 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, col. 6 ll. 24-36, Fig. 2; Ex. 1003, 79.)
A POSA would understand that a typical purpose associated with enteric
coatings is to delay release of an enterically-coated drug until after the drug has
exited the stomach. Also, the POSA would know that a typical patient would have
a pH in the small intestine after exiting the stomach of greater than about 3.5. (Ex.
1003, 80.) Thus, the POSA would have a rationale and a reasonable expectation
of success in preparing a combination therapy, coordinated release, unit dosage
form having a delayed release component, for example an enterically-coated drug
(e.g., NSAID) to prevent the release of the drug from the dosage form unless the
pH of the surrounding medium (e.g., portions of the G.I. tract after exiting the
stomach) is 3.5 or higher. (Ex. 1003, 81-82.)
5.
Gimet discloses this limitation. (Ex. 1003, 83.) Specifically, Gimet discloses
15
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Patent 6,926,907
that the mantle 22 consist[s] of a prostaglandin, which is orally available. (Ex.
1004, col. 1 l. 66 col. 2 l. 3 and col. 6 ll. 24-44; Ex. 1003, 84.)
(Ex. 1004, Fig. 2.) There is nothing, including an enteric coating, surrounding the
prostaglandin. (Ex. 1003, 84.) This means that the prostaglandin (i.e., the acid
inhibitor) is released immediately due to its direct contact with stomach fluids.
(Ex. 1003, 85.) In contrast to enteric coatings, a POSA would have understood
that a given dosage form may employ an uncoated drug and/or a drug coated with
non-enteric coatings, and that, following administration, such formulations may
release their drug quickly upon contact with the surrounding medium (e.g., about
immediate release upon entering the stomach). (Ex. 1003, 86.) Thus, the POSA
would have a rationale and a reasonable expectation of success in preparing a
combination therapy unit dosage form having an immediate release component, for
example an uncoated drug (e.g., acid inhibitor) and/or drug coated with a nonenteric coating that releases regardless of the pH of the surrounding medium. (Ex.
1003, 87.)
16
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Patent 6,926,907
C.
Claim 12:
Gimet discloses this limitation. (Ex. 1003, 93.) Specifically, Gimet discloses
that the pharmaceutical composition is a core/mantle tablet. (Ex. 1004, col. 3 ll. 817
IPR2015-01241
Patent 6,926,907
14; Ex. 1003, 94.)
2.
a single core and one or more layers outside of said single core,
wherein:
Gimet discloses this limitation. (Ex. 1003, 95.) Specifically, Gimet discloses
that [s]urrounding the coated inner core is a mantle 22 consisting of a
prostaglandin. (Ex. 1004, col. 6 ll. 24-44, Fig. 2; Ex. 1003, 96.)
3.
Gimet discloses this limitation. (Ex. 1003, 97.) Specifically, Gimet discloses
that the inner core is piroxicam. (Ex. 1004, col. 4 ll. 34-49; Ex. 1003, 98.)
4.
ii) said coating that does not release said NSAID unless the pH
of the surrounding medium is 3.5 or higher surrounds said
core; and
IPR2015-01241
Patent 6,926,907
of success in preparing a combination therapy, coordinated release, unit dosage
form having a delayed release component, for example an enterically-coated drug
(e.g., NSAID) to prevent the release of the drug from the dosage form unless the
pH of the surrounding medium (e.g., portions of the G.I. tract after exiting the
stomach) is 3.5 or higher. (Ex. 1003, 102.)
5.
iii) said acid inhibitor is in said one more layers outside said
core.
Claim 22:
19
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1.
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Patent 6,926,907
114.)
VIII. Ground 2: Gimet in View of Goldman in Further View of Remington
Renders Obvious Claims 1-5 and 7-23
A.
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Patent 6,926,907
obtain the predictable analgesic effect of said NSAIDs. (Ex. 1003, 120.) It
would have been obvious for a POSA to choose from those identified solutions and
have a reasonable expectation of success in treating pain, inflammation, and other
symptoms with an NSAID while preventing or reducing the undesirable side
effects of the NSAID. (Ex. 1003, 121.) Furthermore, Goldman provides the
POSA with a specific teaching, suggestion, and motivation to look to conventional
techniques for preparing medicament tablets as set forth in Remington and further
incorporates by reference the disclosure of Remington (Ex. 1005, 122.), thereby
providing a design incentive to prepare or improve tablets via known techniques
including enteric and non-enteric coatings to yield predictable results. (Ex. 1005,
col. 6 ll. 26-33; Ex. 1006, at 1604, 1633; Ex. 1003, 122.)
B.
Claim 1:
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range of from about 1.5 to about 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 administration thereof. (Ex. 1003, 130.) Thus, the POSA
would have a rationale and reasonable expectation of success in preparing a
combination therapy unit dosage form having an effective amount of a known acid
inhibitor to raise the gastric pH of a patient to at least 3.5 upon the administration
of one or more unit dosage forms containing the known acid inhibitor. (Ex. 1003,
131.) Further, due to the claim language of one or more of said unit dosage
forms, multiple dosage forms may be administered to achieve the desired effect.
(Ex. 1003, 133.) Thus, the POSA would have a rationale and a reasonable
expectation of success in providing the appropriate dose, including administration
of multiple dosage forms, as needed, to raise the pH to a desired level consistent
with pharmacological effects associated with the known acid inhibitor. (Id.)
3.
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5.
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such as famotidine. (Ex. 1005, col. 5 ll. 9-31; Ex. 1003, 152.) A POSA would
have been motivated to combine Goldman with Gimet as described above. (Ex.
1003, 154.) Furthermore, a POSA would have been motivated to replace
Gimets prostaglandin with Goldmans famotidine because doing so would be a
substitution of one known element for another to obtain predictable results. (Ex.
1003, 155.)
E.
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F.
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(Ground 1 at VII(D); Ex. 1003, 167-69.)
I.
27
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176.) A POSA would have been motivated to combine Goldman with Gimet as
described above. (Ex. 1003, 177.) Furthermore, a POSA would have been
motivated to replace Gimets NSAID with Goldmans NSAID, naproxen, in the
disclosed amount because doing so would be a substitution of one known element
for another to obtain predictable results and because, as shown in Goldman, 200
mg to 500 mg was a known therapeutic dosage range for naproxen. (Ex. 1003,
178.)
K.
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(Ex. 1003, 182.)
L.
Claim 12:
a single core and one or more layers outside of said single core,
wherein:
ii) said coating that does not release said NSAID unless the pH
of the surrounding medium is 3.5 or higher surrounds said
core; and
iii) said acid inhibitor is in said one more layers outside said
core.
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13. (Ground 1 at VII(F); Ex. 1003, 197-99.)
N.
Claim 14:
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provides a POSA with a rationale, e.g., a specific teaching, suggestion and
motivation, to look to conventional techniques for preparing medicament tablets as
set forth in Remington and further incorporates by reference the disclosure of
Remington. (Ex. 1003, 202.)
2.
wherein said outer layer of said tablet is surrounded by a nonenteric film coating that releases said acid inhibitor upon
ingestion by patient.
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209.) Specifically, Goldman discloses a composition containing a PPI such as
omeprazole. (Ex. 1005, col. 5 ll. 9-31; Ex. 1003, 210.) A POSA would have
been motivated to combine Goldman with Gimet as described above. (Ex. 1003,
211.) Furthermore, a POSA would have been motivated to replace Gimets
prostaglandin with Goldmans PPI because doing so would be a substitution of one
known element for another to obtain predictable results. (Ex. 1003, 212.)
P.
Claim 16:
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2.
Claim 17:
33
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discloses a composition containing a PPI such as omeprazole. (Ex. 1005, col. 5 ll.
9-31; Ex. 1003, 225.) A POSA would have been motivated to combine Goldman
with Gimet as described above. (Ex. 1003, 226.) Furthermore, a POSA would
have been motivated to replace Gimets prostaglandin with Goldmans PPI
because doing so would be a substitution of one known element for another to
obtain predictable results. (Ex. 1003, 227.)
2.
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R.
Claim 18: The pharmaceutical composition of any one of claims 714, wherein said acid inhibitor is an H2 blocker.
Claim 19:
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been motivated to combine Goldman with Gimet as described above. (Ex. 1003,
240.) Furthermore, a POSA would have been motivated to replace Gimets
prostaglandin with Goldmans H2 blocker because doing so would be a
substitution of one known element for another to obtain predictable results. (Ex.
1003, 241.)
2.
Claim 20:
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limitation of claim 20.
1.
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pH of the surrounding medium would be 5 or greater. (Ex. 1003, 255.) Thus,
Gimets NSAID would not be released until the pH of the surrounding medium
was 5 or greater. (Ex. 1003, 256-58.)
U.
Claim 22:
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2.
Goldman teaches a unit dosage form suitable for oral administration that
comprises an NSAID and an acid inhibitor (e.g., an H2 receptor blocker such as
famotidine). (Ex. 1003, 273.) In 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 (e.g., famotidine) to provide
predictable results related to selecting and administering the drug. (Ex. 1003,
274.) Thus, a POSA 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. (Ex. 1003, 275.)
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Furthermore, Goldman provides the POSA with a specific teaching,
suggestion, and motivation to look to conventional techniques for preparing
medicament tablets as set forth in Remington and further incorporates by reference
the disclosure of Remington, thereby providing a design incentive to prepare or
improve tablets via known techniques including enteric and non-enteric coatings to
yield predictable results. (Ex. 1005, col. 6 ll. 26-33; Ex. 1006, at 1604, 1633; Ex.
1003, 276.)
B.
Claim 1:
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teaching, suggestion and motivation, for a combination therapy oral unit dosage
form comprising an H2 receptor blocking drug as an acid inhibitor, for example
famotidine from 5 to 40 mg per dose. (Ex. 1003, 283.) The POSA would
understand that a gastric acid inhibitor would be expected upon administration to
have a therapeutic effect on gastric pH. (Ex. 1003, 284.) Furthermore, the
POSA would understand that the therapeutic effect on gastric pH for the 5 to 40
mg of famotidine could be readily determined by referencing prior art clinical
studies such as Abe. (Ex. 1003, 285.)
Abe discloses that famotidine can be dosed in an amount effective to raise
gastric pH to at least 3.5. (Ex. 1039, at 541-43, Table 2, Ex. 1003, 286.) Abe
further discloses that [t]he mean gastric pH in the famotidine-treated groups was
in the range of 5.7-7.2, which indicates that the drug effectively decreased gastric
secretion. (Ex. 1039, at 543, Ex. 1003, 287-88.)
3.
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4.
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By definition, enteric coatings are those which remain intact in the stomach
. . . to delay the release of drugs which . . . may cause nausea or bleeding
by irritating the gastric mucosa . . . Thus, many modern enteric coatings are
those which remain undissociated in the low pH environment of the
stomach, but readily ionize when the pH rises to about 4 or 5.
(Ex. 1006, at 1637.) Thus, Remington teaches that the acid inhibitor of Goldman
is released first in the low pH of the stomach and that the release of the NSAID
does not occur until after the enteric coating has ionized at a pH of about 4 or 5.
(Ex. 1006, at 1637; Ex. 1003, 296-97.)
5.
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medium (e.g., about immediate release upon entering the stomach). (Ex. 1003,
301.) Thus, the POSA would have a rationale and a reasonable expectation of
success in preparing a combination therapy unit dosage form having an immediate
release component, for example an uncoated drug (e.g., acid inhibitor) and/or drug
coated with a non-enteric coating that releases regardless of the pH of the
surrounding medium. (Ex. 1003, 302.)
C.
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E.
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that piroxicam is a COX-2 inhibitor.
H.
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17-20; Ex. 1003, 321.)
K.
Claim 12:
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327.)
2.
a single core and one or more layers outside of said single core,
wherein:
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disclosed remainder of the drug being the claimed NSAID present in said core.
(Ex. 1003, 335.)
4.
ii) said coating that does not release said NSAID unless the pH
of the surrounding medium is 3.5 or higher surrounds said
core; and
iii) said acid inhibitor is in said one more layers outside said
core.
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Remington, which Goldman incorporates by reference. (Ex. 1005, col. 5 ll. 9-31;
Ex. 1003, 342.) Remington discloses that the tablets can contain an outer,
unprotected drug. (Ex. 1006, at 1637; Ex. 1003, 343.) Thus, Remingtons cited
description refers to the disclosed unprotected drug being the claimed acid
inhibitor in said one more layers outside said core. (Ex. 1003, 344.)
M.
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350.) Also, because the outer drug is unprotected, it can be deemed not to be
surrounded by an enteric coating. (Ex. 1003, 351.)
N.
Claim 14:
wherein said outer layer of said tablet is surrounded by a nonenteric film coating that releases said acid inhibitor upon
ingestion by patient.
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Specifically, Goldman discloses that the tablets can be prepared as described in
Remington, which Goldman incorporates by reference. (Ex. 1005, col. 6 ll. 26-33;
Ex. 1003, 361.) Remington discloses that the tablets can include film coating
that imparts the same general characteristics as sugar coating, namely to protect
the drug from its surrounding environment and increase the ease by means of
which the product can be ingested. (Ex. 1006, at 1604, 1633; Ex. 1003, 362.)
Thus, Remingtons cited description refers to a non-enteric film coating that
releases said acid inhibitor upon ingestion by the patient. (Ex. 1003, 363-65.)
O.
Claim 16:
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discloses a composition containing a PPI such as omeprazole. (Ex. 1005, col. 5 ll.
9-31; Ex. 1003, 370.)
2.
Claim 17:
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1.
Claim 18: The pharmaceutical composition of any one of claims 714, wherein said acid inhibitor is an H2 blocker.
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18. (Ex. 1003, 384.) Specifically, Goldman discloses a composition containing
an H2 blocker such as famotidine or a PPI such as omeprazole. (Ex. 1005, col. 5
ll. 9-31; Ex. 1003, 385.)
S.
Claim 22:
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administering to a patient suffering from the symptoms of over- overindulgence a
combination pharmaceutical composition comprising a therapeutically effective
amount of an analgesic and a gastric acid inhibiting effective amount of a proton
pump inhibitor wherein the therapeutically effective amount of analgesic is . . .
naproxen from 200 to 500 mg per dose . . . in combination with an effective
amount of a proton pump inhibitor selected from the group consisting of
omeprazole from 60 to 500 mg per dose . . . . (Ex. 1005, col. 9 ll. 6-27; Ex. 1003,
392.)
X.
Goldman teaches a unit dosage form suitable for oral administration that
comprises an NSAID and an acid inhibitor (e.g., a PPI such as omeprazole). In
evaluating performance of the dosage form, a POSA would have been motivated to
look to clinical studies showing results of omeprazole on gastric acid pH such as
those shown in Fitton. (Ex. 1003, 395-96.) In considering Fittons clinical
studies, a POSA also would have seen comparative results (e.g., a comparison of
omeprazole and pantoprazole) that provide a motivation and reasonable
expectation of success to substitute pantoprazole for omeprazole in the
formulations of Goldman. (Ex. 1003, 397.) Furthermore, as noted previously for
Ground 3, the POSA further would have been motivated to employ conventional
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techniques for preparing medicament tablets as set forth in Remington. (Ex. 1003,
398.)
B.
Claim 1:
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compounds within the PPI class in a given formulation. Further, the POSA tasked
with evaluating and selecting individual compounds from the known drug class
(e.g., PPIs) would be readily motivated to reference prior art clinical studies such
as Fitton. (Ex. 1003, 406-07.) Fitton discloses that 40 mg of omeprazole would
raise the median 24h intragastric pH to 4.0. Ex. 1048, at 467,Table I; Ex. 1003,
408.) Thus, a POSA would have understood that increasing the dose to 60 mg of
omeprazole would raise the median 24h intragastric pH to 4.0 or higher. (Ex.
1048, at 467,Table I; Ex. 1003, 409-10.)
3.
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5.
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success in substituting individual compounds within the PPI class in a given
formulation. (Ex. 1003, 431.) Further, the POSA tasked with evaluating and
selecting individual compounds from the known drug class (e.g., PPIs) would be
motivated to reference prior art clinical studies such as Fitton. (Ex. 1003, 432.)
D.
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Respectfully submitted,
/Amy E. LaValle/
Amy E. LaValle (Reg. No. 51,092)
Jerry C. Harris, Jr. (Reg. No. 66,822)
Rodney B. Carroll (Reg. No. 39,624)
Conley Rose, P.C.
5601 Granite Parkway, Suite 500
Plano, Texas 75024
(972) 731-2288 (phone)
(972) 731-2289 (fax)
alavalle@conleyrose.com
jcharris@conleyrose.com
rcarroll@conleyrose.com
Counsel for Petitioner
Coalition for Affordable Drugs VII LLC
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CERTIFICATE OF SERVICE
Pursuant to 37 C.F.R. 42.6(e), I hereby certify that on May 21, 2015 a copy
of the foregoing PETITION FOR INTER PARTES REVIEW was provided via
FedEx, overnight delivery, to the Patent Owner by serving the correspondence
address of record for the 907 Patent:
Steven L. Highlander
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
Austin, Texas 78746
/Amy E. LaValle/
Lead Counsel for Petitioner
Coalition for Affordable Drugs VII LLC
62