UNITED STATES PATENT AND TRADEMARK OFFICE
`
`________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________________
`
`DR. REDDY’S LABORATORIES S.A. AND
`DR. REDDY’S LABORATORIES, INC.
`Petitioners
`
`
`v.
`
`
`INDIVIOR UK LIMITED.
`Patent Owner
`
`________________________
`
`
`U.S. PATENT NO. 9,687,454
`
`SUBLINGUAL AND BUCCAL FILM COMPOSITIONS
`
`Case No. IPR2019-00328
`________________________
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 9,687,454
`
`
`
`TITLE:
`
`Mail Stop PATENT BOARD
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`
`
`________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________________
`
`DR. REDDY’S LABORATORIES S.A. AND
`DR. REDDY’S LABORATORIES, INC.
`Petitioners
`
`
`v.
`
`
`INDIVIOR UK LIMITED.
`Patent Owner
`
`________________________
`
`
`U.S. PATENT NO. 9,687,454
`
`SUBLINGUAL AND BUCCAL FILM COMPOSITIONS
`
`Case No. IPR2019-00328
`________________________
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 9,687,454
`
`
`
`TITLE:
`
`Mail Stop PATENT BOARD
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`
`
`
`
`Table of Contents
`
`Page
`
`I.
`
`INTRODUCTION ......................................................................................... 1
`
`II. REQUIREMENTS FOR INTER PARTES REVIEW UNDER 37 C.F.R.
`§ 42.104 ........................................................................................................... 3
`
`
`
` Grounds for Standing ............................................................................ 3 A.
`
`
`
` B.
`
`Identification of Challenge .................................................................... 3
`
`III. TECHNOLOGY BACKGROUND .............................................................. 3
`
`
`
` A.
`
`
`
` B.
`
`
`
` C.
`
`Buprenorphine and Naloxone ................................................................ 3
`
`Suboxone® Tablets ............................................................................... 4
`
`Role of Buffers In Controlling the pH of Suboxone ® Tablets ............ 5
`
`IV. OVERVIEW OF THE ’454 PATENT ......................................................... 6
`
`
`
` A.
`
`
`
` B.
`
`
`
` C.
`
`Challenged Claims ................................................................................ 6
`
`The Delaware Court Invalidated Several Claims of the ’832 Patent .... 7
`
`Patent Owner Resumed Prosecution of the ’454 Patent After the
`Delaware Court Decision ...................................................................... 8
`
`V.
`
`THE ASSERTED PRIOR ART PATENTS AND PUBLICATIONS ....11
`
`
`
` A.
`
`
`
` B.
`
`
`
` C.
`
`
`
` D.
`
`
`
` E.
`
`Euro-Celtique (Ex. 1007) ....................................................................11
`
`Fuisz (Ex. 1008) ..................................................................................12
`
`Suboxone® PDR (Ex. 1009) ..............................................................12
`
`EMEA (Ex. 1010)................................................................................13
`
`FDA IIG Database (Ex. 1011).............................................................13
`i
`
`
`
`
`
`
`
`VI. PERSON OF ORDINARY SKILL IN THE ART ....................................14
`
`VII. THE FDA IIG DATABASE AND THE EMEA QUALIFY AS
`PRINTED PUBLICATIONS ......................................................................14
`
`
`
` A.
`
`The FDA IIG Database Is a Printed Publication .................................14
`
`1.
`
`2.
`
`3.
`
`The IIG Database Was Available as of December 2005 ..........15
`
`The IIG Database Was Both Indexed and Catalogued. ............18
`
`POSAs Would Have Known of FDA’s IIG Database and Had
`the Relevant Means to Access It. ..............................................19
`
`
`
` B.
`
`The EMEA Qualifies as a Printed Publication ....................................22
`
`VIII. CLAIM CONSTRUCTION ........................................................................24
`
`IX. DETAILED GROUNDS FOR UNPATENTABLIILTY: CLAIMS 1-3
`AND 5-14 ARE OBVIOUS OVER EURO-CELTIQUE AND FUISZ IN
`VIEW OF THE SUBOXONE® PDR, EMEA, AND THE FDA IIG
`DATABASE ..................................................................................................25
`
`
` A POSA Would Have Been Motivated to Make Films Based on the A.
`Existing Suboxone® Tablet Formulation ...........................................25
`
`1.
`
`2.
`
`3.
`
`Euro-Celtique motivated a POSA to make an oral film dosage
`form of Suboxone® tablets using the techniques disclosed in
`Fuisz. .........................................................................................26
`
`A POSA would have been motivated to copy the acidic buffer
`in Suboxone® tablets. ...............................................................27
`
`Patent Owner is collaterally estopped from contesting that a
`POSA would have been motivated to copy the Suboxone®
`tablet’s buffer and pH and/or make a bioequivalent film version
`of Suboxone® tablets. ...............................................................32
`
`
`
`ii
`
`
`
`
`
`
`
`
` A POSA Would Have Had a Reasonable Expectation of Success in B.
`Making Films That Were Bioequivalent to Suboxone® Tablets ........35
`
`
`
` C.
`
`Patent Owner Conceded That a POSA Would Have Had a Motivation
`to Formulate a Film Dosage Form That Was Bioequivalent to
`Suboxone® Tablets and Would Have Had a Reasonable Expectation
`of Success ............................................................................................37
`
`
`
` D.
`
`Independent Claim 1 ...........................................................................41
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`Euro-Celtique discloses the preamble. ......................................41
`
`Euro-Celtique discloses “about 40 wt % to about 60 wt % of a
`water-soluble polymer matrix” [1(a)] .......................................41
`
`Euro-Celtique discloses “about 2mg to about 16 mg of
`buprenorphine or a pharmaceutically acceptable salt thereof”
`[1(b)]. ........................................................................................42
`
`Euro-Celtique discloses “about 0.5 mg to about 4 mg of
`naloxone or a pharmaceutically acceptable salt thereof” [1(c)].
` ...................................................................................................43
`
`Euro-Celtique and the Suboxone® PDR individually and in
`combination disclose “an acidic buffer” [1(d)].........................43
`
`Euro-Celtique teaches a film that is “mucoadhesive to the
`sublingual mucosa or the buccal mucosa” [1(e)]. ....................44
`
`Euro-Celtique and the Suboxone® PDR individually and in
`combination disclose a “weight ratio of
`[buprenorphine]:[naloxone] [of] about 4:1.” [1(f)] ..................45
`
`Euro-Celtique in combination with the FDA IIG database or
`alternatively routine experimentation discloses a “weight ratio
`of [buffer]:[buprenorphine] is from 2:1 to 1:5” (element 1(g)).
` ...................................................................................................45
`
`iii
`
`
`
`
`
`
`
`9.
`
`Euro-Celtique in combination with the EMEA disclose the
`pharmacokinetic parameters in element 1(h). ...........................47
`
`
`
` E.
`
`Dependent Claims 2-3 and 5-14 ..........................................................48
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`Euro-Celtique in combination with the FDA IIG database or
`alternatively routine experimentation discloses a “weight ratio
`of [buffer]:[buprenorphine] is from 1:1 to 1:5” (claim 2) ......48
`
`Euro-Celtique in combination with the FDA IIG database or
`alternatively routine experimentation discloses a “weight ratio
`of [buffer]:[buprenorphine] is from 1.4:1 to 1:3” (claim 3) ...48
`
`Euro-Celtique in combination with Fuisz discloses a “weight
`ratio of [buprenorphine]:[polymer]of from 1:3 to 1:11.5”
`(claim 5) ....................................................................................49
`
`Euro-Celtique in combination with Fuisz discloses a “weight
`ratio of [buprenorphine]:[polymer][of] about 1:3.” (claim 6) .51
`
`Euro-Celtique discloses a film comprising “about 48.2 wt % to
`about 58.6 wt % of the water-soluble polymeric matrix” (claim
`7) ...............................................................................................51
`
`Euro-Celtique discloses a film comprising “about 48.2 wt % of
`the water-soluble polymeric matrix” (claim 8) .........................52
`
`Euro-Celtique discloses a film “wherein the water-soluble
`polymer matrix comprises a polyethylene oxide polymer alone
`or in combination with a hydrophilic cellulosic polymer” (claim
`9) ...............................................................................................52
`
`Euro-Celtique discloses a film “wherein the hydrophilic
`cellulosic polymer is hydroxypropyl cellulose,
`hydroxylpropylmethyl cellulose, or a combination thereof”
`(claim 10) ..................................................................................53
`
`iv
`
`
`
`
`
`9.
`
`Euro-Celtique discloses a film “wherein the hydrophilic
`cellulosic polymer is hydroxylpropylmethyl cellulose” (claim
`11) .............................................................................................53
`
`10. Euro-Celtique discloses a film “wherein the weight ratio of
`(d):(b) is from about 1:1 to 1:5; wherein the weight ratio of
`(b):(a) is from about 1:3 to about 1:11.5; and wherein the film
`comprise about 48.2 wt% to about 58.6 wt % of the water-
`soluble polymer matrix” (claim 12) ..........................................54
`
`11. Euro-Celtique discloses “[a] method of treating opioid
`dependence … comprising sublingually or buccally
`administering the mucoadhesive film of claim 1 to a sublingual
`or buccal mucosal tissue of the patient …” (claim 13) .............55
`
`12. Euro-Celtique in combination with the FDA IIG database or
`alternative routine experimentation discloses a “weight ratio of
`[buffer]:[buprenorphine] is from 2:1 to 1:1” (claim 14) .........55
`
`
`
` F.
`
`Secondary Considerations Do Not Support Nonobviousness .............56
`
`X.
`
`THE § 325(d) FACTORS FAVOR INSTITUTION .................................58
`
`XI. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8 ..............................61
`
`
`
` A.
`
`
`
` B.
`
`
`
` C.
`
`Real Parties-in-Interest ........................................................................61
`
`Related Matters ....................................................................................61
`
`Lead and Backup Counsel ...................................................................62
`
`XII. SERVICE INFORMATION .......................................................................63
`
`XIII. PAYMENT OF FEES .................................................................................63
`
`XIV. CONCLUSION ............................................................................................63
`
`
`
`v
`
`
`
`
`
`I.
`
`
`
`INTRODUCTION
`
`Dr. Reddy’s Laboratories S.A. and Dr. Reddy’s Laboratories, Inc.
`
`(“Petitioners”) petition for Inter Partes Review (“IPR”) of claims 1-3, 5-14 (the
`
`“challenged claims”) of U.S. Patent No. 9,687,454 (the “’454 patent,” Ex. 1001).
`
`These claims are generally directed toward a film dosage form of the prior art
`
`Suboxone®
`
`tablet—a sublingual tablet containing the active ingredients
`
`buprenorphine and naloxone. (Ex. 1001, 1:65-2:65.) According to the
`
`specification, Patent Owner claims to have “discovered” using a buffer to control
`
`the pH of the film dosage form “to provide[] a system in which the desired
`
`release and/or absorption of the components [i.e., the buprenorphine and
`
`naloxone] is bioequivalent to that of a similar Suboxone® tablet.” (Id., 12:13-
`
`25.)
`
`The ’454 patent descends from U.S. Patent No. 8,475,832 (the “’832
`
`patent,” Ex. 1005). The patents have identical specifications and are directed
`
`toward the same alleged invention. On June 3, 2016, the United States District
`
`Court for the District of Delaware held certain claims of the ’832 patent invalid
`
`as obvious in view of the prior art reference Euro-Celtique and other prior art that
`
`disclosed the properties of Suboxone® tablets. See Reckitt Benckiser Pharms.,
`
`Inc. v. Watson Labs., Inc., 2016 WL 3186659 (D. Del. June 3, 2016) (Ex. 1006).
`
`The Court found that the prior art:
`
`
`
`1
`
`
`
`
`
`- Taught that Suboxone® tablets: “included an acidic buffer of sodium
`citrate and citric acid….” (Id., 17.)
`
`- “[I]nstructed a person of skill in the art to make pharmaceutical films
`containing buprenorphine and, optionally (but preferably), naloxone.”
`(Id.)
`
`- Taught that “[a] skilled artisan would have copied the Suboxone®
`tablet’s buffer and its pH in creating a film dosage form of
`buprenorphine and naloxone.” (Id., 21.)
`
`- Taught all of the pharmacokinetic (“pK”) ranges in claims 15-19 and
`that “[f]ormulating a dosage form to achieve specific pharmacokinetic
`values was routine and formulating orally dissolvable films designed
`for sublingual mucosal absorption was disclosed in Euro-Celtique.”
`(Id., 24.)
`
`
`Patent Owner did not appeal any of these findings to the Federal Circuit.
`
`The invalidity ruling from the Delaware case applies with equal force to
`
`the challenged claims of the ’454 patent. The sole independent claim of the ’454
`
`patent is directed toward a “mucoadhesive film” that contains the active
`
`ingredients buprenorphine and naloxone. Like the invalidated claims of the ’832
`
`patent, the ’454 patent claims require a buffer and a pharmacokinetic profile for
`
`buprenorphine and naloxone that is bioequivalent to Suboxone® tablets. For the
`
`reasons set forth in more detail below, the Board should find the challenged
`
`
`
`2
`
`
`
`
`
`claims of the ’454 patent obvious just like the Delaware court found the ’832
`
`claims obvious.
`
`II. REQUIREMENTS FOR INTER PARTES REVIEW UNDER 37
`C.F.R. § 42.104
`
` Grounds for Standing A.
`Petitioners certify that the ’454 patent is available for IPR and that
`
`Petitioners are not barred or estopped from requesting this review. Patent Owner
`
`filed its waiver of service in the related district court litigation on December 7,
`
`2017, which is less than one year from the filing of this Petition. See e.g.,
`
`Brinkmann Corp. v. A&J Manuf., LLC, IPR2015-00056, Paper No. 10, 6-7
`
`(P.T.A.B. March 23, 2015).
`
`Identification of Challenge
`
`B.
`
`Petitioners request that the Patent Trial and Appeal Board (the “Board”)
`
`institute a trial for IPR of claims 1-3 and 5-14 of the ’454 patent, and cancel those
`
`claims as unpatentable. This Petition contains a single ground: claims 1-3 and 5-
`
`14 are unpatentable as obvious over Euro-Celtique (Ex. 1007) and Fuisz (Ex.
`
`1008) in view of the Suboxone® PDR (Ex. 1009), EMEA (Ex. 1010), and the
`
`FDA IIG Database (Ex. 1011, 9-411) under pre-AIA 35 U.S.C. § 103.
`
`III. TECHNOLOGY BACKGROUND
` Buprenorphine and Naloxone A.
`
`Buprenorphine is an opioid agonist that was first discovered in the mid-
`
`1960s and is used to treat opioid dependence and chronic pain. (Ex. 1003, ¶ 16.)
`3
`
`
`
`
`
`
`Buprenorphine is extensively broken down in both the gastrointestinal (“GI”)
`
`tract and the liver prior to absorption into systemic circulation (known as “first
`
`pass effects”). (Id. ¶ 17.) As a result, when swallowed, the efficacy of
`
`buprenorphine may be compromised. (Id.) As an alternative, by the early 1980s,
`
`sublingual (under the tongue) administration of buprenorphine was reported to be
`
`effective, as the sublingual uptake of buprenorphine is rapid and minimizes first-
`
`pass effects. (Id.)
`
`Naloxone is a well-known opioid antagonist that reverses or prevents the
`
`effects of opioid agonists. (Id., ¶ 18.)
`
`Suboxone® Tablets
`
`B.
`
`In 2003, Reckitt Benckiser (a predecessor-in-interest to Patent Owner)
`
`began selling a sublingual tablet containing buprenorphine and naloxone under
`
`the tradename Suboxone®. (Ex. 1010, 37; Ex. 1009, 3-4.) When administered
`
`properly, the buprenorphine is delivered transmucosally1, avoiding first-pass
`
`effects. (Ex. 1003, ¶ 19.) The naloxone, however, is not significantly absorbed
`
`transmucosally and is not bioavailable from the GI tract because of first-pass
`
`effects. (Id., ¶ 19; Ex. 1010, 6.) This is intentional—as the naloxone is not
`
`
`1 Transmucosal here refers to the route of administration (through a mucous
`
`membrane) versus the location of administration, such as sublingually (under the
`
`tongue).
`
`
`
`4
`
`
`
`
`
`intended to be absorbed when administered orally, but rather is used as a
`
`deterrent “to stop people from injecting (‘shooting up’) SUBOXONE® tablets.”
`
`(Ex. 1003, ¶ 19; Ex. 1025, 20; Ex. 1012, 26.)
`
`As of 2009, Suboxone® sublingual tablets were available in two dosage
`
`strengths, both of which maintained a 4:1 drug ratio of buprenorphine to
`
`naloxone: 2 mg/0.5 mg and 8 mg/2 mg. (Ex. 1003, ¶ 20; Ex. 1009, 3.)
`
`
` Role of Buffers In Controlling the pH of Suboxone ® Tablets C.
`Absorption of a drug across a mucosal membrane is primarily dependent
`
`on the solubility and permeability of the drug. (Ex. 1003, ¶ 21; Ex. 1013, 18, 36,
`
`53-55, 57-59.) Solubility generally refers to the degree to which a drug dissolves
`
`in a particular environment. (Ex. 1003, ¶ 21.) Permeability, the movement of a
`
`drug across biological membranes (e.g., sublingual mucosa), is affected by the
`
`lipophilicity of the drug molecule. (Id.)
`
`Both solubility and permeability of a drug are often dependent on the pH
`
`of the environment. (Id. ¶ 23; Ex. 1013, 18, 36, 53-55, 57-59.) The pH of an
`
`environment is a measure of the level of acidity or basicity. (Ex. 1003, ¶ 23.)
`
`Buffers can be used to control the pH of a drug formulation. (Id. ¶ 31.) Buffers
`
`usually contain mixtures of a weak acid or weak base and one of its salts (i.e.
`
`conjugate base or conjugate acid). (Id.) Buffers will maintain a constant pH
`
`even when small amounts of acid or base are added to the solution. (Id. ¶ 31; Ex.
`
`1013, 47.) A POSA would have understood that the combination of citric acid
`5
`
`
`
`
`
`
`(weak acid) and sodium citrate (conjugate base) in Suboxone® tablets was a
`
`known buffering system that was effective in an acidic pH range of 3.0 to 6.2.
`
`(Ex. 1003, ¶ 108; Ex. 1014, 23.)
`
`IV. OVERVIEW OF THE ’454 PATENT
`The ’454 patent descends from the ’832 patent and shares a specification
`
`with the ’832 patent. (Compare Ex. 1001 with Ex. 1005; Ex. 1003, ¶ 84.) The
`
`’832 patent was filed as Application No. 12/537,571 on August 7, 2009 (the
`
`“’571 application”). (Ex. 1005, 1). Both the ’454 patent and ’832 patent are
`
`directed toward the same alleged invention and the claims contain substantially
`
`similar limitations. (Ex. 1003 ¶¶ 84-87.)
`
`
` Challenged Claims A.
`The claims at issue in this Petition are claims 1-3 and 5-14. Claim 1 is the
`
`only independent claim. It reads:
`
`[1.preamble] An oral, self-supporting, [] mucoadhesive film comprising:
`
`[1.a] about 40 wt % to about 60 wt % of a water-soluble polymeric matrix;
`
`[1.b] about 2 mg to about 16 mg of buprenorphine or a pharmaceutically
`
`acceptable salt thereof;
`
`[1.c] about 0.5 mg to about 4 mg of naloxone or a pharmaceutically acceptable
`
`salt thereof; and
`
`[1.d] an acidic buffer;
`
`
`
`6
`
`
`
`
`
`[1.e] wherein the film is mucoadhesive to the sublingual mucosa or the buccal
`
`mucosa;
`
`[1.f] wherein the weight ratio of (b):(c) is about 4:1;
`
`[1.g] wherein the weight ratio of (d):(b) is from 2:1 to 1:5; and
`
`[1.h] wherein application of the film on the sublingual mucosa or the buccal
`
`mucosa results in differing absorption between buprenorphine and naloxone, with
`
`a buprenorphine Cmax from about 0.624 ng/ml to about 5.638 ng/ml and a
`
`buprenorphine AUC from about 5.431 hr*ng/ml to about 56.238 hr*ng/ml; and a
`
`naloxone Cmax from about 41.04 pg/ml to about 323.75 pg/ml and a naloxone
`
`AUC from about 102.88 hr*pg/ml to about 812.00 hr*pg/ml.
`
`
`Dependent claims 2, 3, 7, 8, 12, and 14 further narrow the ratios and ranges in
`
`claim 1. Dependent claims 5, 6, and 12 introduce limitations directed toward a
`
`weight ratio of buprenorphine-to-polymer (the “(b):(a) ratios”). Dependent
`
`claims 9, 10, and 11 specify particular types of polymers for the “water soluble
`
`polymer component.” Dependent claim 13 recites a method of treating opioid
`
`dependence in a patient by administering the film of claim 1.
`
`B.
`
`
`The Delaware Court Invalidated Several Claims of the ’832
`Patent
`
`The Delaware court already resolved the central obviousness issue
`
`presented in this Petition and held that it would have been obvious to a POSA to
`
`copy the Suboxone® tablet’s buffer and pH in creating a film dosage form of the
`7
`
`
`
`
`
`
`drug. (Ex. 1006, 21.) The Delaware court found that several claims in the ’832
`
`patent were obvious in light of Euro-Celtique (Ex. 1007), Birch (Ex. 1015),
`
`Cassidy (Ex. 1016), and prior art
`
`that described
`
`the formulation and
`
`pharmacokinetic properties of Suboxone® tablets. (Ex. 1006, 16-17, 21.) The
`
`Court concluded: “In light of the overall evidence, I conclude that a skilled
`
`artisan would have copied the Suboxone® tablet’s buffer and its pH in
`
`creating a film dosage form of buprenorphine and naloxone.” (Id., 21
`
`(emphasis added).) In addition, the Delaware court found that the combination of
`
`Euro-Celtique and EMEA rendered the pK limitations in claim 15-19 obvious.
`
`(Id., 24.) Patent Owner did not appeal the Delaware Court’s decision to the
`
`Federal Circuit and is therefore estopped from contesting these issues in this
`
`proceeding. See Section IX.A.3.2
`
`C.
`
`
`Patent Owner Resumed Prosecution of the ’454 Patent After the
`Delaware Court Decision
`
`While the case in Delaware was pending, Patent Owner filed and quickly
`
`abandoned four continuation applications from 2013 through 2015. (Ex. 1003,
`
`2 Claims 15-19 of the ’832 patent were also canceled in IPR2014-00325 filed by
`
`BioDelivery Sciences International. See BioDelivery Sciences Int’l Inc. v. RB
`
`Pharm. Ltd, IPR2014-00325, Paper No. 43, 27 (P.T.A.B. June 30, 2015). The
`
`Federal Circuit summarily affirmed. See RB Pharm. Ltd. v. BioDelivery
`
`Sciences Int’l, Inc., 667 Fed. Appx. 997 (Fed. Cir. 2016).
`
`
`
`8
`
`
`
`
`
`¶ 78.) In the four applications that preceded the application that led to the ’454
`
`patent, Patent Owner responded to only one Office Action, but eventually
`
`abandoned that application. Each of the other three applications was abandoned
`
`shortly after the issuance of a first Office Action.
`
`The application that led to the ’454 patent was pending when the Delaware
`
`court issued its decision. (See Ex. 1002.) On September 9, 2016, three months
`
`after the Delaware trial decision, Patent Owner canceled the pending claims and
`
`submitted new claims. (Id., 615-19.) The “new” claims were just a reordered
`
`collection of claim elements from the invalidated ’832 patent claims. (Ex. 1003,
`
`¶ 86.)
`
`In addition to the claim amendments, the Patent Owner provided
`
`arguments in response to the obviousness rejection. (Ex. 1002, 619-22.) Patent
`
`Owner argued that Euro-Celtique (called “Oksche” during prosecution) provided
`
`“no teaching or suggestion that the buffer has any impact on the efficacy of the
`
`formulation” or that the “weight ratio of buffer to buprenorphine must be from
`
`2:1 to 1:5….” (Id., 620-621.) Patent Owner did not tell the Examiner that the
`
`Delaware court had concluded that a POSA would have been motivated to copy
`
`the acidic buffer in Suboxone® tablets. (See id.) Further, Patent Owner filed a
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`terminal disclaimer prior to the issuance of the ’454 patent to overcome the
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`double patenting rejection over the ’832 patent claims. (Id., 179, 623.) Patent
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`
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`9
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`
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`Owner did not attempt to substantively argue that the amended claims were
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`patentably distinct from the ’832 patent claims. (Id., 622.)
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`Two weeks after the amendment, on September 23, 2016, the Examiner
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`issued the Final Rejection rejecting the new claims as obvious in view of Euro-
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`Celtique. (Id., 173-180.) Patent Owner responded to the rejection on December
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`13, 2016. (Id., 163-171.) In the Response, Patent Owner further amended the
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`claims and provided arguments. (Id.) Patent Owner argued, among other things,
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`that the results presented in Examples 6-8 of the specification produced results
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`that were “unexpected in view of pH partition theory.” (Id., 169.) Patent Owner
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`argued under pH partition theory, “[o]ne would expect that lowering the local pH
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`from 6.5 to about 2-4 would lower the absorption of both buprenorphine and
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`naloxone.” (Id.) Patent Owner did not tell the Examiner that the Delaware court
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`rejected that same argument six months earlier. (Ex. 1006, 22 (“A [POSA]
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`would have credited specific data demonstrating
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`that buprenorphine
`
`is
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`transmucosally absorbed at pH values within or near the claimed range [i.e.,
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`acidic pH values of 3 to 3.5] over the general implications of pH Partition
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`Theory.”).)
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`The Examiner issued another Office Action rejecting all claims on January
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`3, 2017. (Ex. 1002, 77-83.) After an interview concerning a proposed
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`amendment by the Examiner and certain non-substantive changes to the claims,
`
`
`
`10
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`
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`
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`the Examiner issued a Notice of Allowance and Fees Due. (Id., 8-10.) No
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`reasons for allowance were given.
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`V. THE ASSERTED PRIOR ART PATENTS AND PUBLICATIONS
`In this Petition, Petitioners assume the challenged claims of the ’454 patent
`
`are entitled to a priority date of August 7, 2009—the filing date of the ’571
`
`application.3
`
`
` Euro-Celtique (Ex. 1007) A.
`Euro-Celtique is international patent publication number WO 2008/025791
`
`A1 entitled “Buprenorphine-Wafer for Drug Substitution Therapy.” (Ex. 1007,
`
`1.) Euro-Celtique was before the Patent Office during prosecution of the ’454
`
`patent and was referred to as “Oksche.” Euro-Celtique was published on March
`
`6, 2008, and is prior art under pre-AIA 35 U.S.C. § 102(b). (Ex. 1003, ¶ 38; Ex.
`
`1007, 1.) Euro-Celtique instructs a POSA to make pharmaceutical films
`
`containing buprenorphine and naloxone. (Ex. 1003, ¶ 47; Ex. 1007, 25; Ex.
`
`1006, 17.) Euro-Celtique further discloses the target pharmacokinetic parameters
`
`for buprenorphine that are necessary to make a sublingual film that is
`
`bioequivalent to Suboxone® tablets. (Ex. 1003, ¶¶ 47-48; Ex. 1007, 9.)
`
`
`3 In IPR2019-00329, Petitioners contest that the challenged claims are entitled to
`
`the August 7, 2009 priority date.
`
`
`
`11
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`
`
`
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`Fuisz (Ex. 1008)
`
`B.
`
`Fuisz is international patent publication number WO 2003/030883. (Ex.
`
`1008.) It was published on April 17, 2003, and is prior art under pre-AIA 35
`
`U.S.C. § 102(b). (Ex. 1003, ¶ 50; Ex. 1008, 1.) Euro-Celtique specifically
`
`identifies Fuisz as “standard technology” for making pharmaceutical thin films
`
`containing buprenorphine and naloxone:
`
`Another possible technology in order to provide the afore-described
`pharmaceutical dosage forms of buprenorphine and preferably
`naloxone is described in WO 03/030883 [Fuisz] …. The films are
`prepared according to standard technology and the active agents are
`displaced thereon and therein as described in WO 03/030883.
`
`(Ex. 1003, ¶ 145; Ex. 1007, 14; see also Ex. 1048 ¶¶ 76-77.)
`
`Suboxone® PDR (Ex. 1009)
`
`C.
`
`The 2004 Physician’s Desk Reference disclosed information regarding
`
`Suboxone® sublingual tablets distributed by Reckitt-Benckiser Pharmaceuticals,
`
`Inc. (the “Suboxone® PDR”). (Ex. 1003, ¶¶ 53-56; Ex. 1009, 3.) The
`
`Suboxone® PDR was published in 2004, and is prior art under pre-AIA 35
`
`U.S.C. § 102(b). (Ex. 1003, ¶ 53; Ex. 1009, 1; see also Ex. 1048 ¶¶ 71-75.) The
`
`Suboxone® PDR discloses
`
`that Suboxone® contained buprenorphine
`
`hydrochloride and naloxone hydrochloride. (Ex. 1003, ¶ 54, Ex. 1009, 3.) The
`
`Suboxone® PDR further discloses that the Suboxone® sublingual tablet includes
`
`
`
`12
`
`
`
`
`
`the well-known buffer of citric acid and sodium citrate. (Ex. 1003, ¶ 54; Ex.
`
`1009, 3.)
`
`
` EMEA (Ex. 1010) D.
`The European Medicines Agency
`
`Initial Marketing-Authorisation
`
`Document for Suboxone® Tablets, Scientific Discussion (the “EMEA”) was
`
`published on October 19, 2006, and is prior art under pre-AIA 35 U.S.C.
`
`§ 102(b). (Ex. 1003, ¶ 57; Ex. 1010; Ex. 1022, 2.) The EMEA discloses the
`
`pharmacokinetic profile of Suboxone® tablets. (Ex. 1003, ¶ 60, Ex. 1010, 12-
`
`16.) The data were gathered from a study based on the sublingual administration
`
`of buprenorphine, in the range of 4 mg to 24 mg, in combination with naloxone
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`(at a 4:1 ratio) in non-dependent opiate users. (Ex. 1003, ¶ 60; Ex. 1010 at 12.)
`
`FDA IIG Database (Ex. 1011)
`
`E.
`
`The 2006 FDA Inactive Ingredient Database (FDA IIG Database) was an
`
`electronic database made available and downloadable on the FDA website. (Ex.
`
`1011; Ex. 1003, ¶¶ 62-68.) Ex. 1011 is the version of the FDA IIG Database
`
`available to a POSA as of February 6, 2006, and is prior art to the ’454 patent
`
`under pre-AIA 35 U.S.C. § 102(b). See infra section VII.A. The FDA IIG
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`database disclosed that citric acid and sodium citrate were included in approved
`
`sublingual tablet drug products in amounts of up to 5.92 mg and 2.68 mg
`
`respectively. (Ex. 1003, ¶ 68; Ex. 1011, 40, 175.)
`
`
`
`13
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`
`
`
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`VI. PERSON OF ORDINARY SKILL IN THE ART
`For the purposes of this proceeding, a POSA with respect to the technology
`
`disclosed in the ’454 patent would include a person who possesses a Master’s or
`
`Ph.D. in pharmaceutical sciences, formulation chemistry, or a related field, plus a
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`number of years of relevant experience in developing drug formulations. (Ex.
`
`1003, ¶ 71.) As part of a collaborative team working to develop a new drug
`
`product, the POSA would have consulted as needed with others possessing the
`
`skills that are typically employed in drug development and manufacturing. (Id.)
`
`VII. THE FDA IIG DATABASE AND THE EMEA QUALIFY AS
`PRINTED PUBLICATIONS
`
` The FDA IIG Database Is a Printed Publication A.
`“An electronic publication, including an online database or Internet
`
`publication (e.g. discussion group, forum, digital video, and social media post), is
`
`considered a ‘printed publication’ within the meaning of … pre-AIA 35 U.S.C.
`
`102(a) and (b) provided the publication was accessible to persons concerned with
`
`the art to which the document relates.” MPEP § 2128(II)(A) (citing In re Wyer,
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`655 F.2d 221, 227 (C.C.P.A. 1981)). To qualify as a printed publication, the
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`Federal Circuit evaluates (1) “whether the reference was sufficiently indexed or
`
`catalogued” so that it would have been locatable by a POSA or (2) whether a
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`POSA would have been “independently aware” of the publication. See Blue
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`Calypso, LLC v. Groupon, Inc., 815 F.3d 1331, 1348-49 (Fed. Cir. 2016). The
`
`
`
`14
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`
`
`
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`Federal Circuit recently re-affirmed that it has “interpreted § 102 broadly, finding
`
`that even relatively obscure documents qualify as prior art so long as the relevant
`
`public has a means of accessing them.” See GoPro, Inc. v. Contour IP Holding
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`LLC, No. 2017-1936, 2018 WL 5660650, at *2 (Fed. Cir. Nov. 1, 2018) (citing
`
`Jazz Pharm., Inc. v. Amneal Pharm., LLC, 895 F.3d 1347, 1354-60 (Fed. Cir.
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`2018)).
`
`1.
`
`The IIG Database Was Available as of December 2005
`
`For at least the past fifteen years, FDA has maintained a public database of
`
`inactive ingredients (excipients) to guide the development of drug formulations,
`
`referred to as the Inactive Ingredient Database or Inactive Ingredients Guide
`
`(“IIG”). (Ex. 1033, 19.) The IIG contains FDA-compiled data on every
`
`excipient that has been successfully used in an FDA-approved drug product. (Ex.
`
`1011, 5-8.) When a drug product is approved with a new excipient (or a greater
`
`amount of an excipient that has previously been included in another approved
`
`product), FDA adds information about the excipient(s) into the database,
`
`including the name of the excipient, the maximum amount in which it was
`
`included in the approved drug product, and the route of administration for which
`
`the drug product was approved. (Ex. 1003, ¶ 64; Ex. 1011, 6; Ex. 1041, 33) By
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`2005, the IIG was available on FDA’s website and was updated every three
`
`months. (Ex. 1011, 8.)
`
`
`
`15
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`
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`
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`Exhibit 1011 (Butler Affidavit) contains printouts of FDA’s IIG website
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`and the downloadable database itself, as they existed more than a year before the
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`alleged 2009 priority date. Butler Exhibit A (Ex. 1011, 5-8) provides “true and
`
`accurate copies of printouts of Internet Archive’s records of the HTML files …
`
`for the URLs and the dates specified in the footer of the printout (HTML) ….”
`
`(Id., 1.) The printouts of the HTML files of Butler Exhibit A (Exhibit 1011, 5-8)
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`were obtained automatically by “crawler” software programs that “surf the Web
`
`and automatically store copies of web files, preserving [them] as they exi
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