$vrx apriso '688 ipr insituted

Download $VRX Apriso '688 IPR Insituted

Post on 13-Apr-2018

224 views

Category:

Documents

0 download

Embed Size (px)

TRANSCRIPT

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    1/32

    [email protected] Paper: 13571-272-7822 Entered: June 10, 2016

    UNITED STATES PATENT AND TRADEMARK OFFICE

    ____________

    BEFORE THE PATENT TRIAL AND APPEAL BOARD

    ____________

    GENERICO, LLC andFLAT LINE CAPITAL, LLC,

    Petitioners,

    v.

    DR. FALK PHARMA GMBH,Patent Owner.

    ____________

    Case IPR2016-00297

    Patent 8,865,688 B2

    ____________

    Before LORA M. GREEN, GRACE KARAFFA OBERMANN, and

    ELIZABETH M. ROESEL,Administrative Patent Judges.

    ROESEL,Administrative Patent Judge.

    DECISION

    Institution ofInter PartesReview37 C.F.R. 42.108

    mailto:[email protected]:[email protected]:[email protected]
  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    2/32

    IPR2016-00297Patent 8,865,688 B2

    2

    Petitioners, GeneriCo, LLC and Flat Line Capital, LLC, filed a

    Petition seeking inter partesreview of claims 1 and 16 of U.S. Patent No.

    8,865,688 B2 (Ex. 1001, the 688patent). Paper 1 (Pet.). Patent

    Owner, Dr. Falk Pharma GmbH, filed a Preliminary Response. Paper 11

    (Prelim. Resp.).

    We have jurisdiction under 35 U.S.C. 314(a), which provides that an

    inter partesreview may by authorized only if the information presented in

    the Petition and the Preliminary Response shows that there is a reasonable

    likelihood that Petitioners would prevail with respect to at least one of the

    claims challenged in the Petition. Applying that standard, we institute an

    inter partesreview of claims 1 and 16 of the 688 patent for the reasons and

    on the ground set forth below.

    Our findings of fact and conclusions of law are based on the record

    developed thus far, before the filing of Patent Owners Response. This is

    not a final decision as to the patentability of any challenged claim. Any final

    decision will be based on the full record developed during the trial.

    I. BACKGROUND

    A. Related Matters

    Pursuant to 37 C.F.R. 42.8(b)(2), the parties identify the following

    district court actions in which the 688 patent is being asserted: Salix

    Pharmaceuticals, Inc. et al. v. Novel Laboratories, Inc., Nos. 1-15-cv-00027

    and 1-15-cv-00213 (D. Del.) (consolidated) and Salix Pharmaceuticals, Inc.et al v. Mylan Pharmaceuticals, Inc. et al., No. 1-15-cv-00109 (N.D.

    W.Va.). Pet. 1; Paper 6 (Patent Owners mandatory notices). According to

    Patent Owner, Salix Pharmaceuticals, Ltd. is the original assignee and

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    3/32

    IPR2016-00297Patent 8,865,688 B2

    3

    currently the exclusive licensee of the 688 patent and is a real party-in-

    interest. Prelim. Resp. 2 n.1; Paper 6.

    B. Information Relied UponPetitionerspatentability challenges are primarily based on the

    following references:

    S. S. Davis, The Design and Evaluation of Controlled Release

    Systems for the Gastrointestinal Tract, 2 J.CONTROLLED RELEASE2738

    (1985), Ex. 1009 (Davis-1985);

    Salix Announces Statistically Significant Top-Line Results of a Unique

    Granulated Mesalamine Product Registration Study in Ulcerative Colitis

    (September 2007),

    http://www.sec.gov/Archives/edgar/containers/fix021/1009356/00011931

    2507195530/dex992.htm,Ex. 1012 (Sept. 2007 Press Release);

    XIFAXANTrials Initiated in C. difficile-Associated Diarrhea,

    Irritable Bowel Syndrome and Hepatic Encephalopathy. New Article

    [online] EndoNurse, 12 January 2006, Ex. 1014 (Endonurse);

    Bogentoft, EP 0 040 590 A2, published November 25, 1981, Ex. 1015

    (EP590);

    Y. Marakhouski et al.,A Double-blind Dose-escalating Trial

    Comparing Novel Mesalazine Pellets with Mesalazine Tablets in Active

    Ulcerative Colitis, 21 ALIMENT PHARMACOL.THER. 133140 (2005),

    Ex. 1024 (Marakhouski); andM. Brunner et al., Gastrointestinal Transit and Release of 5-

    aminosalicylic Acid from 153Sm-labelled Mesalazine Pellets vs. Tablets in

    Male Healthy Volunteers, 17 ALIMENT.PHARMACOL.THER. 11631169

    (2003), Ex. 1025 (Brunner).

    http://www.sec.gov/Archives/edgar/containers/fix021/1009356/00011931%202507195530/dex992.htmhttp://www.sec.gov/Archives/edgar/containers/fix021/1009356/00011931%202507195530/dex992.htmhttp://www.sec.gov/Archives/edgar/containers/fix021/1009356/00011931%202507195530/dex992.htmhttp://www.sec.gov/Archives/edgar/containers/fix021/1009356/00011931%202507195530/dex992.htmhttp://www.sec.gov/Archives/edgar/containers/fix021/1009356/00011931%202507195530/dex992.htm
  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    4/32

    IPR2016-00297Patent 8,865,688 B2

    4

    In addition, Petitioners rely on the Declaration of George A. Digenis,

    Ph.D., Ex. 1002 (Digenis Decl.).

    C. Asserted Grounds of UnpatentabilityPetitioners assert that claims 1 and 16 are unpatentable under

    35 U.S.C. 103(a) based upon the following grounds:

    Reference(s)

    1 Sept. 2007 Press Release, Endonurse, and Davis-1985

    2 Sept. 2007 Press Release, Endonurse, Davis-1985, and EP590

    3Sept. 2007 Press Release, Endonurse, and Davis-1985, and

    Marakhouski

    4 Sept. 2007 Press Release, Endonurse, and Davis-1985, and Brunner

    II. ANALYSIS

    A. The 688 Patent (Ex. 1001)

    The 688 patent relates to a method of maintaining the remission of

    ulcerative colitis (UC)by administration of a once-daily dosage of

    granulated mesalamine.1 Ex. 1001, Abstract, 1:15. The 688 patent explains

    that UC is an inflammatory disease of the colonic mucosa and that the goal

    of treatment is to induce and maintain remission of the disease. Id.at 1:15

    17, 1:4950. According to the 688 patent,maintenance medications must

    be taken for a prolonged period of time to enable subjects to stay in

    remission. Id.at. 1:5559.

    1 Other names for mesalamine include 5-aminosalicylic acid, 5-ASA, andmesalazine. See, e.g., Ex. 1001, 5:36, cols. 2125 (Example 7, Tables 59);

    Prelim. Resp. 3.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    5/32

    IPR2016-00297Patent 8,865,688 B2

    5

    The 688 patent acknowledges that oral mesalamine formulations are

    known in the art for treating UC. Id.at 1:602:3. The patent identifies

    problems with prior art delivery systems, including: premature release, the

    possibility of dose dumping, and sensitivity to conditions that increase

    gastric pH and cause premature release of mesalamine (e.g., ingestion of a

    meal), id.at 2:38. According to the 688 patent, bowel diseases, such as

    UC, are not adequately controlled using currently available formulations. Id.

    at 2:1215.

    For a description of the granulated mesalamine formulations, the 688

    patent refers to three earlier patents or publications. Id.at 2:911, 10:4752

    (incorporating by reference U.S. Patent/Publication Nos. 6,277,412;

    6,551,620; and 2003/0133983).

    The 688 patent describes two Phase III clinical studies in which 562

    subjects (study 1: 305 subjects; study 2: 257 subjects) were randomized 2:1

    to receive either a 1.5 gram granulated mesalamine formulation or placebo

    once daily in the morning for six months. According to the 688 patent, inboth studies, the proportion of subjects who remained relapse-free at six

    months was greater for the granulated mesalamine formulation than for

    placebo. Id.at 17:135 (Example 5, Table 2); see also id.at Figures 13

    (patient disposition and results of study 1); 6:437:25 (summarizing results

    of phase 3 studies discussed in Examples); 16:125 (Example 2); 25:14

    33:64 (Examples 811, Tables 1014).

    The 688 patent also describes pharmacokinetic studies comparing

    absorption of mesalamine granules: (1) administered once and twice daily,

    and (2) administered under fed and fasted conditions. Id.at 7:2631; id.at

    14:5815:5 (Example 1evaluation of effect of a high fat meal intake on

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    6/32

    IPR2016-00297Patent 8,865,688 B2

    6

    absorption of mesalamine granules); id.at 16:4767 (Example 4Effect of

    Food on Absorption and Disposition of Granulated Mesalamine

    Formulations); id.at 17:3821:15 (Example 6comparison of once daily

    (QD) to twice daily (BID) administration). Based on these studies, the 688

    patent concludes that granulated mesalamine formulation can be

    administered once- or twice-daily, id.at 7:2628, without regard to food,

    id.at 15:45, and that the rate and extent of absorption of mesalamine and

    its metabolite were not affected by a high-fat meal, id.at 16:6364.

    B. Illustrative Claim

    The 688 patent includes 16 claims. The Petition challenges claims 1

    and 16, which are directed to a method of maintaining the remission of

    ulcerative colitis in a subject. Ex. 1001, 34:1022, 35:417.

    Claim 1 is reproduced below with paragraph breaks and bracketed

    lettering added for ease of reference:

    1. A method of maintaining the remission of ulcerative

    colitis in a subject comprising[a] administering to the subject a granulated mesalamineformulation comprising four capsules each comprising 0.375 g

    of granulated mesalamine once per day in the morning, without

    food, wherein:

    [b] said method maintains remission of ulcerative colitisin a subject for a period of at least 6 months of treatment;

    [c] remission is defined as a DAI score of 0 or 1;[d] the granulated mesalamine formulation is not

    administered with antacids; and

    [e] wherein 85% to 90% of the mesalamine reaches theterminal ileum and colon.

    Id.at 34:1022. Claim 16 is identical to claim 1, except that claim 16 recites

    an additional step, advising the subject that granulated mesalamine should

    not be taken with antacids, and claim 16 omits the indefinite article a in

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    7/32

    IPR2016-00297Patent 8,865,688 B2

    7

    the phrase, a granulated mesalamine formulationin paragraph [a].

    Compareid., with id.at 35:417. The parties present the same contentions

    for claim 16 as they present for claim 1. See, e.g., Pet. 39; Prelim. Resp. 21

    42. Accordingly, for purposes of this decision, it is not necessary to

    consider claim 16 separately from claim 1, and we generally confine our

    discussion to claim 1.

    C. Claim Construction

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

    their broadest reasonable interpretation in light of the specification of the

    patent in which they appear. 37 C.F.R. 42.100(b);In re Cuozzo Speed

    Techs., LLC, 793 F.3d 1268, 127579 (Fed. Cir. 2015), cert. granted sub

    nom. Cuozzo Speed Techs. v. Lee, 136 S. Ct. 890 (mem.) (2016). Claim

    terms are given their ordinary and customary meaning, as 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).

    [C]laim terms need only be construed to the extent necessary to

    resolve the controversy. Wellman, Inc. v. Eastman Chem. Co., 642 F.3d

    1355, 1361 (Fed. Cir. 2011)) (citing Vivid Techs., Inc. v. Am. Sci. &Engg,

    Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)).

    Petitioners propose constructions for the terms, without food and

    granulated mesalamine formulation. Pet. 1724. Patent Owner disagrees

    with Petitionersproposed constructions and proposes an alternative

    construction for granulated mesalamine formulation. Prelim. Resp. 17

    20. We determine that it is not necessary to provide an express construction

    for those terms for purposes of this decision.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    8/32

    IPR2016-00297Patent 8,865,688 B2

    8

    We determine further that it is not necessary to provide an explicit

    construction for any claim term at this stage of the proceeding.

    C. Person of Ordinary Skill in the ArtAt this stage, we consider the asserted references to reflect the level of

    ordinary skill in the art at the time of the invention. See Okajima v.

    Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (the prior art, itself, can

    reflect the level of skill in the art). On the present record and based upon the

    stated qualifications of Petitioners declarant, Ex. 1002 210, Ex. A, we

    consider Petitioners declarant qualified to opine from the viewpoint of a

    person of ordinary skill in the art.

    D. Obviousness Grounds 3 and 4

    Petitioners contend that claims 1 and 16 are unpatentable as obvious

    over the Sept. 2007 Press Release, Endonurse, and Davis-1985 in view of

    Marakhouski. Pet. 2539 (Ground 1); Pet. 4447 (addressing Ground 3 and

    incorporating discussion of Ground 1). Alternatively, Petitioners contend

    that claims 1 and 16 are unpatentable as obvious over the Sept. 2007 Press

    Release, Endonurse, and Davis-1985 in view of Brunner. Pet. 4750

    (addressing Ground 4 and incorporating discussion of Ground 1). We

    address Grounds 3 and 4 together because Petitioners rely on Marakhouski

    and Brunner for essentially the same teachings.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    9/32

    IPR2016-00297Patent 8,865,688 B2

    9

    1. Petitioners Cited References

    The Sept. 2007 Press Releaseis Salixs2announcement of the

    successful completion of two Phase III trials evaluating a granulated

    mesalamine formulation for the maintenance of remission of UC. Ex. 1012,

    1. The press release discloses that a greater proportion of subjects dosed

    once-a-day with 1.5 grams of granulated mesalamine remained relapse-free

    over 6 months of treatment than patients dosed with placebo. Id. The press

    release describes the evaluated formulation as having an enteric pH-

    dependent coating, which provides for delayed release, and a polymer matrix

    core, which provides for extended release, where the drug begins to

    release at a pH of 6.0. Id. According to the press release, this formulation

    provide[s] for the distribution of the active ingredient beginning in the

    small bowel and continuing throughout the colon.Id.

    Endonurseis a report from Salix regarding various clinical trials,

    including two late-stage trials designed to evaluate granulated mesalamine

    for the maintenance of remission of ulcerative colitis. Ex. 1014, 1.According to Endonurse, these Phase III trials [are] designed to evaluate

    the efficacy and safety of granulated mesalamine, dosed four 375 mg tablets

    once daily, for the maintenance of remission of ulcerative colitis. Id.at 2.

    Davis-1985is an academic paper discussing three factors relevant to

    the design and evaluation of control release delivery systems for orally

    administered medications: the drug, the delivery system, and the intended

    destination. Ex. 1009, 27 (Abstract, Introduction). Petitioners focus on

    2As noted above, Salix is the original assignee and current exclusivelicensee of the 688 patent.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    10/32

    IPR2016-00297Patent 8,865,688 B2

    10

    Davis-1985s discussion of the third factor: DestinationCharacteristics

    of the Gastrointestinal Tract. Id.at 3437. In this section, Davis-1985

    discusses the physiology of the gastrointestinal tract, including the effect of

    food on the pH of the stomach and on the process of gastric emptying. Id.at

    34. Davis-1985 discusses observations of the transit of various

    pharmaceutical formulations through the gastrointestinal tract using gamma

    scintigraphy and the implications of these observations for controlled release

    systems. Id.at 3436. Davis-1985 also discusses positioned release of

    drugs in the colon, using 5-aminosalicylic acid for the treatment ulcerative

    colitis as an example. Id.at 3637.

    Marakhouskicompares the clinical efficacy of a newpellet

    formulation of mesalazine (5-ASA) with a conventional tablet formulation.

    Ex. 1024, 134-1.3 According to Marakhouski, the pellet formulation has a

    combination of delayed and prolonged release characteristics. Id. at 134-

    1. Both formulations have a pH-dependent coating, Eudragit-L, which

    dissolves at pH 6.0 in the ileocaecal region (junction between the smallintestine and the large intestine). Id.at 135-1. The pellets are small

    (< 2 mm) particles containing 5-ASA embedded in a matrix polymer core,

    which provides for prolonged release of the drug. Id. According to

    Marakhouski, the pellet formulation prevent[s] the so-called dose-dumping

    effect and can be taken independent of meals. Id.at 134-1; see also 138-

    1 (same). Marakhouski concludes that the pellet formulation is as effective

    3 We use the suffix -1 to refer to the first column and -2 to refer to the

    second column.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    11/32

    IPR2016-00297Patent 8,865,688 B2

    11

    and well tolerated as the standard tablet formulation for the therapy of mild

    to moderately active ulcerative colitis. Id.at 138-2.

    Brunnercompares the gastrointestinal transit and release of pellet

    and tablet formulations of mesalazine (5-ASA) using gamma scintigraphy

    and plasma pharmacokinetics. Ex. 1025, Title, Summary. According to

    Brunner, both formulations have a Eudragit L coating, which dissolves at pH

    6.0, and the pellets additionally have a matrix polymer core that provides

    prolonged release. Id.at 1164-2, 1167-2. Brunner states that the pellet

    formulation could show some advantages compared with tablets, such as

    passage through the stomach independent of concomitant food intake. Id.

    at 1167-2. Brunner concludes that both the pellets and tablets release 5-ASA

    in the same target region and pass through the gastrointestinal tract under

    fasting conditions in healthy volunteers in a comparable time. Id.at 1163-1,

    1168-269-1.

    2. Analysis: Claim 1 of the 688 Patent

    Preamble and Paragraphs [a] and [b]

    Petitioners contend that the Sept. 2007 Press Release and Endonurse

    each disclose a method of maintaining the remission of ulcerative colitis, as

    recited in the preamble of claim 1, and that together these references teach

    administering a granulated mesalamine formulation comprising four

    capsules each comprising 0.375 g of granulated mesalamine once per day,

    where the method maintains remission of ulcerative colitis for a period of atleast 6 months of treatment, as recited in paragraphs [a] and [b] of claim 1.

    Pet. 2528, 3334.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    12/32

    IPR2016-00297Patent 8,865,688 B2

    12

    At this stage, Patent Owner does not substantively contest Petitioners

    contentions regarding the Sept. 2007 Press Release and Endonurse, as

    summarized above.

    On this record, Petitioners information is sufficient to support their

    argument that the Sept. 2007 Press Release and Endonurse disclose the

    preamble of claim 1 and above-noted limitations of paragraphs [a] and [b].

    Paragraph [a]: without food

    Petitioners rely on Davis 1985, Marakhouski, and Brunner to argue

    obviousness of administering a granulated mesalamine formulation without

    food, as recited in claim 1, paragraph [a]. Pet. 2933, 4450.

    Petitioners contend that a person of ordinary skill in the art would

    have known to administer granulated mesalamine without food so that its

    bioavailability via absorption through the small intestine would be

    minimized and delivery to the distal ileum and colon would be maximized.

    Id.at 3033, 43 (citing Ex. 1007, 1:2733;4Ex. 1008, 1:1018;5Ex. 1009

    (Davis), 34, 36; Ex. 1010, 886;6Ex. 1011, 4:1518).7 Petitioners further

    contend that Marakhouski and Brunner each discloses that granulated

    mesalamine can be administered independent of food and that it would have

    been obvious to combine this teaching with the other cited references in

    order to avoid dose dumping and premature release of mesalamine.

    4 Hirakawa et al., EP 0 671 168 A1, published Sept. 13, 1995 (EP168).

    5 Ring et al., WO 91/07949, published June 13, 1991 (PCT949).

    6 S.S. Davis et al., Transit of Pharmaceutical Dosage Forms through theSmall Intestine, 27 GUT886892 (1986) (Davis-1986).

    7 Otterbeck, US 6,551,620, issued Apr. 22, 2003 (the 620 Patent).

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    13/32

    IPR2016-00297Patent 8,865,688 B2

    13

    Petitioners also contend that the ability to administer the drug independent of

    food is itself taught as advantageous. Id.at 4546 (citing Ex. 1024, 134); id.

    at 4950 (citing Ex. 1025, 1167).

    Patent Owner contends that the claimed method is contrary to an

    understanding in the art that 5-ASA should be administered withand not

    without food. Prelim. Resp. 35 (citing Ex. 1017, 58);8see also id.at 2

    (Salix surprisingly found that once daily, low dose granulated mesalamine

    formulation could be administered without food and effectively maintain the

    remission of ulcerative colitis.).

    On this record, Petitioners information shows sufficiently that

    Marakhouski and Brunner each discloses administration of granulated

    mesalamine without food. Ex. 1024, 135-1; Ex. 2025, 1164-1. Petitioners

    information also shows sufficiently that Marakhouski and Brunner disclose

    that granulated mesalamine can be taken independent of meals, Ex. 1024,

    134-1, or independent of concomitant food intake, Ex. 1025, 1167-2.

    Patent Owner cites the prosecution history as support for its argumentthat there was an understanding in the art that mesalamine should be

    administered with food. Prelim. Resp. 35 (citing Ex. 1017, 58). The

    prosecution history, in turn, cites dosing information for the FDA-approved

    drug, Lialda, which Applicants represented was the most similar

    formulation to the granulated mesalamine described in the Sept. 2007 Press

    Release. Ex. 1017, 6.

    On this record, however, Petitioners informationincluding

    Marakhouski and Brunnercalls into question Applicantsrepresentation

    8 688 Patent File History, 2014-06-20 Amendment.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    14/32

    IPR2016-00297Patent 8,865,688 B2

    14

    that Lialdawas the most similar formulation. Ex. 1017, 6. Based on the

    current record, it appears that Marakhouski and Brunner discuss the same

    granulated mesalamine formulation as discussed in the Sept. 2007 Press

    Release. That formulation is described as having an enteric pH-dependent

    coating, which provides for delayed release . . . [and] that begins to release

    at a pH of 6.0 and a polymer matrix core, which provides for extended

    release. Ex.1012, 1. Like the Sept. 2007 Press Release, Marakhouski and

    Brunner each describe pellets having an enteric coating that dissolves and

    releases 5-ASA at pH 6.0 and a matrix polymer core that provides

    prolonged release of 5-ASA. Ex. 1024 (Marakhouski), 135-1, 138-1; Ex.

    1025 (Brunner) 1164-2, 1167-2.

    Furthermore, on this record, all four referencesthe Sept. 2007 Press

    Release, Endonurse, Marakhouski, and Brunnerappear to pertain to a

    granulated mesalamine formulation provided by Patent Owner, Dr. Falk

    Pharma. The Sept. 2007 Press Release and Endonurse are both

    announcements relating to Salix Phase III clinical trials to evaluate agranulated mesalamine formulation for the maintenance of remission of

    UCthe same Phase III trials as are discussed in the 688 patent. Compare

    Ex. 1012, 1 and Ex. 1014, 2, withEx. 1001 6:437:25. The Sept. 2007 Press

    Release states: Salix acquired rights to market granulated mesalamine in

    the U.S. from Dr. Falk Pharma GmbH of Freiburg, Germany. Ex. 1012, 2.

    Marakhouski and Brunner likewise appear to relate to a granulated

    mesalamine formulation from Dr. Falk Pharma. Ex. 1025, 1164-2 (Brunner:

    The study medication was provided by Dr[.] Falk Pharma GmbH, Freiburg,

    Germany); Ex. 1024, 134-1, 138-2, 140-2 (Marakhouski cites Brunner (ref.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    15/32

    IPR2016-00297Patent 8,865,688 B2

    15

    21) as disclosing how 5-ASA is released from pellets in gastrointestinal

    tract).

    Accordingly, in view of the disclosures of Marakhouski and Brunner

    and their relationship to the Sept. 2007 Press Release and Endonurse, we are

    not persuaded to deny review based upon Patent Owners argument that

    there was an understanding in the art that granulated mesalamine should be

    administered with food, as argued during prosecution and in the Preliminary

    Response.

    Addressing Petitioners Ground 1, Patent Owner contends that there

    would have been no motivation to combine Davis-1985 with the Sept. 2007

    Press Release or Endonurse. Prelim. Resp. 3435.

    On this record and for purposes of institution, we are not persuaded by

    Patent Owners argument. The Sept. 2007 Press Release and Endonurse

    disclose a method of maintaining the remission of ulcerative colitis,

    including oral administration of a mesalamine (5-aminosalicylic acid).

    Ex. 1012, 1; Ex. 1014, 2. Davis-1985 addresses positioned release of adrug in the various regions of the colon, following oral administration,

    using 5-aminosalicylic acid for the treatment of ulcerative colitis as an

    example. Ex. 1009, 36. Davis-1985 also discusses bioavailability and

    transit times for orally administered drugs in fed and fasted states, i.e., with

    and without food. Id. at 34, 36.

    The Sept. 2007 Press Release and Endonurse are silent on whether

    mesalamine should be administered with or without food. On this record,

    however, Petitioners information is sufficient to support their position that a

    person of ordinary skill in the art would have considered the cited teachings

    of Davis-1985 comparing oral administration in fed and fasted states,

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    16/32

    IPR2016-00297Patent 8,865,688 B2

    16

    Ex. 1009, 34, 36, to be relevant in determining whether a drug that is

    intended reach the lower intestine and colon, such as mesalamine (5-

    aminosalicylic acid), should be administered with or without food. Pet. 30

    33; Ex. 1002 6971, 73, 81, 82 (discussing relevant teachings of Davis-

    1985).

    The relevance and combinability of Davis-1985 is also supported by

    the prosecution history, where the Examiner allowed the claims based, in

    part, on a prior art teaching similar to the cited teaching of Davis-1985

    regarding the effect of food on bioavailability. CompareEx. 1019, 3

    (Reasons for Allowance), with Ex. 1009 (Davis), 34; see alsoPet. 2931

    (analyzing Examiners and Davis-1985s discussions of bioavailability).

    Despite the similarity of the prior art teachings, Petitioners declarantdraws

    a different conclusion from that reached by the Examiner. Ex. 1002 68

    (higher bioavailability translates to lesser amounts of mesalamine available

    to be deposited on the distal ileum and colon.).

    Accordingly, on this record, Petitioners information is sufficient tosupport their position that a person of ordinary skill in the art seeking to

    practice the method disclosed in the Sept. 2007 Press Release and Endonurse

    would have considered the cited teachings of Davis-1985 relevant in

    determining whether granulated mesalamine should be administered with or

    without food.

    Patent Owner further contends that Davis-1985 does not cure the

    deficiencies in the Sept. 2007 Press Release or Endonurse, including the

    failure to disclose administration of granulated mesalamine without food.

    Prelim. Resp. 2324, 3435.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    17/32

    IPR2016-00297Patent 8,865,688 B2

    17

    On this record, it appears that a person of ordinary skill in the art

    would have had two choices when deciding how to administer oral

    granulated mesalamine: with food or without food. Petitioners information

    shows sufficiently that both of these choices would have been available to a

    person of ordinary skill in the art seeking to practice a method of

    maintaining remission of ulcerative colitis, as disclosed in the Sept. 2007

    Press Release and Endonurse. As discussed above, for example,

    Marakhouski and Brunner each discloses administration of granulated

    mesalamine without food. Ex. 1024, 135-1; Ex. 2025, 1164-1.

    Obviousness as to this limitation thus turns on whether administering

    granulated mesalamine without food would have been predictable and would

    have led to anticipated success. KSR Intl v. Teleflex Inc., 550 U.S. 398, 421

    (2007) (When there is a design need or market pressure to solve a problem

    and there are a finite number of identified, predictable solutions, a person of

    ordinary skill has good reason to pursue the known options within his or her

    technical grasp. If this leads to the anticipated success, it is likely theproduct not of innovation but of ordinary skill and common sense.).

    Relevant to predictability and anticipated success, Petitioners offer

    two record-supported rationales for why a person of ordinary skill in the art

    seeking to practice the method disclosed in the Sept. 2007 Press Release and

    Endonurse would have known to administer granulated mesalamine without

    food: First, Petitioners posit that Davis-1985s teachings regarding higher

    bioavailability via absorption through the small intestine and faster

    gastrointestinal transit times in a fasted versus a fed state would have led one

    of ordinary skill in the art to conclude that a formulation intended to be

    delivered to the colon, as disclosed in the Sept. 2007 Press Release and

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    18/32

    IPR2016-00297Patent 8,865,688 B2

    18

    Endonurse, should be administered in a fasted state, i.e., without food.

    Ex. 1002 6871 (citing Ex. 1009, 34, 36; Ex. 1010, 886). Second,

    Petitioners posit that prior art teachings that food raises stomach pH and

    suppresses gastric emptying would have led one of ordinary skill in the art to

    conclude that granulated mesalamine having a pH-dependent coating, as

    disclosed in the Sept. 2007 Press Release, should be administered without

    food, so as to avoid dissolution of the coating and release of the drug in the

    stomach, rather than in the colon. Ex. 1002 7274, 106107 (citing Ex.

    1007 (EP168), 1:2733; Ex. 1008 (PCT949), 1:1018; Ex. 1009 (Davis), 34;

    Ex. 1011 (the 620 Patent), 4:1518).

    On this record and for purposes of institution, we determine that

    Petitioners information, as summarized above, is sufficient to support their

    position that, for a person of ordinary skill in the art seeking to practice a

    method of maintaining the remission of ulcerative colitis, administering

    granulated mesalamine without food would have been known, predictable,

    and led to anticipated success.Addressing Petitioners Grounds 3 and 4, Patent Owner contends that

    neither Marakhouski nor Brunner is directed to maintaining remission of

    ulcerative colitis (UC). Prelim. Resp. 39, 41. Patent Owner further contends

    that Brunner does not suggest a low dose of mesalamine, as recited in claims

    1 and 16. Id. at 4142.

    On this record and for purposes of institution, we are not persuaded by

    Patent Owners arguments. The cited teachings of Marakhouski and

    Brunner pertain to whether granulated mesalamine should be administered

    with or without food. Ex. 1024, 134-1, 138-1; Ex. 1025, 1167-2. Patent

    Owner makes no assertion that this choice depends on whether the objective

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    19/32

    IPR2016-00297Patent 8,865,688 B2

    19

    is to induce remission of UC (as in Marakhouski) or to maintain remission of

    UC (as in the 688 patent, the Sept. 2007 Press Release, and Endonurse).

    Nor does Patent Owner assert that this choice depends on whether the

    dosage is high (as in Brunner) or low (as in the 688 patent, the Sept. 2007

    Press Release, and Endonurse).

    On this record, Patent Owners arguments distinguishing Marakhouski

    and Brunner appear to be inconsistent with Applicants arguments during

    prosecution. There, Applicants asserted that a skilled artisan would look to

    teachings relating to Lialda, including directions for administering the drug

    for the induction of remission in adult patients with active, mild to

    moderate ulcerative colitis using a total daily dose of 2.4 g or 4.8 g. Ex.

    1017, 6. Induction of remission of mild to moderate UC is the same goal as

    disclosed in Marakhouski. Ex. 1024, 134, 135. Furthermore, the Lialda

    dosage range cited by Applicants overlaps the up to 4 g daily that Patent

    Owner asserts is taught by Brunner. Prelim. Resp. 41. Accordingly, on this

    record, Patent Owners arguments do not persuade us to disregard theteachings of Marakhouski and Brunner as not relevant to a method of

    maintaining remission of UC using a low dosage of granulated mesalamine.

    Patent Owner further argues that Marakhouski makes no comparison

    between administration with and without food and only mentions in

    passing that, unlike tablets, pellets avoid the risk of dose-dumping, and

    therefore can be taken independent of meals. Prelim. Resp. 40.

    Patent Owners argument does not persuade us to deny review.

    Marakhouski discloses administration of granulated mesalamine without

    food, Ex. 1024, 135-1, and further discloses that granulated mesalamine

    can be taken independent of meals,id.at 134-1. A comparison between

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    20/32

    IPR2016-00297Patent 8,865,688 B2

    20

    administration with and without food is not necessary to persuade us to

    institute review because Petitioners contention regardinga motivation to

    combine Marakhouskis disclosures with the Sept. 2007 Press Release and

    Endonurse is adequately supported by other information. Ex. 1002 (Digenis

    Decl.) 112 (to avoid dose dumping and premature release of

    mesalamine); id. 121 (ability to administer independent of food is itself

    advantageous).

    Accordingly, on this record, Petitioners information, as summarized

    above, is sufficient to support their position that one of ordinary skill in the

    art would have combined the Sept. 2007 Press Release and Endonurse with

    the cited teachings of Davis-1985, as well as the cited teachings of either

    Marakhouski or Brunner, and that either combination would have made it

    obvious to practice the method of the Sept. 2007 Press Release and

    Endonurse by administering granulated mesalamine without food.

    Paragraph [a]: in the morning

    Petitioners contend that a person of ordinary skill in the art would

    have had a reason to administer granulated mesalamine in the morning

    because that is the time when apatients stomach is mostlikely to be empty.

    Pet. 29. Petitioners further contend that the 688 patent does not show

    criticality for the in the morning limitation. Id. (citing Ex. 1001, 3:64,

    13:2930; Ex. 1002 65).

    At this stage, Patent Owner does not argue patentability based uponclaim 1s recitation of in the morning separate from its arguments, as

    discussed above, regarding administration without food.

    On this record, Petitioners information, as summarized above, is

    sufficient to support their argument that one of ordinary skill in the art would

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    21/32

    IPR2016-00297Patent 8,865,688 B2

    21

    have found it obvious to practice the method of the Sept. 2007 Press Release

    and Endonurse by administering granulated mesalamine in the morning.

    Paragraph [c]: remission is defined as a DAI score of 0 or 1Petitioners contend that a person of ordinary skill in the art would

    have recognized that remaining relapse-free, as disclosed in the Sept. 2007

    Press Release, would be defined by a DAI score of 0 to 1. Pet. 34 (citing Ex.

    1013 20).9

    Meyeroff discloses: a patient is considered to be in remission for UC

    if a UC-DAI score of 1 is obtained, with rectal bleeding and stool

    frequency scores of 0, and at least a 1-point reduction in sigmoidoscopy

    score from baseline. Ex. 1013 20.

    Patent Owner argues that a DAI score of 0 or 1 is not disclosed by

    the Sept. 2007 Press Release, Endonurse, Davis-1985, or Marakhouski, but

    does not otherwise address Petitioners argument regarding this limitation.

    On this record, Petitioners information, as summarized above, is

    sufficient to support their argument that one of ordinary skill in the art would

    have recognized that remaining relapse-free, as disclosed in the Sept. 2007

    Press Release, would be defined by a DAI score of 0 to 1.

    9 Meyeroff et al., US 2010/0035850 A1, published Feb. 11, 2010(Meyeroff).

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    22/32

    IPR2016-00297Patent 8,865,688 B2

    22

    Paragraph [d] the granulated mesalamine formulation

    is not administered with antacids

    Petitioners contend that a person of ordinary skill in the art would

    have known not to administer granulated mesalamine with antacids because

    antacids were known to increase stomach pH and cause dissolution of the

    pH-sensitive coating and release of mesalamine in the stomach and upper

    small intestine instead of the distal ileum and colon. Pet. 3536 (citing Ex.

    1007 (EP168), 1:2733; Ex. 1009 (Davis), 34; and Ex. 1026, 156).10

    Patent Owner does not specifically address Petitioners contentions

    regarding obviousness of administering granulated mesalamine without

    antacids.

    On this record, Petitioners information, as summarized above, is

    sufficient to support their argument that one of ordinary skill in the art would

    have found it obvious to practice the method of the Sept. 2007 Press Release

    and Endonurse by administering granulated mesalamine without antacids.

    Paragraph [e]: wherein 85% to 90% of the mesalaminereaches the terminal ileum and colon

    Petitioners contend that a person of ordinary skill in the art would

    have expected that the formulation disclosed in the Sept. 2007 Press Release

    would have the recited release profile85% to 90% of the mesalamine

    reaches the terminal ileum and colonbecause the press release discloses

    the same formulation as the 688 patent. Pet. 3738.

    10 J.R.B.J. Brouwers,Advanced and Controlled Drug Delivery Systems in

    Clinical Disease Management, 18(5)PHARMACY WORLD &SCIENCE153-162 (1996) (Brouwers).

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    23/32

    IPR2016-00297Patent 8,865,688 B2

    23

    Patent Owner argues that none of the Sept. 2007 Press Release,

    Endonurse, Davis-1985, or Marakhouski discloses that 85% to 90% of the

    mesalamine reaches the terminal ileum and colon, but does not otherwise

    address Petitioners argument regarding this limitation.

    Petitioners contention appears to be based on the doctrine of

    inherency. In order to establish inherency in the context of obviousness,

    the limitation at issuenecessarily must be present, or the natural result of

    the combination of elements explicitly disclosed by the prior art. PAR

    Pharma., Inc. v. TWI Pharmas., Inc., 773 F.3d 1186, 119596 (Fed. Cir.

    2014). We, therefore, consider whether Petitioners objective evidence is

    sufficient to show that the granulated mesalamine formulation disclosed in

    the Sept. 2007 Press Release would necessarily have a release profile within

    the claimed range.

    The objective evidence includes the 688 patent, which provides the

    following description of the granulated mesalamine formulation: each

    granulated mesalamine formulation capsule contains, for example, granulescomposed of mesalamine in a polymer matrix with an enteric coating that

    dissolves at pH 6 and above. Ex. 1001, 10:6366; see also id.at 9:3745.

    The 688 patentteaches that this formulation has a release profile whereby

    85% to 90% of drug reaches the diseased area. Id.at 9:5054.

    The objective evidence also includes the Sept. 2007 Press Release,

    which discloses a granulated mesalamine formulation . . . [that] combines

    an enteric pH-dependent coating, which provides for delayed release, and a

    polymer matrix core, which provides for extended release. . . . [where]

    granulated mesalamine . . . begins to release at a pH of 6.0. Ex. 1012, 1.

    The Sept. 2007 Press Release also discloses that the granulated mesalamine

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    24/32

    IPR2016-00297Patent 8,865,688 B2

    24

    formulation is designed to provide for the distribution of the active

    ingredient beginning in the small bowel and continuing throughout the

    colon. Ex. 1012, 1.11

    Petitioners present no experimental data to show that the granulated

    mesalamine formulation disclosed in the Sept. 2007 Press Release has the

    claimed release profile, i.e., 85% to 90% of the mesalamine reaches the

    terminal ileum and colon. We note, however, that the 688 patent also

    contains no experimental data to support the assertion that the disclosed

    mesalamine formulation provides the claimed release profile. Example 4

    discloses a release profile outside the claimed range. Ex. 1001, 16:6567

    (Approximately 80% of an administered oral dose of mesalamine is

    estimated to be available in the colon, sigmoid, and rectum when dosed as

    mesalamine granules.).

    The 688 patent does not indicate obtaining the release profile

    depends upon whether the drug is administered in the morning, without

    food, orwithout antacidsconditions recited in claim 1, but not disclosedin the Sept. 2007 Press Release. In fact, the 688 patent indicates that the

    rate and extent of absorption of mesalamine and its metabolite were not

    affected by a high-fat meal.Id. at 16:6364.

    On this record, Petitioners objective evidence shows sufficiently that

    the granulated mesalamine formulation disclosed in the Sept. 2007 Press

    Release is the same as the granulated mesalamine formulation disclosed in

    the 688 patent. Under these circumstances and for purposes of institution,

    11 According to Dr. Digenis, a person of ordinary skill would understand

    that the small bowel includes the terminal ileum. Ex. 1002 84.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    25/32

    IPR2016-00297Patent 8,865,688 B2

    25

    we view Petitioners objective evidence as sufficient to support its position

    that the granulated mesalamine formulation disclosed in the Sept. 2007 Press

    Release would necessarily have the same release profile as disclosed in the

    688 patent, i.e., that85% to 90% of the mesalamine reaches the terminal

    ileum and colon.

    3. Secondary Considerations

    Patent Owner contends that non-obviousness is demonstrated by

    secondary considerations, including [f]ailure of others to demonstrate the

    non-inferiority of a low, once daily dose of mesalamine without food for the

    maintenance of remission of ulcerative colitis; [l]ong felt but unmet need

    for a low, once-daily dose of granulated mesalamine for the maintenance of

    remission of ulcerative colitis; and [s]kepticism by those in the field that a

    once daily, low dose of granulated mesalamine administered without food

    could maintain the remission of ulcerative colitis. Prelim. Resp. 43, 45, 47.

    As support for these contentions, Patent Owner cites excerpts from the trial

    testimony of its witnesses, Drs. Forbes, Johnson, and Greinwald, Exs. 2022

    2024,12confidential reports of clinical trials conducted by Dr. Falk Pharma

    and Salix, Exs. 20252029, exhibits purportedly showing problems with

    prior art tablet formulations, Exs. 2030, 2031, and exhibits relating to

    adherence studies conducted before October 2004, Exs. 2016, 2018.

    At this stage, the record regarding secondary considerations is

    incomplete, as Patent Owner has not had an opportunity to submit

    12 Patent Owners Exhibits 20222024 are excerpts from the November 16

    and 18, 2015 trial testimony of its witnesses, William Forbes, LorinJohnson, and Roland Greinwald, in the related Delaware district court

    litigation.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    26/32

    IPR2016-00297Patent 8,865,688 B2

    26

    testimonial evidence, and Petitioners have not had an opportunity to respond

    to Patent Owners arguments and exhibits. We therefore determine that it

    would be premature to reach any conclusion regarding secondary

    considerations. Any final decision will be based on the full record

    developed during the trial, including any evidence of secondary

    considerations.

    4. 35 U.S.C. 325(d) and Redundancy

    Patent Owner argues that Petitioners Ground 1 presents no arguments

    not already considered by the PTO during prosecution, Prelim. Resp. 34, and

    that Grounds 3 and 4 are horizontally redundant because Marakhouski and

    Brunner are substantially similar, id. at 38 n.3.

    Our governing statute provides, in relevant part, that [i]n determining

    whether to institute or order a proceeding under this chapter . . . the Director

    maytake into account whether, and reject the petition or request because, the

    same or substantially the same prior art or arguments previously were

    presented to the Office. 35 U.S.C. 325(d) (emphasis added). Our

    procedural rules provide: (1) the Boardmay authorize the review to

    proceed on all or some of the challenged claims and on all or some of the

    grounds of unpatentability asserted for each claim, and (2) the Board may

    deny some or all grounds of unpatentability for some or all of the challenged

    claims. 37 C.F.R. 42.108(a), (b).

    We have considered the facts and circumstances of the instantproceeding. We decline to exercise our discretion to deny the Petition under

    35 U.S.C. 325(d). And we exercise our discretion to institute review based

    on Grounds 3 and 4 in the alternative.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    27/32

    IPR2016-00297Patent 8,865,688 B2

    27

    5. Conclusion Regarding Grounds 3 and 4

    On this record, we are persuaded that Petitioners demonstrate a

    reasonable likelihood of prevailing on their assertion that claims 1 and 16

    are unpatentable as obvious over the 2007 Press Release, Endonurse, and

    Davis-1985 in view of Marakhouski or Brunner.

    E. Obviousness Ground 1

    Petitioners contend that claims 1 and 16 are unpatentable as obvious

    over the Sept. 2007 Press Release, Endonurse, and Davis-1985. Pet. 2539

    (Ground 1). We view this ground as subsumed by the above-instituted

    Grounds 3 and 4 based on these same references in view of Marakhouski or

    Brunner.

    F. Obviousness Ground 2

    Petitioners contend that claims 1 and 16 are unpatentable as obvious

    over the Sept. 2007 Press Release, Endonurse, Davis-1985, and EP590.

    Pet. 3944 (Ground 2).

    1. Petitioners Cited Reference

    EP590discloses an oral pharmaceutical preparation comprising a core

    containing an active substance, e.g., salicylazo-sulfapyridine (SASP) or 5-

    ASA, and a coating comprising (i) a polymer soluble only above pH 5.5,

    e.g., Eudragit L, and (ii) a water insoluble polymer, with the objective of

    releasing a major part of the active substance in the colon for treating, e.g.,

    ulcerative colitis. Ex. 1015, Abstract, 1:514, 1:282:6, 3:34:2, 4:1216.

    EP590 discloses tests comparing the release properties of such a colon

    release preparation with a conventionalpreparation, using SASP as a

    model substance. Id. at 6:421. In tests in vivo, test preparationseither

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    28/32

    IPR2016-00297Patent 8,865,688 B2

    28

    granular preparations (coated cores containing SASP) or a conventional

    tablet (Salazopyrin)were administered [a]fter at least 10 hours fasting.

    Id. at 6:237:31, 8:2234. Amounts of SASP and its metabolite (acetyl-5-

    ASA) excreted in urine were then measured. Id. at 6:1113, 8:349:35.

    According to EP590, the results of these tests demonstrate that the granular

    preparations provide the desired colon release properties. Id. at 6:1521,

    10:12.

    2. Analysis

    Petitioners contend that EP590 discloses a method of administering

    granulated mesalamine without food. Pet. 41. Petitioners further contend

    that EP590 discloses the same reasoning taught by the 688 Patent for why

    granulated mesalamine can be taken withoutfood. Pet. 42. In addition,

    Petitioners contend that EP590 teaches that administration of granulated

    mesalamine without food lowered the excretion of 5-ASA in the urine,

    thereby increasing the application in the large intestine. Pet. 4243.

    Patent Owner contends that EP590 does not teach using granulated

    mesalamine for the maintenance of remission of UC. Prelim. Resp. 36.

    Patent Owner further contends that EP590 addresses SASP and would not be

    viewed as relevant to mesalamine because the drugs have different

    absorption sites. Id.(citing Ex. 1015, 6:9). In addition, Patent Owner

    asserts that EP590 does not indicate that administration with versus without

    food had any impact on the release profile as a study with food was notdisclosed. Id.at 37.

    Petitioners contention that EP590 discloses a method of

    administering granulated mesalamine without food, Pet. 41, is based on

    EP590s in vivo tests of SASP and Petitioners assertion that SASP .. .

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    29/32

    IPR2016-00297Patent 8,865,688 B2

    29

    comprises 5-ASA. Pet. 40, 41. That assertionis not supported by EP590,

    which teaches that SASP is a chemical precursor to 5-ASA. More

    specifically, EP590 teaches that SASP is broken down by bacteria in the

    colon to produce sulfapyridine (SP) and 5-amino-salicylic acid (5-ASA).

    Ex. 1015, 6:1113; see alsoEx. 1006 (Stolk), 200-1 (same);13Ex. 1026

    (Brouwers), 155-2 (same).

    On this record, Petitioners contention that EP590 discloses the same

    reasoning taught by the 688 Patent for why granulated mesalamine can be

    taken withoutfood, Pet. 42, is not sufficiently supported. Petitioners refer

    to Example 1 of the 688 patent, id., which evaluates urinary excretion of 5-

    ASA, when granulated mesalamine is administered following an overnight

    fast as compared to administration following a high fat meal. Ex. 1001,

    14:5867. In contrast, EP590 evaluates urinary excretion of 5-ASA, when a

    granular preparation of SASP is administered, as compared to administration

    of a conventional tablet formulation. Ex. 1015, 6:1521, 7:3031, 8:229:4,

    9:2835. As noted by Patent Owner, Prelim. Resp. 37, EP590 does notcompare urinary excretion following administration with and without food,

    as in Example 1 of the 688 Patent.

    The record also lacks adequate support for Petitioners assertion that

    EP590 teaches that administration of granulated mesalamine without food

    lowered the excretion of 5-ASA in the urine. Pet. 4243. First, EP590s

    evaluations of urinary excretion of 5-ASA did not involve administration of

    granulated mesalamine, but instead administration of granulated SASPa

    13 L. Stolk et al.,Dissolution Profiles of Mesalazine Formulations in Vitro,12(5) PHARMACEUTISCH WEEKBLAD SCIENTIFIC EDITION20004 (1990)(Stolk).

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    30/32

    IPR2016-00297Patent 8,865,688 B2

    30

    chemical precursor, which as Patent Owner notes, Prelim. Resp. 36, has a

    different absorption profile than mesalamine. Compare Ex. 1015, 6:910

    (SASP is absorbed to a small extent in the stomach and smallintestine),

    withEx. 1025 (Brunner), 1163 (Orally administered mesalazine is rapidly

    and almost completely absorbed from the small intestine.). Second,EP590

    does not teach that urinary excretion was lowered by administration without

    food, but instead teaches that excretion was lowered by administration of a

    colon release preparation instead of a conventional tablet formulation.

    Ex. 1015, 6:1521, 7:3031, 8:229:4, 9:2835.

    Accordingly, on this record, we are not persuaded to institute review

    based on EP590 in combination with the 2007 Press Release, Endonurse,

    and Davis-1985.

    III. CONCLUSION

    For the reasons stated above, we institute an inter partesreview as set

    forth in the Order. At this stage of the proceeding, the Board has not made a

    final determination with respect to the patentability of the challenged claims

    or any underlying factual or legal issues.

    IV. ORDER

    It is

    ORDERED that, pursuant to 35 U.S.C. 314(a), an inter partes

    review of the 688 patent is instituted on the following ground of

    unpatentability asserted in the Petition:

    Claims 1 and 16 under 35 U.S.C. 103(a) as obvious over the

    2007 Press Release, Endonurse, and Davis-1985 in view of

    Marakhouski or Brunner.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    31/32

    IPR2016-00297Patent 8,865,688 B2

    31

    FURTHER ORDERED that pursuant to 35 U.S.C. 314(a), inter

    partesreview of the 688 patent is hereby instituted commencing on the

    entry date of this Order, and pursuant to 35 U.S.C. 314(c) and 37 C.F.R.

    42.4, notice is hereby given of the institution of trial; and

    FURTHER ORDERED that the trial is limited to the ground identified

    above and no other ground of unpatentability is authorized.

  • 7/26/2019 $VRX Apriso '688 IPR Insituted

    32/32

    IPR2016-00297Patent 8,865,688 B2

    PETITIONER:

    Zachary [email protected]

    Gaston Kroub

    [email protected]

    PATENT OWNER:

    Mary [email protected]

    Preston Heard

    [email protected]

    mailto:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]