Paper No. ____
`Date Filed: February 2, 2016
`
`Filed On Behalf Of:
`
`Novartis AG
`
`By:
`
`Nicholas N. Kallas
`NKallas@fchs.com
`ZortressAfinitorIPR@fchs.com
`(212) 218-2100
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`PAR PHARMACEUTICAL, INC.,
`Petitioner
`
`v.
`
`NOVARTIS AG,
`Patent Owner
`
`
`
`Inter Partes Review No. 2016-00075
`
`
`
`U.S. Patent 7,297,703
`
`
`
`PRELIMINARY RESPONSE BY
`PATENT OWNER PURSUANT TO 37 C.F.R. § 42.107
`
`

`
`
`
`
`I. 
`
`TABLE OF CONTENTS
`
`The Board Should Adopt Novartis’s Construction Of The
`Claim Term “Solid Mixture” And Reject Par’s Construction ........................ 1
`
`A. 
`
`The Intrinsic Evidence Repeatedly And Consistently
`Distinguishes The Claimed “Solid Mixture” From A
`Pharmaceutical Composition ................................................................ 2 
`
`1. 
`
`2. 
`
`3. 
`
`The ’703 Patent Claims Distinguish The Claimed
`“Solid Mixture” From A Pharmaceutical
`Composition ................................................................................ 5 
`
`The Specification Also Distinguishes The Claimed
`“Solid Mixture” From A Pharmaceutical
`Composition .............................................................................. 12 
`
`The Prosecution History Also Distinguishes The
`Claimed “Solid Mixture” From A Pharmaceutical
`Composition .............................................................................. 17 
`
`II. 
`
`The Board Should Deny Institution Of Ground 1 As To Claims
`1-3, 6 and 7 Because Guitard Does Not Anticipate Those
`Claims Of The ’703 Patent ............................................................................ 21 
`
`III.  The Board Should Deny Institution Of Ground 1 As To Claims
`8, 9 And 11 Because Guitard Does Not Anticipate Those
`Claims Of The ’703 Patent ............................................................................ 25 
`
`IV.  The Board Should Deny Institution Of Ground 2 Because
`Eastlick And Fricker Do Not Render Obvious Any Claim Of
`The ’703 Patent .............................................................................................. 28 
`
`A. 
`
`B. 
`
`Eastlick Does Not Teach Or Suggest That Everolimus Or
`Rapamycin Is Oxidatively Unstable ................................................... 29 
`
`Fricker Does Not Teach Or Suggest That Everolimus Or
`Rapamycin Is Oxidatively Unstable ................................................... 33 
`
`i
`
`

`
`
`
`
`
`C. 
`
`Because Neither Eastlick Nor Fricker Teach Or Suggest
`That Rapamycin Or Everolimus Are Oxidatively
`Unstable, There Is No Motivation To Combine Them ....................... 40 
`
`ii
`
`

`
`
`
`TABLE OF AUTHORITIES
`
`
`Cases 
`ActiveVideo Networks Inc. v. Verizon Commc’ns, Inc., 694 F.3d
`1312 (Fed. Cir. 2012) .................................................................................... 38
`
`Bd. of Regents v. BENQ Am. Corp., 533 F.3d 1362 (Fed. Cir.
`2008) .................................................................................................... 4, 15, 24
`
`Becton, Dickinson & Co. v. Tyco Healthcare Group, LP, 616
`F.3d 1249 (Fed. Cir. 2010) ........................................................................ 4, 11
`
`Cephalon, Inc. v. Abraxis Bioscience, LLC, 618 Fed. Appx. 663
`(Fed. Cir. 2015) ............................................................................................... 7
`
`Eibel Process Co. v. Minn. & Ont. Paper Co., 261 U.S. 45
`(1923) ....................................................................................................... 26, 39
`
`Forest Labs., Inc. v. Abbott Labs., No. 96-cv-159, 1998 WL
`35285402 (W.D.N.Y. Aug. 3, 1998) ......................................................... 8, 11
`
`Forest Labs., Inc. v. Abbott Labs., 239 F.3d 1305 (Fed. Cir.
`2001) .................................................................................................... 8, 10, 11
`
`In re Omeprazole Patent Litig., 536 F.3d 1361 (Fed. Cir. 2008) ...................... 27, 40
`
`Innogenetics N.V. v. Abbott Labs., 512 F.3d 1363 (Fed. Cir.
`2008) .............................................................................................................. 38
`
`KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007) ................................................ 38
`
`Leo Pharm. Prods., Ltd. v. Rea, 726 F.3d 1346 (Fed. Cir. 2013) ............... 26, 27, 39
`
`Markman v. Westview Instruments, Inc., 52 F.3d 967 (Fed. Cir.
`1995) ................................................................................................................ 2
`
`Merck & Co., Inc. v. Teva Pharm. USA, Inc., 395 F.3d 1364
`(Fed. Cir. 2005) ............................................................................................... 7
`
`iii
`
`

`
`
`
`Microsoft Corp. v. Multi-Tech Sys., Inc., 357 F.3d 1340 (Fed.
`Cir. 2004) ....................................................................................................... 16
`
`Nystrom v. Trex Co., Inc., 424 F.3d 1136 (Fed. Cir. 2005) ........................... 3, 15, 25
`
`Outside the Box Innovations, LLC v. Travel Caddy, Inc., 695
`F.3d 1285 (Fed. Cir. 2012) .............................................................................. 6
`
`Schoenhaus v. Genesco, Inc., 440 F.3d 1354 (Fed. Cir. 2006) ..................... 3, 10, 11
`
`Spectrum Int’l, Inc. v. Sterilite Corp., 164 F.3d 1372 (Fed. Cir.
`1998) ................................................................................................................ 7
`
`Thorner v. Sony Computer Entm’t Am. LLC, 669 F.3d 1362
`(Fed. Cir. 2012) ............................................................................................... 3
`
`Trading Techs. Int’l, Inc. v. eSpeed, Inc., 595 F.3d 1340 (Fed.
`Cir. 2010) ......................................................................................................... 6
`
`Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352 (Fed. Cir.
`2011) .............................................................................................................. 38
`
`Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576 (Fed. Cir.
`1996) ............................................................................................................ 3, 4
`
`
`
`
`
`iv
`
`

`
`
`
`PATENT OWNER’S EXHIBIT LIST 1
`
`
`Exhibit
`No.
`
`Description
`
`Navarro, Francois et al., Application No. 12/497,728,
`
`2001
`
`Amendment After Allowance Under 37 CFR §1.312(a),
`
`January 26, 2010
`
`2002
`
`Navarro, Francois et al., Application No. 12/497,728,
`
`Response to Rule 312 Communication, February 3, 2010
`
`Navarro, Francois et al., Application No. 12/497,728,
`
`2003
`
`Amendment After Allowance Under 37 CFR §1.312(a),
`
`February 17, 2010
`
`2004
`
`Navarro, Francois et al., Application No. 11/020,860,
`
`Information Disclosure Statement, December 23, 2004
`
`Handbook of Pharmaceutical Excipients (Ainley Wade & Paul
`
`2005
`
`J. Weller, eds., Am. Pharm. Assoc. 2d. ed. 1994), pp. 135-36,
`
`entry for “Corn Oil”
`
`v
`
`

`
`
`
`
`
`Exhibit
`No.
`
`Description
`
`Handbook of Pharmaceutical Excipients (Ainley Wade & Paul
`
`2006
`
`J. Weller, eds., Am. Pharm. Assoc. 2d. ed. 1994), pp. 371-74,
`
`entry for “Polyoxyethylene Castor Oil Derivatives”
`
`Handbook of Pharmaceutical Excipients (Ainley Wade & Paul
`
`2007
`
`J. Weller, eds., Am. Pharm. Assoc. 2d. ed. 1994), pp. 267-68,
`
`entry for “Lecithin”
`
`2008
`
`Novartis Pharm. Corp. v. Par Pharm., Inc., No. 14-1494, D.I.
`
`97 (Memorandum Opinion, November 23, 2015)
`
`
`
`vi
`
`

`
`
`
`
`
`Patent Owner Novartis AG (“Novartis”) respectfully submits this
`
`Preliminary Response to the Petition of Par Pharmaceutical, Inc. (“Par”)
`
`seeking inter partes review (“IPR”) of U.S. Patent No. 7,297,703 (“’703
`
`patent”).
`
`I.
`
`
`
`The Board Should Adopt Novartis’s Construction Of The Claim
`Term “Solid Mixture” And Reject Par’s Construction
`
`Par and its expert rely on dictionary definitions to assert that “[a]
`
`POSA would understand the term ‘solid mixture,’ as used in the challenged
`
`claims, to have its plain and ordinary meaning,” and that “[a] POSA would
`
`understand this plain and ordinary meaning to be ‘a solid combination of
`
`two or more solid substances that are mixed, but not chemically combined.’”
`
`Pet., pp. 25-26, citing Ex. 1002, Benjamin Decl. at ¶¶ 75, 77; Ex. 1012.
`
`
`
`Novartis does not dispute that a solid mixture is a solid combination
`
`of two or more solid substances that are mixed, but not chemically
`
`combined. However, contrary to Par’s conclusory assertion, the broadest
`
`reasonable construction of “solid mixture” in the context of the ’703 patent
`
`is not simply “a solid combination of two or more solid substances that are
`
`mixed, but not chemically combined,” without further limitation. (“Par’s
`
`construction”). Rather, in the context of the ’703 patent, the broadest
`
`reasonable construction of “solid mixture” is “a solid combination of two or
`
`1
`
`

`
`
`
`more solid substances that are mixed, but not chemically combined, which
`
`combination is not a pharmaceutical composition.” (“Novartis’s
`
`construction”). Novartis’s construction therefore excludes from the claimed
`
`“solid mixture” a pharmaceutically acceptable diluent or carrier that would
`
`have the effect of transforming the claimed “solid mixture” into a
`
`pharmaceutical composition.
`
`
`
`As explained below, the adoption of Novartis’s construction is
`
`compelled by the intrinsic evidence, and therefore is the broadest reasonable
`
`construction of the claim term “solid mixture” in the context of the ’703
`
`patent. By contrast, Par’s construction not only is contrary to the intrinsic
`
`evidence, but also renders the claims of the ’703 patent superfluous and
`
`nonsensical. For these reasons, the Board therefore should adopt Novartis’s
`
`construction and reject Par’s construction.
`
`A. The Intrinsic Evidence Repeatedly
`And Consistently Distinguishes The Claimed
`“Solid Mixture” From A Pharmaceutical Composition
`
`
`
`A foundational principle of claim construction is that a claim term
`
`must be construed in light of the intrinsic evidence. Markman v. Westview
`
`Instruments, Inc., 52 F.3d 967, 979 (Fed. Cir. 1995) (“To ascertain the
`
`meaning of claims, we consider three sources: The claims, the specification,
`
`2
`
`

`
`
`
`and the prosecution history.”); Vitronics Corp. v. Conceptronic, Inc., 90 F.3d
`
`1576, 1582 (Fed. Cir. 1996) (“It is well-settled that, in interpreting an
`
`asserted claim, the court should look first to the intrinsic evidence of
`
`record.”).
`
`
`
`Courts thus have explained that the “ordinary and customary
`
`meaning” of a claim term is not—as Par and its expert wrongly assume—the
`
`dictionary definition of the term, but rather the ordinary and customary
`
`meaning of the claim term when read in the context of the patent in which
`
`it appears. See, e.g., Thorner v. Sony Computer Entm’t Am. LLC, 669 F.3d
`
`1362, 1365 (Fed. Cir. 2012) (“The words of a claim are generally given their
`
`ordinary and customary meaning as understood by a person of ordinary skill
`
`in the art when read in the context of the specification and prosecution
`
`history.”).
`
`
`
`Courts moreover routinely adopt claim constructions that exclude
`
`particular embodiments from a claim term where the intrinsic evidence
`
`consistently distinguishes those particular embodiments from the claimed
`
`subject matter. See, e.g., Nystrom v. Trex Co., Inc., 424 F.3d 1136, 1144-45
`
`(Fed. Cir. 2005) (construing “board” to exclude a non-wooden board, where
`
`the patentee had consistently used the term in the specification and
`
`3
`
`

`
`
`
`prosecution history to refer only to sawed lumber); Schoenhaus v. Genesco,
`
`Inc., 440 F.3d 1354, 1357 (Fed. Cir. 2006) (construing “orthotic device” to
`
`exclude a shoe, where other claims recited a “footwear product” comprising
`
`the claimed orthotic device); Bd. of Regents v. BENQ Am. Corp., 533 F.3d
`
`1362, 1368-70 (Fed. Cir. 2008) (construing “syllabic elements” to exclude
`
`multi-syllabic words, where the claims and specification consistently
`
`distinguished between the two, and the sole example of a “syllabic element”
`
`provided by the specification was a single syllable); Becton, Dickinson &
`
`Co. v. Tyco Healthcare Group, LP, 616 F.3d 1249, 1255 (Fed. Cir. 2010)
`
`(construing “hinged arm” to exclude “spring means,” where the claims
`
`expressly distinguished the two elements).
`
`
`
`Here, the entirety of the intrinsic evidence—the claims, the
`
`specification and the prosecution history of the ’703 patent—consistently
`
`distinguishes the claimed “solid mixture” from a pharmaceutical
`
`composition that includes a pharmaceutically acceptable diluent or carrier.
`
`4
`
`

`
`
`
`In view of the intrinsic evidence, Novartis’s construction should be adopted
`
`and Par’s construction should be rejected.1
`
`1.
`
`The ’703 Patent Claims Distinguish The Claimed
`“Solid Mixture” From A Pharmaceutical
`Composition
`
`
`
`The claims of the ’703 patent alone compel the conclusion that the
`
`claimed “solid mixture” is not a pharmaceutical composition, and excludes a
`
`pharmaceutically acceptable diluent or carrier.
`
`Claims 1, 6 and 7 of the ’703 patent, at Ex. 1001, col. 8, ll. 36-41, 56-
`
`59, 60-61 are set forth below (emphases added):
`
`1. A solid mixture comprising a poly-ene
`macrolide and an antioxidant wherein the poly-ene
`macrolide is selected from the group consisting of
`rapamycin, a 16-O-substituted rapamycin, and a
`
`
`
` 1
`
` Par’s dictionary definition of “mixture” (Ex. 1012, p. 373) also should be
`
`ignored. See Vitronics Corp., 90 F.3d at 1583, 1585 (reliance on extrinsic
`
`evidence is improper where the intrinsic evidence resolves any ambiguity as
`
`to the meaning of the claim term, and the extrinsic evidence contradicts the
`
`intrinsic evidence).
`
`5
`
`

`
`
`
`
`
`40-O-substituted rapamycin and wherein the
`antioxidant is present in a catalytic amount.
`
`6. A pharmaceutical composition comprising as
`active ingredient, a mixture according to claim 1
`or 2, admixed with one or more pharmaceutically
`acceptable carriers or diluents.
`
`7. A pharmaceutical composition of claim 6 for
`oral administration.
`
`
`Claims 1, 6 and 7 of the ’703 patent thus draw an express distinction
`
`between (i) a solid mixture of rapamycin, a 16-O-substituted rapamycin or a
`
`40-O-substituted rapamycin and an antioxidant, and (ii) a pharmaceutical
`
`composition that incorporates that solid mixture together with a
`
`pharmaceutically acceptable diluent or carrier. In view of that express
`
`distinction, the claimed “solid mixture” in the context of the ’703 patent
`
`cannot be a pharmaceutical composition, and cannot include a
`
`pharmaceutically acceptable diluent or carrier.2
`
`
`
` 2
`
` Although the transitional term “comprising” appears in claim 1 of the ’703
`
`patent, that term cannot be used to negate or materially change the express
`
`6
`
`

`
`
`
`
`
`If—as Par’s construction allows—the claimed “solid mixture” can be
`
`a pharmaceutical composition and can include a pharmaceutically acceptable
`
`diluent or carrier, then claims 6 and 7 of the ’703 patent would be
`
`superfluous. Claim terms generally should not be construed in a way that
`
`
`
`limitations of a claim. See, e.g., Outside the Box Innovations, LLC v. Travel
`
`Caddy, Inc., 695 F.3d 1285, 1305 (Fed. Cir. 2012) (“comprising” did not
`
`permit the addition of plywood to a fabric panel, because “[t]he plywood is
`
`not simply an additional element, but a material change in the fabric panel”);
`
`Trading Techs. Int’l, Inc. v. eSpeed, Inc., 595 F.3d 1340, 1354 (Fed. Cir.
`
`2010) (“comprising” did not permit the claim to cover automatic re-
`
`centering because “automatic re-centering is not an additional feature, but
`
`rather negates a claimed requirement that the price level remains static and
`
`does not move”); Spectrum Int’l, Inc. v. Sterilite Corp., 164 F.3d 1372, 1380
`
`(Fed. Cir. 1998) (“‘Comprising’ is not a weasel word with which to abrogate
`
`claim limitations.”). Here, the addition of a pharmaceutically acceptable
`
`diluent or carrier to claim 1 under the term “comprising” would materially
`
`change or negate the claimed “solid mixture” by transforming it into a
`
`pharmaceutical composition. That is not permitted.
`
`7
`
`

`
`
`
`renders other claims or claim terms in the same patent meaningless or
`
`superfluous. See, e.g., Cephalon, Inc. v. Abraxis Bioscience, LLC, 618 Fed.
`
`Appx. 663, 666 (Fed. Cir. 2015) (“[C]onstruing the two terms to have no
`
`difference in meaning would render one of the terms superfluous, which is
`
`disfavored in claim construction.”); Merck & Co., Inc. v. Teva Pharm. USA,
`
`Inc., 395 F.3d 1364, 1372 (Fed. Cir. 2005) (“A claim construction that gives
`
`meaning to all the terms of the claim is preferred over one that does not do
`
`so.”).
`
`
`
`Moreover, if—as Par’s construction allows—the claimed “solid
`
`mixture” can be a pharmaceutical composition, then that would lead to the
`
`nonsensical result wherein claims 6 and 7 could encompass a
`
`“pharmaceutical composition comprising a pharmaceutical composition.”
`
`Such a construction cannot be correct. Courts have rejected similar
`
`constructions under similar circumstances.
`
`
`
`In Forest Labs., Inc. v. Abbott Labs., No. 96-cv-159, 1998 WL
`
`35285402 (W.D.N.Y. Aug. 3, 1998), the District Court for the Western
`
`District of New York construed the terms of an independent claim 1 reciting
`
`a “surface active material,” and two dependent claims 7 and 9 reciting a
`
`“pharmaceutical composition” comprising the “surface active material” of
`
`8
`
`

`
`
`
`claim 1. As to the terms “surface active material” and “pharmaceutical
`
`composition,” the Court reasoned:
`
`If, as defendants argue, the phrases “surface active
`material” and “pharmaceutical composition” were
`to be used interchangeably, then Claims 7 and 9 of
`the patents would teach that a “pharmaceutical
`composition” may be made by combining a
`“pharmaceutical composition,” which is already
`comprised of the “surface active material” and
`physiological saline, with more physiological
`saline. Such a construction obviously does not
`make sense.
`
`Clearly, the patentees intended to give the terms
`“surface active material” and “pharmaceutical
`composition” distinct meanings. If
`the
`term
`“surface active material” was meant to include a
`“pharmaceutical composition,” then there would
`have been no reason to include Claims 7 and 9 in
`the patents. As stated above, it is well established
`that a claim term must be interpreted so as not to
`make any other claim in the patent meaningless or
`superfluous.
`
`Id. at **6-7 (emphases added).
`
`9
`
`

`
`
`
`
`
`
`On appeal, the Federal Circuit agreed with the District Court that there
`
`was a distinction between the claimed “surface active material” recited in the
`
`independent claim and the pharmaceutical compositions recited in the
`
`dependent claims: namely, that the claimed “surface active material”
`
`referred to a surface active material prior to its inclusion in a pharmaceutical
`
`composition, and that the surface active material thus excluded a
`
`pharmaceutical carrier:
`
`*
`
`*
`
`Abbott argues that the court erred in concluding
`that the “‘surface active material’ is only a part or
`subset of the ‘pharmaceutical composition.’”
`
`*
`
`We conclude that the district court properly
`decided that the term “surface active material”
`means the material containing the prescribed
`materials in the prescribed percentages, when
`measured in the dry state, i.e., before being
`combined with the pharmaceutical carrier.
`
`
`Forest Labs., Inc. v. Abbott Labs., 239 F.3d 1305, 1310 (Fed. Cir. 2001)
`
`(emphasis added).
`
`10
`
`

`
`
`
`
`
`The Federal Circuit moreover found that this narrow construction of
`
`the claim term “surface active material” did not render claims 7 and 9
`
`improperly dependent on claim 1, because, under that construction, an
`
`infringer still could not infringe dependent claims 7 or 9 without also
`
`infringing independent claim 1. Id. at 1311, n. 3 (citing the MPEP §
`
`608.01(n) (7th ed. Feb. 2000) standard for proper dependency: “A proper
`
`dependent claim shall not conceivably be infringed by anything which
`
`would not also infringe the basic claim.”).
`
`
`
`In Schoenhaus, claim 1 of the patent-in-suit recited an “orthotic
`
`device” comprising various components, and claim 2 recited “[a] footwear
`
`product having as an element thereof an orthotic device as claimed in claim
`
`1.” 440 F.3d at 1356. The Federal Circuit rejected the patentee’s assertion
`
`that the claimed “orthotic device” was not limited to a “discrete insert,” but
`
`instead could be so broad as to cover a “shoe built to have the shape of the
`
`interior of the insert,” because claim 2 would then cover a “footwear product
`
`having as an element thereof [a shoe],” and “[o]bviously, a ‘shoe . . .’ cannot
`
`be considered ‘an element’ of a footwear product.” Id. at 1356-57. The
`
`Federal Circuit concluded that “[plaintiffs’ proposed construction] renders
`
`claim 2 nonsensical. Accordingly, plaintiffs ‘proposed construction cannot
`
`11
`
`

`
`
`
`be correct.” Id. at 1357 (emphasis added). See also Becton, 616 F.3d at
`
`1255 (Fed. Cir. 2010) (rejecting as “facially nonsensical” a claim
`
`construction under which the claimed “hinged arm” can be the same
`
`structure as the claimed “spring means,” because then “the hinged arm must
`
`be ‘connected to’ itself and must ‘extend between’ itself and a mounting
`
`means, a physical impossibility”).
`
`
`
`Here, under the same logic of Forest, Schoenhaus, and Becton, the
`
`claimed “solid mixture” of the ’703 patent is not a pharmaceutical
`
`composition, and excludes a pharmaceutically acceptable diluent or carrier.
`
`A construction of “solid mixture” that does not acknowledge those facts
`
`would render claim 3 of the ’703 patent superfluous and nonsensical.
`
`Accordingly, the broadest reasonable construction of “solid mixture” is
`
`Novartis’s construction.
`
`2.
`
`The Specification Also Distinguishes The Claimed
`“Solid Mixture” From A Pharmaceutical
`Composition
`
`
`
`The specification of the ’703 patent also compels the conclusion that
`
`the broadest reasonable construction of “solid mixture” is not a
`
`pharmaceutical composition, and excludes a pharmaceutically acceptable
`
`diluent or carrier.
`
`12
`
`

`
`
`
`
`
`Like the claims, the specification consistently and repeatedly
`
`distinguishes between the claimed subject matter and a “pharmaceutical
`
`composition.” The specification explains that the crux of the invention of
`
`the ’703 patent is the combination of an active ingredient selected from
`
`rapamycin, 16-O-substituted rapamycin derivative or 40-O-substituted
`
`rapamycin derivative and an antioxidant, prior to its transformation into a
`
`pharmaceutical composition by the addition of a pharmaceutically
`
`acceptable diluent or carrier.
`
`
`
`For example, the ’703 patent, at Ex. 1001, col. 1, ll. 37-47, states
`
`(emphases added):
`
`As alternatives to the above the present invention
`also provides:
`
`2. A mixture, e.g. a bulk mixture, comprising a
`poly-ene macrolide and an anti-oxidant, preferably
`a catalytic amount thereof, preferably in solid
`form. . . .
`
`3. Use of a mixture as defined above in 2, in the
`manufacture of a pharmaceutical composition.
`
`
`
`13
`
`

`
`
`
`
`
`The ’703 patent, at Ex. 1001, col. 2, ll. 30-33, also states (emphasis
`
`added):
`
`A particularly preferred mixture of the invention is
`a mixture of rapamycin or 40-O-(2-hydroxy)ethyl
`rapamycin [everolimus] and 0.2% (based on the
`weight of the macrolide) of antioxidant, preferably
`BHT.
`
`The ’703 patent, at Ex. 1001, col. 2, ll. 54-58, further states (emphases
`
`
`
`
`
`added):
`
`Accordingly there is further provided:
`
`4. A pharmaceutical composition comprising, as
`active ingredient, a stabilized mixture as disclosed
`above, together with one or more pharmaceutically
`acceptable diluent or carrier.
`
`
`
`Other parts of the specification—although they do not expressly use
`
`the word “mixture”—clearly and consistently explain that the invention of
`
`the ’703 patent is the combination of an active ingredient selected from
`
`rapamycin, a 16-O-substituted rapamycin derivative or a 40-O-substituted
`
`rapamycin derivative and an antioxidant, which subsequently can be
`
`14
`
`

`
`
`
`transformed into a pharmaceutical composition by the addition of a
`
`pharmaceutically acceptable diluent or carrier.
`
`
`
`For example, the ’703 patent, at Ex. 1001, col. 2, ll. 48-53, states:
`
`The macrolide stabilized according to the
`invention may be used as such for the production
`of the desired galenic formulation. Such
`formulations may be prepared according to
`methods known in the art, comprising the addition
`of one or more pharmaceutically acceptable diluent
`or carrier, including the addition of further
`stabilizer if required.
`
`The ’703 patent, at Ex. 1001, col. 3, ll. 16-21 also states:
`
`This invention is particularly interesting for
`rapamycin compositions in liquid or solid form.
`A particularly preferred composition is a solid
`dispersion, e.g. comprising a stabilized rapamycin
`according to the invention and a carrier medium,
`e.g. a water-soluble polymer such as
`hydroxypropylmethylcellulose, e.g. as disclosed in
`WO 97/03654.
`
`Last, Example 2 of the ’703 patent, at Ex. 1001, col. 5, l. 50 – col. 6, l.
`
`
`
`
`
`
`
`9, describes the preparation of a solid mixture of 40-O-(2-hydroxy)ethyl
`
`15
`
`

`
`
`
`rapamycin, i.e., everolimus, and BHT. Example 2 constitutes the sole
`
`example in the specification of a solid mixture of an active ingredient
`
`selected from rapamycin, 16-O-substituted rapamycin derivative or 40-O-
`
`substituted rapamycin derivative and an antioxidant. This sole example does
`
`not include a pharmaceutically acceptable diluent or carrier.
`
`
`
`In sum, the specification of the ’703 patent consistently and
`
`repeatedly explains that the “invention,” i.e., a solid mixture of an active
`
`ingredient selected from rapamycin, a 16-O-substituted rapamycin derivative
`
`or a 40-O-substituted rapamycin derivative and antioxidant, is not a
`
`pharmaceutical composition, and does not include a pharmaceutically
`
`acceptable diluent or carrier—but, instead, that the invention can be used to
`
`make a pharmaceutical composition by the addition of a pharmaceutically
`
`acceptable diluent or carrier.
`
`
`
`In view of the specification of the ’703 patent, the claimed “solid
`
`mixture” clearly is not a pharmaceutical composition, and excludes a
`
`pharmaceutically acceptable diluent or carrier. Accordingly, the broadest
`
`reasonable construction of “solid mixture” is Novartis’s construction. See,
`
`e.g., Bd. of Regents, 533 F.3d at 1368-70 (refusing to adopt a construction of
`
`“syllabic elements” that encompassed multi-syllabic words, where the
`
`16
`
`

`
`
`
`specification “repeatedly distinguishes between a ‘word’ and a ‘syllabic
`
`element’ and indicates that a word is comprised of syllabic elements,” and
`
`the only example in the specification of a “syllabic element” in the
`
`specification was limited to one syllable); Nystrom, 424 F.3d at 1144
`
`(construing “board” to exclude a non-wooden board, where “[t]hroughout
`
`the written description, Nystrom consistently used the term ‘board’ to
`
`describe wood decking material cut from a log.”).
`
`3.
`
`The Prosecution History Also Distinguishes The
`Claimed “Solid Mixture” From A Pharmaceutical
`Composition
`
`
`
`The prosecution history of U.S. Patent No. 7,741,338 (“’338
`
`patent”)—which is a continuation of the ’703 patent and recites claims to a
`
`“solid mixture” of everolimus and BHT—further compels the conclusion
`
`that the broadest reasonable construction of “solid mixture” is not a
`
`pharmaceutical composition, and excludes a pharmaceutically acceptable
`
`diluent or carrier. See, e.g., Microsoft Corp. v. Multi-Tech Sys., Inc., 357
`
`F.3d 1340, 1349 (Fed. Cir. 2004) (“the prosecution history of one patent is
`
`relevant to an understanding of the scope of a common term in a second
`
`patent stemming from the same parent application”).
`
`17
`
`

`
`
`
`
`
`During the prosecution of the ’338 patent, the applicant submitted an
`
`Amendment After Allowance dated January 26, 2010. Ex. 2001. That
`
`Amendment set forth the following claims, including new dependent claim
`
`3:
`
`
`
`Claim 1. (Original): A solid mixture comprising
`40-O-(2-hydroxy)ethyl-rapamycin and 2,6-di-tert-
`butyl-4-methylphenol (BHT)
`
`Claim 3. (New): A pharmaceutical composition
`comprising the solid mixture of claim 1.
`
`New dependent claim 3, as submitted on January 26, 2010, thus
`
`recited a “pharmaceutical composition” requiring only the solid mixture of
`
`claim 1.
`
`
`
`In the remarks to the January 26, 2010 amendment, the applicant
`
`noted that:
`
`Applicants provide the instant amendment after
`allowance in order to add a new dependent
`pharmaceutical composition claim (new claim 3).
`This claim finds support in the originally filed
`application at page 4 [corresponding to col. 2, l. 55
`– col. 3, l. 31 of the issued ’703 patent].
`
`
`18
`
`

`
`
`
`
`
`Ex. 2001.
`
`
`In a February 3, 2010 Response to Rule 312 Communication, the
`
`Examiner disapproved of new claim 3, noting that it was a “duplicate of
`
`claim 1,” and advising that “[i]nsertion of the language in page 4 which
`
`reads ‘together with one or more pharmaceutically acceptable diluent or
`
`carrier’ would overcome the objection.” Ex. 2002. In other words, the
`
`Examiner communicated to the applicant his understanding, based upon the
`
`shared specification of the ’703 and ’338 patents—and consistent with
`
`Novartis’s construction—that the claimed “solid mixture” is not a
`
`pharmaceutical composition, and that the addition of a pharmaceutically
`
`acceptable diluent or carrier is required for a pharmaceutical composition.
`
`
`
`In a February 17, 2010 Amendment After Allowance, the applicant
`
`amended claim 3 to recite (emphasis added):
`
`Claim 3. (New): A pharmaceutical composition
`comprising the solid mixture of claim 1 together
`with one or more pharmaceutically acceptable
`diluent or carrier.
`
`
`Ex. 2003.
`
`
`
`Thus, the applicant agreed with the Examiner that the claim term
`
`“solid mixture,” when read in the context of the specification, is different
`
`19
`
`

`
`
`
`from a pharmaceutical composition in that a pharmaceutical composition
`
`includes a pharmaceutically acceptable diluent or carrier whereas the
`
`claimed “solid mixture” does not.
`
`
`
`The prosecution history of the related ’338 patent thus further
`
`reinforces the consistent distinction throughout the intrinsic evidence
`
`between the claimed “solid mixture” and a pharmaceutical composition. In
`
`view of the intrinsic evidence, it is clear the claimed “solid mixture” of the
`
`’703 and ’338 patents is not a pharmaceutical composition, and excludes a
`
`pharmaceutically acceptable diluent or carrier.
`
`
`
`For at least these reasons, Novartis respectfully requests that the
`
`Board adopt Novartis’s construction of the claim term “solid mixture” and
`
`reject Par’s construction. 3
`
`
`
` 3
`
` Contra Ex. 2008, D. Del. No. 14-cv-1494, D.I. 97 (District Court decision
`
`in related proceeding adopting Par’s construction). Novartis disagrees with
`
`the District Court’s decision for the reasons discussed herein.
`
`20
`
`

`
`
`
`II. The Board Should Deny Institution Of Ground 1 As To Claims 1-
`3, 6 and 7 Because Guitard Does Not Anticipate Those Claims Of
`The ’703 Patent
`
`
`
`The Board should deny institution of Par’s Ground 1 as to claims 1-3,
`
`6 and 7 of the ’703 patent because each of claims 1-3, 6 and 7 of the ’703
`
`patent requires a “solid mixture,” whereas Guitard (Ex. 1004) fails to
`
`disclose a “solid mixture.”
`
`
`
`Contrary to the conclusory assertions of Par and its expert (e.g., Pet.,
`
`pp. 5-7, 31-32; Ex. 1002, Benjamin Decl. at ¶¶ 30, 93), the “solid
`
`dispersion” disclosed by Guitard is not a type of “solid mixture” as that term
`
`is used in the context of the ’703 patent. As explained in the preceding
`
`Section I, it is clear from the claims and the specification of the ’703 patent,
`
`and the prosecution history of the related ’338 patent, that the claimed “solid
`
`mixture” of the ’703 patent is not a pharmaceutical composition, and
`
`excludes a pharmaceutically acceptable carrier.
`
`
`
`It is equally clear from the claims and the specification of Guitard that
`
`the claimed “solid dispersions” of Guitard are pharmaceutical compositions
`
`that necessarily include a pharmaceutically acceptable carrier. As such,
`
`Guitard’s “solid dispersions”