`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`CATALENT PHARMA SOLUTIONS, INC.,
`Petitioner,
`
`v.
`
`PATHEON SOFTGELS INC.,
`Patent Owner.
`
`
`Case IPR2018-00421
`Patent 9,693,978
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 9,693,978
`
`
`
`
`
`
`
`
`
`
`
`
`Mail Stop PATENT BOARD
`Patent Trial and Appeal Board
`U.S. Patent & Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`
`I.
`
`TABLE OF CONTENTS
`
`INTRODUCTION ......................................................................................... 1
`
`II. GROUNDS FOR STANDING (37 C.F.R. § 42.104(A)) ............................. 1
`
`III. MANDATORY REQUIREMENTS, NOTICES AND FEES ................... 1
`
`A. Real Party-In-Interest (35 U.S.C. § 312(a)(2) and 37 C.F.R.
`§ 42.8(b)(1)) .......................................................................................... 1
`
`B.
`
`C.
`
`D.
`
`E.
`
`Related Matters (37 C.F.R. §42.8(b)(2)) ............................................ 1
`
`Lead and Back-Up Counsel (37 C.F.R. §42.8(b)(3)) and
`Service Information (37 C.F.R. §42.8(b)(4)) ..................................... 2
`
`Power of Attorney (37 C.F.R. §42.10(b)) .......................................... 3
`
`Petition Fees (35 U.S.C. § 312(a)(1) and 37 C.F.R. §§ 42.15
`and 42.103) ........................................................................................... 3
`
`F.
`
`Proof of Service (37 C.F.R. §§ 42.6(e) and 42.105(a)) ...................... 3
`
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED (37 C.F.R.
`§§ 42.22(A)(1) AND 42.104(B)(2)) ................................................................ 3
`
`V.
`
`TECHNOLOGY BACKGROUND .............................................................. 5
`
`VI. RELEVANT INFORMATION CONCERNING THE CONTESTED
`PATENT ......................................................................................................... 6
`
`A.
`
`B.
`
`C.
`
`D.
`
`The ’978 Patent .................................................................................... 6
`
`Brief Summary of the Prosecution History of the ’978
`Patent ................................................................................................... 7
`
`Issued Claims ....................................................................................... 8
`
`Person of Ordinary Skill in the Art .............................................. 10
`
`E. Construction of Terms Used in the Claims ................................. 11
`
`1.
`
`2.
`
`“about 5%” ............................................................................12
`
`“fill material” ........................................................................13
`
`F.
`
`Summary of Expert Declaration of Peter Draper ...................... 15
`
`VII. THERE IS A REASONABLE LIKELIHOOD THAT AT LEAST
`ONE CLAIM OF THE ’978 PATENT IS UNPATENTABLE
`UNDER 37 C.F.R. §42.104(B)(4) .............................................................. 16
`
`i
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`
`A. Ground 1: Claims 1-38 are invalid under 35 U.S.C. § 102
`as anticipated by, or 35 U.S.C. § 103 as obvious in view of,
`U.S. Patent No. 6,383,471 to Chen. .................................................. 17
`
`B. Ground 2: Claims 1-38 are invalid under 35 U.S.C. § 103
`as obvious in view of U.S. Publication No. 20040157928 to
`Kim, alone or in combination with U.S. Patent No.
`6,383,471 to Chen. ............................................................................. 35
`
`1.
`
`2.
`
`Claims 1-38 are invalid under 35 U.S.C. § 103 as
`obvious in view of U.S. Publication No. 20040157928
`to Kim alone ...........................................................................35
`
`Claims 1-38 are invalid under 35 U.S.C. § 103 as
`obvious in view of U.S. Publication No. 20040157928
`to Kim in view of U.S. Patent No. 6,383,471 to Chen ........37
`
`C. Ground 3: Claims 1-38 are invalid under 35 U.S.C. § 102
`as anticipated by, or under 35 U.S.C. § 103 as obvious in
`view of, U.S. Publication No. 20040224020 to Schoenhard. .......... 49
`
`VIII. CONCLUSION ............................................................................................ 59
`
`
`
`ii
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`
`Cases
`
`TABLE OF AUTHORITIES
`
`
`Chore-Time Equipment, Inc. v. Cumberland Corp.,
`713 F.2d 774 (Fed. Cir. 1983) .....................................................................11
`
`KSR Int’l Co. v. Teleflex, Inc.,
`550 U.S. 398, 127 S.Ct. 1727 (2007) ..........................................................59
`
`Okajima v. Bourdeau,
`261 F.3d 1350 (Fed. Cir. 2001) ...................................................................11
`
`
`
`iii
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`
`Exhibit
`No.
`
`EXHIBIT LIST
`
`Description
`
`1001 Declaration of Peter Draper
`
`1002 Curriculum Vitae of Peter Draper
`
`1003 U.S. Patent No. 9,693,978
`
`1004
`
`Prosecution History of U.S. Patent No.
`9,693,978 (App. No. 60/659,679)
`
`1005
`
`Prosecution History of U.S. Patent No.
`9,693,978 (App. No. 11/367,238)
`
`1006
`
`Prosecution History of U.S. Patent No.
`9,693,978 (App. No. 14/977,808)
`
`1007
`
`Prosecution History of EP 1863458
`(Counterpart of U.S. Patent No. 9,693,978)
`
`1008
`
`Prosecution History of U.S. Patent No.
`9,693,979 (App. No. 15/159,972)
`
`Issue or Publication
`Date
`
`
`
`
`
`July 4, 2017
`
`
`
`
`
`
`
`
`
`
`
`
`1009 U.S. Patent No. 6,383,471 (“Chen”)
`
`May 7, 2002
`
`1010 U.S. Publication No. 20040157928 (“Kim”)
`
`August 12, 2004
`
`1011
`
`U.S. Publication No. 20040224020
`(“Schoenhard”)
`
`November 11, 2004
`
`1012 U.S. Patent No. 5,141,961 (“Coapman”)
`
`August 25, 1992
`
`1013 U.S. Patent No. 5,641,512 (“Cimileuca”)
`
`December 27, 1994
`
`1014 U.S. Patent No. 5,360,615 (“Yu”)
`
`November 1, 1994
`
`1015 U.S. Patent No. 6,383,515 (“Sawyer”)
`
`May 7, 2002
`
`iv
`
`

`

`
`
`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`1016 U.S. Publication No. 20060099246 (“Tanner”)
`
`May 11, 2006
`
`1017 Wikipedia, Conjugate acid (July 8, 2016)
`
`
`
`1018 U.S. Publication No. 20050158377 (“Popp”)
`
`July 21, 2005
`
`1019 U.S. Patent No. 6,066,339 (“Stark”)
`
`May 23, 2000
`
`1020 U.S. Patent No. 6,251,426 (“Gullapalli”)
`
`June 26, 2001
`
`1021
`
`Banner Pharmacaps, Inc. Citizen Petition to the
`Food and Drug Administration
`
`October 10, 2002
`
`1022
`
`Wikipedia, Robert Pauli Scherer,
`https://en.wikipedia.org/wiki/Robert_Pauli_Sc
`herer (January 8, 2018)
`
`1023
`
`R.M.C. Dawson et al., Data for Biochemical
`Research (Oxford: Clarendon Press 1959)
`
`1024
`
`1025
`
`Jarkko Rautio et al., “In Vitro Evaluation of
`Acyloxyalkyl Esters as Dermal Prodrugs of
`Ketoprofen
`and Naproxen,”
`Journal of
`Pharmaceutical Sciences, Vol. 87, No. 12,
`1622-1628 (December 1998)
`
`Letter from Sharon Hertz, Department Of
`Health & Human Services, to Roche Palo Alto
`LLC regarding NDA 18-965 (November 10,
`2004)
`
`
`
`1959
`
`December 1998
`
`November 10, 2004
`
`1026 U.S. Patent No. 3,035,973 (“Klotz”)
`
`May 22, 1962
`
`1027
`
`H. Sevelius et al., “Bioavailability of Naproxen
`Sodium and Its Relationship
`to Clinical
`Analgesic Effects,” 10 Br. J. Clin. Pharmac.
`259-263 (1980)
`
`1980
`
`1028
`
`Inc. NDA 21-920,
`Banner Pharmacaps
`Naproxen Sodium Capsules
`
`February 16, 2006
`
`v
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`
`1029
`
`Robert Thornton Morrison & Robert Neilson
`Boyd, Organic Chemistry (4th ed., Allyn and
`Bacon, Inc. 1983)
`
`1983
`
`vi
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`I.
`
`INTRODUCTION
`
`Catalent Pharma Solutions, Inc. (“Petitioner”) hereby requests Inter Partes
`
`Review (“IPR”) of Claims 1-38 (“challenged claims”) of U.S. Patent No.
`
`9,693,978 (“the ’978 Patent,” Ex.1003) pursuant to 35 U.S.C. §§ 311 et seq. and 37
`
`C.F.R. §§ 42.1 et seq.
`
`II. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a))
`
`Petitioner certifies that the ’978 Patent, which issued on July 4, 2017, is
`
`available for IPR and that Petitioner is not barred or estopped from requesting an
`
`IPR for the challenged claims of the ’978 Patent.
`
`III. MANDATORY REQUIREMENTS, NOTICES AND FEES
`
`A. Real Party-In-Interest (35 U.S.C. § 312(a)(2) and 37 C.F.R. §
`42.8(b)(1))
`
`Petitioner Catalent Pharma Solutions, Inc. is the sole real party-in-interest.
`
`No other party exercised or could have exercised control over this petition; no
`
`other parties funded or directed this petition. (See Office Patent Practice Trial
`
`Guide, 77 Fed. Reg. 48750-60).
`
`B. Related Matters (37 C.F.R. §42.8(b)(2))
`
`The following administrative matters may affect, or be affected by, a
`
`decision in this proceeding: IPR2018-00422 (simultaneously filed by Petitioner).
`
`Additionally, the ’978 Patent and U.S. Patent No. 9,693,979 are the subject of two
`
`1
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`cases recently filed by Patent Owner: Patheon Softgels Inc. v. Apotex Inc. et al.,
`
`No. 3:17-cv-13819 (D. N. J.) and Patheon Softgels Inc. v. Apotex Inc. et al., No.
`
`1:18-cv-00003 (D. Del.).
`
`C. Lead and Back-Up Counsel (37 C.F.R. §42.8(b)(3)) and Service
`Information (37 C.F.R. §42.8(b)(4))
`
`LEAD COUNSEL
`
`BACK-UP COUNSEL
`
`
`Gregory L. Porter, Esq., Reg. No.
`40,131
`Andrews Kurth Kenyon, LLP
`600 Travis, Suite 4200
`Houston, TX 77002
`Tel.: (713) 220-4621
`Fax: (713) 238-4257
`Email:
`GregPorter@andrewskurth.com
`
`
`Rose Cordero Prey, Esq.
`Andrews Kurth Kenyon, LLP
`One Broadway
`New York, NY 10004
`Tel.: (212) 425-7200
`Fax: (212) 425-5288
`Email: rprey@andrewskurthkenyon.com
`
`David Bradin, Esq., Reg. No. 37,783
`Andrews Kurth Kenyon, LLP
`4505 Emperor Blvd, Suite 330
`Durham, NC 27703
`Tel.: (919) 864-7201
`Fax: (919) 244-9570
`Email:
`DavidBradin@andrewskurth.com
`
`
`
`
`
`Petitioner consents to email service. Please address all papers concerning
`
`this matter to lead counsel and back-up counsel at the above addresses. As
`
`necessary, back-up counsel will seek authorization to submit a motion to appear
`
`pro hac vice before the Board on behalf of Petitioner.
`
`2
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`
`D.
`
`Power of Attorney (37 C.F.R. §42.10(b))
`
`A Power of Attorney is submitted herewith pursuant to 37 C.F.R. §42.10(b).
`
`E.
`
`Petition Fees (35 U.S.C. § 312(a)(1) and 37 C.F.R. §§ 42.15 and
`42.103)
`
`The Director is authorized to charge the fee specified by 37 C.F.R. §
`
`42.15(a) to Deposit Account No. 50-0897.
`
`F.
`
`Proof of Service (37 C.F.R. §§ 42.6(e) and 42.105(a))
`
`Proof of service is provided herein at the end of this Petition.
`
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED (37 C.F.R.
`§§ 42.22(a)(1) AND 42.104(b)(2))
`
`The Petitioner respectfully requests IPR under 37 C.F.R. § 42.108 as to
`
`Claims 1-38 of the ’978 Patent and a ruling that the claims are unpatentable based
`
`on one or more of the grounds under 35 U.S.C. §§ 102 and 103 for the reasons set
`
`forth herein.
`
`Petitioner requests cancellation of the challenged claims based on the
`
`following references and the Declaration of Peter Draper (“Draper Declaration,”
`
`Ex.1001) and exhibits cited therein:
`
`•
`
`U.S. Patent No. 6,383,471 to (“Chen,” Ex.1009) filed on April
`
`6, 1999, issued on May 7, 2002, and is prior art under at least
`
`pre-AIA 35 U.S.C. § 102(b);
`
`3
`
`

`

`
`
`•
`
`U.S. Publication No. 20040157928 (“Kim,” Ex.1010) filed on
`
`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`October 14, 2003, published on August 12, 2004, and is prior
`
`art under at least pre-AIA 35 U.S.C. § 102(a) and/or (e); and
`
`•
`
`U.S. Publication No. 20040224020 (“Schoenhard,” Ex.1011)
`
`filed on December 18, 2003, published on November 11, 2004,
`
`and is prior art under at least pre-AIA 35 U.S.C. § 102(a) and/or
`
`(e).
`
`The specific grounds of unpatentability are as follows:
`
`Ground Claim(s)
`
`Claims 1-
`38
`
`Claims 1-
`38
`
`Claims 1-
`38
`
`1
`
`2
`
`3
`
`
`
`Basis for Challenge
`
`Anticipated under §102 by, or Obvious under §103 in view
`of, U.S. Patent No. 6,383,471 to Chen
`
`Obvious under §103 in view of U.S. Publication No.
`20040157928 to Kim by itself, or in combination with U.S.
`Patent No. 6,383,471 to Chen
`
`Anticipated under §102 by, or Obvious under §103 in view
`of, U.S. Publication No. 20040224020 to Schoenhard
`
`
`Petitioner’s detailed statement of the reasons for the relief requested is set
`
`forth in Section VII below and supported by the Draper Declaration and the other
`
`exhibits. The Draper Declaration explains: (i) the scope and content of the prior
`
`art; (ii) the differences, if any, between the prior art and the claimed subject matter
`
`4
`
`

`

`
`in the ’978 Patent; (iii) the level of ordinary skill in the art; and (iv) the lack of any
`
`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`objective indicia of non-obviousness.
`
`V. TECHNOLOGY BACKGROUND
`
`The ’978 Patent generally pertains to naproxen soft gelatin capsules.
`
`Naproxen is a non-steroidal anti-inflammatory drug (NSAID) having the formula:
`
`
`
`Due to its acidic nature and poor solubility, it is frequently administered in
`
`the form of a pharmaceutically-acceptable salt such as naproxen sodium. A typical
`
`adult dosage for naproxen and/or naproxen sodium is around 200 or 250 mg for
`
`naproxen or 220 mg for naproxen sodium while a child dosage is 125mg.
`
`(Ex.1001,¶¶29,36,105).
`
`Soft gelatin capsules (“softgels”) encapsulating pharmaceuticals in liquid
`
`form have been in existence since the early 1900s. Prior to the ’978 Patent filing,
`
`certain acidic drugs, like naproxen, were well-known to be difficult to dissolve in
`
`their acid form. Moreover, it was known that the pH of the softgel fill liquid should
`
`be controlled, e.g., maintained between 2.5 and 7.5 so as not to hydrolyze or tan the
`
`gelatin shell. Common approaches for addressing these issues included using
`
`5
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`appropriate solvent systems and/or partial ionization to form compositions which
`
`include both the acid and the conjugate base. (Ex.1001,¶31).
`
`Since the early 1990s common solvent systems for naproxen and its salts in
`
`softgels have included solvents such as polyethylene glycols, polyvinylpyrrolidone,
`
`and propylene glycol. (Ex.1001,¶¶32-34 (citing Exs.1012-1013)). Such systems
`
`were used in conjunction with partial ionization to improve dissolution rates and not
`
`deleteriously affect the gelatin shell. (Ex.1001,¶35 (citing Ex.1014)). Accordingly,
`
`the soft gelatin capsule solvent systems and partial ionization techniques of the type
`
`used in the ’978 Patent were well known for use in naproxen salt and other softgel
`
`formulations well before March 8, 2005. (Ex.1001,¶34).
`
`VI. RELEVANT INFORMATION CONCERNING THE CONTESTED
`PATENT
`
`A. The ’978 Patent
`
`After nearly eight years of prosecution, the’978 Patent issued on July 4,
`
`2017 with 38 claims. The earliest priority date of the ’978 Patent is March 8,
`
`2005. The broadest independent claims, Claims 1 and 10, relate to a soft
`
`gelatin capsule comprising a fill material “comprising: (a) a naproxen salt; (b)
`
`about 5% lactic acid by weight of the fill material; and (c) polyethylene glycol.”
`
`(Ex.1003, 9:63-10:34).
`
`6
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`
`B. Brief Summary of the Prosecution History of the ’978 Patent
`
`The specification of the ’978 Patent relates to the partial neutralization of
`
`acidic or basic drugs, generally, before encapsulation in gelatin capsules. The
`
`original claims in the parent utility application filed March 3, 2006, attempted to
`
`broadly claim this concept. (Ex.1005,pp.24-26). After a number of Office
`
`Actions, claim amendments, and responses, the Examiner’s rejection of the
`
`pending claims was affirmed on appeal to the PTAB in October 2015.
`
`(Ex.1005,pp.424-435).
`
`The Patentee filed a continuation application in December 2015 again
`
`maintaining claims focused on numerous active agents, polyethylene glycol and a
`
`deionizing agent “in an amount of from about 0.2 to about 1.0 mole equivalents per
`
`mole of active agent.” (Ex.1006,pp.55-63). There were again numerous Office
`
`Actions, claim amendments, and responses which resulted in the Patentee
`
`narrowing the broadest independent claim, Claim 1, to:
`
`A pharmaceutical composition comprising: (a) a naproxen salt;
`(b) lactic acid in an amount from about 0.2 to about 1.0 mole
`equivalents per mole of naproxen salt; and (c) polyethylene
`glycol.
`
`(Ex.1006,pp.173-179).
`
` A
`
` December 2016 Advisory Action held that that the pending claims were
`
`still obvious. (Ex.1006,pp.191-193). The Patentee filed a supplemental response
`
`7
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`on February 7, 2017, amending all the independent claims to “about 5% lactic acid
`
`by weight of the fill material” and referring to a January 23, 2017 Prosecution Pilot
`
`Program (P3) Conference. (Ex.1006,pp.207-216).1 The amended claims were
`
`allowed on March 10, 2017, with the only stated “reason” being that “the prior art
`
`does not reasonably teach a composition comprising about 5% of lactic acid with
`
`naproxen salt in a gelatin capsule with the other ingredients as claimed by
`
`Applicant.” (Ex.1006,pp.232-239).
`
`C.
`
`Issued Claims
`
`Certain of the issued claims of the ’978 Patent (Claims 1-7 and 22-24) relate
`
`to compositions which comprise a softgel capsule which encapsulates a fill
`
`material which includes a naproxen salt, about 5% lactic acid by weight of the fill
`
`material, and polyethylene glycol. Claims 2-7 specify the amount of polyethylene
`
`glycol (Claim 2), the molecular weight range for the polyethylene glycol (Claim
`
`3), that the composition comprises one or more excipients (Claims 4 and 5), or a
`
`solubilizer (glycerin, polyvinylpyrrolidone, propylene glycol, or a combination
`
`thereof (Claim 6)), and the amount of the solubilizer in Claim 6 (Claim 7). Claim
`
`22 depends from Claim 1, Claim 24 depends from Claim 8, and each specifies that
`
`
`1 The “about 5% lactic acid” limitation first appeared in dependent claims 3, 21,
`43, 50, and 58 in a September 27, 2016 amendment and response referring to
`Examples 7-12 as support. (Ex.1006,pp.127-143).
`
`8
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`the naproxen salt comprises sodium naproxen. Claim 23 depends from Claim 6
`
`and specifies that the solubilizer comprises polyvinylpyrrolidone.
`
`Claims 8-9 are directed to methods of making these capsules by mixing the
`
`components “at an appropriate temperature” and then encapsulating them in a soft
`
`gelatin capsule (Claim 8), where the “appropriate temperature” can be from about
`
`50°C to about 70°C (Claim 9).
`
`Claims 10-16 are similar to Claims 1-7, but focus on the capsule itself rather
`
`than a composition comprising the capsule.
`
`Claim 17 is directed to a method of using the capsule of Claim 10 by
`
`administering it to a patient.
`
`Claim 18 is directed to a soft gelatin capsule similar to that claimed in Claim
`
`10, but specifies the amount and molecular weight range for the polyethylene
`
`glycol, and Claim 19 is directed to a method of using the capsule of Claim 18.
`
`Claim 20
`
`is a product-by-process claim, where a pharmaceutical
`
`composition is prepared by a mixing together a naproxen salt, about 5% lactic acid
`
`by weight of the fill material, and polyethylene glycol with a molecular weight
`
`between 300 and 1500. Claim 21 is similar to Claim 20, but further specifies that
`
`the process involves encapsulating the mixture in a soft gelatin capsule.
`
`9
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
`
`
`
`Claim 25 is directed to a capsule produced by the method of claim 8. Claim
`
`26 is directed to the capsule of claim 10, wherein the naproxen salt comprises
`
`sodium naproxen. Claim 27 is directed to the capsule of claim 15, wherein the
`
`solubilizer comprises polyvinylpyrrolidone. Claim 28 is directed to the capsule of
`
`Claim 18, wherein the fill further comprises a solubilizer; Claim 29 specifies the
`
`amount of the solubilizer, and Claim 30 specifies that the solubilizer comprises
`
`polyvinylpyrrolidone.
`
`Claim 31 depends from Claim 20, and specifies that the naproxen salt
`
`comprises sodium naproxen. Claim 32 also depends from Claim 20, and specifies
`
`that the fill material further comprises a solubilizer; Claim 33 specifies the amount
`
`of the solubilizer, and Claim 34 specifies that the solubilizer comprises
`
`polyvinylpyrrolidone.
`
`Claim 35 depends from Claim 21 and specifies that the naproxen salt
`
`comprises sodium naproxen. Claim 36 also depends from Claim 21, and specifies
`
`that the fill material further comprises a solubilizer; Claim 37 specifies the amount
`
`of the solubilizer, and Claim 38 specifies that the solubilizer comprises
`
`polyvinylpyrrolidone.
`
`D. Person of Ordinary Skill in the Art
`
`The field of invention for the ’978 Patent is soft gelatin capsule formulations
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`Patent No. 9,693,978
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`as described in the preamble for all independent claims of the ’978 Patent. The
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`level of ordinary skill in the art as of the effective filing date of the ’978 Patent,
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`March 8, 2005, is appropriately reflected in the disclosure of the prior art discussed
`
`above in Section V and below in Section VII. Chore-Time Equipment, Inc. v.
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`Cumberland Corp., 713 F.2d 774 (Fed. Cir. 1983); see also Okajima v. Bourdeau,
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`261 F.3d 1350, 1355 (Fed. Cir. 2001).
`
`The person of ordinary skill in this art (“POSA”) would have at least a
`
`bachelor’s degree or the equivalent, and potentially some advanced schooling, in
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`pharmaceutical sciences, chemistry, or a related discipline, and a minimum of 5
`
`years of additional training and experience in the field of pharmaceutical
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`formulations, particularly as they relate to soft gelatin capsules. (Ex. 1001,¶26).
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`E. Construction of Terms Used in the Claims
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`A claim subject to inter partes review receives the “broadest reasonable
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`construction in light of the specification of the patent in which it appears.” 42
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`C.F.R. §42.100(b). The broadest reasonable construction of “about 5%” and “fill
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`material,” which each appear in all the independent claims, may be useful to
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`consider as described below.
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`For the purposes of this inter partes review only, the remainder of the claim
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`terms are to be given their ordinary and customary meaning that the terms would
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`have to a POSA. None of the challenged claims contain a means-plus-function or
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`Petition for Inter Partes Review
`Patent No. 9,693,978
`IPR2018-00421
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`step-plus-function limitation.
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`1.
`
`“about 5%”
`
`Every claim includes the “about 5% lactic acid by weight” limitation, but the
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`term “about 5%” does not appear anywhere in the specification of the ’978 Patent.
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`“About 5% lactic acid” first appeared in dependent claims 3, 21, 43, 50, and 58 in
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`a September 27, 2016 amendment and response referring to Examples 7-12 as
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`support.
`
` (Ex.1006,pp.127-143).
`
` Accordingly, to determine the broadest
`
`reasonable construction of “about 5%” to a POSA, it is relevant to look to the
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`amount of lactic acid that is included in Examples 7-12. (Ex.1001,¶75).
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`Examples 9-12 refer to 5.00% lactic acid, and Example 7 refers to 5.27%
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`lactic acid. Example 8 refers to 0.24-0.35M lactic acid, which a POSA would
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`understand to be 0.24-0.35 mole equivalents of lactic acid per mole equivalent of
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`naproxen sodium. (Ex.1003, 8:38; Ex.1001,¶76). Therefore, to a POSA, the
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`broadest reasonable interpretation of “about 5%” must include at least a range that
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`encompasses 0.24-0.35 mole equivalents of lactic acid per mole equivalent of
`
`naproxen sodium. Appropriate calculations to convert mole equivalents to weight
`
`percent show that the broadest reasonable interpretation of “about 5%” to a POSA
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`includes at least from 2 to 8% lactic acid by weight of the fill material.
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`(Ex.1001,¶¶76-79).
`
`The specification of the ’978 Patent supports this interpretation, noting that
`
`softgels are sensitive to pH, and the pH of the encapsulated liquid must be between
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`about 2.5 and about 7.5. (Ex.1003, 1:37-41). The ’978 Patent teaches combining
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`the salt of one or more active agents (like naproxen sodium) with 0.2-1.0 mole
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`equivalents of a de-ionizing agent (like lactic acid) to bring the pH within the range
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`of 2.5-7.5. (Ex.1003, 2:41-51). The 0.24 mole equivalents of lactic acid in
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`Example 8 is within the broad range of molar equivalents of a de-ionizing agent
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`and, when combined with a naproxen sodium solution, would lower the pH to
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`within the required pH range, and the examples support this construction. (Ex.
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`1001,¶¶78-79).
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`2.
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`“fill material”
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`“Fill material” is included in every independent claim. The broadest
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`reasonable interpretation to a POSA is that “fill material” simply means “the
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`material for filling the soft gelatin capsule prepared by mixing the claimed
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`ingredients in the claimed amounts prior to encapsulation.” (Ex.1001,¶80). This is
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`supported by the specification stating beneath the “A. Fill Material” heading:
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`The fill material is prepared by mixing the agent (such as a salt of the
`drug), the deionizing agent, water, and polyethylene glycol at a
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`temperature of 50°C to 70°C. The resulting solution is encapsulated
`using the appropriate gel mass.
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`(Ex.1003, 5:51-53). The 12 examples in the specification mix various amounts of
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`naproxen sodium with acids such as lactic acid prior to encapsulation. (Ex.1003,
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`6:57-9:35). This further supports the construction.
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`For inter parte review purposes, the broadest reasonable interpretation of
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`“fill material” would include a mixture of a naproxen salt, lactic acid and other
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`claimed ingredients, as well as a mixture of naproxen, lactate salts like sodium
`
`lactate, and other claimed ingredients. That is, the POSA understands that in either
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`scenario, the same cations and anions result at equilibrium as the patentee
`
`expressed during prosecution.
`
`(Ex.1001,¶¶40-42,58,82
`
`(referring
`
`to, e.g.,
`
`Ex.1006,pp.1-6,Kalkreuter Declaration)). Specifically, whether one starts with
`
`naproxen salt like naproxen sodium and adds lactic acid, or starts with naproxen
`
`and adds salts like sodium lactate, assuming the stoichiometric amounts of each
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`component is the same, the result will always be a mixture of naproxen salt like
`
`naproxen sodium, naproxen, lactic acid, and a salt like sodium lactate.
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`(Ex.1001,¶41). The equilibrium is depicted below:
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`Patent No. 9,693,978
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`F.
`
`Summary of Expert Declaration of Peter Draper
`
`The Declaration of technical expert Peter Draper (“Draper Declaration”)
`
`supports the unpatentability of the claims of the ’978 Patent based on the
`
`references described in Section VII below. (Ex.1001). The Draper Declaration
`
`supports at least the following:
`
`a) equilibrium concentrations of naproxen, salts like naproxen sodium,
`
`citric/lactic acid, and salts like sodium citrate/lactate are achieved whether one
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`starts with naproxen and adds sodium citrate/lactate, or with naproxen sodium and
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`adds citric/lactic acid (Ex.1001,¶¶40-42,58,82);
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`b) citric acid and lactic acid are equivalent for purposes of neutralizing
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`naproxen sodium (Ex.1001,¶39); and
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`c) the prior art partially neutralized naproxen and salts thereof to avoid a pH
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`that would disrupt the membrane of the soft gelatin capsule (Ex.1001,¶35 (citing
`
`Ex.1014)).2
`
`
`2 The Patentee’s purported other goals of
`increasing naproxen sodium
`bioavailability by partially neutralizing it with lactic acid, and suppressing PEG
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`Patent No. 9,693,978
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`The above points along with the teachings of the prior art cited and described
`
`herein lead to the inevitable conclusion that Claims 1-38 of the’978 Patent are
`
`invalid and unpatentable.
`
`VII. THERE IS A REASONABLE LIKELIHOOD THAT AT LEAST
`ONE CLAIM OF THE ’978 PATENT IS UNPATENTABLE
`UNDER 37 C.F.R. §42.104(b)(4)
`
`Inter Partes Review of Claims 1-38 of the ’978 Patent (Ex.1003) is
`
`requested on the grounds for unpatentability listed in the chart below. Per 37
`
`C.F.R. §42.6(d), copies of the prior art references are filed herewith as Exhibits.
`
`The grounds raised are meaningfully distinct and rely on fundamentally different
`
`prior art references that are not duplicative of the references previously considered
`
`during prosecution and, therefore, are not redundant. Specifically, the primary
`
`reference of U.S. Patent No. 5,360,615 (“Yu,” Ex.1014) and secondary references
`
`relied on during prosecution were distinguished by the Patentee as allegedly
`
`deficient in some respect. (Ex.1001,¶83). Specifically, the Patentee claimed Yu
`
`did not use a carboxylic acid de-ionizing agent to neutralize naproxen sodium, U.S.
`
`Publication No. 20060099246 (“Tanner,” Ex.1016) did not use gelatin capsules,
`
`and U.S. Publication No. 20050158377 (“Popp,” Ex.1018) did not encapsulate
`
`naproxen. (Ex.1001,¶¶54,56,83). In contrast, each of the Chen, Kim, and
`
`ester formation by adding lactic acid, are scientifically flawed. (Ex.1001,¶¶108-
`122).
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`Patent No. 9,693,978
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`Schoenhard references described below pertain to naproxen or a naproxen salt,
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`gelatin capsules, and include a de-ionizing agent like lactic acid, citric acid, or
`
`their salts for neutralizing naproxen and salts thereof. (Ex.1001,¶83, all claim
`
`charts).
`
`Ground Claim(s)
`
`Claims 1-
`38
`
`Claims 1-
`38
`
`Claims 1-
`38
`
`1
`
`2
`
`3
`
`
`
`Basis for Unpatentability
`
`Anticipated (§102) by, or Obvious (§103) in view of U.S.
`Patent No. 6,383,471 to Chen
`
`Obvious (§103) in view of, U.S. Publication No.
`20040157928 to Kim alone or in combination with U.S.
`Patent No. 6,383,471 to Chen
`
`Anticipated (§102) by, or Obvious (§103) in view of U.S.
`Publication No. 20040224020 to Schoenhard
`
`
`A. Ground 1: Claims 1-38 are invalid under 35 U.S.C. § 102 as
`anticipated by, or 35 U.S.C. § 103 as obvious in view of, U.S.
`Patent No. 6,383,471 to Chen.
`
`U.S. Pat. No. 6,383,471 (“Chen”) issued May 7, 2002, roughly three years
`
`before the earliest priority date to which the ’978 Patent claims priority (i.e., March
`
`8, 2005). Accordingly, Chen is prior art to the ’978 Patent. 35 U.S.C. §102(b).
`
`Chen discloses softgel capsules (Ex.1009, 12:38) which encapsulate a
`
`hydrophobic therapeutic agent, having at least one ionizable functional group, and
`
`a carrier. The carrier includes an “ionizing agent capable of ionizing the functional
`
`group,” a surfactant, and optionally solubilizers, triglycerides, and neutralizing
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`agents (Ex.1009, Abstract). Chen further discloses a method of preparing such
`
`compositions by providing a composition of an ionizable hydrophobic therapeutic
`
`agent, an ionizing agent, and a surfactant, and neutralizing a portion of the
`
`therapeutic agent with a neutralizing agent. (Ex.1009, Abstract).
`
`Naproxen is listed in Chen as one of the “most preferred” hydrophobic
`
`therapeutic agents having at least one ionizable acidic functional group. (Ex.1009,
`
`7:40-49). Salts of naproxen and other agents are also disclosed “for the sake of salt
`
`exchange with the acid or base ionizing agent, leading to better salt selection.”
`
`(Ex.1009, 10:42-46). It is well known that naproxen sodium is a recognized
`
`naproxen salt. (Ex.1001,¶¶29,86).
`
`Chen discloses pharmaceutically acceptable salts of inorganic or organic
`
`acids as ionizing agents for the therapeutic agent. (Ex.1009, 11:33-54).
`
`Specifically, “bases which are salts of pharmaceutically acceptable acid such
`
`as…lactic acid” are disclosed. (Ex.1009, 11:25). A POSA would understand that
`
`the carboxylate group in naproxen sodium is a basic functional group, whereas the
`
`carboxylic acid group in