`
`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 IPR2018-00422
`Patent 9,693,979
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 9,693,979
`
`
`
`
`
`
`
`
`
`
`
`
`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. 9,693,979
`IPR2018-00422
`
`
`
`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 ’979 Patent .................................................................................... 6
`
`Brief Summary of the Prosecution History of the ’979
`Patent ................................................................................................... 7
`
`Issued Claims ..................................................................................... 10
`
`Person of Ordinary Skill in the Art .............................................. 11
`
`E. Construction of Terms Used in the Claims ................................. 11
`
`1.
`
`2.
`
`“about 5%” ............................................................................12
`
`“liquid matrix” ......................................................................13
`
`F.
`
`Summary of Expert Declaration of Peter Draper ...................... 15
`
`VII. THERE IS A REASONABLE LIKELIHOOD THAT AT LEAST
`ONE CLAIM OF THE ’979 PATENT IS UNPATENTABLE
`UNDER 37 C.F.R. §42.104(B)(4) .............................................................. 16
`
`i
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
`
`
`
`A. Ground 1: Claims 1-19 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. .................................................. 18
`
`B. Ground 2: Claims 1-19 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. ............................................................................. 36
`
`1.
`
`2.
`
`Claims 1-19 are invalid under 35 U.S.C. § 103 as
`obvious in view of U.S. Publication No. 20040157928
`to Kim alone ...........................................................................36
`
`Claims 1-19 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 ........38
`
`C. Ground 3: Claims 1-19 are invalid under 35 U.S.C. § 103
`as obvious in view of U.S. Publication No. 20040224020 to
`Schoenhard, alone or in combination with U.S. Patent No.
`6,383,471 to Chen. ............................................................................. 49
`
`VIII. CONCLUSION ............................................................................................ 61
`
`
`
`ii
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
`
`
`
`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) ..........................................................58
`
`Okajima v. Bourdeau,
`261 F.3d 1350 (Fed. Cir. 2001) ...................................................................11
`
`
`
`iii
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
`
`
`
`Exhibit
`No.
`
`EXHIBIT LIST
`
`Description
`
`1001 Declaration of Peter Draper
`
`1002 Curriculum Vitae of Peter Draper
`
`1003 U.S. Patent No. 9,693,979
`
`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. 9,693,979
`IPR2018-00422
`
`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. 9,693,979
`IPR2018-00422
`
`
`
`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. 9,693,979
`IPR2018-00422
`
`
`I.
`
`INTRODUCTION
`
`Catalent Pharma Solutions, Inc. (“Petitioner”) hereby requests Inter Partes
`
`Review (“IPR”) of Claims 1-19 (“challenged claims”) of U.S. Patent No.
`
`9,693,979 (“the ’979 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 ’979 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 ’979 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: IPR2018-00421 (simultaneously filed by Petitioner).
`
`Additionally, U.S. Patent No. 9,693,978 and the ’979 Patent are the subject of two
`
`1
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
`
`
`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. 9,693,979
`IPR2018-00422
`
`
`
`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 1-19 of the ’979 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. 9,693,979
`IPR2018-00422
`
`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)
`
`1
`
`2
`
`3
`
`Claims 1-
`19
`
`Claims 1-
`19
`
`Claims 1-
`19
`
`
`
`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
`
`Obvious under §103 in view of U.S. Publication No.
`20040224020 to Schoenhard by itself, or in combination
`with U.S. Patent No. 6,383,471 to Chen
`
`
`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 ’979 Patent; (iii) the level of ordinary skill in the art; and (iv) the lack of any
`
`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
`
`objective indicia of non-obviousness.
`
`V. TECHNOLOGY BACKGROUND
`
`The ’979 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 mg for naproxen
`
`or 220 mg
`
`for naproxen sodium while a child dosage
`
`is 125mg.
`
`(Ex.1001,¶¶29,36,112).
`
`Soft gelatin capsules (“softgels”) encapsulating pharmaceuticals in liquid
`
`form have been in existence since the early 1900s. Prior to the ’979 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. 9,693,979
`IPR2018-00422
`
`
`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 ’979 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 ’979 Patent
`
`The’979 Patent issued on July 4, 2017 with 19 claims. The earliest
`
`priority date of the ’979 Patent is March 8, 2005. The independent claims,
`
`Claims 1, 8 and 17, relate to a soft gelatin capsule encapsulating a “liquid
`
`matrix”. In the broadest independent claim, Claim 1, the liquid matrix comprises:
`
`(a) naproxen salt or naproxen sodium; (b) “about 5%” lactic acid by weight of the
`
`matrix; (c) one or more polyethylene glycols; and (d) one or more solubilizers
`
`6
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
`
`
`comprising polyvinylpyrrolidone, propylene glycol, or a combination thereof.
`
`(Ex.1003,10:54-61).
`
`B. Brief Summary of the Prosecution History of the ’979 Patent
`
`The specification of the ’979 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 those
`
`pending claims was affirmed on appeal to the PTAB in October 2015.
`
`(Ex.1005,pp.424-435).
`
`The Patentee filed a continuation application, App. No. 14/977,808 (“the
`
`’808 Application”), in December 2015 with 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 numerous Office Actions, claim amendments, and responses during
`
`that prosecution, which resulted in the Patentee narrowing the broadest
`
`independent claim of the ’808 Application 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.
`
`7
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
`
`
`
`
`(Ex.1006,pp.173-179).
`
` A
`
` December 2016 Advisory Action held that that the pending claims were
`
`still obvious (Ex.1006,pp.191-193), and the Patentee filed a supplemental response
`
`on February 7, 2017, amending all the independent claims to specify “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 of the ’808 Application 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). The ’808 Application issued as U.S. Patent No. 9,693,978 (“the ’978
`
`Patent”), on July 4, 2017.
`
`During the prosecution of the parent ’808 Application, the Patentee filed a
`
`divisional application, App. No. 15/159,972, in May 2016. (Ex.1008,pp.1-41). As
`
`in the prosecution of the ’808 Application described above, there were numerous
`
`
`1 The “about 5% lactic acid” limitation first appeared during prosecution of the
`’808 Application 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. 9,693,979
`IPR2018-00422
`
`
`Office Actions, claim amendments, and responses which resulted in the Patentee
`
`narrowing the broadest independent claim, Claim 1, to:
`
`A pharmaceutical composition comprising a soft gel capsule
`encapsulating a liquid matrix comprising:
`(a) naproxen sodium;
`(b) about 0.2 to about 1.0 mole equivalents of lactic acid per mole of
`naproxen sodium;
`(c) one or more polyethylene glycols; and
`(d) one or more solubilizers comprising polyvinylpyrrolidone,
`propylene glycol, or a combination thereof.
`
`(Ex.1008,p.162).
`
` A
`
` December 2016 Advisory Action held that that the pending claims were
`
`still obvious. (Ex.1008,pp.178-179). The Patentee filed a supplemental response
`
`on February 7, 2017, amending all the independent claims to “about 5% lactic acid
`
`by weight of the matrix” and referring to a January 23, 2017 Prosecution Pilot
`
`Program (P3) Conference. (Ex.1008,pp.193-200).2 Like the parent ’978 Patent,
`
`the amended claims were allowed on March 10, 2017, with the only stated
`
`
`2 As described above in FN1, the “about 5% lactic acid” limitation first appeared in
`dependent claims 3, 21, 43, 50, and 58 of the parent ’808 Application, which
`became the ’978 Patent, in a September 27, 2016 amendment and response
`referring to Examples 7-12 as support. (Ex.1006,pp.127-143). For the ’979
`Patent, the “about 5% lactic acid” limitation appeared during prosecution of the
`divisional application in independent claim 23, with Examples 6 and 8-12 being
`referenced as support in a September 27, 2016 amendment and response.
`(Ex.1008,pp.119-130). Independent claim 23 became issued Claim 17 of the ’979
`Patent. (Ex.1003,12:18-25).
`
`9
`
`

`

`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
`
`
`“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.1008,pp.204-210).
`
`C.
`
`Issued Claims
`
`Independent Claim 1 of the ’979 Patent relates to a composition comprising
`
`a softgel capsule which encapsulates a liquid matrix fill material which includes
`
`naproxen sodium, about 5% lactic acid by weight of the matrix, one or more
`
`polyethylene
`
`glycols,
`
`and
`
`one
`
`or more
`
`solubilizers
`
`comprising
`
`polyvinylpyrrolidone, propylene glycol, or a combination thereof. Claims 2-7
`
`specify the amount of polyethylene glycol (Claim 2), the molecular weight range
`
`for the polyethylene glycol (Claims 3-4), the amount and type of solubilizer
`
`(Claims 5-6), and that the composition comprises one or more excipients (Claim
`
`7).
`
`The other two independent claims, independent Claims 8 and 17, like Claim
`
`1, provide a composition comprising a softgel capsule which encapsulates a liquid
`
`matrix fill material. The fill material in each of Claim 8 and 17 includes about
`
`25% naproxen sodium, about 5% lactic acid, polyethylene glycol 600, and 1-10%
`
`of one or more solubilizers comprising polyvinylpyrrolidone, propylene glycol, or
`
`a combination thereof. The dependent claims relate to specific solubilizers and
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`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
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`amounts (Claims 9, 11, and 18); mole ratio of lactic acid to naproxen sodium
`
`(Claims 10 and 19); further excipients (Claim 12) or ingredients (Claim 14); pH
`
`(Claim 13); and method for making (Claim 15).
`
`D. Person of Ordinary Skill in the Art
`
`The field of invention for the ’979 Patent is soft gelatin capsule formulations
`
`as described in the preamble for all independent claims of the ’979 Patent. The
`
`level of ordinary skill in the art as of the effective filing date of the ’979 Patent,
`
`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.
`
`Cumberland Corp., 713 F.2d 774 (Fed. Cir. 1983); see also Okajima v. Bourdeau,
`
`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
`
`pharmaceutical sciences, chemistry, or a related discipline, and a minimum of 5
`
`years of additional training and experience in the field of pharmaceutical
`
`formulations, particularly as they relate to soft gelatin capsules. (Ex. 1001,¶26).
`
`E. Construction of Terms Used in the Claims
`
`A claim subject to inter partes review receives the “broadest reasonable
`
`construction in light of the specification of the patent in which it appears.” 42
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`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
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`C.F.R. §42.100(b). The broadest reasonable construction of “about 5%” and
`
`“liquid matrix,” which each appear in all the independent claims of the ’979 Patent,
`
`may be useful to consider as described below.
`
`For the purposes of this inter partes review only, the remainder of the claim
`
`terms are to be given their ordinary and customary meaning that the terms would
`
`have to a POSA. None of the challenged claims contain a means-plus-function or
`
`step-plus-function limitation.
`
`1.
`
`“about 5%”
`
`Every claim includes the “about 5% lactic acid by weight” limitation, but the
`
`term “about 5%” does not appear anywhere in the specification of the ’979 Patent.
`
`“About 5% lactic acid” appeared in what became Claim 17 of the ’979 Patent with
`
`Examples 6 and 8-12 being referenced as support, in a September 27, 2016
`
`amendment and response. (Ex.1008,pp.119-130). Accordingly, to determine the
`
`broadest reasonable construction of “about 5%” to a POSA, it is relevant to look to
`
`the amount of lactic acid that is included in Examples 8-12. (Ex.1001,¶¶79-80).
`
`Examples 9-12 refer to 5.00% lactic acid. Example 8 refers to 0.24-0.35M
`
`lactic acid, which a POSA would understand to be 0.24-0.35 mole equivalents of
`
`lactic acid per mole equivalent of naproxen sodium. (Ex.1003, 9:55-65;
`
`Ex.1001,¶81). Therefore, to a POSA, the broadest reasonable interpretation of
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`Patent No. 9,693,979
`IPR2018-00422
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`“about 5%” must include at least a range that 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 includes at least from 2 to 8%
`
`lactic acid by weight. (Ex.1001,¶¶81-84).
`
`The specification of the ’979 Patent supports this interpretation, noting that
`
`softgels are sensitive to pH, and the pH of the encapsulated liquid must be between
`
`about 2.5 and about 7.5. (Ex.1003, 1:33-37, dependent Claim 13). The ’979
`
`Patent teaches combining the salt of one or more active agents (like naproxen
`
`sodium) with 0.2-1.0 mole equivalents of a de-ionizing agent (like lactic acid) to
`
`bring the pH within the range of 2.5-7.5. (Ex.1003, 2:39-49). The 0.24 mole
`
`equivalents of lactic acid in Example 8 is within the broad range of molar
`
`equivalents of a de-ionizing agent and, when combined with a naproxen sodium
`
`solution, would lower the pH to within the required pH range. (Ex. 1001,¶¶83,84).
`
`2.
`
`“liquid matrix”
`
`The term “liquid matrix” is included in every independent claim of the ’979
`
`Patent but did not appear in the provisional application or the two parent
`
`applications to which the ’979 Patent claims priority. Those priority applications
`
`instead referred to “fill material.” “Liquid matrix” is synonymous with “fill
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`Patent No. 9,693,979
`IPR2018-00422
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`material” and simply means “the material for filling the soft gelatin capsule
`
`prepared by mixing the claimed ingredients in the claimed amounts prior to
`
`encapsulation.” (Ex.1001,¶85). This is supported by the specification stating
`
`beneath the “A. Fill Material” heading:
`
`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
`temperature of 50°C to 70°C. The resulting solution is encapsulated
`using the appropriate gel mass.
`
`(Ex.1003, 6:59-63). The 12 examples in the specification mix various amounts of
`
`naproxen sodium with acids such as lactic acid prior to encapsulation. (Ex.1003,
`
`8:10-10:50). This further supports the construction.
`
`For inter parte review purposes, the broadest reasonable interpretation of
`
`“liquid matrix” would include a fill material that is a liquid mixture of a naproxen
`
`sodium salt, lactic acid and other claimed ingredients, as well as a mixture of
`
`naproxen, sodium lactate salt, and other claimed ingredients. That is, the POSA
`
`understands that in either scenario, the same cations and anions result at
`
`equilibrium as the patentee expressed during prosecution. (Ex.1001,¶¶40-42,66,87
`
`(referring to Ex.1006,pp.1-6, Kalkreuter Declaration)). Specifically, whether one
`
`starts with naproxen sodium and adds lactic acid, or starts with naproxen and adds
`
`sodium lactate, assuming the stoichiometric amounts of each component is the
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`Patent No. 9,693,979
`IPR2018-00422
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`same, the result will always be a mixture of naproxen sodium, naproxen, lactic
`
`acid, and sodium lactate. (Ex.1001,¶41). The equilibrium is depicted below:
`
`
`
`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 ’979 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, naproxen sodium, citric/lactic
`
`acid, and sodium citrate/lactate are achieved whether one starts with naproxen and
`
`adds sodium citrate/lactate, or with naproxen sodium and adds citric/lactic acid
`
`(Ex.1001,¶¶40-42,66,87);
`
`b) citric acid and lactic acid are equivalent for purposes of neutralizing
`
`naproxen sodium (Ex.1001,¶39); and
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`Patent No. 9,693,979
`IPR2018-00422
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`c) the prior art partially neutralized naproxen and salts thereof to avoid a pH
`
`that would disrupt the membrane of the soft gelatin capsule (Ex.1001,¶35 (citing
`
`Ex.1014)).3
`
`The above points along with the teachings of the prior art cited and described
`
`herein lead to the inevitable conclusion that Claims 1-19 of the’979 Patent are
`
`invalid and unpatentable.
`
`VII. THERE IS A REASONABLE LIKELIHOOD THAT AT LEAST
`ONE CLAIM OF THE ’979 PATENT IS UNPATENTABLE
`UNDER 37 C.F.R. §42.104(b)(4)
`
`Inter Partes Review of Claims 1-19 of the ’979 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,¶¶58-61). Specifically, the Patentee claimed
`
`3 The Patentee’s purported other goals of
`increasing naproxen sodium
`bioavailability by partially neutralizing it with lactic acid, and suppressing PEG
`ester formation by adding lactic acid, are scientifically flawed. (Ex.1001,¶¶117-
`130).
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`Patent No. 9,693,979
`IPR2018-00422
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`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,¶¶57-61). In contrast, each of the Chen, Kim,
`
`and Schoenhard references described below pertain to naproxen or a naproxen
`
`salt, gelatin capsules, and include a de-ionizing agent like lactic acid, citric
`
`acid, or their salts for neutralizing naproxen and salts thereof. (Ex.1001,¶¶88-
`
`115, all claim charts).
`
`Ground Claim(s)
`
`1
`
`2
`
`3
`
`Claims 1-
`19
`
`Claims 1-
`19
`
`Claims 1-
`19
`
`
`
`Basis for Unpatentability
`
`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
`
`Obvious under §103 in view of U.S. Publication No.
`20040224020 to Schoenhard by itself, or in combination
`with U.S. Patent No. 6,383,471 to Chen
`
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`Petition for Inter Partes Review
`Patent No. 9,693,979
`IPR2018-00422
`
`
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`A. Ground 1: Claims 1-19 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 ’979 Patent claims priority (i.e., March
`
`8, 2005). Accordingly, Chen is prior art to the ’979 Patent. 35 U.S.C. §102(b).
`
`Chen discloses softgel capsules 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 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
`