IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`___________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`
`APOTEX, INC.
`Petitioner,
`v.
`UCB BIOPHARMA S.A.
`Patent Owner.
`U.S. Patent No. 8,633,194 to Fanara et al.
`Issue Date: January 21, 2014
`Title: Pharmaceutical composition of piperazine derivatives
`Inter Partes Review No.: IPR2019-00400
`
`Petition for Inter Partes Review of U.S. Patent No. 8,633,194
`Under 35 U.S.C. §§ 311-319 and 37 C.F.R. §§ 42.1-.80, 42.100-.123
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`TABLE OF CONTENTS
`I.
`INTRODUCTION ............................................................................... 1
`II. OVERVIEW ....................................................................................... 1
`III. STANDING
`(37 C.F.R. §
`42.104(A)); PROCEDURAL
`STATEMENTS ................................................................................... 2
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(A)(1)) ................................ 3
`A.
`Each Real Party in Interest (37 C.F.R. § 42.8(b)(1)) ........................3
`B. Notice of Related Matters (37 C.F.R. § 42.8(b)(2)) ..........................3
`1.
`Judicial Matters Involving the ’194 Patent............................. 3
`2.
`Administrative Matters ....................................................... 3
`C. Designation of Lead and Back-Up Counsel and Service (37
`C.F.R. §§ 42.8(b)(3), 42.8(b)(4))...................................................3
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 C.F.R. § 42.22(A))...................................... 4
`VI. THE ’194 PATENT ............................................................................. 4
`VII. CLAIM CONSTRUCTION .................................................................. 5
`VIII. PERSON OF ORDINARY SKILL IN THE ART (“POSA”) ..................... 6
`IX.
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(B)) ................ 7
`X.
`INVALIDITY ANALYSIS ................................................................... 8
`A.
`The Level of Ordinary Skill in the Pertinent Art ..............................8
`B.
`The Scope and Content of the Prior Art .........................................8
`1.
`Levocetirizine Was a Known Prior Art Compound and
`Was Suitable for Liquid Preparations.................................... 8
`2. Methylparaben and Propylparaben Are “Widely Used”
`Preservatives ................................................................... 12
`
`V.
`
`i
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`b)
`
`c)
`
`d)
`
`3. WO 2004/050094 (“WO ’094”) (EX1007) .......................... 13
`4.
`European Patent Application No. 0605203 A2 (“EP ’203”)
`(EX1004)........................................................................ 15
`The Handbook (EX1006) .................................................. 17
`5.
`U.S. Patent No. 5,698,558 (EX1015) .................................. 18
`6.
`C. Ground 1: Claims 1-11 Would Have Been Obvious over WO
`’094 in View of the Handbook .................................................... 19
`1.
`Independent Claim 1 ........................................................ 19
`a)
`“A liquid pharmaceutical composition comprising
`(i) levocetirizine or a pharmaceutically acceptable salt
`of levocetirizine” .................................................... 21
`“a preservative mixture consisting essentially of a
`mixture of methyl parahydroxybenzoate and propyl
`parahydroxybenzoate in a ratio of 9/1 expressed in
`weight”.................................................................. 22
`(1) There Is No Teaching Away in the Handbook.... 24
`“said [paraben] mixture being present in an amount of
`more than 0 and up to 0.75 mg/ml of the composition” 26
`“wherein said composition is substantially free of
`bacteria” ................................................................ 30
`Dependent Claim 2 .......................................................... 32
`Dependent Claim 3 .......................................................... 32
`Dependent Claim 4 .......................................................... 33
`Dependent Claims 5 and 10 ............................................... 33
`Dependent Claim 6 .......................................................... 34
`a)
`“wherein the hydrochloride salt of levocetirizine is
`present in amount of 0.5 mg/ml” ............................... 34
`“the mixture of methyl p-hydroxybenzoate and propyl
`p-hydroxybenzoate
`is present
`in
`amount of
`0.75 mg/ml.” .......................................................... 37
`
`2.
`3.
`4.
`5.
`6.
`
`b)
`
`ii
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`b)
`
`b)
`
`7.
`Dependent Claim 7 .......................................................... 37
`Dependent Claim 8 .......................................................... 38
`8.
`Dependent Claim 9 .......................................................... 40
`9.
`10. Dependent Claim 11......................................................... 40
`a)
`“the composition is in the form of an oral solution
`comprising
`0.50
`mg/ml
`levocetirizine
`dihydrochloride”..................................................... 41
`“0.675 mg/ml methyl p-hydroxybenzoate, and
`0.075 mg/ml propyl p-hydroxybenzoate” ................... 41
`D. Ground 2: Claims 1-11 Are Obvious over EP ’203 in View of
`US ’558 and the Handbook ........................................................ 43
`1.
`Independent Claim 1 ........................................................ 43
`a)
`“A liquid pharmaceutical composition comprising
`(i) levocetirizine or a pharmaceutically acceptable salt
`of levocetirizine” .................................................... 46
`“a preservative mixture consisting essentially of a
`mixture of methyl parahydroxybenzoate and propyl
`parahydroxybenzoate in a ratio of 9/1 expressed in
`weight”.................................................................. 48
`“said [paraben] mixture being present in an amount of
`more than 0 and up to 0.75 mg/ml of the composition” 50
`“wherein said composition is substantially free of
`bacteria” ................................................................ 52
`Dependent Claim 2 .......................................................... 53
`Dependent Claim 3 .......................................................... 53
`Dependent Claim 4 .......................................................... 53
`Dependent Claims 5 and 10 ............................................... 54
`Dependent Claim 6 .......................................................... 54
`a)
`“wherein the hydrochloride salt of levocetirizine is
`present in amount of 0.5 mg/ml” ............................... 55
`
`2.
`3.
`4.
`5.
`6.
`
`c)
`
`d)
`
`iii
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`b)
`
`“the mixture of methyl p-hydroxybenzoate and propyl
`p-hydroxybenzoate
`is present
`in
`amount of
`0.75 mg/ml” ........................................................... 56
`Dependent Claim 7 .......................................................... 57
`7.
`Dependent Claim 8 .......................................................... 57
`8.
`Dependent Claim 9 .......................................................... 58
`9.
`10. Dependent Claim 11......................................................... 59
`a)
`“the composition is in the form of an oral solution
`comprising
`0.50
`mg/ml
`levocetirizine
`dihydrochloride”..................................................... 59
`“0.675 mg/ml methyl p-hydroxybenzoate, and
`0.075 mg/ml propyl p-hydroxybenzoate” ................... 62
`E. Objective Indicia of Nonobviousness........................................... 63
`XI. THE BOARD SHOULD INSTITUTE TRIAL BASED ON
`APOTEX’S PETITION (35 U.S.C. § 325(D)) ....................................... 64
`XII. CONCLUSION ................................................................................. 66
`
`
`b)
`
`iv
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Amgen Inc. v. F. Hoffmann-La Roche Ltd.,
`580 F.3d 1340 (Fed. Cir. 2009) ........................................................... 39, 58
`Amneal Pharmaceuticals LLC v. Alkermes Pharma Ireland Ltd.,
`IPR2018-00943, Paper 8 (P.T.A.B. Nov. 7, 2018) ...................................... 65
`Amneal Pharmaceuticals, LLC v. Supernus Pharmaceuticals, Inc.,
`IPR2013-00368 [Paper 8, pp. 12–13] ........................................................ 64
`Becton, Dickinson and Company v. B. Braun Melsungen AG,
`IPR2017-01586, slip op. at 17–18 (P.T.A.B. Dec. 15, 2017) (Paper
`8) (informative) (factors (a), (b) and (d)) ................................................... 64
`Biomarin Pharmaceutical Inc. v. Genzyme Therapeutic Products Ltd.
`Partnership,
`IPR2013-00534, Paper 81 (P.T.A.B. Feb. 23, 2015) ............................. passim
`Chevron Oronite Co. LLC. v. Infineum USA L.P.,
`IPR2018-00922 Paper 6 (P.T.A.B. Nov. 7, 2018) ....................................... 50
`Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc.,
`807 F.2d 955 (Fed. Cir. 1986) .................................................................... 6
`Digital Check Corp. d/b/a ST Imaging v. E-Imagedata Corp.,
`IPR2017-00178, Paper 6 (P.T.A.B. Apr. 25, 2017) ..................................... 65
`Ex parte Obiaya,
`227 U.S.P.Q. 58 (Bd. Pat. Appendix & Inter. 1985) .................................... 31
`Fox Factory, Inc. v. SRAM, LLC,
`IPR2016-01876, Paper 8 (P.T.A.B. Apr. 3, 2017) ....................................... 65
`Fresenius Kabi USA LLC, v. Cubist Pharma.,
`IPR2015-01566, Paper 20 (P.T.A.B. Jan. 28, 2016) .................................... 39
`Graham v. John Deere Co. of Kansas City,
`383 U.S. 1 (1966) ..................................................................................... 8
`
`v
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`Hoffmann-La Roche Inc. v. Apotex Inc.,
`748 F.3d 1326 (Fed. Cir. 2014) ................................................................ 63
`HyperBranch Medical Technology, Inc. v. Confluent Surgical, Inc.,
`IPR2018-01099, Paper 14 (P.T.A.B. Nov. 27, 2018) ................................... 65
`In re Aller,
`220 F.2d 454 (C.C.P.A. 1955) ........................................................... passim
`In re Applied Materials, Inc.,
`692 F.3d 1289 (Fed. Cir. 2012) ......................................................... passim
`In re Clay,
`966 F.2d 656 (Fed. Cir. 1992) .................................................................. 24
`In re Fout,
`675 F.2d 297 (C.C.P.A. 1982) .................................................................. 10
`In re Fritch,
`972 F.2d 1260 (Fed. Cir. 1992) ................................................................ 25
`In re Gurley,
`27 F.3d 551 (Fed. Cir. 1994) .................................................................... 26
`In re Herz,
`537 F.2d 549 (C.C.P.A. 1976) .................................................................. 22
`In re Huai-Hung Kao,
`639 F.3d 1057 (Fed. Cir. 2011) ........................................................... 31, 32
`In re ICON Health and Fitness, Inc.,
`496 F.3d 1374 (Fed. Cir. 2007) ................................................................ 24
`In re Papesch,
`315 F.2d 381 (C.C.P.A. 1963) .................................................................. 31
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) ......................................................... passim
`In re Thorpe,
`777 F.2d 695 (Fed. Cir. 1985) .................................................................. 39
`
`vi
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`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`In re Wertheim,
`541 F.2d 257 (C.C.P.A. 1976) .................................................................. 36
`Iron Grip Barbell Co. v. USA Sports, Inc.,
`392 F.3d 1317 (Fed. Cir. 2004) ......................................................... passim
`KSR Int’l Co. v. Teleflex, Inc.,
`550 U.S. 398 (2007) ...................................................................... 6, 29, 49
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) .................................................................. 63
`NXP USA, Inc. v. Inside Secure et al.,
`IPR2016-00681, Paper 29 (P.T.A.B. Aug. 30, 2017) ................................... 49
`Par Pharmaceuticals v. TWi Pharmaceuticals, Inc.,
`773 F.3d 1186 (Fed. Cir. 2014) ..................................................... 30, 31, 52
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2008) ................................................................ 63
`Pfizer, Inc. v. Chugai Pharm. Co. Ltd.,
`IPR2017-01357, Paper 56 (P.T.A.B. Nov. 28, 2018) ................................... 27
`Pharmacosmos A/S v. Luitpold Pharms., Inc.,
`IPR2015-01490, Paper 54 (Final Written Decision) (P.T.A.B. Jan.
`4, 2017) ................................................................................ 23, 26, 37, 55
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) (en banc) .................................................... 5
`Praxair Distribution, Inc.,
`IPR2015-00893, Paper 14........................................................................ 65
`Provepharm Inc. v. Wista Laboratories Ltd,
`IPR2018-00182, Paper 16 (Institution Decision) (P.T.A.B. July 5,
`2018) ...................................................................................................... 9
`Purdue Pharma. L.P. v. Epic Pharma., LLC,
`811 F.3d 1345 (Fed. Cir. 2016) ........................................................... 39, 40
`Purdue Pharma Prods. L.P. v. Par Pharm., Inc.,
`377 F. App’x 978 (Fed. Cir. 2010)............................................................ 64
`
`vii
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`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`Santarus, Inc. v. Par Pharm., Inc.,
`694 F.3d 1344 (Fed. Cir. 2012) ........................................................... 31, 52
`SteadyMed Ltd. v. United Therapeutics Corp.,
`IPR 2016-00006, Paper 82, 53 (P.T.A.B. March 31, 2017), aff’d __
`F.3d ___ (Fed. Cir. 2017) ........................................................................ 39
`UCB, Inc. et al. v. Apotex Inc.,
`1:18-cv-03404 (S.D.N.Y.) ......................................................................... 3
`UCB, Inc. et al. v. Apotex Inc.,
`No. 0-18-cv-60846 (S.D. Fla.).................................................................... 3
`Watson Labs., Inc. v. United Therapeutics Corp.,
`IPR2017-01621, Paper 10, 12 (P.T.A.B. Jan. 11, 2018) ............................... 13
`Statutes
`35 U.S.C. § 102 ...................................................................................... 9, 22
`35 U.S.C. § 102(a) ........................................................................ 9, 10, 13, 14
`35 U.S.C. § 102(b) ............................................................................... passim
`35 U.S.C. § 102(e) ................................................................................. 13, 14
`35 U.S.C. § 102(f)....................................................................................... 14
`35 U.S.C. § 102(g) ...................................................................................... 14
`35 U.S.C. § 103 .......................................................................................... 22
`35 U.S.C. § 103(a) ........................................................................................ 8
`35 U.S.C. § 103(c) ...................................................................................... 14
`35 U.S.C. § 103(c)(1) .................................................................................. 14
`35 U.S.C. § 103(c)(2)(c) .............................................................................. 14
`35 U.S.C. § 325(d) ........................................................................... 64, 65, 66
`Regulations
`37 C.F.R. § 42.6(d) ....................................................................................... 7
`
`viii
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`37 C.F.R. § 42.10(b)...................................................................................... 2
`37 C.F.R. § 42.63(e) ...................................................................................... 2
`37 C.F.R § 42.100(b)..................................................................................... 5
`37 C.F.R. § 42.106(a) .................................................................................... 2
`
`
`ix
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`Petitioner’s Exhibit List
`
`Description
`U.S. Patent No. 8,633,194 (“the ’194 patent”)
`Declaration of Dr. Laskar
`CV of Dr. Laskar
`European Patent Application Publication No. 0605203 A2 (“EP
`’203”)
`levocetirizine, and
`Wang D.Y., “Effect of cetirizine,
`dextrocetirizine on histamine-induced nasal response in healthy
`adult volunteers,” Allergy 56 (2001), pp. 339-343 (“Wang”)
`Kibbe, “Handbook of Pharmaceutical Excipients,” 3rd ed. 2000
`(the “Handbook”)
`International Patent Application No. WO 2004/050094 (“WO
`’094”)
`Tillement, Jean-Paul et al., “Compared pharmacological
`characteristics in humans of racemic cetirizine and levocetirizine,
`two
`histamine H1-receptor
`antagonists,” Biochemical
`Pharmacology Volume 66,
`Issue 7, 1 October 2003,
`pages 1123-1126
`Potter, P.C., “Levocetirizine is effective for symptom relief
`including nasal congestion in adolescent and adult (PAR)
`sensitized to house dust mites,” Allergy (Oxford, United
`Kingdom) Volume 58, Issue 9, pages 893-899, Journal 2003
`Gandon, J.M. et al., “Lack of effect of single and repeated doses
`of Levocetirizine, a new antihistamine drug, on cognitive and
`psychomotor functions in healthy volunteers,” British Journal of
`Clinical Pharmacology (2002), 54(1), 51-58
`Orange Book Entry for XYZAL
`R.J. Davies et al., Antihistamines: topical vs. oral administration,
`Clinical and Experimental Allergy 26(3):11-17 (1996) (“Davies”)
`File Wrapper of ’194 patent
`Gennaro, A. R., Remington: The Science and Practice of
`Pharmacy 20th ed. (2000)
`U.S. Patent No. 5,698,558 to Nancy M. Grey (“US ’558”)
`EPO opposition
`Saeedi et al., “The treatment of atopic dermatitis with licorice
`gel,” Journal of Dermatological Treatment (2003) 14, 1–5
`
`Petitioner
`Exhibit #
`1001
`1002
`1003
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`1012
`
`1013
`1014
`1015
`1016
`1017
`
`x
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`1018
`
`1019
`1020
`1021
`
`1022
`
`1023
`
`1024
`
`Duconge et al., “Topical disposition of two strengths of a
`125I-rhEGF jelly in rat skin wounds,” Biopharm. Drug Dispos.
`25: 193–201 (2004)
`U.S. Patent No. 4,275,076
`U.S. Patent No. 5,643,584
`Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery
`Systems 7th ed. 1999
`Soni et al., “Evaluation of the health aspects of methyl paraben:
`a review of the published literature,” Food and Chemical
`Toxicology 40 (2002) 1335–1373
`Sutton et al., “Development of the Antimicrobial Effectiveness
`Test as USP Chapter <51>” PDA Journal of Pharmaceutical
`Science and Technology, Vol. 56, No. 6, 300-311,
`November/December 2002
`Darwish et al., Effect of ethanol, propylene glycol and glycerol on
`the interaction of methyl and propyl p-hydroxybenzoate with
`Staphylococcus aureus and Pseudomonas aeruginosa,” Int. J. of
`Pharm. 147:51-60 (1997).
`
`
`
`
`xi
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`I.
`
`INTRODUCTION
`Apotex, Inc. (“Petitioner”) petitions for Inter Partes Review (“IPR”), seeking
`
`cancellation of claims 1-11 (“challenged claims”) of U.S. Patent No. 8,633,194 (“the
`
`’194 patent”) (EX1001), which is owned by UCB Biopharma S.A. (“UCB” or
`
`“Patent Owner”).
`
`II. OVERVIEW
`There is nothing patent worthy in the ’194 patent. In fact, the European Patent
`
`Office has already revoked an EP equivalent to the ’194 patent based on similar
`
`arguments presented in this petition. At a high level, the ’194 patent covers liquid
`
`preparations of levocetirizine (a well-known prior art pharmaceutical compound)
`
`with a 9/1 ratio of methylparaben to propylparaben (two “widely used”
`
`preservatives). The prior art taught liquid preparations of levocetirizine with
`
`methylparaben and propylparaben. As to the 9/1 ratio of methylparaben to
`
`propylparaben, put simply, that particular ratio was widely reported in numerous
`
`pieces of prior art and shown to be useful in a variety of dosage forms.
`
`Patent Owner may argue that it surprisingly discovered that its compositions
`
`were “substantially free of bacteria.” As patentee admitted, any such consequence
`
`was a property of the compound levocetirizine itself and, thus, any antibacterial
`
`properties of levocetirizine would have been present in the prior art compositions.
`
`Unremarkably, none of the prior art aqueous compositions using levocetirizine with
`
`1
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`methylparaben and propylparaben reported any problems with bacterial
`
`contamination.
`
`Finally, to the extent Patent Owner suggests that the invention involves
`
`optimizing or lowering various amounts of levocetirizine, methylparaben or
`
`propylparaben—all such amounts were suggested by the prior art. In re Peterson,
`
`315 F.3d 1325, 1330 (Fed. Cir. 2003) (“The normal desire of scientists or artisans to
`
`improve upon what is already generally known provides the motivation to determine
`
`where in a disclosed set of ... ranges is the optimum combination....”); Biomarin
`
`Pharmaceutical Inc. v. Genzyme Therapeutic Products Ltd. Partnership,
`
`IPR2013-00534, Paper 81 at 15 (P.T.A.B. Feb. 23, 2015) (“all that remained to be
`
`achieved over the prior art was the determination that a specific dose within a
`
`previously suggested dose range… would have been safe and effective for the
`
`treatment of human patients”).
`
`III. STANDING (37 C.F.R. § 42.104(A)); PROCEDURAL STATEMENTS
`Petitioner certifies that: (1) the ’194 patent is available for IPR; and
`
`(2) Petitioner is not barred or estopped from requesting IPR of any claim of the
`
`’194 patent on the grounds identified herein. This Petition is filed in accordance
`
`with 37 C.F.R. § 42.106(a). Filed herewith are a Power of Attorney and an Exhibit
`
`List pursuant to § 42.10(b) and § 42.63(e), respectively. The required fee is paid
`
`2
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`when filing the Petition and the Office is authorized to charge any fee deficiencies
`
`and credit overpayments to Deposit Acct. No. DA501290 (Customer ID No. 27160).
`
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(A)(1))
`A. Each Real Party in Interest (37 C.F.R. § 42.8(b)(1))
`The following real parties in interest are identified: Apotex Inc., Apotex
`
`Corp., Apotex Holdings Inc. and Apotex Pharmaceuticals Holdings Inc.
`
`B. Notice of Related Matters (37 C.F.R. § 42.8(b)(2))
`Judicial Matters Involving the ’194 Patent
`1.
`The ’194 patent is currently the subject of the following litigations: UCB, Inc.
`
`et al. v. Apotex Inc., No. 0-18-cv-60846 (S.D. Fla.); and UCB, Inc. et al. v. Apotex
`
`Inc., 1:18-cv-03404 (S.D.N.Y.).
`
`Administrative Matters
`2.
`The Public Patent Application Retrieval (PAIR) website indicates that there
`
`are no related United States patents or pending applications.
`
`C. Designation of Lead and Back-Up Counsel and Service (37 C.F.R.
`§§ 42.8(b)(3), 42.8(b)(4))
`Lead Counsel
`Jitendra Malik, Ph.D.
`Reg. No. 55,823
`Katten Muchin Rosenman LLP
`550 S. Tryon Street, Suite 2900
`Charlotte, NC 28202-4213
`jitty.malik@kattenlaw.com
`
`Back-Up Counsel
`Alissa M. Pacchioli
`Reg. No. 74,252
`Katten Muchin Rosenman LLP
`550 S. Tryon Street, Suite 2900
`Charlotte, NC 28202-4213
`alissa.pacchioli@kattenlaw.com
`
`
`3
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`Joseph M. Janusz
`Reg. No. 70,396;
`Katten Muchin Rosenman LLP
`550 S. Tryon Street, Suite 2900
`Charlotte, NC 28202-4213
`joe.janusz@kattenlaw.com
`
`Lance Soderstrom
`Reg. No. 65,405
`Katten Muchin Rosenman LLP
`575 Madison Avenue
`New York, NY 10022-2585
`lance.soderstrom@kattenlaw.com
`
`
`
`Petitioner consents to email service. Telephone: (704) 444-2000. Facsimile:
`
`(704) 444-2050.
`
`V.
`
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 C.F.R. § 42.22(A))
`Petitioner requests IPR and cancellation of claims 1-11 of the ’194 patent.
`
`Petitioner’s full statement of the reasons for the relief requested is set forth in detail
`
`below.
`
`VI. THE ’194 PATENT
`The ’194 patent issued on January 21, 2014, from U.S. Appl. No. 10/599,451
`
`(“the ’451 application”), which was filed on July 6, 2005, and claims a benefit of
`
`priority from EP Application No. 04016519, filed July 14, 2004. The ’194 patent
`
`issued with one independent claim and 11 dependent claims.
`
`4
`
`

`

`Petition for Inter Partes Review of USPN 8,633,194
`
`At a high level, the ’194 patent is purportedly directed to “a liquid composition
`
`containing an active substance belonging to the family of substituted benzhydryl
`
`piperazines with reduced amounts of preservatives.” EX1001, Abstract. The
`
`claimed active substance is levocetirizine and salts thereof. EX1001, 2:16-21. The
`
`’194 patent does not dispute that levocetirizine is in the prior art and readily
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`available. EX1001, 2:42-48.
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`The ’194 patent alleges that “[i]t has now been surprisingly found that the
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`active substances belonging to the family of substituted benzhydryl piperazines
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`possess a preservative effect in aqueous solutions,” and a pharmaceutical
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`composition comprising one of these active substances “and a reduced amount of
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`preservatives is stable during a long period of time.” EX1001, 1:51-54, 60-64. With
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`respect to the preservatives, the ’194 patent states that “[b]est results have been
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`obtained with a preservative mixture of methyl parahydroxybenzoate and propyl
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`parahydroxybenzoate in a ratio of 9/1 expressed in weight.” EX1001, 3:45-48.
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`VII. CLAIM CONSTRUCTION
`Under applicable guidance, the claims must be given “the meaning that the
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`term would have to a person of ordinary skill in the art in question at the time of the
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`invention.” See 37 C.F.R § 42.100(b); Phillips v. AWH Corp., 415 F.3d 1303, 1313
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`(Fed. Cir. 2005) (en banc). Petitioner is unaware of any prior claim construction
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`determination concerning the ’194 patent in a civil action or a proceeding before the
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`Petition for Inter Partes Review of USPN 8,633,194
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`International Trade Commission. The ’194 patent defines various terms within the
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`specification. See, e.g., Cols. 2—3. For the purposes of this Petition, Petitioner
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`applies those definitions. For all other terms, Petitioner submits that no further
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`construction is necessary for the purposes of this IPR.
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`VIII. PERSON OF ORDINARY SKILL IN THE ART (“POSA”)
`A person of ordinary skill in the art (“POSA”) is a hypothetical person who is
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`presumed to be aware of all pertinent art, thinks along conventional wisdom in the
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`art, and is a person of ordinary creativity. KSR Int’l Co. v. Teleflex, Inc., 550 U.S.
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`398, 420 (2007); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d
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`955, 962 (Fed. Cir. 1986). As of the relevant priority date, a POSA in the relevant
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`field would have had: (i) a Pharm. D. or Ph.D. in chemistry, biochemistry,
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`pharmacy, pharmaceutics, or in a related field, and at least two years of relevant
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`experience in developing and formulating aqueous pharmaceutical formulations;
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`(ii) a master’s degree in the same fields and at least five years of the same relevant
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`experience; or (iii) a bachelor’s degree in the same fields and at least seven years of
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`the same relevant experience. EX1002, ¶ 32-33.
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`A POSA would also have knowledge of the scientific literature concerning
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`the same as of the priority date. A POSA may also work as part of a
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`multi-disciplinary team and draw upon not only his or her own skills, but also take
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`Petition for Inter Partes Review of USPN 8,633,194
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`advantage of certain specialized skills of others in the team to solve a given problem.
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`Id.
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`IX.
`
`
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(B))
`Petitioner respectfully requests IPR of claims 1–11 of the ’194 patent on each
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`specific ground of unpatentability outlined below. Per 37 C.F.R. § 42.6(d), copies
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`of the references are filed herewith. In support of the proposed grounds, this Petition
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`includes the declaration of a technical expert, Dr. Paul A. Laskar (EX1002),
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`explaining what the art would have conveyed to a POSA. Dr. Laskar is an expert in
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`the relevant field. EX1003.
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`
`
`Ground
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`References
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`WO ’094 in view of the
`Handbook
`EP ’203 in view of US ’558
`and the Handbook
`
`1
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`2
`
`
`
`Basis
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`§ 103
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`§ 103
`
`Claims
`Challenged
`1-11
`
`1–11
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`The above-mentioned and other prior art references provide further
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`background in the art, further motivation to combine the references, and/or further
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`show a reasonable expectation of success in combining the teachings of the primary
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`references to arrive at the claimed invention.
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`Petition for Inter Partes Review of USPN 8,633,194
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`X.
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`INVALIDITY ANALYSIS
`The inquiry for obviousness was established in Graham v. John Deere Co. of
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`Kansas City, 383 U.S. 1 (1966). The Graham factors require an examination of:
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`(1) the scope and content of the prior art; (2) differences between the prior art and
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`the claims at issue; (3) the level of ordinary skill in the pertinent art; and
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`(4) secondary considerations of non-obviousness. For the reasons explained below,
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`claims 1–11 of the ’194 patent are unpatentable under 35 U.S.C. § 103(a).
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`A. The Level of Ordinary Skill in the Pertinent Art
`The level of ordinary skill in the art has been described above. Supra at X.A.
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`B. The Scope and Content of the Prior Art
`Levocetirizine Was a Known Prior Art Compound and Was
`1.
`Suitable for Liquid Preparations
`Prior to the effective filing date of the ’194 patent, there is no dispute that
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`Petition for Inter Partes Review of USPN 8,633,194
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`levocetirizine was a well-known pharmaceutical agent. EX1009, 893.1, 2
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`Levocetirizine is the levo-isomer of the racemate cetirizine. EX1007, 2:37-38 (“The
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`term ‘levocetirizine’ as used herein means the levorotary enantiomer of cetirizine.”);
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`EX1008, 1123 (“Cetirizine is a racemate which consists in equal amounts of
`
`
`1 Potter, P.C., “Levocetirizine is effective for symptom relief including nasal
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`congestion in adolescent and adult (PAR) sensitized to house dust mites,” 58 Allergy
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`2003 (Oxford, United Kingdom) Issue 9, pages 893–899, published in August 2003
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`(EX1009). EX1009 was not disclosed to or cited by the Examiner during
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`prosecution. Accordingly, it is available as prior art to the ’194 patent under
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`35 U.S.C. § 102(a).
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`2 If Patent Owner contends that Petitioner has not made a sufficient showing that any
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`printed publication cited in the Petition is not available as prior art under 35 U.S.C.
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`§ 102, Petitioner notes that all of the printed publications have conventional markers
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`that indicate they were indeed published when and where they claim to have been
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`published. Provepharm Inc. v. Wista Laboratories Ltd, IPR2018-00182 at 13–18
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`(Paper 16, Institution Decision) (P.T.A.B. July 5, 2018) (“These indicia are
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`conventional markers that, in this case, signal that Akkermans was published in
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`1999. Thus, absent evidence to the contrary, we have no reason to suspect
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`otherwise.”).
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`Petition for Inter Partes Review of USPN 8,633,194
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`(R)-levocetirizine and (S)-dextrocetirizine.”). As admitted by the ’194 patent,
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`separation and/or preparation of the individual isomers from the racemate was not a
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`challenge: “Each individual optical isomer may be obtained by conventional means,
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`i.e., resolution from the corresponding racemic mixture or by asymmetric synthesis.”
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`EX1001, 2:40-42. In re Fout, 675 F.2d 297, 300, (C.C.P.A. 1982) (“Valid prior art
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`may be created by the admissions of the parties.”).
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`
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`Moreover, the activity and properties of levocetirizine were well known by
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`the time of the priority date of the ’194 patent. For example, Tillement3 discusses
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`the properties of levocetirizine: “it appears indeed that levocetirizine is the eutomer
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`for pharmacodynamics and pharmacokinetic reasons. To summarize, all evidence
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`available indicates that levocetirizine is intrinsically more active and more
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`effi