Paper No. 1
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`___________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`
`MICRO LABS LIMITED AND MICRO LABS USA INC.
`Petitioners,
`
`v.
`
`SANTEN PHARMACEUTICAL CO., LTD. AND ASAHI GLASS CO., LTD.
`Patent Owners.
`___________________
`
`Case: To be Assigned
`Patent No. 5,886,035
`___________________
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 5,886,035
`UNDER 35 U.S.C. § 311 AND C.F.R. § 42.108
`
`
`
`
`
`
`
`
`Mail Stop Patent Board
`Patent Trial and Appeal Board
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`

`

`TABLE OF CONTENTS
`
`I.
`
`INTRODUCTION ........................................................................................... 1
`
`II. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(a)(1) .......................... 4
`
`A.
`
`B.
`
`C.
`
`D.
`
`Real Parties-In-Interest under 37 C.F.R. § 42.8(b)(1). ......................... 4
`
`Related Matters under 37 C.F.R. § 42.8(b)(2) ...................................... 4
`
`Lead and Back-Up Counsel Under 37 C.F.R. § 42.8 (b)(3). ................ 5
`
`Service Information – 37 C.F.R. § 42.8(b)(4) ....................................... 5
`
`III.
`
`PAYMENT OF FEES – 37 C.F.R. §§ 42.15(a) AND 42.103 ........................ 6
`
`IV. POWER OF PAYMENT OF FEES – 37 C.F.R. §§ 42.15(a) AND
`42.103 .............................................................................................................. 6
`
`V.
`
`POWER OF ATTORNEY – C.F.R. §42.10(b) ............................................... 6
`
`VI. GROUNDS FOR STANDING AND PROCEDURAL STATEMENT ......... 6
`
`VII. STATEMENT OF PRECISE RELIEF REQUESTED UNDER 37
`C.F.R. §§ 42.22(a)(1) and 42.104(b) ............................................................... 7
`
`VIII. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW ........... 10
`
`IX. STATEMENT OF REASONS FOR THE RELIEF REQUESTED ............. 10
`
`X. OVERVIEW .................................................................................................. 12
`
`A.
`
`B.
`
`Summary of U.S. Patent No. 5,886,035 .............................................. 12
`
`Prosecution Background of the ’035 Patent ........................................ 14
`
`XI. TECHNICAL BACKGROUND AND STATE OF THE ART PRIOR
`TO DECEMBER 26, 1996 ............................................................................ 15
`
`XII. LEVEL OF ORDINARY SKILL IN THE ART ........................................... 23
`
`XIII. CLAIM CONSTRUCTION .......................................................................... 25
`
`XIV. SCOPE AND CONTENT OF THE PRIOR ART ......................................... 26
`i
`
`
`
`

`

`A.
`
`European Patent Application Publication EP0639563A2
`(“Klimko”) (Ex. 1003) ........................................................................ 26
`
`B.
`
`U.S. Patent No. 5,292,754 (“Kishi”) (Ex. 1005) ................................. 34
`
`A. Ueno Japan (Ex. 1006) ........................................................................ 37
`
`C.
`
`D.
`
`Bezuglov 1982 (Ex. 1007) .................................................................. 39
`
`Bezuglov 1986 (Ex. 1008) .................................................................. 40
`
`XV. DETAILED EXPLANATION OF GROUNDS FOR
`UNPATENTABILITY .................................................................................. 41
`
`A. GROUND 1: Claims 1-14 of the ’035 Patent Are Obvious Over
`Klimko, Kishi and Ueno Japan ........................................................... 41
`
`a.
`
`Claims 1-3 Directed to Compounds Are Obvious over
`Klimko in view of Kishi and Ueno Japan. ................................ 41
`
`i.
`
`ii.
`
`Klimko Discloses Compound C - A Lead
`Compound Possessing Significant IOP-Reducing
`Activity ........................................................................... 45
`
`Kishi Teaches that Removal of the Hydroxyl
`Group at the C-15 Position of Compound C
`Eliminates Hyperemia .................................................... 50
`
`iii. Ueno Japan Teaches Substitution of a Difluoro
`Group in Place of the Hydroxyl Group at the C-15
`Position of Compound C ................................................ 51
`
`Claims 4-6 Directed To Medicines Containing Tafluprost
`Are Obvious Over Klimko, Kishi and Ueno Japan. ................. 54
`
`Claims 7-11 Directed to Medicines Containing
`Tafluprost Are Obvious Over Klimko, Kishi and Ueno
`Japan. ......................................................................................... 57
`
`Claims 12-14 Directed to Medicines Containing
`Tafluprost Are Obvious Over Klimko, Kishi and Ueno
`Japan. ......................................................................................... 60
`
`b.
`
`c.
`
`d.
`
`
`
`ii
`
`

`

`B.
`
`GROUND 2: Claims 1-14 of the ’035 Patent Are Obvious Over
`Klimko, Kishi and Ueno Japan in further view of Bezuglov
`1982 and/or Bezuglov 1986 ................................................................ 62
`
`a.
`
`b.
`
`c.
`
`Klimko and Kishi Teach Removal of the Hydroxyl
`Group at the C-15 Position to Eliminate Hyperemia ................ 62
`
`Bezuglov 1982 and Bezuglov 1986 Teach Monofluorine
`Substitution of the C-15 Position of the Hydroxyl Group ........ 63
`
`Ueno Japan Teaches Difluorination at the C-15 Position ......... 65
`
`XVI. SECONDARY CONSIDERATIONS DO NOT REBUT THE PRIMA
`FACIE CASE ................................................................................................. 66
`
`A. No Unexpected Results Over the Closest Prior Art ............................ 67
`
`B.
`
`No Long-Felt and Unmet Need ........................................................... 68
`
`XVII. CONCLUSION .............................................................................................. 69
`
`
`
`
`
`iii
`
`

`

`TABLE OF AUTHORITIES
`
`Cases
`
`Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc.,
`752 F.3d 967 (Fed. Cir. 2014), reh’g and reh’g en banc denied 769 F.3d
`1339 (Fed. Cir. 2014) ................................................................................... passim
`
`Connell v. Sears, Roebuck & Co.,
`722 F.2d 1542 (Fed. Cir. 1983) .............................................................................. 8
`
`Cuozzo Speed Techs., LLC v. Lee,
`136 S.Ct. 2131 ( 2016) ......................................................................................... 26
`
`DyStar Textifarben GmbH v. C.H. Patrick, Co.,
`464 F.3d 1356 (Fed. Cir. 2006) ............................................................................ 10
`
`Eisai Co. Ltd. v. Dr. Reddy’s Labs.,
`533 F.3d 1353 (Fed. Cir. 2008) .............................................................................. 9
`
`Eli Lilly and Co. v. Zenith Goldline Pharma, Inc.,
`471 F.3d 1369 (Fed. Cir. 2006) .............................................................................. 9
`
`In re De Blauwe,
`736 F.2d 699 (Fed. Cir. 1984) .............................................................................. 69
`
`In re Deuel,
`51 F.3d 1552 (Fed. Cir. 1995) ................................................................................ 9
`
`In re Dillon,
`919 F.2d 688 (Fed. Cir. 1990) ......................................................................... 9, 55
`
`In re Grabiak,
`769 F.2d 729 (Fed. Cir. 1985) ................................................................................ 9
`
`In re Longi,
`759 F.2d 887 (Fed. Cir. 1985) ................................................................................ 9
`
`In re Muchmore,
`433 F.2d 824 (CCPA 1970) ................................................................................. 45
`
`
`
`iv
`
`

`

`KSR Int’l Co. v. Teleflex, Inc.,
`127 S. Ct. 1727 (2007) .................................................................................... 8, 24
`
`Leapfrog Enterprises Inc. v. Fisher-Price Inc.,
`485 F.3d 1157 (Fed. Cir. 2007) ............................................................................ 68
`
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) .............................................................................. 68
`
`Otsuka Pharm. Co., Ltd. v. Sandoz, Inc.,
`678 F.3d 1280 (Fed. Cir. 2012) ..................................................................... 49, 55
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ............................................................................ 10
`
`Soverain Software LLC v. Victoria’s Secret Direct Brand Mgmt., LLC,
`778 F.3d 1311 (Fed. Cir. 2015). ........................................................................... 45
`
`Takeda Chem. Indus. Ltd. v. Alphapharm Pty., Ltd.,
`492 F.3d 1350 (Fed. Cir. 2007) ................................................................ 9, 10, 47
`
`Statutes and Codes
`
`United States Code
`Title 35, section 102(b) ................................................................................ passim
`Title 35, section 103 ............................................................................................... 8
`Title 35, section 103(a) ........................................................................... 4, 7, 8, 10
`Title 35, section 311 ............................................................................................... 7
`Title 35, section 314(a) ........................................................................................ 11
`Title 35, sections 311-319 ...................................................................................... 1
`
`Rules and Regulations
`
`Code of Federal Regulations
`Title 37, sections 42.1-.80, 42.100-.123 ................................................................ 1
`Title 37, section 42.6(c) ....................................................................................... 10
`Title 37, section 42.8(a)(1) ..................................................................................... 4
`Title 37, section 42.8(b)(1) .................................................................................... 4
`Title 37, section 42.8(b)(2) .................................................................................... 4
`Title 37, section 42.8(b)(3) .................................................................................... 5
`Title 37, section 42.8(b)(4) .................................................................................... 6
`v
`
`
`
`

`

`Title 37, section 42.10(a) ....................................................................................... 5
`Title 37, section 42.10(b) ....................................................................................... 7
`Title 37, section 42.15(a) ...................................................................................6, 7
`Title 37, section 42.22(a)(1) ................................................................................... 7
`Title 37, section 42.100(b) ............................................................................ 26, 27
`Title 37, section 42.103 ......................................................................................6, 7
`Title 37, section 42.104 .......................................................................................... 7
`Title 37, section 42.104(b) ..................................................................................... 7
`
`
`
`
`
`
`
`
`vi
`
`

`

`
`Exhibit No.
`
`
`
`
`EXHIBITS
`
`
`Document
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`U.S. Patent No. 5,886,035 to Shirasawa et al. (issued March 23,
`1999).
`
`File History of U.S. Patent No. 5,886,035 to Shirasawa et al.
`
`EP0639563A2 to Klimko et al. (published February 22, 1995).
`
`EP0471856A1 to Kishi et al. (published February 26, 1992).
`
`U.S. Patent No. 5,292,754 to Kishi et al. (issued March 8, 1994).
`
`JP-A-7070054 to Ueno Japan et al. (published March 14, 1995).
`
`Bezuglov, V. V. & L. D. Bergelson, “Fluoroprostaglandins—A
`New Class of Biologically Active Analogues of Natural
`Prostaglandins”
`in Lipids of Biological Membranes (L.D.
`Bergelson, ed., 1982).
`
`Bezuglov, Vladimir V. “Fluorodeoxy Prostaglandins, Synthesis
`and Perspectives” in Prostaglandins and Cardiovascular Diseases
`(Takayuki Ozawa et al. eds., 1986).
`
`Camras et al. “Reduction of intraocular pressure in normal and
`glaucomatous primate (Aotus trivirgatus) eyes by topically applied
`PGF2α,” Curr. Eye Res. 1:205-209 (1981).
`
`Stjernschantz, J.W. “From PGF2α-Isopropyl Ester to Latanoprost:
`A Review of the Development of Xalatan,” Investig. Ophthal. &
`Vis. Sci. 42(6):1134-1145 (2001).
`
`Nixon, D. “Hyperemia in Glaucoma Patients,” (2008) available
`online at http://www.medscape.org/viewarticle/577054.
`
`
`
`vii
`
`

`

`
`Exhibit No.
`
`
`
`
`
`Document
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`
`PCT/US97/20671 to Klimko et al. (published May 22, 1998).
`
`U.S. Provisional Patent Application No. 60/030,519 to Klimko et
`al. (made accessible as of May 22, 1998).
`Alm A 1989 Progress in Clin and Biological Research pg 447-458.
`
`Stjernschantz J 1992 Drugs of the Future 691-704.
`
`Product Details for NDA 020597 (XALATAN) available online at
`https://www.accessdata.fda.gov/scripts/cder/ob/results_product.cf
`m?Appl_Type=N&Appl_No=020597.
`
`Patent and Exclusivity for: N202514 (ZIOPTAN) available online
`at
`https://www.accessdata.fda.gov/scripts/cder/ob/patent_info.cfm?Pr
`oduct_No=001&Appl_No=202514&Appl_type=N.
`
`Lee, P.Y. et al., “The effect of prostaglandin F2 alpha on
`intraocular pressure in normotensive human subjects,” Invest.
`Ophthalmol. Vis. Sci. Oct. 29(10):1474–1477 (1988).
`
`Camras, C.B. et al., “Maintained reduction of intraocular pressure
`by prostaglandin F2 alpha-1-isopropyl ester applied in multiple
`doses
`in ocular hypertensive
`and glaucoma patients,”
`Ophthalmology Sep. 96(9):1329–1337 (1989).
`
`Nilsson, S.F. et al., “Increased uveoscleral outflow as a possible
`mechanism of ocular hypotension caused by prostaglandin F2
`alpha-1-isopropylester in the cynomolgus monkey,” Exp. Eye Res.
`May 48(5):707–716 (1989).
`
`Pederson, J.E. et al., “Laser-induced primate glaucoma. I.
`Progression of cupping,” Arch. Ophthalmol. Nov. 102(11):1689-
`
`
`
`viii
`
`

`

`
`Exhibit No.
`
`
`
`
`
`Document
`
`92 (1984).
`
`Radius, R.L. et al., “Laser-induced primate glaucoma. II.
`Histopathology,” Arch. Ophthalmol. Nov. 102(11):1693-8 (1984).
`
`Lee, P.Y. et al., “Pharmacological testing in the laser-induced
`monkey glaucoma model,” Curr. Eye Res. Jul. 4(7):775-81 (1985).
`
`Bito, L.Z. “Species differences in the responses of the eye to
`irritation and trauma: a hypothesis of divergence in ocular defense
`mechanisms, and the choice of experimental animals for eye
`research,” Exp. Eye Res. Dec. 39(6):807-29 (1984).
`
`U.S. Patent No. 3,914,265 to Middleton (issued October 21, 1975).
`
`Nelson, N.A. “Prostaglandin Nomenclature,” J. Med. Chem.
`17(9):911-918 (1974).
`
`Declaration of Mitchell deLong, Ph.D.
`
`Declaration of Aron D. Rose, M.D.
`
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`
`
`
`
`
`
`ix
`
`

`

`Pursuant to 35 U.S.C. § 311-319 and 37 C.F.R. § 42.1-.80, 42.100-.123,
`
`Micro Labs Limited and Micro Labs USA Inc. (together, “Petitioners”) petition for
`
`Inter Partes Review of claims 1-14 of U.S. Patent No. 5,886,035, entitled
`
`“Difluoroprostaglandin Derivatives and Their Use” (“the ’035 patent,” Ex. 1001).
`
`I.
`
`INTRODUCTION
`The claims of the ’035 patent are directed to both a genus of PGF2α
`
`analogues that encompasses tafluprost and medicines containing these analogues
`
`inclusive of tafluprost. The claims were allowed under the mistaken premise that
`
`the prior art neither taught nor suggested tafluprost to a person of ordinary skill in
`
`the art (“POSA”) at the time of the alleged invention. As set forth in this Petition,
`
`the most relevant combination of invalidating prior art known in December 1996
`
`was not brought before the Examiner during prosecution. Significantly, the
`
`Examiner never had the opportunity to consider whether tafluprost would have
`
`been obvious to a POSA over European Patent Application EP 0639563A2
`
`(“Klimko,” Ex. 1003), which discloses a prostaglandin F2α (PGF2α) analogue
`
`referred to as “compound C” as a potential treatment for glaucoma and ocular
`
`hypertension. Klimko teaches that compound C can be useful as a medicine for
`
`reducing intraocular pressure (“IOP”), that is commonly associated with eye
`
`diseases such as glaucoma and ocular hypertension. Tafluprost is likewise a
`
`compound directed toward the treatment of IOP and eye disease associated with
`
`1
`
`

`

`IOP. Compound C differs in its chemical structure from tafluprost only slightly in
`
`that a hydroxyl group (i.e., —OH) is present at the C-15 position of compound C,
`
`whereas two fluorine (F) atoms are substituted at the C-15 position in tafluprost.
`
`Prior to December 1996, it would have been further obvious to a POSA to
`
`substitute the hydroxyl group at the C-15 position of naturally occurring PGF2α, or
`
`its known synthetic analogues including compound C, with two fluorine (F) atoms
`
`to eliminate hyperemia. Hyperemia is a negative side effect often associated with
`
`prostaglandins, such as compound C, that are directed toward the treatment of eye
`
`disease by reducing intraocular pressure. Thus, the slight difference in chemical
`
`structure between compound C and tafluprost does not render tafluprost and
`
`medicines containing tafluprost patentable. In particular, a POSA looking to make
`
`a PGF2α analogue useful for treating glaucoma and ocular hypertension would be
`
`motivated to start with compound C taught by Klimko and replace the hydroxyl
`
`group at the C-15 position of that compound with two fluorine (F) atoms, in view
`
`of the benefits of making such a modification taught by the prior art.
`
`Specifically, a POSA would have replaced the hydroxyl group with two
`
`fluorine (F) atoms at the C-15 position of compound C because:
`
`(1) U.S. Patent No. 5,292,754 (“Kishi,” Ex. 1005) discloses that
`
`(a) naturally occurring PGF2α prostaglandins that are useful in treating
`
`elevated intraocular pressure are easily subject to metabolic degradation due
`
`2
`
`

`

`to the presence of a hydroxyl group (—OH) at the C-15 position, (b)
`
`removing this hydroxyl group stabilizes the PGF2α analogue against
`
`degradation, thereby improving its efficacy in treating glaucoma and
`
`hypertension, and (c) removing this hydroxyl group eliminates the negative
`
`side effect of hyperemia often associated with PGF2α prostaglandins and
`
`their analogues;
`
`(2)
`
`Japanese Patent Application JP-A-7070054 (“Ueno Japan,”
`
`Ex. 1006), which references Kishi and discusses removal of the hydroxyl
`
`group (—OH) at the C-15 position as taught by Kishi, teaches the direct
`
`substitution of two fluorine (F) atoms for the hydroxyl group at the C-15
`
`carbon of PGF2α analogues; and
`
`(3)
`
`(a) Bezuglov, V. V. & L. D. Bergelson,
`
`“Fluoroprostaglandins—A New Class of Biologically Active Analogues of
`
`Natural Prostaglandins” in Lipids of Biological Membranes (L.D.
`
`Bergelson, ed., 1982) (“Bezuglov 1982,” Ex. 1007) and/or (b) Bezuglov,
`
`Vladimir V. “Fluorodeoxy Prostaglandins, Synthesis and Perspectives” in
`
`Prostaglandins and Cardiovascular Diseases (Takayuki Ozawa et al. eds.,
`
`1986) (“Bezuglov 1986,” Ex. 1008), teach the potential for improved
`
`stability and activity of PGF2α analogues when a singular fluorine (F) atom
`
`3
`
`

`

`is substituted for the hydroxyl group (—OH) at the C-15 in naturally
`
`occurring PGF2α prostaglandins.
`
`The prior art summarized above and described in greater detail herein
`
`teaches that tafluprost, as encompassed by the claims of the ’035 patent, would
`
`have been obvious to a POSA at the time of its purported invention. Because
`
`tafluprost is covered by genera claimed in the ’035 patent, each and every claim of
`
`the ’035 patent that encompasses either tafluprost or a medicine that contains
`
`tafluprost is invalid under pre-AIA 35 U.S.C. §103(a) in view of the prior art. This
`
`Petition demonstrates by a preponderance of the evidence that claims 1-14 of the
`
`’035 patent are obvious in view of the prior art, and Petitioners request that all
`
`fourteen claims of the ’035 patent be judged unpatentable and cancelled.
`
`II. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(a)(1)
`A. Real Parties-In-Interest under 37 C.F.R. § 42.8(b)(1).
`Micro Labs Limited and Micro Labs USA Inc. are the real parties in interest
`
`for Petitioners.
`
`B. Related Matters under 37 C.F.R. § 42.8(b)(2)
`Petitioners are aware of the following matters: The ’035 patent is the subject
`
`of litigation in Santen Pharmaceutical Co., Ltd., Asahi Glass Co., Ltd. and Oak
`
`Pharmaceuticals, Inc. v. Micro Labs Limited and Micro Labs USA Inc., Case No.
`
`16-cv-00353 (D. Del. 2016); and Santen Pharmaceutical Co., Ltd., Asahi Glass
`
`4
`
`

`

`Co., Ltd. and Oak Pharmaceuticals, Inc. v. Sandoz Inc., Case No. 16-cv-00354 (D.
`
`Del. 2016).
`
`C. Lead and Back-Up Counsel Under 37 C.F.R. § 42.8 (b)(3).
`Pursuant to 37 C.F.R. § 42.8(b)(3) and 42.10(a), Petitioners provide the
`
`following designation of counsel:
`
`Lead Counsel
`
`
`Cedric C.Y. Tan
`Reg. No. 56,082
`PILLSBURY WINTHROP
`SHAW PITTMAN LLP
`1200 Seventeenth Street, NW
`Washington, DC 20036
`Tel.: (202) 663-8000
`Fax.: (202) 663-8007
`Email: cedric.tan@pillsburylaw.com
`
`Back-Up Counsel
`
`
`Sean M. Weinman
`Reg. No. 69,515
`PILLSBURY WINTHROP
`SHAW PITTMAN LLP
`1650 Tysons Boulevard, 14th Floor
`McLean, VA 22102
`Tel.: (703) 770-7511
`Fax.: (703) 770-4856
`Email: sean.weinman@pillsburylaw.com
`
`
`
`
`D. Service Information – 37 C.F.R. § 42.8(b)(4)
`Please direct all correspondence to lead counsel and back-up counsel at the
`
`contact information above, with a copy to MicroLabsIPR@pillsburylaw.com.
`
`Petitioners also consent to service by electronic mail at the email addresses set
`
`forth above, and request that a copy of all services made by electronic mail be
`
`provided to MicroLabsIPR@pillsburylaw.com.
`
`
`
`5
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`

`

`III. PAYMENT OF FEES – 37 C.F.R. §§ 42.15(a) AND 42.103
`Pursuant to 37 C.F.R § 42.103, the fee set forth in § 42.15(a) accompanies
`
`this Petition. Petitioners authorize the Patent and Trademark Office to charge at
`
`any time during this proceeding any additional fees or fee deficiencies to Deposit
`
`Acct. No. 033975.
`
`IV. POWER OF PAYMENT OF FEES – 37 C.F.R. §§ 42.15(a) AND 42.103
`Pursuant to 37 C.F.R § 42.103, the fee set forth in § 42.15(a) accompanies
`
`this Petition. Petitioners authorize the Patent and Trademark Office to charge at
`
`any time during this proceeding any additional fees or fee deficiencies to Deposit
`
`Acct. No. 033975.
`
`V.
`
`POWER OF ATTORNEY – C.F.R. §42.10(b)
`
`Concurrently filed herewith are Powers of Attorney pursuant to 37 C.F.R.
`
`§42.10(b).
`
`VI. GROUNDS FOR STANDING AND PROCEDURAL STATEMENT
`Pursuant to 37 C.F.R. § 42.104, Petitioners certify that the ’035 patent is
`
`available for inter partes review (“IPR”) and that Petitioners are not barred or
`
`estopped from requesting IPR of the ʼ035 patent claims on the grounds identified
`
`herein, and have not been party to any post-grant review of the challenged claims.
`
`6
`
`

`

`VII. STATEMENT OF PRECISE RELIEF REQUESTED UNDER 37
`C.F.R. §§ 42.22(a)(1) and 42.104(b)
`
`Petitioners request IPR of claims 1-14 of the ’035 patent under 35 U.S.C.
`
`§311 and AIA §6. Petitioners challenge claims 1-14 of the ’035 patent on the
`
`grounds that each of the claims are invalid as obvious and should be cancelled as
`
`unpatentable under pre-AIA 35 U.S.C. § 103(a).
`
`Under 35 U.S.C. §103(a), the subject matter of a claim is considered
`
`obvious, and the claim, therefore, invalid, when the claimed “subject matter as a
`
`whole would have been obvious at the time the invention was made to a person
`
`having ordinary skill in the art to which said subject matter pertains.” 35 U.S.C. §
`
`103(a) (pre-AIA). The test for obviousness requires the analysis of four
`
`inquiries: “1) the scope and content of the prior art; 2) the differences between the
`
`art and the claims at issue; 3) the level of ordinary skill in the art; and 4) whatever
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`objective evidence may be present as indicia of nonobviousness.” Connell v.
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`Sears, Roebuck & Co., 722 F.2d 1542, 1547 (Fed. Cir. 1983).
`
`The Supreme Court has stated that “[t]he question is not whether the
`
`combination was obvious to the patentee but whether the combination was obvious
`
`to a person with ordinary skill in the art,” and “any need or problem known in the
`
`field of endeavor at the time of invention and addressed by the patent can provide a
`
`reason for combining the elements in the manner claimed.” KSR Int’l Co. v.
`
`Teleflex, Inc., 127 S. Ct. 1727, 1742 (2007). Accordingly, a patent can be
`
`7
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`

`

`invalidated under 35 U.S.C. § 103 using a combination of prior art for any of the
`
`reasons articulated above.
`
`When the invention at issue is a chemical compound, the Federal Circuit has
`
`held that a prima facie case of obviousness is created by “structural similarity
`
`between claimed and prior art subject matter, proved by combining references or
`
`otherwise, where the prior art gives reason or motivation to make the claimed
`
`compositions. . . .” Takeda Chem. Indus. Ltd. v. Alphapharm Pty., Ltd., 492 F.3d
`
`1350, 1356-57 (Fed. Cir. 2007) (quoting In re Dillon, 919 F.2d 688, 692 (Fed. Cir.
`
`1990) (en banc)). In addition, “a prima facie case of obviousness also requires a
`
`showing of ‘adequate support in the prior art’ for the change in structure.” Id.
`
`(quoting In re Grabiak, 769 F.2d 729, 731-32 (Fed. Cir. 1985)). The prior art must
`
`also provide “a
`
`reasonable expectation of success,
`
`[but] not absolute
`
`predictability.” Eli Lilly and Co. v. Zenith Goldline Pharma, Inc., 471 F.3d 1369,
`
`1377 (Fed. Cir. 2006) (quoting In re Longi, 759 F.2d 887, 896 (Fed. Cir. 1985)).
`
`In the pharmaceutical arts, a prima facie case of obviousness is often based
`
`on a known compound, called a “lead compound,” which serves as a starting point
`
`for a person of ordinary skill developing the claimed invention. Eisai Co. Ltd. v.
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`Dr. Reddy’s Labs., 533 F.3d 1353, 1357 (Fed. Cir. 2008). The Federal Circuit
`
`stated that “[n]ormally a prima facie case of obviousness is based upon structural
`
`similarity, that is, an established structural relationship between a prior art
`
`8
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`

`

`compound [i.e., a lead compound] and the claimed compound.” Takeda, 492 F.3d
`
`at 1356 (quoting In re Deuel, 51 F.3d 1552, 1558 (Fed. Cir. 1995)). Such
`
`structural similarities “may provide the requisite motivation or suggestion to
`
`modify known compounds to obtain new compounds.” Id. (quoting Deuel, 51 F.3d
`
`at 1558).
`
`Thus, a party asserting invalidity of a chemical compound can establish a
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`prima facie case of obviousness by identifying: 1) a prior art compound having
`
`structural similarity to the claimed compound; and 2) reason or motivation in the
`
`prior art
`
`to modify
`
`the compound as necessary
`
`to obtain
`
`the claimed
`
`compound. As explained by the Takeda court, “in cases involving new chemical
`
`compounds, it remains necessary to identify some reason that would have led a
`
`chemist to modify a known compound in a particular matter to establish prima
`
`facie obviousness of a new claimed compound.” Takeda, 492 F.3d at 1357. Such
`
`reason or motivation need not be explicit “in the prior art references sought to be
`
`combined, but rather ‘may be found in any number of sources, including common
`
`knowledge, the prior art as a whole, or the nature of the problem itself.’” Pfizer,
`
`Inc. v. Apotex, Inc., 480 F.3d 1348, 1362 (Fed. Cir. 2007) (quoting DyStar
`
`Textifarben GmbH v. C.H. Patrick, Co., 464 F.3d 1356, 1361 (Fed. Cir. 2006)).
`
`Under the standards cited above, claims 1-14 of the ’035 patent should be
`
`found invalid as obvious, and should be cancelled as unpatentable under pre-AIA
`
`9
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`

`

`35 U.S.C. § 103(a). Petitioners’ detailed statement of reasons for the relief
`
`requested is set forth below in the section titled “Statement of Reasons for Relief
`
`Requested.” In accordance with 37 C.F.R. § 42.6(c), copies of the exhibits are
`
`filed herewith. In addition, this Petition is accompanied by the Declaration of Dr.
`
`Mitchell deLong (Ex. 1027) and the Declaration of Dr. Aron Rose (Ex. 1028).
`
`VIII. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`A petition for IPR must demonstrate “a reasonable likelihood that the
`
`petitioner would prevail with respect to at least 1 of the claims challenged in the
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`petition.” 35 U.S.C. § 314(a). This Petition meets this threshold. As explained
`
`below, there is a reasonable likelihood that Petitioners will prevail with respect to
`
`at least one of the challenged claims, and IPR should therefore be instituted.
`
`IX. STATEMENT OF REASONS FOR THE RELIEF REQUESTED
`The challenged claims of the ’035 patent claim PGF2α analogues, including
`
`tafluprost and the use of those analogues in a medicine for treatment of eye
`
`diseases including diseases such as glaucoma and ocular hypertension. However,
`
`as of the December 1996 priority date claimed by the applicants for the ’035
`
`patent, the prior art disclosed a structurally similar PGF2α analogue -- 16-phenoxy-
`
`17,18,19,20-tetranorprostaglandin F2α, isopropyl ester -- that differs from tafluprost
`
`only in that there are two fluorine (F) atoms in the place of the hydroxyl substituent
`
`10
`
`

`

`at the C-15 position. A comparison of that prior art, namely, compound C taught
`
`by Klimko (Ex. 1003) to tafluprost, is set forth below:
`
`
`
`As of December 1996, it would have been obvious for a POSA to modify
`
`compound C disclosed in Klimko by replacing the hydroxyl group at the C-15
`
`position in compound C with two fluorine (F) atoms to improve stability and
`
`eliminate the known undesirable potential for hyperemic effect of prostaglandin
`
`PGF2α analogues such as compound C as taught by Klimko and other prior art.
`
`Tafluprost would thus have been obvious to a POSA. Accordingly, the claims of
`
`the ’035 patent that encompass tafluprost or a medicine containing tafluprost are
`
`unpatentable in view of the prior art on the following grounds:
`
`
`
`
`
`11
`
`

`

`Ground
`
`1
`
`2
`
`Challenged Grounds
`
`
`’035 patent are
`the
`Claims 1-14 of
`unpatentable as obvious under 35 U.S.C.
`§103(a) over at least (1) Klimko (Ex. 1003)
`in view of (2) Kishi (Ex. 1005) and (3)
`Ueno Japan (Ex. 1006).
`
`
`’035 patent are
`the
`Claims 1-14 of
`unpatentable as obvious under 35 U.S.C.
`§103(a) over at least (1) Klimko (Ex. 1003)
`in view of (2) Kishi (Ex. 1005), (3) Ueno
`Japan (Ex. 1006) and (4) Bezuglov 1982
`(Ex. 1007) and/or (5) Bezuglov 1986 (Ex.
`1008).
`
`
`Claims
`
`1-14
`
`1-14
`
`
`X. OVERVIEW
`A. Summary of U.S. Patent No. 5,886,035
`The ’035 patent, entitled “Difluoroprostaglandin Derivatives and Their
`
`Use,” issued March 23, 1999, based on U.S. Application Serial No. 09/993,017
`
`(“the ’017 application”) which was filed December 18, 1997. The ’035 patent
`
`purports to claim the benefit of Japanese Patent Application Nos. JP 8-348614 (“JP
`
`’614”) filed December 26, 1996, JP 9-074054 (“JP ’054”) filed March 26, 1997,
`
`and JP 9-172477 (“JP ’477”) filed June 27, 1997. The ’035 patent is assigned on
`
`its face to Patent Owners Asahi Glass Company Ltd. and Santen Pharmaceutical
`
`Co., Ltd. Patent Owners have listed the ’035 patent in the FDA’s Electronic
`
`Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations
`
`12
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`

`

`in connection with the drug ZIOPTAN, which contains the compound tafluprost as
`
`its active ingredient. (Ex. 1017.)
`
`The inventors of the ’035 patent claim to have synthesized and measured the
`
`biological activities of 15,15-difluoro-15-deoxy-PGF2α and certain derivatives of it
`
`to arrive at a genus of compounds that lowers intraocular pressure associated with
`
`certain eye diseases that is superior to other compounds known at the time based
`
`on (1) increased efficacy, and (2) reduction of negative inflammatory and irritating
`
`side effects. (Ex. 1001, col. 1, l. 67 - col. 2, l. 15.)
`
`The ’035 patent claims a genus of fluorine-containing prostaglandin
`
`compounds with two fluorine atoms at the C-15 position, their alkyl esters, or their
`
`salts and medicines containing one of these compounds as an active ingredient,
`
`particularly as a preventative or therapeutic medicine for eye diseases that include
`
`glaucoma and ocular hypertension. (Ex. 1001, Abstract, col. 1, ll. 1-5, co. 2, ll. 65-
`
`67.)
`
`The ’035 patent issued with fourteen claims, of which claims 1 and 12 are
`
`independent. Claims 1-3 encompass a genus of compounds that includes
`
`tafluprost. Claims 4-11 depend directly or indirectly from claim 1 and are directed
`
`to medicines that