SENJU EXHIBIT 2018
`LUPIN v SENJU
`IPR2015-01105
`
`PAGE 1 OF 74
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`Innopharma’s ANDA for filing and has assigned the application No. 206326. The ANDA
`contains
`the
`required bioavailability and/or bioequivalence data
`fi'om studies on
`Innopharma’s Bromfenac Product that is the subject of the ANDA.
`
`Innopharma originally submitted its ANDA under 21 U.S.C. § 355(j)( 1) and (2)(A)
`with Paragraph IV certifications to U.S. Patent Nos. 8,129,431 (“the ’431 patent”) and the
`8,669,290 (“the ’290 patent”).
`On September 19, 2014,
`Innopharma sent
`to Senju
`Pharmaceuticals and Bausch & Lomb written notification of its Paragraph IV certification
`and a detailed statement of its then-existing factual and legal bases of Innopharma’s belief
`that each of the ’43l and ’290 patents is invalid, unenforceable, or will not be infringed by
`the manufacture, use, sale, offer for sale, or importation of the drug product described in
`Innopharma’s ANDA. On October 30, 2014, Innopharma sent to Senju Pharmaceuticals and
`Bausch & Lomb written notification of its" amendment to Innopharma’s ANDA to further
`include a Paragraph IV certification to U.S. Patent No. 8,754,131 (“the ‘I31 patent”) and a
`detailed statement of its then-existing factual and legal bases of Innopharma’s belief that the
`’l3l patent is invalid, unenforceable, or will not be infringed by the manufacture, use, sale,
`offer for sale, or importation of the drug product described in Innopharma’s ANDA. On
`March 25, 2015, Innopharma sent to Senju Pharmaceuticals and Bausch & Lomb, written
`notification of its amendment to Innopharma’s ANDA to further include a Paragraph IV
`certification to U.S. Patent No. 8,927,606 (“the ’606 patent”) and a detailed statement of its
`then-existing factual and legal bases of Innophanna’s belief that the ’606 patent is invalid,
`unenforceable, or will not be infringed by the manufacture, use, sale, offer for sale, or
`importation of the drug product described in Innopharma’s ANDA.
`Innopharma has
`amended its ANDA under 21 C.F.R. § 314.94(a)(12)(vi) to further include a Paragraph IV
`certification to’the ’8l3 patent, which lists as an issuance date on its face of October 28,
`2014. Each of the ’43l, ’290, ’l31, ’606, and ’813 patents is listed in Approved Drug
`Products with Therapeutic Equivalence Evaluations (“the Orange Book”) in connection with
`Bausch & Lomb, Inc.’s (“B&L”) approved NDA No. 203168 for PROLENSATM ophthalmic
`solution.
`
`:
`Innopharma seeks the FDA’s approval to market its proposed Bromfenac Product
`prior to the expiration of the Orange Book Patents.
`Innopharma alleges, and originally 2
`certified to the FDA that, to the best of Innopharma’s knowledge, the ’43l and ’290 patents
`are invalid, unenforceable, and/or will not be infringed by the manufacture, use, sale, offer
`for sale, or importation of the drug product described in Innopharma’s ANDA.
`Innopharma
`
`PAGE 2 OF 74
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`PAGE 2 OF 74
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`to 21 U.S.C.
`Attached as Exhibit A is a detailed statement, made pursuant
`§355(j)(2)(B)(iv)(Il) and 21 C.F.R. § 314.95, of the present factual and legal bases for
`lnnopharrna’s Paragraph IV certification to the ’8l3 patent of the Orange Book Patents. The
`statements made therein are based on the information currently available to Innopharma.
`Innopharma reserves all rights to raise any additional defenses relating to invalidity,
`unenforceability, and/or noninfringement should additional information become known to
`Innopharma.
`
`Offer of Confidential Access to ANDA
`
`Pursuant to 21 U.S.C. § 355(j)(5)(C), this notice letter includes an Offer of Confidential
`Access to Innophanna’s ANDA and any supplement(s) thereto. As required by Section
`355(]')(5)(C)(i)(III), Innopharma offers to provide confidential access to certain information
`from its ANDA No. 206326 for the sole and exclusive purpose o_f determining whether an
`infringement action referred to in Section 355(j)(5)(B)(iii) can be brought.
`
`Section 355(j)(5)(C)(i)(III) allows Innopharma to impose restrictions “as to persons
`entitled to access, and on the use and disposition of any information accessed, as would apply
`had a protective order been entered for the purpose of protecting trade secrets and other
`confidential business information.” That provision also grants Innopharma the right to redact
`its ANDA to exclude non-relevant information in response to a request for Confidential Access
`under this Offer.
`'
`
`As permitted bylstatute, Innopharma imposes the following terms and restrictions on its
`Offer of Confidential Access:
`
`(1)
`
`Innopharma will permit confidential access to certain information from its
`proprietary ANDA No. 206326 to attorneys from one outside law firm
`representing B&L; provided, however,
`that such attorneys do not engage,
`fonnally or infonnally,
`in any patent prosecution for B&L or any FDA
`counseling,
`litigation, or other work before or involving the FDA. Such
`information (hereinafter, “Confidential
`Innopharma Information”) shall be 1
`marked
`with
`the
`legend
`“CONFIDENTIAL
`INNOPI-IARMA
`INFORMATION.”
`
`PAGE 3 OF 74
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`PAGE 3 OF 74
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`

`
`(4)
`
`(5)
`
`(6)
`
`prosecute any future or pending patent application by B&L in connection with
`any filing to, or communication with, the FDA relating to Innophar1na’s ANDA
`No. 206326. B&L’s outside law firm agrees to take all measures necessary to
`prevent unauthorized disclosure or use of the Confidential
`Innopharma
`Information, and" that all Confidential Innopharma Information shall be kept
`confidential and not disclosed in any manner inconsistent with this Offer of
`Confidential Access.
`
`the
`Innopharma Information disclosed is, and remains,
`The Confidential
`property of
`Innopharma. By providing said Confidential
`Innopharma
`Information, Innopharma does not grant B&L and/or its outside law firm any
`interest in or license for and to the Confidential Innophanna Information.
`
`B&L’s outside law firm shall, within thirty-five (35) days from the date that it
`first receives the Confidential Innopharma Information, return to Innopharma
`all Confidential
`Innopharma Information and any copies thereof B&L’s
`outside law firm shall return all Confidential
`Innopharma Information to
`Innopharma before any infringement suit is filed by B&L, if suit is commenced
`before this 35-day period expires.
`In the event that B&L opts to file suit, none
`of the information contained in or obtained fiom any Confidential Innopharma
`Information that Innopharma provides, including Exhibit A to this letter, shall
`be included in any publicly-available complaint or other pleading.
`
`Nothing in this Offer of Confidential Access shall be construed as an admission
`by Innopharma regarding the validity, enforceability, and/or infringement of
`any US. patent. Further, nothing herein shall be construed as an agreement or
`admission by Innopharma with respect
`to the competency,
`relevance, or
`materiality of any such Confidential Innopharma Information, document, or
`thing. The fact that Innopharma provides Confidential Innopharma Information
`to B&L upon B&L’s request shall not be construed as an admission by
`Innopharma that such Confidential Innophanna Information is relevant to the
`disposition of any issue relating to any alleged infringement of the Orange
`Book Patents or to the validity or enforceability of any or all of these patents.
`
`(7)
`
`The attorneys from B&L’s outside law firm shall acknowledge in writing their
`receipt of a copy of these terms and restrictions prior to production of any
`
`PAGE 4 OF 74
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`PAGE 4 OF 74
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`

`
`that the “restrictions and other terms of [this] offer of confidential access shall be considered
`terms of an enforceable contract.” Thus,
`to the extent
`that B&L requests access to
`Confidential Innopharma Information,
`it necessarily accepts the terms and restrictions
`outlined above.
`
`Written notice requesting access under this Offer of Confidential Access should be
`made to:
`
`Deepro R. Mukerjee
`Alston & Bird LLP
`
`90 Park Avenue
`
`New York, New York 10016
`Tel: (212) 210-9400
`Fax: (212) 210-9444
`deepro.mukerjee@alston.coin '
`
`By providing this Offer of Confidential Access, Innopharina maintains the right and
`ability to bring and maintain a Declaratory Judgment action under 28 U.S.C. § 2201 et seq.,
`pursuant to 21 U.S.C. § 355(j)(5)(C).
`
`Copies of this letter and the attached exhibits are also being provided by U.S.
`Registered mail, return receipt requested.
`‘
`
`Sincerely,
`
`/'2
`
`Deepro R. Mukerj ee
`
`Enclosures: Exhibits A & B
`
`PAGE 5 OF 74
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`PAGE 5 OF 74
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`

`
`PAGE 6 OF 74
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`PAGE 6 OF 74
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`
`4
`
`Obviousness Under 35 U.S.C. § 103 ........................................................ .. 5
`
`a)
`
`b)
`
`c)
`
`Level of Ordinary Skill in the Art ................................................. .. 6
`
`Scope and Content of the Prior Art ............................................... .. 6
`
`Differences between the Prior Art and the Claimed
`Invention ....................................................................................... .. 7
`
`5.
`
`Obviousness of Structurally Similar Compounds ..................................... .. 7
`
`a)
`
`pb)
`
`c)
`
`d)
`
`Lead Compound ............................................................................ .. 8
`
`Structural Modifications ............................................................... .. 8
`
`Reasonable Expectation of Success ............................................ .. 10
`
`Objective Indicia of Non-Obviousness ....................................... .. 10
`
`6.
`
`Infringement Analysis ............................................................................. .. 10
`
`a)
`
`b)
`
`Direct Infringement ..................................................................... .. 10
`
`Infringement under the Doctrine of Equivalents ........................ .. 11
`
`i)
`
`ii)
`
`The Tri—Partite Test (Triple Identity Test) ...................... .. 12
`
`The All Elements Rule .................................................... .. 12
`
`iii)
`
`. Prosecution History Estoppel .......................................... .. 13
`
`iv)
`
`V)
`
`vi)
`
`Festo Exception: Foreseeable Equivalents ...................... .. 14
`
`Pesto Exception: Tangential Relationship ...................... .. 14
`
`Festo Exception: The “Some Other Reason” .................. .. 14
`
`B.
`
`U.S. Patent No. 8,871,813 ................................................................................... .. 15
`
`1.
`
`2
`3.
`
`4
`
`Priority Information and Related Applications ....................................... .. 15
`
`Claims of the ’813 Patent........................................................................ .. 15
`Specification of the ’813 Patent .............................................................. .. 19
`
`Prosecution Histories .............................................................................. .. 20
`
`1
`
`PAGE 7 OF 74
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`
`PAGE 7 OF 74
`
`

`
`iii)
`
`iv)
`
`v)
`
`vi)
`
`Response dated March 26, 2008 ..................................... .. 23
`
`Office Action dated July 18, 2008 .................................. .. 25
`
`Response dated January 15, 2009 ................................... .. 26
`
`Office Action dated June 3, 2009 ................................... .. 27
`
`vii)
`
`RCE and Rejection .......................................................... .. 27
`
`viii)
`
`Response dated March 24, 2010 ..................................... .. 27
`
`ix)
`
`X)
`
`xi)
`
`Office Action dated June 24, 2010 ................................. .. 28
`
`Response dated October 25, 2010 ................................... .. 28
`
`Office Action of May 6, 2011 and Interview of
`September 1, 2011 .......................................................... .. 29
`
`xii)
`
`Response dated September 6, 2011 ................................ .. 30
`
`xiii) Notice of Allowance ....................................................... .. 30
`
`xiv)
`
`Inter Partes Review ......................................................... .. 31
`
`Prosecution History of U.S. Patent No. 8,497,304 ..................... .. 31
`
`i)
`ii)
`iii)
`
`Preliminary Amendments, Restriction and Election....... .. 31
`Office Action ofAugust 30, 2012....... Q.......................... .. 31
`H Response dated January 30, 2013
`and Final
`rejection ........................................................................... .. 32
`
`iv)
`
`Response after Final and Notice of Allowance ............... .. 32
`
`Cl)
`
`Prosecution history of U.S. Patent 8,669,290 ............................. .. 32
`
`i)
`ii)
`
`iii)
`
`iv)
`
`v)
`
`Preliminary Amendment ................................................. .. 33
`Office Action dated August 1, 2013 ............................... .. 33
`
`Response dated October 22, 2013 ................................... .. 34
`
`Notice of Allowance ....................................................... .. 35
`
`Inter Partes Review ......................................................... .. 36
`
`ii
`
`PAGE 8 OF 74
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`PAGE 8 OF 74
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`

`
`.I,CZ‘T7i“'”"")”‘”““C)7V1’:3"‘?=”V7“”7T3C?'C‘
`
`
`»'WC\(“\K“.../‘\.(“—r\.r“\(‘~K“xr\F\f‘1r‘\flF‘/VT‘-.”“xf\f‘i
`
`
`
`A_/‘E\_‘,_A_'\__.__\1A.___,.‘\A_\_.-'__-I,___..‘vA
`
`i)
`
`ii)
`
`iii)
`
`iv)
`
`v)
`
`U.S. Patent No. 4,910,225 to Ogawa et al. ..................... .. 37
`
`WO 02/13804 to Kapin et al. .......................................... .. 38
`
`U.S. Patent No. 5,414,011 to Fu et al. ............................ .. 39
`
`Regev and Zana, Journal of Colloid and Interface
`Science (210) 8-17 (1999). .................................
`.......... .. 41
`
`Yuan et al., J. Phys. Chem. B, 2001, 105, 4611-
`4615 ................................................................................. .. 42
`
`vi)
`
`U.S. Patent No. 2,454,541 to Book et al. ........................ .. 42
`
`b)
`
`Claim Interpretation .................................................................... .. 42
`
`i)
`
`Interpretation of Independent Claims 1 and 13 ............... .. 42
`
`d)
`
`Obviousness of Claims 1 and 13 In Light of the ’804
`Publication, the ’0l1 Patent and Regev ...................................... .. 44.
`
`i)
`
`ii)
`
`iii)
`
`iv)
`
`Scope and Content of the Prior Art ................................. .. 44
`
`Level of Ordinary Skill in the Art ................................... .. 45
`
`Differences Between the Art and the Claims .................. .. 45
`
`Motivation to Combine the References .......................... .. 47
`
`e)
`
`Obviousness of Claims 1 and 13 In Light of the ’804
`Publication, the '01] Patent, Yuan, and the ’541 Patent ............ .. 49
`
`i)
`
`ii)
`
`iii)
`
`iv)
`
`Scope and Content of the Prior Art ................................. .. 49
`
`Level of Ordinary Skill in the Art ................................... .. 49
`
`Differences Between the Art and the Claims .................. .. 49
`
`Motivation to Combine the References .......................... .. 49
`
`Obviousness of Independent Claim 7 ......................................... .. 50
`
`Secondary Considerations ........................................................... .. 53
`
`Obviousness of Claims 2, 8 and 14: Sodium Sulfite .................. .. 53
`
`Obviousness of Claims 3 and 15: Bromfenac Sodium Salt ........ .. 54
`
`f)
`
`g)
`
`h)
`
`i)
`
`iii
`
`PAGE 9 OF 74
`
`PAGE 9 OF 74
`
`

`
`1.
`
`2.
`
`An Invalid Claim Cannot Be Infiinged ................................................... .. 58
`
`There Is No Literal Infringement ............................................................ .. 58
`
`a)
`
`b)
`
`Claims 6, 12, 18 And 23: Specific Formulations ........................ .. 59
`
`Claims 24, 25 And 26: Absence of a Preservative ...................... .. 60
`
`3.
`
`There Is No Infringement Under the Doctrine Of Equivalents ............... .. 60
`
`a)
`
`b)
`
`Claims 6, 12, 18 and 23: Specific Formulations ......................... .. 60
`
`Claims 24, 25 And 26: Absence of a Preservative ...................... .. 61
`
`iv
`
`PAGE 10 OF 74
`
`PAGE 10 OF 74
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`

`
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`
`
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`
`,r*~(N.(N.(‘TA/\/‘V./W(WF.K“\.(NA(N.:’\FtK“,-”\K‘F“‘/.I,_,\_.‘_.'\\___\_.4~‘__'X,x.,_-‘,,-
`
`I.
`
`Introduction
`
`Bausch & Lomb (“B&L.”) markets an ophthalmic solution having an active agent known
`as bromfenac under the name PROLENSATM. Bromfenac is a nonsteroidal anti—inflammatory drug
`(“NSAID”) for ophthalmic use. The FDA has approved PROLENSATM for the treatment of
`postoperative inflammation and reduction of ocular pain in patients who have undergone cataract
`surgery. Exhibit 1, PR0LENSATMLabel.
`
`PROLENSATM is formulated as bromfenac sodium sesquihydrate. The USAN name for
`bromfenac sodium sesquihydrate is bromfenac sodium. The standard chemical name for
`bromfenac sodium is sodium [2-amino-3-(4-bromobenzoyl)phenyl] acetate sesquihydrate. It has
`an empirical formula of C15H11BrNNaO3-1‘/2 H20. The structural formula for bromfenac sodium
`is:
`
` Ha’
`
`I C«HgC'QgNa
`
`-1%!2H2O
`
`The Orange Book lists the following patents for PROLENSATM: the ’813 patent; U.S.
`Patent No. 8,754,131 (“the ’13l patent”); U.S. Patent No. 8,128,431 (“the ’43l patent”); and
`U.S. Patent No. 8,669,290 (“the ’290 patent”); and U.S. Patent No. 8,927,606 (“the ’606 patent”)
`(collectively, “the Orange Book Patents”). The Orange Book also indicates that PROLENSATM is
`associated with New Drug Application No. 203-168, which is held by B&L. The FDA has
`approved NDA No. 203-168 for PROLENSATM 0.07% ophthalmic solution.
`
`3‘
`
`H
`
`to raise any additional defenses relating to invalidity,
`Innopharma reserves the right
`'
`unenforceability, and non-infringement in any and all proceedings.
`
`PAGE 11 OF 74
`
`PAGE 11 OF 74
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`

`
`’606 patent and set forth the factual and legal bases for Innopharma’s certification that the ’606
`patent is invalid, unenforceable, and/or will not be infringed by the manufacture, use, sale, offer
`for sale, or importation of Innopharma’s Bromfenac Product as defined by ANDA No. 206-326.
`
`II.
`
`Summary
`
`Innopharma’s manufacture, use, sale, offer for sale, or importation of its Bromfenac
`Product will not infringe any of the claims of the ’8l3 patent for at least the following reasons:2
`
`The ’813 Patent
`
`As set forth in detail below, Innopharma cannot infringe claims 1-27 of the ’813 patent
`because each of these claims is invalid under 35 U.S.C. § 103 or Innopharma’s Bromfenac
`Product does meet each and every limitation of the claims as follows:
`
`0 As set forth in detail below, each of claims 1-5, 7-1 1, 13-17, 19-22, and 27 of the
`’8l3 patent is invalid as obvious in light of U.S. Patent No. 4,910,225 (“the ’225
`patent”) in view of W0 02/ 13804 (“the ’804 publication”); U.S. Patent No.
`5,414,011 (“the ’0l1 patent”); and Regev, Journal of Colloid and Interface
`Science 210, 8-17 (1999) (“Regev”).
`
`- As set forth in detail below, each of claims 1-3, 5, 7-9, 10, 11, 13-15, 17, 19, 20,
`and 27 of the ’8l3 patent is invalid as obvious in light of the ’225 patent in view
`of the ’804 publication; the ’011 patent; Yuan et al., J. Phys. Chem. B 2001, 105,
`4611-15 (“Yuan”) and U.S. Patent No. 2,454,541 (the ’54l patent).
`
`0
`
`Innopharma cannot infringe claims 6, 12, 18, and 23-26 of the ’813 patent,
`literally or under the doctrine of equivalents, because none of these claims
`encompasses Innophai-rna’s Bromfenac Product. Specifically, each of these claims
`
`2 In addition to the reasons of invalidity set forth in this Exhibit A, Innopharrna incorporates by
`reference, and reserves the right to assert, any invalidity positions set forth in any inter partes
`review related to any patent at issue.
`
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`
`1.
`
`Burdens and Presumptions
`
`Each claim of a patent issued by the United States Patent and Trademark Office (“PTO”)
`is presumed to be valid; this presumption is independent of the validity of other claims. 35
`U.S.C. §282. A party may overcome this presumption by presenting clear and convincing
`evidence of a patent’s invalidity. See, e. g., Beckson Marine, Inc. v. NFM, Inc, 292 F.3d 718, 725
`(Fed. Cir. 2002). The presumption of validity includes a “presumption of nonobviousness which
`the patent challenger must overcome by proving facts with clear and convincing evidence.” See
`e.g., Apotex USA, Inc. V. Merck & C0,, 254 F.3d 1031, 1036 (Fed. Cir. 2001).
`
`The “clear and convincing evidence” standard of proof applies even if the prior art under
`consideration was not previously considered by the PTO during prosecution. Microsoft Corp. v.
`i4i Ltd. Partnership, 131 S. Ct. 2238, 2250 (2011). A patent may also be found invalid based
`upon prior art already considered by the examiner if it can be shown through clear and
`convincing evidence that the examiner erred in interpreting or applying the prior art. Thus, after
`due consideration of the presumption of validity, a trial court is free to come to a different
`conclusion of patentability from the PTO on the basis of evidence before the court. See, e.g.,
`Purdue Pharma 15.1’. v. Faulding, Inc., 230 F.3d 1320, 1329 (Fed. Cir. 2000); AK Steel Corp. v.
`Sollac & Ugine, 344 F.3d 1234, 1245 (Fed. Cir. 2003).
`
`2.
`
`Claim Construction
`
`The first step in an invalidity or non-infringement analysis is to construe the claims of the
`patent. See, e.g., Rapoport v. Dement, 254 F.3d 1053, 1058 (Fed. Cir. 2001). The general rule is
`that claim language is given its ordinary and accustomed meaning as understood by one of
`ordinary skill in the art, unless the patentee ascribed a different meaning to a claim in either the
`specification or the prosecution history. Phillips v. AW Corp., 415 F.3d 1303, 1312, 1321 (Fed.
`Cir. 2005). Claim interpretation involves consideration of the language of the patent claim itself,
`the other claims, the specification, the prosecution history, and extrinsic evidence if necessary.
`See, e.g., Phillips, 415 F.3d at 1312; Vitronics Corp. v. Conceptronic, Inc, 90 F.3d 1576, 1582
`(Fed. Cir. 1996); Markrnan v. Wesiview Instruments, Inc, 52 F.3d 967, 979-80 (Fed. Cir. 199:5)
`(en banc) ("Marlcman I ”). When construing a claim, a court principally consults the evidence
`intrinsic to the patent: the claims themselves, the specification, and the prosecution history.
`Phillips, 415 F.3d at 1317; Vitronics, 90 F.3d at 1582-83. Usually, analysis of the intrinsic
`
`
`
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`PAGE 13 OF 74
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`1997); Wang Lab, Inc. v. Am. Online, Inc., 197 F.3d 1377, 1382-83 (Fed. Cir. 1999).
`
`Where the specification contains nothing to indicate that phrases are to be given anything
`other than their ordinary meanings, then those are the meanings the court must give them. See,
`e.g., Vitronics, 90 F.3d at 1582. Thus, a technical term used in a patent document is interpreted
`as having the meaning that it would be given by persons experienced in the field of the patent,
`unless it is apparent from the specification or the prosecution history that the patentee used the
`term with a different meaning. See, eg, CVI/Beta Ventures, Inc. v. Tura Lp, 112 F.3d 1146,
`1153 (F ed. Cir. 1997) (citation omitted) (“[i]t is always necessary to review the specification to
`determine whether the inventor has used any terms in a manner inconsistent with their ordinary
`meaning.’’). In addition, unambiguous claim language controls over alternative contradictory
`interpretations found in the specification. See, e. g., Elekta Instrument S.A. v. UR Scientific Intl,
`Inc, 214 F.3d 1302, 1308 (Fed. Cir. 2000).
`
`A court may also look to extrinsic evidence to assist in claim construction, which
`includes any evidence which is external to the patent and prosecution history, such as expert
`testimony, inventor testimony, dictionaries, technical treatises, and articles. Id_; Vitronics, 90
`F.3d at 1584. While extrinsic evidence may be usefial in shedding light on the relevant prior art, a
`reviewing court is limited in relying on extrinsic evidence for claim interpretation purposes.
`Phillips, 415 F.3d at 1317-18. Thus,
`if the intrinsic evidence (specification, claims, and
`prosecution history) resolves any ambiguity in a disputed claim, extrinsic evidence cannot be
`used to contradict the established meaning of the claim language. See, e.g., Mantech Envtl. Corp.
`v. Hudson Envil. .S'ervs., 152 F.3d 1368, 1373 (Fed. Cir. 1998); Bell & Howell Document Mgmt.
`Prods. Co. v. Altelc Sys., 132 F.3d 701, 706 (Fed. Cir. 1999). In addition, while use of expert
`testimony to explain an invention is admissible, courts may only rely upon such extrinsic
`evidence to construe a claim term when the claim language remains genuinely ambiguous after
`consideration of the intrinsic evidence. See, e.g., Phillips, 415 F.3d at 1318; Bell & Howell, 132
`F.3d at 706. Any expert testimony which is inconsistent with unambiguous intrinsic evidence,
`therefore, should be accorded no weight. Phillips, 415 F.3d at 1318.
`
`3.
`
`Invalidity Analysis
`
`Once the claims have been properly construed, in the case of an invalidity analysis, the
`second step requires the properly construed claims to be compared to the prior art reference(s) to
`
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`Under 35 U.S.C. § 103, an applicant is not entitled to a patent “if the differences between
`the claimed invention and the prior art are such that the claimed invention as a whole would have
`been obvious before the effective filing date of the claimed invention to a person having ordinary
`skill in the art to which the claimed invention pertains.” The Supreme Court set the standard for
`obviousness in Graham 12. John Deere, 383 U.S.
`1 (1966), identifying the factual inquiries for
`determining obviousness. The relevant factual inquiries include:
`
`(a)
`
`(b)
`
`(c)
`
`(d)
`
`determining the scope and contents of the prior art;
`
`ascertaining the differences between the prior art and the claims in issue;
`
`resolving the level of ordinary skill in the pertinent art; and
`
`evaluating evidence of secondary considerations.
`
`Id; see also Ruiz v. AB Chance C0,, 234 F.3d 654, 663 (Fed. Cir. 2000). The Supreme Court
`reiterated the applicability of the Graham factors in KSR Co.
`v.‘ Teleflex Inc., 550 U.S. 398
`(2007).
`
`To establish a prima facie case of obviousness, three basic criteria must be met. First,
`there must be some reason to modify or combine the prior art references. See, e. g., Tszkeda Chem.
`Indus. Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1356-57 (Fed. Cir. 2007). This motivation
`need not come from the references themselves nor must it be explicitly stated, but may reside in
`the knowledge generally known to one of ordinary skill in the art. Id. at 1357 (citing KSR, 550
`U.S. at 401). For chemical compounds,
`as prima facie case of obviousness further requires
`“structural similarity between claimed and prior art subject matter...where the prior art gives
`reason or motivation to make the claimed compositions.” In re Mayne, 104 F.3d 1339, 1342
`(Fed. Cir. 1997) (citation omitted).
`
`there must be a reasonable expectation of success. See, e.g., 'PharmaStem
`Second,
`Therapeutics, Inc. v. I/iaCell, Inc., 491 F.3d 1342, 1360 (Fed. Cir. 2007) (citing KSR, 550 U.S. at
`417). This expectation, however, need not be guaranteed or amount to absolute predictability. In
`re 0’Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988) (citation omitted).
`‘
`
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`combination would have been obvious to one of ordinary skill in the art. Id. at 416. The Court
`recognized the creativity of an ordinary practitioner, and that a skilled artisan may “be able to fit the
`teachings of multiple patents together like pieces of a puzzle.” Id. at 420. “A person of ordinary skill
`is also a person of ordinary creativity, not an automaton.” Id. at 421. Accordingly, simple
`substitution of known elements for another, or use of known techniques to improve a method in a
`similar way, such that the substitution or techniques are “obvious to try” to one of ordinary skill,
`may form the basis of establishing obviousness. Id.
`
`a)
`
`Level ofOrdinary Skill in the Art _
`
`The hypothetical person of ordinary skill in the art is not an extraordinarily innovative
`person, nor a researcher of inexhaustible patience, but is a person who thinks conventionally in
`matters affecting the art in which he or she is skilled. Standard Oil Co. v. Am. Cyanamid C0,,
`774 F.2d 448, 454 (Fed. Cir. 1985). “Ordinary skill means at least the ability to understand the
`technology and make modest adaptations or advances.” See In re Mahurkar Patent Lz'tig., 831 F.
`Supp. 1354, 1374 (N.D. Ill. 1993), afi”d 71 F.2d 1573 (Fed. Cir. 1995). Factors that may be
`considered for determining the level of a skilled practitioner include: the educational level of the
`inventor; types of problems encountered in the art; prior art solutions to these problems; rapidity
`with which innovations are made; sophistication of the technology; and educational level of
`active workers in the field. Daiichi Sankyo, Ltd. v. Apotex, Inc, 501 F.3d 1254, 1256 (Fed. Cir.
`2007) (citation omitted). The hypothetical person of ordinary skill in the art is assumed to be
`aware of all pertinent prior art. See, e. g., Standard Oil Co., 774 F.2d at 454.
`
`-1))
`
`Scope and Content ofthe Prior Art
`
`As an initial inquiry under Graham, the scope and content of the prior art must be
`considered. See, e.g., Eolas Techs. Inc. v. Microsoft Corp, 399 F.3d 1325, 1335 (Fed. Cir. 2005)
`(citation omitted); see also MPEP § 2144.08. A prior art reference is relevant if it is reasonably
`pertinent to the problem being addressed. See In re ICON Health and Fitness, Inc., 496 F.3d
`1374, 1379-80 (Fed. Cir. 2007). “‘A reference is reasonably pertinent if, even though it may be
`in a different field from that of the inventor’s endeavor, it is one which, because of the matter
`with which it deals,
`logically would have commended itself to an inventor’s attention in
`considering his problem.” Id. (quoting In re Clay, 966 F.2d 656, 659 (Fed. Cir. 1992)). A
`
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`c)
`
`Differences between the Prior Art and the Claimed Invention
`
`The differences between the prior art and the scope of the claimed invention must also be
`ascertained to determine those aspects of the claimed subject matter that may be obvious or
`nonobvious against the prior art and the knowledge of a skilled artisan. Graham, 383 U.S. at 22-
`23; see also Dystar Textilfarben GmbI-I & Co. Deutschland KG v. CH. Patrick Co., 464 F.3d
`1356, 1369 (Fed. Cir. 2006). In Graham, the Supreme Court found patentee’s plastic sprayer
`with a “hold-down” lid serving as obvious, holding that the differences from the claimed subject
`matter to the prior art were “exceedingly small and quite nontechnical” and that the device was
`“old in the art.” Graham, 383 U.S. at 36-37. Accordingly, the degree of differences between the
`prior art and the claimed invention may be useful to a reviewing court in determining whether an
`invention is obvious.
`
`5.
`
`Obviousness ofStrnctarally Similar Compounds
`
`The Federal Circuit has opined that the case law concerning prima facie obviousness for
`structurally similar compounds is “well-established.” Takeda, 492 F.3d at 1356. In Takeda, the
`court stated 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...” Id. (quoting In re
`Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990) (en banc)). In addition, “a prima facie case of
`obviousness further 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 (2006) (quoting In re Longi, 759 F.2d
`887, 896 (Fed. Cir. 1985)).
`
`Thus, a party asserting invalidity of a chemical compound can establish a 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
`
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`begins with the reasoned identification of a lead compound”). The Federal Circuit stated that
`“[n]onnally a prime faeie case of obviousness is based upon structural similarity,
`;'.e., an
`established structural relationship between a prior art 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).4
`
`13)
`
`Structural Mbdifications
`
`In the context of structurally