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`
`ALsTON&BIRD LLP
`
`90 Park A venue
`New York, NY 10016
`212-210-9400
`Fax:212-210-9444
`WW\Y·aiston·com
`
`Deepro R. Mula!rjee
`
`Direct OW: 212-210-9501
`
`E-mail: deepro.mula!rjee@alslon.com
`
`March 27, 2015
`
`CONFIDENTIAL
`
`VIA FEDEX OVERNIGHT DELIVERY 1
`
`President & CEO
`SENJU PHARMACEUTICAL Co., LTD.
`2-5-8, Hiranomichi, Chuo-Ku
`Osaka 541-0046 Osaka, Japan
`
`President & CEO
`SENJU USA, INC.
`21700 Oxnard Street, Suite 1070
`Woodland Hills, CA 91367
`
`President & CEO
`BAUSCH & LOMB
`1 Bausch & Lomb Place
`Rochester, NY 14604
`
`President & CEO
`SENJU PHARMACEUTICAL Co., LTD.
`5-8, Hiranomichi 2-Chome, Chuo-Ku
`Osaka-Shi, Osaka, Japan 541-0046
`
`President & CEO
`BAUSCH & LOMB PHARMA HOLDINGS CORP.
`700 Route 202/206 North
`Bridgewater, NJ 08807
`
`President & CEO
`BAUSCH & LOMB INCORPORATED
`1400 North Goodman Street
`Rochester, NY 14609
`
`Re: ANDA No. 206326 (Bromfenac) Notification of Certification of
`Noninfringement and/or Invalidity for U.S. Patent No. 8,927,606
`Pursuant to § 505(j)(2)(B)(ii) of the U.S. Federal Food, Drug and
`Cosmetic Act
`
`To whom it may concern:
`
`We represent Innopharma Licensing, Inc. ("Innopharma") in connection
`with this letter and in connection with any litigation that ensues therefrom.
`Pursuant to Section 505(j)(2)(B)(ii) of the Federal Food, Drug and Cosmetic Act and
`21 C.F.R. § 314.95, Innopharma hereby provides notice that today it has amended
`Abbreviated New Drug Application No. 206326 ("ANDA") certifying, as described in
`
`1 Innopharrna has obtained approval from the FDA to use Federal Express in lieu of the U.S. Postal
`Service for the purpose of providing notice to the NDA holder and any patent assignees associated
`with Paragraph IV certitication(s) contained within ANDA 206326 (attached as Exhibit 8). The
`assignee's name for the '606 patent is taken from the face page of the '606 patent. The USPTO's web(cid:173)
`based assignment records accessed on March 27, 2015 report that the assignment data for the '606
`patent is not currently available.
`
`Atlant3· Brussels· Charlotte. Dallas· Los Angeles· New York. Research Triangle· SWean VaUcy· Washington. D.C.
`
`Page 1 of 50
`
`SENJU EXHIBIT 2017
`LUPIN v. SENJU
`IPR2015-01100
`
`

`
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`
`CONFIDENTIAL
`March 27, 2015
`Page 2
`
`21 C.F.R. § 319.94(a)(12)(i)(A)(4) ("Paragraph IV"), that U.S. Patent No. 8,927,606
`("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 Innopharma's ANDA No. 206326.
`
`Innopharma's ANDA is for a generic drug product having the established
`name PROLENSA TM. The active ingredient in the proposed drug product is bromfenac,
`which is present in the PROLENSA TM ophthalmic solution product in the form of
`bromfenac sodium sesquihydrate. PROLENSA TM is supplied as a sterile, aqueous 0.07%
`solution with a pH of7.8.
`
`The United States Food and Drug Administration ("FDA") has accepted
`Innopharma's ANDA for filing and has assigned the application No. 206326. The
`ANDA contains the required bioavailability and/or bioequivalence data from 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)(I) 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 PIV
`certification and a detailed statement of its then-existing factual and legal bases of
`Innopharma's belief that each of the '431 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 PIV certification to
`U.S. Patent No. 8,754,131 ("the ' 131 patent") and a detailed statement of its then(cid:173)
`existing factual and legal bases ofInnopharma' s belief that the ' 131 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)(l2)(vi) to further include a
`Paragraph IV certification to the ' 606 patent, which lists as an issuance date on its
`face of January 6, 2015. Each of the '431, '290, '131 and '606 patents is listed in
`Approved Drug Products with Therapeutic Equivalence Evaluations ("the Orange
`Book") in connection with Bausch & Lomb, Inco's ("B&L") approved NDA No.
`203168 for PROLENSA TM 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 certified to the FDA that, to the best of Innopharma's knowledge, the ' 431
`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 additionally alleges and has certified to the FDA
`that, to the best of Innopharma' s knowledge, the ' 131 patent is invalid, unenforceable,
`and/or will not be infringed by the manufacture, use, sale, offer for sale, or
`
`Page 2 of 50
`
`

`
`CONFIDENTIAL
`March 27, 2015
`Page 3
`
`importation of the drug product described in Innopharrna's ANDA.
`Further,
`Innopharrna additionally alleges and has certified to the FDA that, to the best of
`Innopharrna's knowledge, the '606 patent is invalid, unenforceable, and/or will not be
`infringed by the manufacture, use, sale, offer for sale, or importation of the drug
`product described in Innopharrna's ANDA. With regard to the '606 patent, according
`to the FDA's Orange Book:
`
`•
`
`the '606 patent will expire on January 16,2024.
`
`Attached as Exhibit A is a detailed statement, made pursuant to 21 U.S.C.
`§ 355G)(2)(B)(iv)(II) and 21 C.F.R. § 314.95, of the present factual and legal bases
`for Innopharrna' s Paragraph IV certification to the '606 patent of the Orange Book
`Patents. The statements made therein are based on the information currently
`available to Innopharrna.
`Innopharrna reserves all rights to raise any additional
`defenses relating to invalidity, unenforceability, and/or noninfringement should
`additional information become known to Innopharrna.
`
`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 Innopharrna's ANDA and any supplement(s) thereto. As
`required by Section 355(j)(5)(C)(i)(III), Innopharrna offers to provide confidential
`access to certain information from its ANDA No. 206326 for the sole and exclusive
`purpose of 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 Innopharrna 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
`Innopharrna the right to redact its ANDA to exclude non-relevant information in
`response to a request for Confidential Access under this Offer.
`
`As permitted by statute, Innopharrna imposes the following terms and
`restrictions on its Offer of Confidential Access:
`(1)
`Innopharrna 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, formally or informally, in any patent prosecution for B&L or
`any FDA counseling, litigation, or other work before or involving the
`FDA. Such
`information
`(hereinafter, "Confidential
`Innopharrna
`Information") shall be marked with the legend "CONFIDENTIAL
`INNOPHARMA INFORMATION."
`The attorneys from the outside law firm representing B&L shall not
`disclose any Confidential Innopharrna Information to any other person
`
`(2)
`
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`('
`
`Page 3 of 50
`
`

`
`CONFIDENTIAL
`March 27, 2015
`Page 4
`
`(3)
`
`(4)
`
`(5)
`
`(6)
`
`or entity, including B&L employees, outside scientific consultants,
`and/or other outside counsel retained by B&L, without the prior written
`consent of Innopharma.
`As provided by Section 355G)(5)(C)(i)(III), B&L's outside law finn
`shall make use of the Confidential Innopharma Infonnation for the sole
`and exclusive purpose of detennining whether an action referred to in
`Section 355G)(5)(B)(iii) can be brought and for no other purpose. By
`way of example only, the Confidential Innopharma Infonnation shall
`not be used to prepare or prosecute any future or pending patent
`application by B&L in connection with any filing to, or communication
`with, the FDA relating to Innopharma's ANDA No. 206326. B&Vs
`outside law finn agrees to take all measures necessary to prevent
`unauthorized disclosure or use of the Confidential Innopharma
`Infonnation, and that all Confidential Innopharma Infonnation shall be
`kept confidential and not disclosed in any manner inconsistent with this
`Offer of Confidential Access.
`The Confidential Innopharma Infonnation disclosed is, and remains, the
`property of Innopharma. By providing said Confidential Innopharma
`Infonnation, Innopharma does not grant B&L and/or its outside law
`finn any interest in or license for and to the Confidential Innopharma
`Infonnation.
`B&L's outside law finn shall, within thirty-five (35) days from the date
`that it first receives the Confidential Innopharma Infonnation, return to
`Innopharma all Confidential Innopharma Infonnation and any copies
`thereof.
`B&L' s outside
`law finn shall return all Confidential
`Innopharma Infonnation 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 infonnation
`contained in or obtained from any Confidential Innopharma Infonnation
`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 U.S. 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 Infonnation, document, or thing. The fact that Innopharma
`provides Confidential Innopharma Infonnation to B&L upon B&L's
`request shall not be construed as an admission by Innopharma that such
`Confidential Innopharma Infonnation 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.
`
`c
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`Page 4 of 50
`
`

`
`CONFIDENTIAL
`March 27, 2015
`Page 5
`
`(7)
`
`(8)
`
`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 Confidential
`Innopharma
`Information.
`Such written
`acknowledgement shall be provided to the undersigned.
`This Offer of Confidential Access shall be governed by the laws of the
`State of New Jersey, USA.
`
`Section 3SSG)(S)(C)(i)(I1I) provides that any request for access that B&L
`makes under this Offer of Confidential Access "shall be considered acceptance of the
`offer of confidential access with restrictions as to persons entitled to access, and on
`the use and disposition of any information accessed, contained in [this] offer of
`confidential access" and 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. MukeIjee
`Alston & Bird LLP
`90 Park Avenue
`New York, New York 10016
`Tel: (212) 210-9400
`Fax: (212) 210-9444
`deepro.mukeIjee@alston.com
`
`By providing this Offer of Confidential Access, Innopharma 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. § 3SS(j)(S)(C).
`
`Copies of this letter and the attached exhibits are also being provided by U.S.
`Registered mail, return receipt requested.
`
`Sincerely,
`
`d-A.. r~~
`
`Deepro R. MukeIjee
`
`Enclosures: Exhibits A & B
`
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`(
`
`Page 5 of 50
`
`

`
`EXHIBIT A
`
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`Page 6 of 50
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`

`
`Table of Contents
`
`I.
`II,
`m.
`
`Introduction ""''',., ................................ , ..... , , ........ ,""" , ........... " ..... " .. ' ... ........ " .... " ....... ,., ... I
`Summary .... ,.,.,." ....... " ...... ,." ...................... ,, ...... "., ................ , ....... , .............. , .................... 2
`Analysis .... , ..... " ........ ,., ...................................................................................... ..... ......... .... 3
`
`A,
`
`General Legal Princip les"" ...... " ... " '''''''''''''"." ... """""" .. " .. " .. " .. "".".""'"'''''''''' 3
`I.
`Burdens and Presumptions"." ... "" ....... "" .. """."""" .. ,, ..... ,,",, ..... "" .. ",,"" 3
`Cia i m Construction .. "".""". " ... ""."".".". """" """" ... " .. "".""" .. ""." .. ",,. 3
`
`2.
`
`3.
`4.
`
`5.
`
`0)
`
`Invalidity Analysis "" """ .. " .. """""""".,,""""""".",, .... ,,""" " .... " ".""",,. 4
`Obviousness Under 35 U.S.C. § 103 " ... ... " .......... .......... ... , ......... ..... " .. ...... 5
`Level of Ordinary Skill in the ArL ........ " ......... ,."" ..... " ...... "" ....... 6
`Scope and Content orthe Prior Art ......... , ......... ,."" ..... " ....... " ....... , 6
`Differences between the Prior An and
`the Claimed
`Invention ....... , ............. " ............... ,,, ....... ,',, ....... ,.,", ..... , ....... ,", .. ..... 7
`Obviousness of StrucNrally Similar Compounds .. " ........ " .. " ... "" ..... ". " .... 7
`
`b)
`c)
`
`B,
`
`6.
`
`Lead Compound .. ,,, ....... " ............. ,""" .. ".,,"""""" "." .. "".,,""""". 8
`a)
`StrueNral Modifications ....... """ ......... " ............. "" .. "" ...... "" ... ",,. 8
`b)
`Reasonable Expectation of Success ..... " .. "."" .. ,,"" """" .............. 10
`c)
`Objective Indicia of Non·Obviousness .................. " .. " .. " ......... " .. 10
`d)
`Infringement Analysis ....... .............................. , ...... , .............. , ...... , ...... . , .... 10
`a)
`Direct Infringement, ........ ",., ............. ", ...... " ........... "" .... " ...... ,,, .. [0
`U.S. Patent No. 8,927,606 .............. " ..... ,."."" .............. " .. "" ." .......... " ... ", ......... ". II
`I.
`Priority Information and Related Applications .......... " ..... "" ...... "" ....... ". I I
`2.
`Claims of the '606 Patent.. ................................. " ................. " .... .............. 12
`3.
`Specification oflhe '606 PatenL ............................................ " .... " .......... 16
`4.
`Prosecution Histories ........................ ...................................... , ................. 16
`a)
`Prosecution History of The '606 Patent" ...... "" ......... " ...... , ........ " 16
`i)
`Preliminary Amendment .......... " ....... """ ............... " ...... ,,. 16
`ii)
`Terminal Disclaimers dated November 5, 2014 ... " ....... ". 17
`iii)
`Notice of Allowance .... " .......... "" " .. "."."" .... "" .... ",, ...... . 17
`Prosecution History of The '431 Paten!.." ...... "."" ..... " .... "" ...... " 17
`i)
`Preliminary Amendments .. " ............... """" .... "" ....... " .. ,,. 17
`ii)
`Office Action dated September 27, 2007 ......... " ............... 17
`
`b)
`
`\.)
`C
`C
`C
`C
`C
`C
`C
`C
`C
`C
`C
`C
`C
`C
`C
`C
`C
`C
`
`C c
`c
`c
`c
`c
`('
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`c
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`c
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`c
`c
`
`Page 7 of 50
`
`

`
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`iii)
`
`iv)
`
`v)
`
`vi)
`
`Response dated March 26, 2008 ....................................... 19
`
`Office Action dated July 18, 2008 .................................... 21
`
`Response dated January 15,2009 ..................................... 22
`
`Office Action dated June 3, 2009 ..................................... 23
`
`RCE and Rejection ............................................................ 23
`vii)
`viii) Response dated March 24, 2010 ....................................... 23
`
`ix)
`
`x)
`
`xi)
`
`Office Action dated June 24, 2010 ................................... 24
`
`Response dated October 25,2010 ..................................... 24
`
`Office Action of May 6, 20 II and Interview of
`September I, 20 II ............................................................ 25
`
`xii)
`
`Response dated September 6, 20 II .................................. 25
`
`xiii) Notice of Allowance ......................................................... 26
`xiv)
`Inter Partes Review ........................................................... 26
`
`c)
`
`Prosecution History of U.S. Patent No. 8,497,304 ....................... 27
`i)
`Preliminary Amendments, Restriction and Election ......... 27
`
`ii)
`
`iii)
`
`iv)
`
`Office Action of August 30, 2012 ..................................... 27
`
`Response dated January 30, 2013 and Final
`rejection ............................................................................. 27
`Response after Final and Notice of Allowance ................. 28
`
`d)
`
`Prosecution history of U.S. Patent 8,669,290 ............................... 28
`
`i)
`
`ii)
`
`iii)
`
`iv)
`v)
`
`Preliminary Amendment ................................................... 28
`Office Action dated August I, 2013 ................................. 29
`Response dated October 22,2013 ..................................... 30
`
`Notice of Allowance ......................................................... 31
`
`Inter Partes Review ........................................................... 31
`
`e)
`
`Prosecution History of The '131 Patent.. ...................................... 31
`
`i)
`ii)
`
`iii)
`
`iv)
`
`Preliminary Amendment... ................................................ 31
`Office Action dated March 13,2014 ................................ 32
`
`Response dated March 20, 2014 ....................................... 33
`
`Notice of Allowance ......................................................... 33
`
`f)
`
`Prosecution History of The '813 Paten!... ..................................... 33
`
`i)
`
`ii)
`
`Preliminary Amendment... ................................................ 33
`
`Office Action dated July 24,2014 .................................... 34
`
`ii
`
`Page 8 of 50
`
`

`
`iii)
`
`Response dated July 31,20 14 ........................................... 34
`
`Notice of Allowance ................................. ........................ 34
`iv)
`INVALIDITY OF THE '606 PATENT ................................................................ 34
`
`c.
`
`I.
`
`Invalidity Analysis of the '606 Patent ...................................................... 35
`a)
`The Scope and Content of the Prior Art ... ..................................... 35
`
`i)
`
`ii)
`
`iii)
`iv)
`
`v)
`
`vi)
`
`U.S. Patent No. 4,910,225 to Ogawa et al. ....................... 35
`
`WO 02fl 3804 to Kapin et al. ............................................ 36
`
`U.S. Patent No. 5,414,011 to Fu et al. ...... ........................ 38
`Regev and Zana, Journal of Colloid and Interface
`Science (210) 8- 17 (1999) ................................................ 39
`Yuan et aI., J. Phys. Chern. B, 200 1, 105,4611-
`4615 ................................................................................... 40
`U.S. Patent Number 2,454,541 to Bock et al. ................... 41
`
`vii) U.S. Patent Number 6,107,343 to Sallmann et al. ............ 41
`
`vii i) U.S. Patent No. 6,274,609 to Yasueda et al... .................. .42
`
`ix)
`
`Ham, Yoshiyuki, Clinics & Drug Therapy 2002,
`19:1014· 1015 .................................................................... 44
`Claim Interpretation ...................................................................... 44
`
`i)
`
`Interpretation ofIndependent Claims I and 13 ................. 44
`
`Obviousness of Claim lOver the '255 Patent In Light of
`the '804 Publication, the '0 II Patent and Regev .......................... 45
`
`i)
`ii)
`
`iii)
`
`Scope and Content of the Prior Art ................................... 45
`Level of Ordinary Skill in the Art ..................................... 45
`
`Differences Between the Art and the Claims .................... 46
`
`iv) Motivation to Combine the References ............................ 47
`Obviousness of Claim lOver the '225 Patent In Light of
`the '804 Publication, the '011 Patent, Yuan, and the '541
`Patent. ............................................................................................ 49
`i)
`Scope and Content of the Prior Art ................................... 49
`
`ii)
`
`iii)
`
`Level of Ordinary Skill in the Art ..................................... 49
`
`Differences Between the Art and the Claims .................... 49
`
`iv) Motivation to Combine the References ............................ 49
`Ohviousness of Claim lOver the '225 Patent In Light of
`the '343 Patent, the '609 Patent, and Hara, or Alternatively,
`Over the '343 Patent In View of the '225 Patent and Hara .......... 50
`
`iii
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`Scope and Content of the Prior Art ................................... 50
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`Level of Ordinary Skill in the Art ..................................... 51
`
`Differences Between the Art and the Claims .................... 51
`
`Motivation to Combine the References ............................ 51
`
`Secondary Considerations ............................................................. 55
`
`Obviousness of Claim II .............................................................. 56
`Obviousness of Claim 19 .............................................................. 57
`
`Obviousness of Claims 2, 3, 13, 14,20, and 21: Particular
`Diseases ......................................................................................... 58
`
`Obviousness of Claims 4 and 22: Bromfenac Sodium Salt .......... 59
`
`Obviousness of Claims 5, 6, 8, 15, 16,23, and 27: Amounts
`of Bromfenac and Tyloxapol ........................................................ 59
`
`Obviousness of Claims 7 and 17: Quaternary Ammonium
`Salt ................................................................................................ 61
`Obviousness of Clams 9, 18 and 25: Specific Formualtions ........ 62
`
`Obviousness of Claim 10: Dose .................................................... 64
`
`Obviousness of Claims 12 and 26: Storage Stability .................... 64
`Obviousness of Claims 28, 29 and 30: Preservative
`Efficacy Standard .......................................................................... 65
`
`t)
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`D.
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`NON-INFRINGEMENT OF THE '606 PATENT ............................................... 67
`
`iv
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`Page 10 of 50
`
`

`
`EXHIBIT A
`DETAILED STATEMENT OF THE FACTUAL AND LEGAL BASIS FOR
`INNOPHARMA LICENSING INC.'S CERTIFICATION THAT U.S. PATENT NO.
`8,927,606 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
`
`For at least the reasons sel forth below, U.S. Patent No. 8,927,606 ("the '606 patent")
`does not prohibit Innopharma Licensing Inc. ("Innopharma") from manufacturing, using, sell ing,
`offering for sale, or importing [nnopharma' s Bromfenac Product as covered by ANDA No. 206-
`326 after the FDA approves its ANDA.I
`
`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 PROLENSA™ for the treatment of
`postoperative inflammation and reduction of ocular pain in patients who have undergone cataract
`surgery. Exhibit 1, PROLENSATM Label.
`
`PROLENSA ™ 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 ofCI\HlI BrNNaOJol y, H20 . The structural formula for bromfenac sodium
`is:
`
`The Orange Book lists the following patents for PROLENSA™: the '606 patent; U.S.
`Patent No.8, 128,431 ("the '431 patent"); U.S. Patent No. 8,475,131 ("the ' 131 patent"); U.S.
`Patent No. 8,871,813 ("the '813 patent"); and U.S. Patent No. 8,669,290 ("the '290 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 PROLENSA ™ 0.07% ophthalmic solution.
`
`I Innopharma reserves its rights to raise any additional defenses relating to invalidity,
`unenforceability, and non-infringement
`in any and all proceedings for alleged patent
`infringement.
`
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`Page 11 of 50
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`

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`
`Innopharma hereby incorporates by reference all prior Notification letters, including
`those dated September 19, 2014 and October 30, 2014, and related exhibits, the combined
`contents of which provided notice to the NDA holder and assignee of the' 431, '131, and '290
`patents and set forth the factual and legal bases for Innopharma's certification that the '431,
`'131, and
`'290 patents are invalid, unenforceable, andlor 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 '606 patent for at least the following reasons:2
`
`The '606 Patent
`
`As set forth in detail below, Innopharma cannot infringe claims 1-30 of the '606 patent
`because each of these claims is invalid under 35 U.S.C. § 103 as follows:
`
`• Each of claims 1-30 of U.S. Patent Number 8,927,606 is invalid as obvious in
`light of U.S. Patent No. 4,910,225 ( .. the '225 patent") in view of WO 02113804
`("the '804 publication"); U.S. Patent Number 5,414,011 ("the 'Oil patent"); and
`Regev, Journal of Colloid and lnte,face Science 210, 8-17 (1999) ("Regev").
`
`• Each of claims 1-30 of U.S. Patent Number 8,927,606 is invalid as obvious in
`light of the'225 patent in view of the '804 publication; the '0 II patent; Yuan et
`aI., 1. Phys. Chern. B 2001, lOS, 4611-4615 ("Yuan") and U.S. Patent No.
`2,454,541 (the '541 patent).
`
`• Each of claims 1-30 of U.S. Patent Number 8,927,606 is invalid as obvious in
`light of the '225 patent in view of U.S. Patent No. 6,107,343 ("the'343 patent")
`and U.S. Patent No. 6,274,609 ("the '609 patent").
`
`• Each of claims 1-30 of U.S. Patent Number 8,927,606 is invalid as obvious in
`light of the'343 patent in view of the '225 patent and Hara, Yoshiyuki, Clinics &
`Dmg Therapy, 2002,19:1014-1015 ("Hara").
`
`2 In addition to the reasons of invalidity set forth in this Exhibit A, Innopharma incorporates by
`reference, and reserves the right to assert, any invalidity positions set forth in any intel' partes
`review related to any patent at issue.
`
`2
`
`Page 12 of 50
`
`

`
`III. Analysis
`
`A.
`
`General Legal Principles
`
`1.
`
`Burdells alld 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 val idity of other claims. 35
`U.S.c. § 282. A party may overcome this presumption by presenting clear and convincing
`evidence ofa 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 non obviousness which
`the patent challenger must overcome by proving facts with clear and convincing evidence." See
`e.g., Apotex USA, Inc. v. Merck & Co., 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 CO/po v.
`i4i Ltd. Partnership, 131 S.C!. 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 Phal"llla L.P. v. Faulding, Inc., 230 F.3d 1320, 1329 (Fed. Cir. 2000); AK Steel CO/po v.
`Sollac & Ugine, 344 F.3d 1234, 1245 (Fed. Cir. 2003).
`
`2.
`
`Claim Constl1/ction
`
`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. 200 I). 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. AWH CO/p., 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 CO/po v. Conceptronic, Inc., 90 F.3d 1576, 1582
`(Fed. Cir. 1996); Markman v. Westview Instl1lments, Inc., 52 F.3d 967, 979·80 (Fed. Cir. 1995)
`(en banc) ("Markman /"). 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
`evidence suffices to enable one to determine the meaning of claim terms. Vitronics, 90 F.3d at
`1582. If the intrinsic evidence resolves ambiguity in a disputed claim, extrinsic evidence cannot
`be used to contradict the established meaning of the claim language. See, e.g., Mallleell Envll.
`Corp. v. Hudson Envll. Servs., 152 F.3d 1368, 1373 (Fed. Cir. 1998); Bell & Howell Documenl
`Mgml. Prods. Co. v. Allek Sys., 132 F.3d 70 I, 706 (Fed. Cir. 1999). Extrinsic evidence may
`include, for example, treatises and expert testimony.
`
`3
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`Page 13 of 50
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