Page 1 of 166
`
`SENJU EXHIBIT 2015
`LUPIN v. SENJU
`IPR2015-01100
`
`

`
`CONFIDENTIAL
`
`September 19, 2014
`Page 2
`
`(“the ’290 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
`Innopharn1a’s ANDA No. 206326.
`
`Innopharma’s ANDA is for a drug product having the established name PROLENSATM.
`The active ingredient in the proposed drug product is bromfenac, which is present in the
`PROLENSATM ophthalmic solution product in the form of bromfenac sodium sesquihydrate.
`PROLENSATM is supplied as a sterile, aqueous 0.07% solution with a pH of 7.8.
`
`accepted
`The United States Food and Drug Administration (“FDA”) has
`lnnopharma’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.
`
`§ 355(j)(l) and (2)(A) with
`Innopharma submitted its ANDA under 21 U.S.C.
`Paragraph IV certifications to the ’431 and the ’290 patents (collectively “the Orange Book
`Patents”), which are 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 PROLBNSATM ophthalmic solution.
`
`Innopharrna seeks the FDA’s approval to market its proposed Bromfenac Product
`prior to the expiration of the Orange Book Patents. According to the FDA’s Orange Book:
`
`0
`
`0
`
`the ’43l patent will expire on September 1 1, 2025; and v
`
`the ’290 patent will expire on January 16, 2024.
`
`Innopharma alleges, and has certified to the FDA that, to the best of Innopharma’s
`knowledge, each of the Orange Book Patents 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 Innopharma’s ANDA.
`
`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 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 Innopharma’s ANDA and any supplement(s) thereto. As required by Section
`355(i)(5)(C)(i)(IlI), 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.
`‘
`
`Page 2 of 166
`
`

`
`CONFIDENTIAL
`
`September 19, 2014
`Page 3
`
`Section 355(i)(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 reclact
`its ANDA to exclude non~relevant information in response to a request for Confidential Access
`under this Offer.
`
`As permitted by statute, Innopharma 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 infonnally,
`in any patent prosecution for B&L or any FDA
`counseling, 1itigation,~or other work before or involving the FDA. Such
`information (hereinafter, “Confidential Innopharma 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
`Innopharma Information to any other person 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 355(j)(5)(C)(i)(III), B&L’s outside law firm shall make
`use of the Confidential Innopharma Information for the sole and exclusive
`purpose of determining whether
`an
`action referred
`to
`in Section
`3S5(j)(5)(B)(iii) can be brought and for no other purpose. By way of example
`only, the Confidential Innopharma Information 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&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 Infonnation 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 Innopharma 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
`
`Page 3 of 166
`
`

`
`CONFIDENTIAL
`
`September 19, 2014
`Page 4
`
`l I 1 1 1 1 I i G G E G G G G G G
`
`In the event that B&L opts to file suit, none
`before this 35 -day period expires.
`of the information contained in or obtained from 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 U.S. patent. Further, nothing herein shall be construed as an agreement or
`admission by Innopharrna with respect
`to the competency, relevance, or
`materiality of any such Confidential Innopharrna Information, document, or
`thing. The fact that lnnopharma provides Confidential Innopharma Information
`to B&L upon B&L’s request shall not be construed as an admission by
`Innopharma that such Confidential lnnopharma 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.
`
`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.
`
`(3)
`
`This Offer of Confidential Access shall be governed by the laws of the State of
`New Jersey, USA.
`
`Section 355(j)(5)(C)(i)(IlI) 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
`tenns 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:
`
`Thomas J. Parker
`
`Deepro R. Mukerjee
`Alston & Bird LLP
`90 Park Avenue
`
`New York, New York 10016
`Tel: (212) 210-9400
`Fax: (212) 210-9444
`thomas.parker@alston.com
`deepro.mukerjee@alston.c0m
`
`Page 4 of 166
`
`

`
`CONFIDENTIAL
`
`September 19, 2014
`Page 5
`
`By providing this Offer of Confidential Access, Innopharrna maintains the right and
`ability to bring and maintain a Declaratory Judgment action under 28 U.S.C. § 2201 el seq.,
`pursuant to 21 U.S.C. § 355(j)(5)(C).
`
`Page 5 of 166
`
`

`
`CONFIDENTIAL
`
`September 19, 2014
`Page 6
`
`Copies of this letter and the attached exhibits are also being provided by U.S.
`Registered mail, return receipt requested.
`
`Sincerely,
`
`z/91/Q
`
`Thomas J. Parker
`
`Enclosures: Exhibits A & B
`
`Page 6 of 166
`
`

`
`EXHIBIT A
`
`Page 7 of 166
`
`

`
`Table of Contents
`
`Introduction .............................................................. Q ....................................................... .. 1
`
`Summary ........................................................................................................................... .. 2
`
`Analysis ............................................................................................................................. .. 3
`
`A.
`
`General Legal Principles ....................................................................................... .. 3
`
`1.
`
`2.
`
`3.
`
`4
`
`Burdens and Presumptions ........................................................................ .. 3
`
`Claim Construction ................................................................................... .. 4
`
`Invalidity Analysis .................................................................................... .. 5
`
`Obviousness Under 35 U.S.C. § 103 ........................................................ .. 5
`
`a)
`
`b)
`
`c)
`
`Level of Ordinary Skill in the Art ................................................. .. 7
`
`Scope and Content of the Prior Art ............................................... .. 7
`
`Differences between the Prior Art and the Claimed
`Invention ....................................................................................... ..7
`
`Obviousness of Structurally Similar Compounds ..................................... .. 8
`
`a)
`
`b)
`
`c)
`
`d)
`
`Lead Compound ............................................................................ .. 8
`
`Structural Modifications ............................................................... .. 9
`
`Reasonable Expectation of Success ............................................ .. 10
`
`Objective Indicia of Non-Obviousness ....................................... .. 11
`
`Infringement Analysis ............................................................................. .. 11
`a)
`Direct Infringement..................................................................... .. 11
`THE LISTED ORANGE BOOK PATENTS FOR PROLENSATM ................... .. 12
`
`1.
`
`U.S. Patent No. 8,128,431 ....................................................................... .. 12
`
`a)
`
`b)
`
`c)
`
`d)
`
`Priority Information and Related Applications ........................... .. 12
`
`Claims of the ’43l Patent ............................................................ .. 13
`
`Specification of the ’431 Patent .................................................. .. 15
`
`Prosecution History of the “-1131 Patent ....................................... .. 15
`
`i)
`
`ii)
`
`iii)
`
`iv)
`
`v)
`
`vi)
`
`The ’006 Application Claims as Filed ............................ .. 15
`
`Preliminary Amendments Dated February 17, 2005;
`March 20, 2007; and April 3, 2007 ................................. .. 17
`
`Restriction Requirement Mailed on May 23, 2007 ......... .. 19
`
`Applicants’ Response Dated June 4, 2007 ...................... .. 20
`
`Restriction Requirement Mailed on July 24, 2007 ......... .. 20
`
`Applicants’ Response Dated August 20, 2007 .............. ..'. 21
`
`Page 8 of 166
`
`

`
`Non-Final Office Action Mailed September 27,
`2007 ................................................................................. ..21
`
`Interview Summary Mailed March 20, 2008 .................. .. 24
`
`Applicants’ Response Dated March 26, 2008 ................. .. 24
`
`Non-Final Office Action Mailed July 18, 2008 .............. .. 33
`
`interview Summary Mailed December 23, 2008 ............ .. 37
`
`Applicants’ Response Dated January 15, 2009 ............... .. 37
`
`Final Rejection Mailed June 3, 2009 .............................. .. 43
`
`Applicants’ Response and Request for Continued
`Examination Dated October 5, 2009 ............................... .. 45
`
`xv)
`
`Interview Summary Mailed October 8, 2009
`
`47
`
`xvi)
`
`Non-Final Office Action Mailed December 24,
`2009 ................................................................................. ..47
`
`xvii)
`
`Applicants’ Response Dated March 24, 2010 ................. .. 49
`
`xviii)
`
`Final Rejection Mailed June 24, 2010 ............................ .. 55
`
`xix)
`
`Applicants’ Response and Request for Continued
`Examination Dated October 25, 2010 ............................. .. 57
`
`xx)
`
`Interview Summary Mailed January 20, 201 1 ................ .. 61
`
`xxi)
`
`Non-Final Office Action Mailed May 6, 201 1 ............... .. 61
`
`xxii)
`
`Applicants’ Response Dated September 6, 2011 ............ .. 62
`
`xxiii)
`
`Final Office Action Mailed November 15, 201 1 ............ .. 65
`
`Xxiv)
`
`Interview Summary Mailed November 15, 2011 ........... .. 65
`
`xxv)
`
`Notice of Allowance and Examiner’s Amendment
`
`mailed December 23, 2011 ............................................. .. 66
`
`xxvi)
`
`Issuance of the ’43l Patent on March 6, 2012 ................ .. 67
`
`2.
`
`U.S. Patent No. 8,669,290 ....................................................................... .. 67
`
`Priority Information and Related Applications ................................................... .. 67
`
`Claims of the ’290 Patent .................................................................................... .. 68
`
`Specification of the ’290 Patent .......................................................................... .. 72
`
`Prosecution History of the ’290 Patent ............................................................... .. 72
`
`i)
`
`ii)
`
`iii)
`
`iv)
`
`The ’242 Application Claims as Filed and Track 1 Request .................. .. 72
`
`Preliminary Amendment Dated November 28, 2012 ............................. .. 72
`
`Restriction Requirement Mailed on March 25, 2013 .............................. .. 81
`
`Applicants‘ Response Dated April 9, 2013 ............................................. .. 81
`
`Page 9 of 166
`
`

`
`v)
`
`vi)
`
`Non-Final Office Action Mailed August 8, 2013 ................................... .. 81
`
`and Terminal Disclaimers Submitted
`Applicants’ Response
`October 22, 2013 ..................................................................................... .. 86
`
`vii)
`
`Interview Summary Mailed January 15, 2014 ........................................ .. 91
`
`viii) Notice of Allowance and Examiner’s Amendment mailed January
`15, 2014 ................................................................................................... .. 91
`
`INVALIDITY OF THE ORANGE BOOK LISTED PATENTS ....................... .. 93
`
`1.
`
`2.
`
`3.
`
`Invalidity of the ’431 Patent ................................................................... .. 93
`
`Invalidity Analysis of the ’431 Patent .................................................... .. 94
`
`The Scope and Content of the Prior Art .................................................. .. 94
`
`a)
`
`b)
`
`c)
`
`d)
`
`e)
`
`1‘)
`
`g)
`
`h)
`
`i)
`
`j)
`
`k)
`
`U.S. Patent No. 4,910,225 to Ogawa et al. ................................. .. 94
`
`W0 02/13804 to Kapin et al. ...................................................... .796
`
`US. Patent No. 5,414,011 to Fu et al. ........................................ .. 97
`
`W0 O0/57887 to Shull et al. . ...................................................... .. 98
`
`Regev and Zana, Journal of Colloid and Interface Science
`(210) 8-17 (1999). ...................................................................... .. 93
`
`Yuan et al., J. Phys. Chem. B 2001, 105, 4611-4615 ................. .. 99
`
`U.S. Patent No. 2,454,541 to Book et al. .................................. .. 100
`
`U.S. Patent No. 6,107,343 to Sallmann et al ............................. .. 100
`
`U.S. Patent No. 6,274,609 to Yasueda et al. ............................. .. 101
`
`Hara, Yoshiyuki, Clinics & Drug Therapy 2002, 1911014-
`1015 ........................................................................................... .. 102
`
`Differences between the Prior Art and the Claims of the
`’431 Patent ................................................................................ .. 103
`
`i)
`
`ii)
`
`Independent Claim 1 of the ’431 Patent is obvious
`under 35 U.S.C. § 103 over the ’225 Patent in view
`of the ’804 Publication, the ’011 Patent, and Regev..... .. 103
`
`Independent Claim 1 of the ‘431 Patent is obvious
`under 35 U.S.C. § 103 over the ’225 Patent in view
`of the ’804 Publication, the ’011 Patent, Yuan, and
`the ’541 patent ............................................................... .. 108
`
`Independent Claim 1 of the ’431 Patent is obvious
`' under 35 U.S.C. § 103 over the ’225 Patent in view
`of
`the’343 Patent
`and the
`°609 Patent, or
`alternatively, over the ’343 Patent in view of the
`’225 Patent and I-Iara ..................................................... .. 109
`
`OQQQQQQQQQQQQQQJQ-Q~Q-Q-nu-.n.a\an.-.-\4v\n»-A-\----
`
`Page 10 of 166
`
`

`
`Dependent Claim 2 of the ’431 Patent is obvious
`under 35 U.S.C. § 103, over (A) the ’225 Patent in
`view of the ’804 Publication, the ’011 Patent, and
`Regev or alternatively, (B) the ’225 Patent in view
`of the ’804 Publication, the ‘O11 Patent, Yuan, and
`the ’54l patent, or alternatively, (C) the ’225 Patent
`in View the ’343 Patent and the ’609 Patent, or
`
`alternatively, (D) the ’343 Patent in view of the
`’225 Patent and Hara ..................................................... .. 113
`
`Dependent Claims 3-5 and 11 of the ’43l Patent are
`obvious under 35 U.S.C. § 103 over (A) the ’225
`Patent in View of the ’804 Publication,
`the ’011
`
`(B) the ’225
`Patent, and Regev or alternatively,
`Patent in view of the ’804 Publication, the ‘O11
`Patent, Yuan, and the ’541 patent, or alternatively,
`(C) the ’225 Patent in View the ’343 Patent and the
`’609 Patent, or alternatively, (D) the ’343 Patent in
`view of the ’225 Patent and Hara .................................. .. 114
`
`Dependent Claims 6, 12 and 15 of the ’431 Patent
`are obvious under 35 U.S.C. § 103 over (A) the
`’225 Patent in view of the ’804 Publication, the
`’011 Patent, and Regev or alternatively, (B) the
`’225 Patent in view of the ’804 Publication,
`the
`’()11 Patent, Yuan,
`and the
`‘S41
`patent, or
`alternatively, (C) the ’225 Patent in view the ’343
`Patent and the ’609 Patent, or alternatively, (D) the
`’343 Patent in view ofthe ’225 Patent and Hara
`
`Dependent Claims 7, 8, 13, 14, 16 and 17 of the
`’431 Patent are obvious under 35 U.S.C. § 103 over
`(A) the 225 Patent in View ofthe ’804 Publication,
`the ’011 Patent, and Regev or alternatively, (B) the
`’225 Patent in view of the ’804 Publication, the
`
`patent, or
`’54l
`and the
`’011 Patent, Yuan,
`alternatively, (C) the ’225 Patent in View the ’343
`Patent and the ’609 Patent, or alternatively, (D) the
`’343 Patent in View of the ’225 Patent and Hara .......... .. 117
`
`Dependent Claims 9 and 10 of the ’431 Patent are
`obvious under 35 U.S.C. § 103 over (A) the ’225
`Patent in View of the ’804 Publication, the ’O11
`Patent, and Regev or altematively,
`(B) the ’225
`Patent in View Of the ’804 Publication,
`the “O11
`Patent, Yuan, and the ’54l patent, or alternatively,
`(C) the ’225 Patent in view the ’343 Patent and the
`’609 Patent, or alternatively, (D) the ’343 Patent in
`view of the ’225 Patent and Hara .................................. .. 118
`
`Page 11 of 166
`
`

`
`Independent Claim 18 of the ’43l Patent is obvious
`under 35 U.S.C. § 103 over the ’225 Patent in view
`of the ‘S04 Publication, the ’0ll Patent, and Regev
`or, alternatively, in view of the ’804 Publication, the
`‘U11 Patent, Yuan, and the ‘S41 patent ......................... .. 119
`
`Independent Claim 18 of the ’43l Patent is obvious
`under 35 U.S.C. § 103 over the ’225 Patent in View
`of
`the ’343 Patent
`and the
`°609 Patent, or
`alternatively, over the ’343 Patent in view of the
`’225 Patent and Hara ..................................................... .. 122
`
`Dependent Claim 19 of the ’43l Patent is obvious
`under 35 U.S.C. § 103 over (A) the ’22S Patent in
`view of the ’804 Publication, the ’O11 Patent, and
`Regev or alternatively, (B) the ’225 Patent in view
`of the ’804 Publication, the ’011 Patent, Yuan, and
`the ’S4l patent, or alternatively, (C) the ’225 Patent
`in view the ’343 Patent and the ’609 Patent, or
`alternatively, (D) the ’343 Patent in view of the
`’225 Patent and Hara ..................................................... .. 123
`
`Dependent Claim 20 of the ’43l Patent is obvious
`under 35 U.S.C. § 103 over (A) the ’225 Patent in
`View of the ’804 Publication, the ‘O11 Patent, and
`Regev or alternatively, (B) the ’225 Patent in view
`of the ’804 Publication, the ’0l1 Patent, Yuan, and
`the ’54l patent, or alternatively, (C) the ’225 Patent
`in View the ’343 Patent and the ’609 Patent, or
`alternatively, (D) the ’343 Patent in view of the
`’225 Patent and Hara ..................................................... .. 124
`
`Dependent Claims 21 and 22 of the ’446 Patent are
`obvious under 35 U.S.C. §'103 over (A) the ’225
`Patent
`in view of the ‘E304 Publication,
`the ‘D11
`
`the ’225
`(B)
`Patent, and Regev or alternatively,
`Patent in view of the ’804 Publication, the ’O11
`Patent, Yuan, and the ‘S41 patent, or alternatively,
`(C) the ’225 Patent in view the 343 Patent and the
`’609 Patent, or alternatively, (D) the ’3-43 Patent in
`view of the ’225 Patent and Hara .................................. .. 125
`
`Secondary Considerations of Nonobviousness ..................................... .. 126
`
`Invalidity of U.S. Patent No. 8,669,290 ................................................ ,. 127
`
`a)
`
`Invalidity Analysis of the ’290 Patent ...................................... .. 127
`
`i)
`
`The Scope and Content of the Prior Art ........................ .. 127
`
`b)
`
`Differences between the Prior Art and the Claims of the
`’290 Patent ................................................................................ .. 127
`
`”.'T_"’IT"1
`
`
`
`
`rt"’~.'¥"’~rt"-5xzf‘>\Li:/L»:Li,I‘i,‘_.
`.‘_’”tl'C‘_"C".'CCC”.T.“""‘
`
`Page 12 of 166
`
`

`
`Independent Claims 1 and 14 of the ’290 Patent are
`obvious under 35 U.S.C. § 103 over the ’225 Patent
`in view of the ’8G4 Publication, the ’011 Patent, and
`Regev
`
`Independent Claims 1 and 14 of the ’290 Patent are
`obvious under 35 U.S.C. § 103 over the 2225 Patent
`in view of the ‘804 Publication, the ’0l1 Patent,
`Yuan, and the ’541 Patent ............................................. .. 132
`
`Independent Claims 1 and 14 of the ’290 Patent are
`obvious under 35 U.S.C. § 103 over the ’225 Patent
`in View of the’343 Patent and the ’609 Patent, or
`
`alternatively, over the ’343 Patent in view of the
`’225 Patent and Hara ..................................................... .. 133
`
`Independent Claim 8 of the ’290 Patent is obvious
`under 35 U.S.C. § 103 over the ’225 Patent in view
`of the ’804 Publication, the ’011 Patent, and Regev
`or, alternatively, in view of the "804 Publication, the
`’011 Patent, Yuan, and the ‘S41 patent ......................... .. 137
`
`Independent Claim 8 of the ’?.90 Patent is obvious
`under 35 U.S.C. § 103 over the ’225 Patent in view
`of
`the’343 Patent
`and
`the
`’609 Patent,
`or
`
`alternatively, over the 7343 Patent in view of the
`’225 Patent and Hara ..................................................... .. 139
`
`Dependent Claims 10, 20 and 22 of the ’29() Patent
`are obvious under 35 U.S.C. § 103 over (A) the
`’225 Patent
`in view of the ’804 Publication,
`the
`
`’0l1 Patent, and Regev or alternatively, (B) the
`‘225 Patent in view of the ’804 Publication, the
`
`’54l patent, or
`and the
`’01l Patent, Yuan,
`alternatively, (C) the ’225 Patent in view the ’343
`Patent and the ’609 Patent, or alternatively, (D) the
`’343 Patent in view of the ’225 Patent and I-Iara .......... .. 140
`
`Dependent Claims 2, 9, 15 and 21 of the ’290 Patent
`are obvious under 35 U.S.C. § 103 over (A) the
`’225 Patent in view of the ‘S04 Publication, the
`’0l1 Patent, and Regev or alternatively, (B) the
`’225 Patent in view of the ’804 Publication,
`the
`
`patent, or
`’541
`and the
`’Ol1 Patent, Yuan,
`alternatively, (C) the ’225 Patent in View the ’343
`Patent and the ’609 Patent, or alternatively, (D) the
`’3-43 Patent in view of the ’225 Patent and Hara .......... .. 141
`
`Dependent Claims 3 and 16 of the ’29O Patent are
`obvious under 35 U.S.C. § 103 over (A) the ’225
`
`Page 13 of 166
`
`

`
`the ’0ll
`Patent in view of the ’804 Publication,
`Patent, and Regev or alternatively, (B) the ’225
`Patent in View of the ’804 Publication,
`the ’01l
`Patent, Yuan, and the ’541 patent, or alternatively,
`(C) the ‘225 Patent in view the ’343 Patent and the
`’609 Patent, or alternatively, (D) the ’343 Patent in
`view of the ’225 Patent and Ham .................................. .. 142
`
`Dependent Claims 4, ll, 17 and 23 of the ’29O
`Patent are obvious under 35 U.S.C. § 103 over (A)
`the ‘Z25 Patent in View of the ’804 Publication, the
`’01] Patent, and Regev or alternatively,
`(B) the
`’225 Patent in view of the ’804 Publication, the
`’01l Patent, Yuan,
`and the
`’541 patent, or
`alternatively, (C) the ’225 Patent in view the ’343
`Patent and the ’609 Patent, or alternatively, (D) the
`’343 Patent in view of the ’225 Patent and Ham .......... .. 142
`
`Dependent Claim 5 of the ‘Z90 Patent is obvious
`under 35 U.S.C. § 103 over (A) the ’225 Patent in
`view of the ’804 Publication, the ’0l1 Patent, and
`Regev or alternatively, (B) the ’225 Patent in view
`of the ’804 Publication, the ’0ll Patent, Yuan, and
`the ’54I patent, or alternatively, (C) the ’225 Patent
`in view the ’343 Patent and the ’609 Patent, or
`alternatively, (D) the ’343 Patent
`in view of the
`’225 Patent and Hara ..................................................... .. 144
`
`l8 and 24 of the ’29()
`l2,
`Dependent Claims 6,
`Patent are obvious under 35 U.S.C. § 103. over (A)
`the ’225 Patent in view of the ’804 Publication, the
`“O11 Patent, and Regev or alternatively,
`(B) the
`’225 Patent in View of the ’804 Publication,
`the
`
`patent, or
`’541
`and the
`’Oll Patent, Yuan,
`alternatively, (C) the ’225 Patent in View the ’343
`Patent and the ’609 Patent, or alternatively, (D) the
`’343 Patent in view of the ’225 Patent and I-Iara .......... .. 144
`
`Dependent Claims 7, 13, 19, and 25 of the ’290
`Patent are obvious under 35 U.S.C. § 103 over (A)
`the ’225 Patent in View of the ‘S04 Publication, the
`’0I1 Patent, and Regev or alternatively,
`(B) the
`’225 Patent in view of the ’804 Publication,
`the
`’Oll Patent, Yuan,
`and
`the
`’54l Patent, or
`alternatively, (C) the ’225 Patent in view the ’343
`Patent and the ’609 Patent, or alternatively, (D) the
`’343 Patent in view of the ’225 Patent and Hara .......... .. 145
`
`*T~"T'~‘f""
`
`Page 14 of 166
`
`

`
`Dependent Claims 26-30 of the ’29() Patent are
`obvious under 35 U.S.C. § 103 over (A) the ’225
`Patent in View of the ’804 Publication,
`the ’0II
`Patent, and Regev or alternatively,
`(B)
`the ’225
`Patent
`in View of the ‘S04 Publication,
`the ‘O11
`
`Patent, Yuan, and the ’54l Patent, or alternatively,
`(C) the ’225 Patent in view the ’343 Patent and the
`’609 Patent, or alternatively, (D) the ’343 Patent in
`view of the ’22S Patent and Hara .................................. .. 147
`
`(3)
`
`Secondary Considerations ofhlonobviousness ......................... .. 149
`
`NON-INFRINGEMENT OF THE ’431 PATENT ........................................... .. 149
`
`NON-INFRINGEMENT OF THE ’290 PATENT ........................................... .. 149
`
`D.
`
`E.
`
`Page 15 of 166
`
`

`
`EXHIBIT A
`DETAILED STATEMENT OF THE FACTUAL AND LEGAL BASIS FOR
`INNOPHARMA LICENSING INC.’S CERTIFICATION
`
`THAT U.S. PATENT NOS. 8,128,431 AND 8,669,290 ARE
`INVALID, UNENFORCEABLE, AN D/OR WILL NOT BE INFRINGED BY
`THE MANUFACTURE, USE, SALE, OFFER FOR SALE, OR IMPORTATION OF
`INN OPHARMA’S BROMFENAC PRODUCT AS DEFINED BY ANDA NO. 206-326
`
`For at least the reasons set forth below, U.S. Patent Nos. 8,128,431 (“the ’431 patent”)
`and 8,669,290 (“the ’290 patent”) do not prohibit Innopharma Licensing Inc (“In.nopharma”)
`from manufacturing, using, selling, offering for sale, or importing Innopharmas’s Bromfenac
`Product as covered by ANDA No. 206-326 after the FDA approves its ANDA.1
`
`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, PROLENSA TMLabel.
`‘
`
`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 C1 5H11BrNNaO3-11/-. H20. The structural formula for bromfenac sodium
`
`H2“
`
`CH3COgNa
`
`‘ I IIEHQO
`
`The Orange Book lists the following patents for PROLENSATM: the ’43l patent; and 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 PROLENSATM 0.07% ophthalmic solution.
`
`Innopharma reserves its rights to raise any additional defenses relating to invalidity,
`1
`unenforceability,
`and non—infringement
`in any and all proceedings
`for alleged patent
`infringement.
`‘
`
`Page 16 of 166
`
`

`
`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 Orange Book Patents for at least the following
`TBESOIISI
`
`The '43] Patent
`
`As set forth in detail below, Innopharma cannot infringe claims 1-22 of the ’43l patent
`because each of these claims is invalid under 35 U.S.C. § 103 as follows:
`
`Independent Claim 1 of the ‘431 patent would have been obvious under 35 U.S.C.
`§ 103 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 ‘O11 patent”),
`and Regev and Zana, Journal of Colloid and Interface Science (210) 8-17 (1999)
`(“Regev”).
`
`Independent Claim 1 of the ’43l patent would have been obvious under 35 U.S.C.
`§ 103 in light of the ’225 patent in view of the ’804 publication, the ’0l1 patent,
`Yuan er al., J. Phys. Chem. B., 2001, 105, 4611-4615, and U.S. Patent No.
`2,454,541 (“the ’54I patent”).
`
`Independent Claim 1 of the ’43l patent would have been obvious under 35 U.S.C.
`§ 103 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”); or alternatively, in
`light of the ’343 patent in view of the ’225 patent and Ham, Yoshiyuki, Clinics &
`Drug Therapy, 2002, 19: 1014-1015 (“Hara”).
`
`Dependent Claims 2-17 of the ’43l patent would have been obvious under 35
`U.S.C. § 103, in light of (A) the ’225 Patent in view of the ’804 Publication, the
`’011 Patent, and Regev; or alternatively, (B) the ’225 Patent in view of the ’804
`publication, the ’01l patent, Yuan, and the ’541 patent; or alternatively, (C) the
`’225 patent in view the ’343 patent and the ’609 patent; or alternatively, (D) the
`’343 patent in view of the ’225 patent and Hara.
`
`Independent Claim 18 of the ’43l patent would have been obvious under 35
`U.S.C. § 103 in light of the ’225 patent in view ofthe ’804 Publication, the ’0l1
`Patent, and Regev; or, alternatively, in view of the ’804 publication, the ’01l
`patent, Yuan, and the ’541 patent.
`
`Dependent Claims 19-22 of the ’431 patent would have been obvious under 35
`U.S.C. § 103 in light of (A) the ’225 patent in view of the ’804 Publication, the
`’0l1 Patent, and Regev; or alternatively, (B) the ’225 patent in view of the ’804
`publication, the ‘O11 patent, Yuan, and the ‘S41 patent; or altematively, (C) the
`’22S patent in view the ’343 patent and the ’609 patent; or alternatively, (D) the
`’343 patent in view of the ’225 patent and Hara.
`
`Page 17 of 166
`
`

`
`The ’290 Patent
`
`As set forth in detail below, Innopharma cannot infringe claims 1-22 of the ’290 patent
`because each of these claims is invalid under 35 U.S.C. § 103 as follows:
`
`0
`
`Independent Claims 1 and 14 of the ’290 patent would have been obvious under
`35 U.S.C. § 103 in light of the ‘Z25 patent in View o