Ex. 1114 is a redacted version of Ex. 1066
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`AMNEAL PHARMACEUTICIALS, LLC
`
`Petitioner
`
`V.
`
`SUPERNUS PHARMACEUTICALS, INC.
`Patent Owner
`
`US. Patent No. 8,394,406
`
`
`Case IPR20 1 3-003 72
`
`
`Second Declaration of Glenn A. Van Buskirk, Ph.D.
`
`Amneal 1 1 14
`
`Amneal v. Supernus
`IPR2013-00372
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
`
`Second Declaration of Glenn A. Van ankirk, PhD. (Exhibit 1066)
`
`TABLE OF CONTENTS
`
`I.
`
`Overview .......................................................................................................... I
`
`II.
`
`Summary of opinions ....................................................................................... 2
`
`111. My Background and Qualifications ................................................................. 6
`
`IV.
`
`List of documents I considered in formulating my opinions ........................... 6
`
`V.
`
`Person of ordinary skill in the art .................................................................. 12
`
`VI. Disclosures in the '406 patent regarding "delayed release" ........................... 13
`
`VII.
`
`I disagree with Dr. Rudnic’s opinions regarding disclosures in the
`prior art .......................................................................................................... M
`
`A.
`
`B.
`
`Dr. Rudnic does not consider the prior art as a whole ........................ 15
`
`The Ashley references and Sheth '748 patent do not "teach
`away" from the claimed invention ...................................................... 17
`
`(i)
`
`Doxycycline formulations disclosed in the Ashley ‘932
`publication and '854 application do not "require" a
`sustained release component _____________________________________________________ 18
`
`(ii)
`
`Dr. Rudnic construes the term "delayed release" too
`narrowly in the context of the '406 patent................................. 24
`
`(iii) The "blended polymer" secondary loading portion of the
`Sheth '748 patent is a DR portion ............................................. 29
`
`(iv) Dr- Rudnic overstates the differences between
`doxycycline and minocycline ................................................... 32
`
`(v)
`
`Dr. Rudnic overstates the relevance of the “antibacterial
`doses” disclosed in the Sheth ‘748 patent ................................. 35
`
`VIII. Knowledge of the absmption window of doxycycline was not
`necessary for a POSA to develop an IR/DR doxycycline formulation
`prior to 2003 .................................................................................................. 36
`
`Ex. 1114 is a redacted version of Ex. 1066
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`

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`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
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`Second Declaration of Glenn A. Van ankirk, PhD. (Exhibit 1066)
`
`IX.
`
`X.
`
`I am not aware of any evidence that an IR/DR ratio of 75/25 is critical
`for achieving the steady—state blood levels claimed in the '406 patent .........40
`
`I disagree with Dr. Rudnic's opinions on secondary considerations of
`nonobviousness .............................................................................................. 43
`
`A.
`
`B.
`
`D.
`
`E.
`
`The Faulding study was not a "failure of others" ................................43
`
`Dr. Rudnic provides no actual evidence of a long—felt, but
`unmet need recognized in the art .........................................................49
`
`Dr. Rudnic provides no actual evidence of copying ........................... 52
`
`Dr. Rudnic provides no actual evidence of skepticism followed
`by acceptance in the industry .............................................................. 53
`
`I disagree with Dr. Rudnic’s opinion that Oracea® is a
`commercial success ............................................................................. 54
`
`XI.
`
`There was no actual reduction to practice of the claimed invention
`before October 17, 2002 ................................................................................ 56
`
`XII. A POSA would have understood the ‘932 publication unambiguously
`identifies the Ashley ‘854 application ........................................................... 59
`
`XIII. Quotes from my deposition transcript were mischaracterized and
`taken out of context ....................................................................................... 60
`
`XIV. Conclusion ..................................................................................................... 81
`
`_ii_
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
`
`Second Declaration of Glenn A. Van ankirk, PhD. (Exhibit 1066)
`
`I.
`
`Overview
`
`1.
`
`I am over the age of eighteen (18) and otherwise competent to make
`
`this declaration.
`
`2.
`
`I have been retained as an expert witness on behalf of AMNEAL
`
`PHARMACEUTICALS, L.L.C and AMNEAL PHARMACEUTICALS COMPANY PVT. LTD.
`
`(together "AMNEAL") for the above—captioned inter partes review (IPR). 1 am being
`
`compensated for my time in connection with this IPR at my standard consulting
`
`rate, which is $400 per hour.
`
`I understand that the petition for inter partes review
`
`involves US. Patent No- 8,394,406 ("the '406 patent"), Exhibit 1009, which
`
`resulted from US. Application No. 12/926,934 (”the ‘934 application"), filed on
`
`December 17, 2010, naming Rong-Kun Chang, Arash Raoufinia, and Niraj Shah as
`
`inventors. The '406 patent issued on March 12, 2013, from the '934 application. I
`
`further understand that, according to the USPTO records,
`
`the '406 patent
`
`is
`
`currently assigned to Supernus Pharmaceuticals, Inc.
`
`I understand that the earliest
`
`possible priority date for the ‘406 patent is April 7, 2003.
`
`3.
`
`I provided a previous declaration in this proceeding (Ex1022). My
`
`first declaration in this proceeding set forth my opinions on the disclosures in the
`
`prior art and the understanding of a person of ordinary skill in the art reading the
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
`
`Second Declaration of Glenn A. Van Buskirk, PhD. (Exhibit 1066)
`
`disclosures in the prior art- I maintain the same opinions today that were set forth
`
`in my first declaration. [Ex1022; see also, Ex2015, 268:13-21.]l
`
`4.
`
`I am submitting this second declaration in reply to Supernus' Patent
`
`Owner Reply (Case IPR2013-00368, Paper 39;
`
`IPR2013-00371, Paper 40;
`
`IPR2013-00372, Paper 38) and declarations of Supemus witnesses that were
`
`submitted with the Patent Owner Reply (Ex2016 and Ex2146).
`
`5.
`
`I understand that certain documents associated with this inter partes
`
`review proceeding are considered confidential. I reviewed the Proposed Protective
`
`Order (Exhibit 2171) and signed the corresponding acknowledgement form.
`
`[1.
`
`Summary of opinions
`
`6.
`
`I have been asked by Counsel for Amneal to consider and respond to
`
`declaration testimony of Supernus declarants submitted with the Patent Owner
`
`Reply (Case IPR2013—00368, Paper 39;
`
`IPR2013-0037l, Paper 40;
`
`IPR2013—
`
`00372, Paper 38). In particular, this declaration is submitted in response to the
`
`1 Throughout this declaration,
`
`I use the following citation formats where
`
`applicable: Columned articles, Exhibit number, page number : column number :
`
`paragraph number; Patents, Exhibit number, column number :
`
`line numbers;
`
`Declarations, Exhibit number, paragraph number.
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
`
`Second Declaration of Glenn A. Van Buskirk, PhD. (Exhibit 1066)
`
`Declaration of Dr. Edward Rudnic, Ex2016. I have also considered and responded
`
`to the Declaration of Dr. Jones Blyan (EX2146).
`
`7.
`
`I disagree with Dr. Rudnic’s assertion that my opinions set forth in my
`
`first declaration, ExlO22, rely on hindsight analysis of the prior art. As I stated in
`
`my first declaration and reiterate in this second declaration, a person of ordinary
`
`skill in the art would have been motivated to combine the Ashley ‘932 publication,
`
`which incorporates by reference the ‘854 application, with the Sheth ‘748 patent
`
`because a viable once-daily formulation of a tetracycline drug with improved
`
`controlled release (as disclosed in the ‘748 patent)
`
`is a desirable feature for
`
`compositions of doxycycline for the treatment of rosacea (as disclosed in the
`
`Ashley ‘932 publication). Furthermore, a person of ordinary skill in the art reading
`
`the “932 publication and ‘748 patent would have immediately envisaged at least
`
`the common incremental range of lR/DR ratios from 50:50 to 80:20 because this
`
`range is disclosed in the art. See, eg, Ex1022,1fl] 198—207.
`
`8.
`
`I disagree with Dr. Rudnic’s analysis of the prior art. Dr. Rudnic
`
`considers each prior art reference individually, rather than considering the prior art
`
`as a whole. Even when considering a single prior art reference, Dr. Rudnic focuses
`
`his analysis on a single embodiment of the disclosure rather than the teachings of
`
`the reference as a whole. Furthermore, Dr. Rudnic’s analysis implies that a person
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
`
`Second Declaration of Glenn A. Van Buskirk, PhD. (Exhibit 1066)
`
`of ordinary skill
`
`in the art would have required explication in every reference,
`
`ignoring a skilled altisan’s recourse to logic, judgment, and common sense.
`
`9.
`
`I disagree with Dr. Rudnic’s opinions that the Ashley ‘932 publication
`
`and c854 application “teach away” from doxycycline formulations containing only
`
`an IR and DR portion. Dr. Rudnic provides no actual evidence that the Ashley’932
`
`publication and ‘854 application criticize, discredit, or otherwise discourage
`
`developing a doxycycline formulation containing only IR and DR portions. Dr.
`
`Rudnic also ignores disclosures in the Ashley ‘854 application that are contrary to
`
`his opinions. For example, the Ashley ‘854 application expressly states that the
`
`fonnulations can contain an “instantaneous-release agent, a sustained-release
`
`agent, a delayed-release agent, and combinations thereof." [Ex1003, 524—26.] The
`
`Ashley ‘854 application also states that the amount of drug released from the
`
`formulations can vary. [Ex1003, 5:15-20] Furthermore, Dr. Rudnic focuses his
`
`analysis on a single preferred embodiment disclosed in the Ashley ‘854
`
`application, rather than considering the prior art (which includes the Sheth ‘748
`
`patent) as a whole.
`
`10.
`
`I also disagree with Dr. Rudnic’s opinions that the Sheth ‘748 patent
`
`“teaches away’
`
`from doxycycline formulations due to differences between
`
`3
`
`minocycline and doxycycline. As above, Dr. Rudnic provides no actual evidence
`
`that
`
`the Sheth “748 patent criticizes, discredits, or otherwise discourages
`
`-4-
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
`
`Second Declaration of Glenn A. Van Buskirk, PhD. (Exhibit 1066)
`
`developing a once—daily, controlled—release doxycycline formulation. Furthermore,
`
`Dr. Rudnic overstates the differences between minocycline and doxycycline. As
`
`the Patent Trial and Appeal Board stated, with which I agree, “the otherwise close
`
`relatedness of these two drugs in structure and fiinction makes information about
`
`formulation of one relevant to formulation of the other.” [Case IPR2013—00368,
`
`Paper 8 at 12; [PR2013-0037l, Paper 11 at 12; IPR2013-00372, Paper 8 at 13.]
`
`11.
`
`I also disagree with Dr. Rudnic’s opinions that the “blended polymer”
`
`formulations of the Sheth ‘748 patent are not lR/DR formulations. Dr. Rudnic
`
`imputes a “rapid release” limitation to the DR portion of the “406 patent that is not
`
`recited or required by the claims of the “406 patent. Discussed below,
`
`the
`
`secondary-loading portions of the formulations disclosed in the Sheth ‘748 patent
`
`are consistent with a POSA’s understanding of the term, “delayed release.”
`
`12.
`
`I disagree with Dr. Rudnic’s opinions that secondary considerations
`
`support the nonobviousness of the invention as claimed in the ‘406 patent. Dr.
`
`Rudnic fails to provide actual evidence of secondary considerations and sets forth
`
`unsubstantiated opinions- Dr. Rudnic also fails to consider the purported evidence
`
`in view of the claims.
`
`Instead, Dr. Rudnic imputes
`
`limitations
`
`such as
`
`bioavailability that are not recited or required by the claims of the ‘406 patent.
`
`l3.
`
`1 disagree with Supernus' argument that the '932 publication does not
`
`identify the Ashley '854 application with sufficient particularity. The '932
`
`-5-
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
`
`Second Declaration of Glenn A. Von Buskirk, PhJ). (Exhibit 1066)
`
`publication identifies the '854 application by title, filing date, and assignee. A
`
`POSA would have understood that the title and filing date are identical to those of
`
`the '854 application. A POSA would have also understood that the ‘854 application
`
`is directed to controlled release tetracycline formulations — the same subject matter
`
`recited in the title of the application incorporated by reference in the '932
`
`publication.
`
`[11. My Background and Qualifications
`
`14.
`
`I am an expert in the field of drug development and formulation, and
`
`l have been an expert in this field since prior to 2003. I am presently the managing
`
`member of Nonelinical Drug Development Consulting Services (NDDCS), LLC.
`
`My background and qualifications are detailed in {[1]
`
`1 1—20 of my first declaration,
`
`Ex1022. My curriculum vitae has already been provided in this proceeding as
`
`Ex1021. In view of my experiences and expertise outlined in Ex1021 and Ex1022,
`
`I am an expert in the field of drug development and formulation.
`
`IV.
`
`List of documents 1 considered in formulating my opinions
`
`Exhibit or
`
`Paper No. Description
`
`Paper 8
`Patent Trial & Appeal Board, Decision to Institute, Case
`IPR2013-00368;
`Patent Trial & Appeal Board, Decision to Institute, Case
`IPR2013—0037l ;
`Patent Trial & Appeal Board, Decision to institute, Case
`Paper 8
`
`[PR2013-00372;
`
`Paper 11
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Second Declaration of Glenn A. Van Buskirk, PhD. (Exhibit 1066)
`
`
`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
`
`Exhibit 01'
`
`Pa 1 er No.
`
`Description
`
`Paper 39
`
`Supemus' Patent Owner Response, Case 1PR20'13-00368;
`
`Paper 40
`
`Supernus' Patent Owner Response, Case 1PR2013-00371;
`
`
`Paper 38
`Supernus' Patent Owner Response, Case 1PR2OI3-00372;
`1001
`Chang et (11., U.S. Patent No. 8,206,740, “Once daily
`formulations of tetracyclines” (filed June 6, 2008;
`issued June 26, 2012
`"the '740
`
`1002
`
`Ashley, WO 2002/080932, “Method of treating acne” (filed
`April 5, 2002; published October 17, 2002) ("the ‘932
`sublication"
`
`Ashley, U.S. Prov. App]. No. 60/281,854 (filed April 5,
`"the '854 a u lication"
`
`Ashley, WO 2002/083106, “Controlled delivery of
`tetracycline compounds and tetracycline derivatives” (filed
`April 5, 2002; issued October 24, 2002) ("the '106
`
`publication")
`Sheth et al., U.S. Patent No. 5,348,748, “Pulsatile once-a—day
`delivery system for minocycline” (filed June 23,1993; issued
`Se tember 20, 1994
`"the '748
`File histor of the ‘740 atent
`
`
`
`Chang et (11., U.S. Patent No. 8,394,405, “Once daily
`formulations of tetracyclines” (filed December 17,
`2010; issued March 12, 2013
`"the ‘405
`
`1008
`
`File histo
`
`of the '405 uatent
`
`Chang et al., U.S. Patent No. 8,394,406, “Once daily
`formulations of tetracyclines” (filed December 17,
`2010; issued March 12, 2013
`"the ‘406
`
`File histo
`
`of the ’406 atent
`
`Physician s Desk Reference pp. 1208—1210, 2442—2444,
`2735—2736 and 3357—3358, 56m ed. 2002
`
`Skidmore et 01., ”Effects of Subantimic-robial-Dose
`Doxycycline in the Treatment of Moderate Acne," Arch.
`Dermatol. 139:439-464 (2003)
`Opinion, August 26, 2011, Mylar: Pharm., Inc. v.
`(falderma Labs, Inc, No. 10—892—LPS D. Del. 20] 1
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`Transcriit of Bench Trial, Jul 5, 2011, M {an Pharm.,
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Second Declaration of Glenn A. Van Baskirk, PhD. (Exhibit 1066)
`
`
`Ex. 1114 is a redacted version of Ex. 1066
`Case IPR2013-003 72
`
`Exhibit 01'
`Pa 1 er No.
`
`Descri
`
`tion
`
`9
`
`Inc. v. Galderma Labs, Inc, No. 10-892-LPS (D. Del.
`2011, Vol. A, pp. 66-259)
`Cole ei al., "Enteric coated HPMC capsules designed to
`achieve intestinal targeting," 1m. .1. Pharmaceutics
`231:83—95 (2002)
`Chang et a!., US Patent No. 7,749,532, “Once daily
`formulations of tetracycline” (filed April 7, 2004; issued
`Jul 6,2010 "the '532
`
`Chambers, "Antimicrobial Agents: Protein Synthesis
`Inhibitors and Miscellaneous Antibacterial Agents," in
`Goodman & Gilman's 7he Pharmacological Basis of
`
`Them euiics, Chater 47, I . 1239-1271 2001
`
`OF. Webster, "Treatment of Rosacea," Seminars in Cutaneous
`Medicine (1’: SW (3
`20 3 : 207-208 2001
`
`Joshi ei a!., US Patent No. 5,030,447, "Pharmaceutical
`compositions having good stability" (filed March 31,
`1988; issued Jul 9, 1991
`
`1020
`
`1022
`
`Amendment in Response to September 9, 2010 Final Office
`Action and Substance of Interview in US. Appl. No.
`10/474,240 (filed October 3, 2003)
`
`Declaration of Glenn A. Van Buskirk, PhD. ("First
`Declaration"
`
`
`
`1025
`
`Benet ei at, "Pharmacokinetics: The Dynamics of Drug
`Absorption, Distribution, and Elimination," in Goodman (Yr
`Gilman's The Pharmacological Basis ofThei'apeuiics, 7th ed.
`Ch. 1, pp. 3-33 (1985)
`Rudnic ei a}, US. Patent No. 6,730,320, “Tetracycline
`Antibiotic Product, Use, and Formulation Thereof” (filed
`December 20, 2001; issued Ma 4, 2004
`"the '320
`
`Transcript of deposition of Edward M. Rudnic, Ph.D., Case
`IPR2013—00368; IPR2013—00371; and IPR2013-00372, April
`25, 2014
`
`Transcript of deposition of Jones W. Bryan, Ph.D., Case
`IPR2013-00368; IPR2013-00371; and IPR2013-00372, April
`29,2014
`Transcript of Deposition of Henry G. Grabowski, Ph.D., Case
`IPR2013—00368; lPR2013—00371; and lPR2013-00372, Ma
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Second Declaration of Glenn A. Van Bus‘kirk, PhD. (Exhibit 1066)
`
`
`Ex. 1114 is a redacted version of Ex. 1066
`Case 1PR2013-003 72
`
`Exhibit 01'
`Pa . er No.
`
`13, 2014
`
`Description
`
`Williams 6:01., "Absorption of Doxycycline from a Controlled
`Release Pellet Formulation: the Influence of Food on
`
`Bioavailability," Biopharmaceutics & Drug Disposition 11:93-
`
`105 (1990)
`Lordi, "Sustained Release Dosage Forms," in The Theory and
`Practice oflndustria! Pharmacy, Chapter 14, pp. 430, 442—
`443, 453—455 1986
`
`Goodman & Gilman s ”The Pharmacological Basis of
`
`Therapeutics," 10lh ed. (2001)
`Rudnic et (.11., US. Patent Application Publication No.
`2002/0136766, "Tetracycline Antibiotic Product, Use and
`Formulation Thereof," (filed December 20, 2001; published
`Se tember 26, 2002)
`
`1092
`
`2012
`
`Savin e101, "Clinical Pharmacokinetics," 15:355—366 1988
`
`
`
`Transcript of Deposition of Glenn A. Van Buskirk, Ph.D.,
`
`February 12, 2014
`
`Declaration of Edward M. Rudnic, PhD.
`
`Declaration of Henry G. Grabowski, PhD.
`
`Declaration of Guy F. Webster, M.D., PhD.
`Chang, R. & Robinson, J .R., "Sustained Drug Release from
`Tablets and Particles Through Coating," Ch. 4, 199—302, in
`Pharmaceutical Dosage Forms: Tablets (Lieberman, H.A., e!
`al. eds., 2d ed-, 1990
`
`Mayersohn, M., ”Principles of Drug Absorption" in Modern
`Pharmaceutics 23-66 Banker, G.S. er al., eds, 4th ed. 2002)
`
`L-eung, S.H.S. & Robinson, J.R., "The Contribution of Anionic
`Polymer Structural Features to Mucoadhesion," J. Controlled
`Release (1988 223-31
`
`Depomed, Inc. website entitled "Our Technology,"
`httn ://deomed.com/technolo_
`last Visited March 9, 2014
`
`Adibi, S.A., "The Oligopeptide Transporter (Pept-l) in Human
`Intestine: Biology and Function," Gastroenrerology 332 (1997)
`113:332-40
`
`Davis, 88. et al., "Transit of pharmaceutical dosage forms
`throu h the small intestine," Gut 1986 27:886-92
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Second Declaration of Glenn A. Van Buskirk, Ph.D. (Exhibit 1066)
`
`
`Ex. 1114 is a redacted version of Ex. 1066
`ChseITHQ2013-00372
`
`Exhibit 01'
`Pa 1 er No.
`
`Descri
`
`tion
`
`D
`
`2026
`
`US. Pat. No. 5,840,332, issued to Lerner et al.
`
`Excerpt from Periostat® (doxycycline hyclate) 20 mg Tablets —
`
`NDA Annual Report (NDA 50—783)
`Email from A. Raouflnia to R. Chang et al., dated October 29,
`
`2002
`
`Email from K. Mallari to J. McPartland, dated October 15,
`
`2002
`
`Agwuh, K.N. & MacGowan, A., ”Pharmacokinetics and
`Pharmacodynamics of the Tetracyclines Including
`glycylcyclines," J. Antimicrobial Chemotherapy (2006)
`
`58:256-65
`
`Package Insert for Periostat® Capsules, 20 mg
`
`Document entitled "Status - Manufacturing" dated May 2001
`Document entitled " Doxycycline Bioavailability Study No.
`CM4899, 1. Stud Summa
`"
`
`2034
`
`Fax from S. Lukas to C. Phillips re Pilot Blood Study, dated
`Februa
`3, 2000
`
`2036
`
`Document titled “Development Agreement: Evaluation
`of Doxycycline Hyclate in Controlled Release Technology,”
`
`dated May 22, 2001
`Document entitled "Shire - Project Update," dated January 1 I,
`2037
`
`2002
`
`2039
`
`Document entitled "Doxycycline Population Steady State
`Simulation Re nort," dated December 9, 2002
`
`Excerpt from NDA No. 50-805, entitled "Clinical Study
`2040
`
`Report, Sponsor Reference: PERIO-DOXYSR-103"
`Excerpt from NDA No. 50-805, entitled "Clinical Study
`RCIOIT, Sonsor Reference: PERIO-DOXYSR-104"
`
`2041
`
`2042
`
`2043
`
`Excerpt from NDA No. 50-805, entitled "Clinical Study
`Recort, S onsor Reference: COL-lOl—SSPK-106"
`
`FDA Approval Letter for Oraceaa: (NDA 50—805), dated May
`26,2006
`
`
`
`2044
`2045
`
`Physicians' Desk Reference (55th et. 2001), 3037-39
`Excerpt from NDA No. 50-805, entitled "Clinical Study
`Report, Sponsor Reference: COL-101-SSPK-106: Table
`14.2.1-1"
`
`2046
`Excerpt from NDA No. 50-805, entitled "Clinical Study
`
`-10-
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Case 1PR2013-003 72
`
`Second Declaration of Glenn A. Van Bus‘kirk, PhD. (Exhibit 1066)
`
`
`Exhibit 0r
`
`Pa 1 er No.
`
`Description
`
`Report, Sponsor Reference: COL-lOl-SSPK-106: Table
`
`14.2.2.1"
`
`Skelly, JP et a1., Workshop II Report—Scaleup of Oral
`Extended Release Dosage Forms, J. of Pharmaceutical Science
`
`& Technology Vol. 48 No. 2 I March-April 1994
`Excerpt from NDA No. 50-805, entitled "3.2.P.1:
`
`Description/Composition of Drug Product"
`Document entitled "Status — Manufacturing" dated August 24,
`2000
`
`Fax from C. Phillps to S. Lukas re Pilot Blood Study, dated
`
`December 3, 1999
`
`Augmentin XR-e Product Label, dated Sept. 25, 2002
`Fabre, er al., Schweiz. Med. Wschr. 101:593-598 (1971 )
`
`version with translation
`
`Exceipt from Amneal's Notice of Paragraph IV Certification of
`US. Patent No. 8,206,740 Concerning ANDA 203—278 for
`-3
`Dox c cline Oral Casule, 40 m dated Se tember 14, 2012
`
`Excerpt from Mylan's Notice of Paragraph [V Certification of
`U.S. Patent No. 7,211,267, 7,232,572, 5,789,395, and
`
`5,919,775 for doxycycline delayed release capsules, 40 mg,
`dated Februar 4, 2009
`
`Excerpt from Impax's Notice of Paragraph 1V Certification of
`US. Patent No. 8,206,740, 8,394,405 and 8,394,406
`Concerning ANDA 91-477 for Doxycycline Delayed—Release
`Casules, 40 m_, dated June 24, 2013
`
`Excerpt from Lupin's Notice of Paragraph 1V Certification of
`US. Patent No. 7,749,532 Concerning ANDA 91-277 for
`Dox c cline Oral Casule, 40 m_, dated November 9, 2010
`
`
`
`Excerpt from Sandoz's Notice of Paragraph IV Certification of
`US. Patent Nos. 7,211,267; 7,232,572; 5,789,395; 5,919,775;
`and 7,749,532 Concerning ANDA 202—303 for Doxycycline
`Oral Casule, 40 m_, dated Janua
`12, 2011
`
`FDA Guidance for Industry, SUPAC-MR (1997)
`Excerpt from NDA No. 50-805, entitled "Clinical Study
`
`Report, Sponsor Reference: PERIO—DOXYSR—104"
`Excerpt from NDA No. 50-805, entitled "Clinical Study
`Reort, S onsor Reference: PERIO-DOXYSR—104"
`
`-11-
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Second Declaration of Glenn A. Van Bus‘kirk, PhD. (Exhibit 1066)
`
`
`Ex. 1114 is a redacted version of Ex. 1066
`Case 1PR2013-003 72
`
`Exhibit 01'
`Pa 1 er No.
`
`Descri
`
`tion
`
`D
`
`Declaration of Ste hen G. Kunin with attached Exhibits A-P
`2145
`
`
`2147
`
`Periostat XR Pro'ect Timeline
`
`
`
`Excerpt of June 2002 Development and Licensing Agreement
`2148
`
`between Shire and CollaGenex
`
`Excerpt of Document entitled "Clinical Study Report, Sponsor
`2149
`
`Reference: 5732.11 QD”
`Shire Labs Monthl Pro'ect Reort: October 2002
`2150
`
`2151
`Email from Dr. Arash Raoufinia dated Oct. 17, 2002
`
`2152
`
`Email from Hen
`
`Flanner dated Oct. 17, 2002
`
`Email from Jones “Wood ” B an dated Oct. 18, 2002
`2153
`
`2154
`Email from Jones “Woody” Bryan dated Oct. 23, 2002
`2155
`Excerpt of Program Expansion 2 Agreement between Shire
`and CollaGenex
`
`2156
`
`Email from Jennifer Wilson dated Oct. 24, 2002
`
`Excerpt of Program Expansion 3 Agreement between Shire
`2157
`
`and CollaGenex
`
`V.
`
`Person of ordin ary skill in the art
`
`15.
`
`I understand that a person of ordinary skill in the art ("POSA“) is a
`
`hypothetical person who is presumed to be aware of all pertinent art, thinks along
`
`conventional wisdom in the art, and is a person of ordinary creativity. A POSA
`
`would have had education and experience in drug delivery and formulation as of
`
`2003. The education and experience levels may vary between persons of ordinary
`
`skill, with some persons holding a Bachelor's degree with many years of
`
`experience and others holding higher degrees but having less work experience. A
`
`POSA would have knowledge and skill
`
`relating to the use,
`
`function, and
`
`-12-
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
`
`Second Declaration of Glenn A. Van ankr'rk, PhD. (Exhibit 1066)
`
`formulation of pharmaceutical excipients; knowledge and training regarding the
`
`equipment, processes and techniques used to analyze and test
`
`formulation
`
`materials; and an understanding of pharmacokinetic principles and how they relate
`
`to drug development. Such a person would have specific experience with modified
`
`release drug systems.
`
`16.
`
`A person of ordinary skill
`
`typically would work as part of a
`
`multidisciplinary team and draw upon not only his or her own skills, but also take
`
`advantage of certain specialized skills of others in the team,
`
`to solve a given
`
`problem. For example, a clinician may be part of the team.
`
`17.
`
`I understand that when considering the prior art, a POSA can rely on
`
`disclosures in the prior art as well as recourse to logic, judgment, and common
`
`sense. I understand that a POSA does not necessarily require explicit explication in
`
`any reference to understand the teachings therein.
`
`VI. Disclosures in the '406 patent regarding "delayed release"
`
`18.
`
`According to Dr. Rudnic, the term ”delayed release" (DR) as recited
`
`in the claims of the '406 patent should be construed to mean a DR portion that
`
`releases "substantially no drug in the stomach, and delays release of substantially
`
`all drug until a later point in the GI tract." [Ex2016, 1] 180.]
`
`1 disagree with Dr.
`
`Rudnic‘s construction of "delayed release" in the context of the '406 patent.
`
`-13-
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`ChselTUQ2013-00372
`
`Second Declaration of Glenn A. Von Buskirk, PhJ). (Exhibit 1066)
`
`19.
`
`A POSA reading the '406 patent would understand that the term, DR,
`
`encompasses a broad range of formulations. For example, the '406 patent refers to
`
`"a composition having a substantially immediate release dose of doxycycline,
`
`followed by at least one additional dose at a predetermined time,
`
`in a unit
`
`dosage." [Ex1009, 5:33—36 (emphasis added).] The '406 patent also states that the
`
`doxycycline from the DR portion "becomes available when the pH-sensitive layer
`
`dissolves at the greater pH of the small intestine; after a certain delayed time; or
`
`after the unit passes through the stomach." [Ex1009, 7:58-61 (emphasis
`
`added).] The '406 patent also states that one embodiment of the DR portion
`
`"contains layers of the doxycycline, separated by protective layers, and finally an
`
`enteric coating, resulting in a 'repeat-action' dosage delivery.” [Ex1009, 7:63—66
`
`(emphasis added).] The ‘406 patent also states that the DR portion "can be coated
`
`granular, coated beadlet, coated tablet, or uncoated matrix tablet." [Ex1009, 5:38-
`
`40 (emphasis added).]
`
`20.
`
`In view of the variety of DR formulations described in the '406 patent,
`
`a POSA would have interpreted the term "delayed release" to mean release of a
`
`drug at a time "other than immediately following oral administration." [Ex2058,
`
`30.]
`
`VII.
`
`I disagree with Dr. Rudnic's opinions regarding disclosures in the prior
`art
`
`-14-
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Cuse IPR2013-003 72
`
`Second Declaration of Glenn A. Van Buskr'rk, PhD. (Exhibit 1066)
`
`A.
`
`Dr. Rudnic does not consider the prior art as a whole
`
`21.
`
`As I state above in 1] 15, I understand that a POSA is a hypothetical
`
`person presumed to be aware of all pertinent alt. Accordingly, a POSA would have
`
`read a prior art reference such as the Ashley '932 publication not in a vacuum, but
`
`with a collective awareness of all the pertinent arr. Moreover, a POSA can rely on
`
`recourse to logic, judgment, and common sense; and does not necessarily require
`
`eXplication in any reference.
`
`22.
`
`I disagree with Dr- Rudnic's opinions regarding disclosures in the
`
`Ashley references and the Sheth '748 patent because Dr. Rudnic does not consider
`
`the prior art as a whole. Dr. Rudnic mentions considering the Ashley ‘854
`
`application — i.e., a single reference — "as a whole"2 (EX2016, 1] 120), yet fails to
`
`consider the prior art as a whole. For example, Dr. Rudnic states:
`
` 2
`
`While Dr. Rudnic states that
`
`the Ashley '854 application must be
`
`considered "as a whole" (Ex2016, 1] 120), I note that Dr. Rudnic's opinions on the
`
`teachings of the '854 application are narrowly based on a single embodiment of the
`
`‘854
`
`application that discloses
`
`a doxycycline
`
`formulation comprising an
`
`instantaneous release agent, a delayed release agent, and a sustained release agent.
`
`[Ex2016,11113.]
`
`-15-
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Chsellfl?2013-00372
`
`Second Declaration of Glenn A. Van Buskirk, PhD. (Exhibit 1066)
`
`[N]othing in the Ashley '932 publication discloses that
`
`once—daily administration or obtaining such target serum
`
`levels can be achieved with any formulation containing
`
`solely [R and DR components,
`
`let alone a once-daily
`
`doxycycline formulation with an IR/DR ratios [sic] of
`
`75:25 falling within the claims of the Chang '406patent.
`
`[Ex2016, 193 (emphasis in original).]
`
`23.
`
`Such statements show that Dr. Rudnic focuses only on limited
`
`language in the Ashley '932 publication and fails to consider the disclosures in the
`
`Ashley '854 application, which is incorporated by reference in the '932 publication,
`
`as well as the disclosures in the Sheth '748 patent.
`
`24.
`
`Similarly, Dr. Rudnic also views the Sheth '748 patent in isolation:
`
`In sum, there is no teaching, suggestion or motivation to
`
`use the Sheth '748 patent
`
`to formulate a once-daily
`
`fonnulation of doxycycline, and does not provide a
`
`skilled artisan with a reasonable expectation of success in
`
`doing so.
`
`[Ex2016, 11185.]
`
`25.
`
`Again, Dr. Rudnic focuses only on disclosures in the ‘748 patent and
`
`excludes from his analysis a POSA's understanding of the teachings in the Ashley
`
`‘932 publication and the '854 application, which is incorporated by reference-
`
`-16-
`
`Ex. 1114 is a redacted version of Ex. 1066
`
`

`

`Ex. 1114 is a redacted version of Ex. 1066
`Chseilfl?2013-00372
`
`Second Declaration of Glenn A. Van ankr'rk, PhD. (Exhibit 1066)
`
`26.
`
`Thus, Dr. Rudnic‘s analysis of the disclosures in the prior art differs
`
`from my own. Furthermore, Dr. Rudnic's analysis of the disclosures in the Ashley
`
`references and the Sheth '748 patent ignores a POSA's recourse to logic, judgment,
`
`and common sense. Instead, Dr. Rudnic's analysis implies that a POSA would have
`
`needed explication in every reference to understand the teachings therein.
`
`Therefore, 1 disagree with Dr. Rudnic's opinions on the disclosures and teachings
`
`in the prior art references.
`
`B.
`
`The Ashley references and Sheth '748 patent do not "teach away"
`from the claimed invention
`
`27.
`
`Dr. Rudnic states that the Ashley '932 publication and '854 application
`
`"teach away" from formulations having only IR and DR components. [Ex2016, 1111
`
`104, 123.] Dr. Rudnic also states that the Sheth '748 patent "teaches away" from
`
`formulations having a DR portion. [Ex2016, 1] 184.] 1 disagree with Dr. Rudnic that
`
`any of the aforementioned prior art references teaches away from the invention as
`
`claimed in the '406 patent.
`
`28.
`
`I understand t