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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`_______________________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`_______________________
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`AQUESTIVE THERAPEUTICS, INC.
`
`Petitioner
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`v.
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`HALE BIOPHARMA VENTURES, LLC
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`Patent Owner
`
`_______________________
`
`Case: IPR2019-00449
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`U.S. Patent No. 9,763,876 B2
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`_______________________
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`
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`DECLARATION OF NICHOLAS A. PEPPAS, Sc.D.
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`IN SUPPORT OF PETITION FOR INTER PARTES REVIEW
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`OF U.S. PATENT NO. 9,763,876
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`1
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`AQUESTIVE EXHIBIT 1041 PAGE 0001
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`U.S. Patent No. 9,763,876 B2
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`TABLE OF CONTENTS
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`Table of Contents
`I. PRELIMINARY STATEMENT .......................................................................... 5
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`II. BASIS FOR OPINIONS GIVEN ......................................................................... 6
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`III. BACKGROUND AND QUALIFICATIONS ....................................................13
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`IV. THE ‘876 PATENT’S FILING HISTORY....................................................22
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`V. EARLIEST APPEARANCE OF CERTAIN CLAIM ELEMENTS ..................35
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`A. Claim 1 (and All Claims Dependent Therefrom) ................................................37
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`B. Claims 8-10 ..........................................................................................................38
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`C. Claim 15 ...............................................................................................................40
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`D. Claims 30-32 ........................................................................................................42
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`E. Claim 33 ...............................................................................................................43
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`F. Claims 34-36 ........................................................................................................44
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`VI. THE PERSON OF ORDINARY SKILL IN THE ART ................................46
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`VII. OTHER RELEVANT CONSIDERATIONS ..............................................49
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`VIII. CLAIM CONSTRUCTION ........................................................................50
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`A. “Vitamin E” in Claims 1 and 30-33 .....................................................................51
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`B. “Bioavailability” in Claims 34, 35, and 36 ..........................................................53
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`C. “% (W/W)” in Claim 1 and “% (W/V)” in Claims 8, 15, and 30-33 ..................56
`IX. GENERAL STATE OF THE PRIOR ART – A VERY BRIEF HISTORY .57
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`X. THE ‘876 PATENT (EXHIBIT 1001) ...............................................................62
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`XI.
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`INTRANASAL ADMINISTRATION OF PHARMACEUTICALS ............63
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`A. Brief History of Intranasal Administration ..........................................................63
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`B. Benefits of Intranasal Administration ..................................................................64
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`C. Problems Associated with Intranasal Delivery ....................................................67
`2
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`AQUESTIVE EXHIBIT 1041 PAGE 0002
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`D. Solution #1 For Solving Permeation Problem – Increasing the Drug Solubility to
`Allow More Drug to Dissolve Per Unit Solvent/Formulation .............................70
`
`E. Solution #2 For Solving Permeation Problem – Using Penetration Enhancers to
`Increase the Permeability of the Nasal Mucosa With Respect to the Drug .........79
`
`1. Alkyl Glycosides In General ............................................................................84
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`2. Dodecyl Maltoside in Particular ......................................................................88
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`XII.
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`SUMMARY OF THE PRIOR ART REFERENCES .................................93
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`A. Cartt’865 (Exhibit 1010) ......................................................................................94
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`1. Problem to be Solved and Solution ..................................................................94
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`2. Cartt’865 (Exhibit 1010) Was Well Before Claims 8, 9, 10, 15, and 30-36 ...95
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`3. Cartt’865’s (Exhibit 1010) Teachings as Applied to Claim 1 of ‘876 Patent .95
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`4. Cartt’865 (Exhibit 1010) as Applied to ‘876 Patent’s Claims .......................105
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`B. Meezan‘962 (Exhibit 1011) ...............................................................................144
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`1. Problem to be Solved and Solution ................................................................145
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`2. Meezan‘962’s (Exhibit 1011) General Teachings .........................................146
`C. Jamieson (Exhibit 1012) ....................................................................................153
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`1. Problem to be Solved and Solution ................................................................153
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`2. Jamieson’s (Exhibit 1012) General Teachings ..............................................155
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`D. Ueda (Exhibit 1019) ...........................................................................................161
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`XIII. MOTIVATION TO COMBINE ................................................................165
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`XIV. THE ‘876 PATENT CLAIM CHARTS ....................................................167
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`XV. GROUND 1 – CLAIMS 8-10, 15, and 30-33 AS ANTICIPATED BY
`CARTT’865 (EXHIBIT 1010) .........................................................................169
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`A. Claims 8 and 15..................................................................................................169
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`B. Claims 9 And 10 ................................................................................................171
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`C. Claims 30-33 ......................................................................................................173
`3
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`AQUESTIVE EXHIBIT 1041 PAGE 0003
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`1. Claims 30-31 ..................................................................................................173
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`2. Claims 32-33 ..................................................................................................178
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`XVI. GROUND 2 – CLAIMS 8, 9, 10, 15, AND 30-33 AS OBVIOUS OVER
`CARTT’865 (EXHIBIT 1010) EITHER ALONE OR COMBINED WITH
`UEDA (EXHIBIT 1019) ...................................................................................182
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`A. Cartt’865 Alone ..................................................................................................182
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`B. A Posita Would Have Ample Motivation to Combine Cartt’865 With Ueda ...184
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`XVII. GROUND 3 – CLAIMS 34-36: THERE IS CLEAR MOTIVATION TO
`COMBINE CARTT’865 (EXHIBIT 1010) WITH MEEZAN‘962 (EXHIBIT
`1011) AND JAMIESON (EXHIBIT 1012) ......................................................190
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`XVIII. CONCLUDING OPINION ....................................................................199
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`XIX. APPENDIX A – CLAIMS CHART..........................................................200
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`A. Grounds 1 and 2 .................................................................................................200
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`B. Ground 3 ............................................................................................................209
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`4
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`AQUESTIVE EXHIBIT 1041 PAGE 0004
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`I.
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`I, Dr. Nicholas A. Peppas, do hereby make the following declaration:
`
`PRELIMINARY STATEMENT
`
`1.
`
`I have agreed to provide expert testimony in support of Aquestive, Inc.’s
`
`Petition for Inter Partes Review of U.S. Patent No. 9,763,876 B2, entitled
`
`“Administration of Benzodiazepine Compositions” (“the ‘876 Patent”).
`
`2.
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`I have been asked to provide my opinion in regards to the state of
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`technology relevant to the ‘876 Patent’s disclosure and its claims based on
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`knowledge existing prior to March 27, 2009, prior to June 14, 2011, and
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`prior to December 13, 2011.
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`3.
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`I have been asked to provide my opinion regarding whether one of ordinary
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`skill in the art at the relevant time would have understood that certain prior
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`art references, alone or in combination, disclose or teach each of the
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`elements and limitations recited in the claims of the ‘876 Patent. I have also
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`been asked to provide my opinion regarding whether a person of ordinary
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`skill in the art (a “POSITA”) would have been motivated or had a rationale
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`or reason to modify or combine those certain prior art references to arrive at
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`the elements recited in the claims of the ‘876 Patent. In my opinion, the
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`5
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`AQUESTIVE EXHIBIT 1041 PAGE 0005
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`references discussed below disclose or teach each of the elements and
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`limitations recited in the claims of the ‘876 Patent, and a POSITA would
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`have had a strong rationale to combine the references.
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`4.
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`I am being compensated for my time working on this case at my customary
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`rate of $650.00 per hour for all work performed on the case. My
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`compensation is not in any way related to the outcome of the case. I have no
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`financial interest in this proceeding, and the potential for any future financial
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`benefit is unaffected by the content of my testimony or the outcome of this
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`proceeding. I have reviewed the ‘876 Patent and am familiar with it.
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`
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`II.
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`BASIS FOR OPINIONS GIVEN
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`5.
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`In forming my opinion, I have relied on my own education, work
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`experiences and knowledge and my review of the following documents:
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`EXHIBIT NO.
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`1001
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`EXHIBIT DESCRIPTION
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`U.S. Patent No. 9,763,876, Administration Of
`Benzodiazepine Compositions, filed October 29, 2014
`(‘876 Patent)
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`6
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`AQUESTIVE EXHIBIT 1041 PAGE 0006
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`1002
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`1003
`
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`1004
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`1005
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`1006
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`1007
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`
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`File History for ‘876 Patent, Ser. No. 14/527,613 (‘876
`FH)
`1002 Part 1 - Pages 1-270
`1002 Part 2 - Pages 271-530
`
`U.S. Patent No. 8,895,546, Administration Of
`Benzodiazepine Compositions, filed June 13, 2012 (‘546
`Patent)
`
`File History for ‘546 Patent, Ser. No. 13/495,942 (‘546
`FH)
`1004 Part 1 – Pages 1-350
`1004 Part 2 – Pages 351-700
`1004 Part 3 – Pages 701-1050
`1004 Part 4 – Pages 1051-1400
`1004 Part 5 – Pages 1401-1750
`1004 Part 6 – Pages 1751-2100
`1004 Part 7 – Pages 2101-2450
`1004 Part 8 – Pages 2451-2681
`
`Provisional Patent Application No. 61/497,017, filed
`June 14, 2011 (‘017 Provisional)
`
`Provisional Patent Application No. 61/570,110, filed
`December 13, 2011 (‘110 Provisional)
`
`File History for Non-Provisional Patent Application
`Serial No. 12/413,439, filed March 27, 2009 (‘439 FH)
`1007 Part 1 – Pages 1-400
`1007 Part 2 – Pages 401-800
`1007 Part 3 – Pages 801-1200
`1007 Part 4 – Pages 1201-1600
`1007 Part 5 – Pages 1601-2000
`1007 Part 6 – Pages 2001-2400
`1007 Part 7 – Pages 2401-2800
`1007 Part 8 – Pages 2801-3200
`1007 Part 9 – Pages 3201-3488
`7
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`AQUESTIVE EXHIBIT 1041 PAGE 0007
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`1008
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`1009
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`1010
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`1011
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`1012
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`1013
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`1014
`
`Provisional Patent Application No. 61/040,558, filed
`March 28, 2008 (‘558 Provisional)
`
`Cartt et al., WO 2009/121039, Administration Of
`Benzodiazepine Compositions, published October 1,
`2009, International Filing Date March 27, 2009
`(PCT/US2009/038696) (Cartt ‘039)
`
`U.S. Patent Application Publication No. US
`2009/0258865, Administration of Benzodiazepine
`Compositions, Serial No. 12/413,439 (Cartt‘865)
`
`Meezan et al., U.S. Patent Application Publication No.
`US 2006/0046962, Absorption Enhancers for Drug
`Administration, Serial No. 11/127,786, published March
`2, 2006 (Meezan‘962)
`
`Jamieson et al., U.S. Patent Application Publication No.
`US 2008/0070904, Pharmaceutical Compositions of
`Benzodiazepines and Method of Use Thereof, Serial No.
`11/897,028, published March 20, 2008 (Jamieson)
`
`Sonne, U.S. Patent No. 6,193,985, Tocopherol
`Compositions For Delivery Of Biologically Active
`Agents, issued February 27, 2001 (Sonne)
`
`Gwozdz et al., WO 2009/120933, Pharmaceutical
`Solutions And Method For Solubilizing Therapeutic
`Agents, published October 1, 2009, International Filing
`Date March 27, 2009 (PCT/US2009/038518) (Gwozdz)
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`8
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`AQUESTIVE EXHIBIT 1041 PAGE 0008
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`1015
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`1016
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`1017
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`1018
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`1019
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`1020
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`1021
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`1022
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`1023
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`
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`Cartt et al., U.S. Patent Application Publication No. US
`2008/0279784, Nasal Administration Of
`Benzodiazepines, Serial No. 12/116,842, published
`November 13, 2008 (Cartt ‘784)
`
`Kee et al., U.S. Patent No. 5,369,095, Compositions And
`Method Comprising Substituted Glycosides As Mucus
`Membrane Permeation Enhancers, issued November 29,
`1994 (Kee)
`
`Cartt et al., WO 2008/137960, Nasal Administration Of
`Benzodiazepines, published November 13, 2008,
`International filing date May 7, 2008
`(PCT/US2008/062961) (Cartt ‘960)
`
`Tenta, U.S. Patent No. 3,949,072, Seborrheic Keratosis
`Treatment, issued April 6, 1976 (Tenta)
`
`Ueda et al., U.S. Patent No. 4,657,901, Pharmaceutical
`Composition, issued April 14, 1987 (Ueda)
`
`Meezan et al., U.S. Patent No. 5,661,130, Absorption
`Enhancers For Drug Administration, issued August 26,
`1997 (Meezan‘130)
`
`Merkus, U.S. Patent Application Publication No. US
`2005/0153956, Serial No. 11/034,474, published July 14,
`2005 (Merkus)
`
`Liversidge et al., U.S. Patent Application Publication No.
`US 2006/0198896, Serial No. 11/354,249, published
`September 7, 2006 (Liversidge)
`
`Ritschel, Handbook of Basic Pharmacokinetics, Chapter
`36 (Bioavailability and Bioequivalence), Drug
`Intelligence Publications, Illinois, 1992 (Ritschel)
`
`9
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`AQUESTIVE EXHIBIT 1041 PAGE 0009
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`1024
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`1025
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`1026
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`1027
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`1028
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`
`1029
`
`
`1030
`
`Osborne et al., Skin Penetration Enhancers Cited in the
`Technical Literature, Pharmaceutical Technology,
`November 1997 (Osborne)
`
`Lindhardt et al., Electroencephalographic effects and
`serum concentrations after intranasal and intravenous
`administration of diazepam to healthy volunteers,
`Blackwell Science Ltd Br J Clin Pharmacol, 52, 521-527,
`2001 (Lindhardt)
`
`Kibbe, editor, Handbook of Pharmaceutical Excipients,
`Third Edition (2000), American Pharmaceutical
`Association, Washington DC (Kibbe)
`
`Illum, Nasal drug delivery-possibilities, problems and
`solutions, Journal of Controlled Release 87 (2003) 187-
`198 (Illum)
`
`Ivaturi et al., Pharmacokinetics and tolerability of
`intranasal diazepam and midazolam in healthy adult
`volunteers, Acta Neurol Scand. 2009 Nov;120(5):353-7.
`doi: 10.1111/j.1600-0404.2009.01170.x. Epub 2009 May
`14 (Ivaturi)
`
`O’Dell et al., School nurses’ experience with
`administration of rectal diazepam gel for seizures, J Sch
`Nurs., June 2007, 23(3):166-9 (O’Dell)
`
`Gizurarson et al., Intranasal Administration of Diazepam
`Aiming at the Treatment of Acute Seizures: Clinical
`Trials in Healthy Volunteers, Biological and
`Pharmaceutical Bulletin, Volume 22 (1999) Issue 4
`Pages 425-427 (Gizurarson)
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`10
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`AQUESTIVE EXHIBIT 1041 PAGE 0010
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`1032
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`1033
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`1034
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`1035
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`1036
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`1037
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`U.S. Patent No. 9,763,876 B2
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`Rowe et al., editors, Handbook of Pharmaceutical
`Excipients, Fourth Edition (2003), Monographs for
`“Alcohol” (i.e., ethanol), “Alpha Tocopherol”, “Benzyl
`Alcohol”, “Glycerin”, “Olive Oil”, “Polyethylene
`Glycol”, “Propylene Glycol”, “Sesame Oil”, and
`“Triacetin”, American Pharmaceutical Association,
`Washington DC (Rowe)
`
`Edman [II] et al., Microspheres as a nasal delivery
`system for peptide drugs, Journal of Controlled Release,
`Vol. 21 (1992) 165-172 (Edman II)
`
`French et al., Pharmacopeial Standards and
`Specifications for Bulk Drugs and Solid Oral Dosage
`Forms, Journal of Pharmaceutical Sciences, December
`1967, Vol. 56(12):1622-1641 (French)
`
`Edman [I] et al., (D) Routes of Delivery: Case Studies -
`(1) Nasal delivery of peptide drugs, Advanced Drug
`Delivery Reviews, 8 (1992) 165-177 (Edman I)
`
`Davis, Delivery of peptide and non-peptide drugs
`through the respiratory tract, Pharmaceutical Science &
`Technology Today, Vol. 2, No. 11 November 1999,
`pages 450-456 (Davis)
`
`Deshmukh et al., Lorazepam in the Treatment of
`Refractory Neonatal Seizures, Am J Dis Child.
`1986;140(10):1042-1044 (Deshmukh)
`
`Colombo, Mucosal Drug Delivery, Nasal, pp. 592-605,
`Vol 2, Encyclopedia of Controlled Drug Delivery
`(Mathiowitz, editor), John Wiley & Sons, 1999
`(Colombo)
`
`
`
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`AQUESTIVE EXHIBIT 1041 PAGE 0011
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`1038
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`1039
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`1040
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`1041
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`1042
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`1043
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`1044
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`1045
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`
`
`Bara, U.S. Patent Application Publication No.
`US/2006/0178290, Serial No. 10/563,967, published
`August 10, 2006 (Bara)
`
`Behl et al., Effects of physicochemical properties and
`other factors on systemic nasal drug delivery, Advanced
`Drug Delivery Reviews 29 (1998) 89–116 (Behl)
`
`File History for EP 128 01372.9, based on WO
`2012/174158 and PCT/US2012/042311
`1040 Part 1 - Pages 1-250
`1040 Part 2 - Pages 251-500
`1040 Part 3 – Pages 501-662
`
`(this Declaration)
`
`PDR 54th Edition 2000, DIASTAT® (diazepam rectal
`gel); MIACALCIN® (Calcitonin Nasal Spray);
`VALIUM® (diazepam injection), Physicians’ Desk
`Reference.
`
`Knoester, et al., Pharmacokinetics and
`pharmacodynamics of midazolam administered as a
`concentrated intranasal spray. A study in healthy
`volunteers, Br J Clin Pharmacol. 2002 May;53(5):501-7.
`
`USP NF 2003, The United States Pharmacopeia, The
`National Formulary, United States Pharmacopeial
`Convention, Inc. (“USP/NF 2003”).
`
`Maitani, et al., Design of ocular/lacrimal and nasal
`systems through analysis of drug administration and
`absorption, Journal of Controlled Release, Volume 49,
`Issues 2–3, 15 December 1997, Pages 185-192.
`
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`AQUESTIVE EXHIBIT 1041 PAGE 0012
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`1047
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`1048
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`U.S. Patent No. 9,763,876 B2
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`Provisional Patent Application No. 61/040,281,
`Pharmaceutical Solutions and Method for Solubilizing
`Therapeutics Agents, filed March 28, 2008, Gwozdz,
`(Gwozdz ‘281 Provisional)
`
`Gwozdz Assignment of Provisional in Non-Provisional
`Case, dated April 21, 2008, recorded September 23, 2010
`(Gwozdz Assignment).
`
`Kagatani, et al., U.S. Patent No. 4,690,952,
`Pharmaceutical Compositions for Nasal administration
`Comprising Calcitonin and an Absorption-Promoting
`Substance, issued September 1, 1987 (Kagatani).
`
`
`
`
`BACKGROUND AND QUALIFICATIONS
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`III.
`
`6.
`
`I am the Cockrell Family Regents Chair (i.e., Chaired Professor) in
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`Engineering at the University of Texas at Austin with appointments in the
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`Departments of Chemical Engineering, Biomedical Engineering of the
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`Cockrell College of Engineering, and the Division of Molecular
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`Pharmaceutics and Drug Delivery of the College of Pharmacy of the
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`University of Texas at Austin since January 1, 2003. I am also a tenured full
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`professor with a joint appointment in the Department of Pediatrics at the
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`Dell Medical School of the same University. From September 2009 to
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`August 2015, I was also the Chairman of the Biomedical Engineering
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`Department in the same University.
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`7.
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`Previously, I was the Showalter Distinguished Professor of Chemical and
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`Biomedical Engineering at Purdue University, in West Lafayette, Indiana,
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`with joint appointments in the School of Chemical Engineering and in the
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`Department of Biomedical Engineering. I joined Purdue University in 1976.
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`8.
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`I have degrees in chemical engineering from the National Technical
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`University of Athens, Greece (Dipl. Eng., 1971) and the Massachusetts
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`Institute of Technology - MIT (Sc.D., 1973).
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`9.
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`I did one year of postdoctoral work with Professors Clark Colton, Kenneth
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`Smith and Robert Lees at the Arteriosclerosis Center of the Massachusetts
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`Institute of Technology (1975-76).
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`10.
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`I am an elected member of the (US) National Academy of Engineering, the
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`(US) National Academy of Medicine, the American Academy of Arts and
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`Sciences, the National Academy of Inventors, the Academy of Engineering,
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`Medicine and Sciences of Texas, the Chinese Academy of Medicine, the
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`National Academy of Pharmacy of France, the Royal Academy of Pharmacy
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`of Spain, the Academy of Athens, Greece and the International Academy of
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`Medical and Biological Engineering.
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`11.
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`I have received honorary doctorate degrees from the University of Ghent,
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`Belgium (1999), the University of Parma, Italy (1999), the University of
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`Athens (2000), and the University of Ljubljana, Slovenia (2012), granted by
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`their respective Faculties of Pharmacy. The doctorate from the University of
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`Parma also carries the title “Doctor of Pharmacy”. I have also received an
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`honorary doctorate (in Chemical Engineering) from the University of Patras
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`(2015) and the National Technical University of Athens (2017).
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`12.
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`I have served as a Visiting Professor at the Faculty of Pharmacy of the
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`University of Geneva, Switzerland (Fall 1982), the Department of Chemical
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`Engineering of the California Institute of Technology (Spring 1983), the
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`Faculty of Pharmacy of the University of Paris-Sud (Fall 1986), the
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`Department of Pharmacy of the University of Parma, Italy (Fall 1987), the
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`School of Pharmacy of the Hoshi University of Tokyo, Japan (Spring 1994),
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`the School of Pharmacy of the Hebrew University of Jerusalem, Israel
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`(Spring 1994), the Departments of Pharmacy and Materials Science of the
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`University of Naples, Italy (May 1996), the Department of Pharmacy of the
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`Free University of Berlin, Germany (January-March 2001), the Department
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`of Pharmacy of the Complutense University of Madrid, Spain (March-May
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`2001) and the Department of Materials Science of the Nanyang
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`Technological Institute of Singapore (2006).
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`13. My teaching assignments at the University of Texas in the past ten years
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`have been courses on “Polymer Science and Engineering”, “Advances in
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`Biomedical Engineering”, “Advances in Biomaterials Science and
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`Engineering”, “Bionanotechnology”, “Kinetics and Reaction Engineering”,
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`and “Mass Transfer”.
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`14. Starting in 1979, I developed and taught, along with Professors Robert
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`Langer of MIT, Frank Szoka of the University of California at San Francisco
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`and others, the course “Advances in Controlled Release Technology”
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`offered every summer at MIT. This is a five-day course offered to industrial
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`and university researchers who do not have a sufficient background in the
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`preparation and characterization of drug delivery systems such as tablets,
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`films, capsules and microspheres, and related pharmaceutical systems. The
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`past summer (2018) was the 40h year I taught this course.
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`15. My research contributions have been in several areas of drug and protein
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`delivery including therapeutic agents for treatment of diabetes, cancer,
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`autoimmune diseases and cardiovascular problems, biomaterials,
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`bionanotechnology, mass transfer, kinetics and reaction engineering,
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`polymers and biomedical engineering.
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`16. Since 1979, I have also worked on the design, development and
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`investigation of the pharmaceutical and medical applications of bioadhesive
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`and mucoadhesive polymers and drug delivery formulations based on
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`mucoadhesive polymers. I have published numerous papers on the design
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`and use of mucoadhesive polymers and I have participated in the
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`development of a number of products that incorporated mucoadhesive
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`materials in order to function as adhesives.
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`17. For over forty years I have been involved with the preparation,
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`characterization and evaluation of the behavior of hydrophilic polymers and
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`their crosslinked networks known as hydrogels used in controlled release
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`devices, especially in controlled delivery of drugs, peptides and proteins. My
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`laboratory pioneered the use of these polymer carriers in drug delivery
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`applications and I have extensive experience in formulation, preparation and
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`testing of polymer formulations, including sustained release formulations. I
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`received the 2012 National Academy of Engineering Founders Award in
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`recognition of this pioneering work in the field of drug delivery. The
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`National Academy of Engineering citation for the Founders Award lists “For
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`contributions to biomedical and drug delivery applications of polymer
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`networks and hydrogels and for leadership in the bioengineering
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`community”.
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`18.
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`I am the author of approximately 1,400 publications, 450 abstracts, and
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`approximately 35 issued or pending US and international patents.
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`19.
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`I am the coauthor or coeditor of 37 books and volumes, including the three-
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`volume monograph “Hydrogels in Medicine and Pharmacy” (CRC Press,
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`1987).
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`20.
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`I am the Editor-in-Chief of “Regenerative Biomaterials”, Deputy Editor of
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`the journal “Science Advances”, the journal “Biomedical Microdevices” and
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`the Biomedical Engineering Book Series of Cambridge University Press.
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`21.
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`I sit on the editorial boards of numerous journals, including the “Journal of
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`Controlled Release”, “Advanced Drug Delivery Reviews”, “International
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`Journal of Pharmaceutics”, “Journal of Applied Polymer Science”, “Journal
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`of Biomedical Materials Research”, “Journal of Biomaterials Science”,
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`“Journal of Drug Delivery Science and Technology”, “European Journal of
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`Pharmaceutics and Biopharmaceutics”, and “Nanomedicine”.
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`22. From 2008-2016, I was the President of the 26,000-member International
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`Union of Societies of Biomaterials Science and Engineering.
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`23. Since 1981, I have been one of the leaders of the 4,000-member Controlled
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`Release Society. I guided it as its President in 1987-88, and organized the
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`1985 (Geneva) and 1993 (Washington) meetings of the Society as well as
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`many other conferences and workshops. The Controlled Release Society is
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`the world’s leading Society for technical information in the field of
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`controlled release; it is a leading group addressing controlled release and
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`bioadhesive controlled release systems. In July 2017 I received the CRS
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`Distinguished Service Award.
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`24. Since 1975 I have been also active in the Society for Biomaterials. I was
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`elected as President-elect in April 2002 and I took over as its President in
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`April 2003 by automatic succession. The Society for Biomaterials is the
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`world’s premier scientific and technical organization for the dissemination
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`of knowledge related to biomaterials for medical devices, and polymers in
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`pharmaceutical technology.
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`25.
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`I am Past Chair of the Engineering section of the American Association for
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`the Advancement of Science (AAAS).
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`26.
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`I have received numerous US and international awards that are awarded by
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`the leading world organizations of scientific and technical excellence. These
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`include the 2012 Founders Award of the National Academy of Engineering,
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`the 2010 Acta Biomaterialia Gold Medal; the 2010 Maurice-Marie Janot
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`Award, of the French and German Pharmaceutical Associations APGI and
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`APV; the 2018 Distinguished Pharmaceutical Scientist Award of the
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`American Association of Pharmaceutical Scientists (AAPS, the highest
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`research recognition of the most important pharmaceutical association of the
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`USA); the 2002 Dale Wurster Award in Pharmaceutics also from AAPS; the
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`2002 Eurand Award for Life Achievements in Oral Drug Delivery (the
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`highest scientific recognition in oral delivery by the Controlled Release
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`Society); the 2010 Distinguished Achievement Award of the Biomedical
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`Engineering Society; the 2010 Acta Biomaterialia Gold Medal; the 2010
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`Distinguished Scientist of the Southern Universities Research Association;
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`the 2008 Pierre Galletti Award of the American Institute of Medical and
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`Biological Engineering; the 2008 Institute Lecturer Award of the American
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`Institute of Chemical Engineers; the 2008 Jay Bailey Award of the
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`Biological Engineering Society; the 2000 General Electric Senior Research
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`Award of ASEE recognizing the best engineering researcher of the U.S.; the
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`1999 Research Achievement Award in Pharmaceutical Technology of the
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`American Association of Pharmaceutical Scientists (the highest scientific
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`recognition in pharmaceutical technology); the 1995 International
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`Pharmaceutical Technology Medal of the International Pharmaceutical
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`Association (APV); the 1994 Pharmaceutical and Bioengineering Award of
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`the American Institute of Chemical Engineers, and many others.
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`27.
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`I have supervised the theses of 109 Ph.D. students, including 54 current
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`professors in other Universities, and many other students, postdoctoral
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`fellows and visiting scientists. My former students include many industrial
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`leaders in chemical, pharmaceutical or medical companies. Several of them
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`are in senior administrative positions.
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`28. A copy of my curriculum vitae, including a list of publications I authored is
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`attached as Exhibit A.
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`IV.
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`THE ‘876 PATENT’S FILING HISTORY
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`29. The ‘876 Patent states that it is a continuation of application No. 13/495,942,
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`filed on June 13, 2012, now U.S. Patent No. 8,895,546 (henceforth
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`designated “the ‘546 patent”), which in turn is a continuation-in-part of
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`application No. 12/413,439 (“the ‘439 application”), filed on March 27,
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`2009, published as US 2009/0258865 (“Cartt’865”)1 on October 15, 2009,
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`which in turn claims priority to U.S. provisional application No. 61/040,558
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`(“the ‘558 Provisional”), filed March 28, 2008. The ‘876 Patent also states
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`that the ‘546 Patent also claims priority to U.S. provisional application No.
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`61/497,017 (“the ‘017 Provisional”), filed on June 14, 2011, and also to U.S.
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`provisional application No. 61/570,110 (“the ‘110 Provisional”), filed
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`December 13, 2011. I have been advised that the timelines on the following
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`pages depict the chain of applications:
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`1
`For the remainder of my Declaration, I will generally refer to both the ‘439
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`application and its published version, i.e., Cartt’865, as Cartt’865 for
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`simplicity (unless otherwise indicated).
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`Provisionals
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`Serial No. 61/040,558
`Filed: March 28, 2008
`‘558 Provisional
`Exhibit 1008
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`Serial No. 61/497,017
`Filed: June 14, 2011
` ‘017 Provisional
`Exhibit 1005
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`Serial. No. 61/570,110
`Filed: Dec. 13, 2011
`‘110 Provisional
`Exhibit 1006
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`U.S. Patent No. 9,763,876 B2
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`Non-Provisionals
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`Non-Provisional
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`FIRST DISCLOSURE OF
`ALKYL GLYCOSIDES
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`Serial No. 12/413,439
`Filed: March 27, 2009
`US 2009/0258865 – Exhibit 1010
`(abandoned)
`Published: Oct. 15, 2009
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`
`Non-Provisional
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`C-I-P
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`Serial No. 13/495,942
`Filed: June 13, 2012
`USP 8,895,546
`Exhibit 1003
`Issued: Nov. 25, 2014
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`Continuation
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`Serial No. 14/527,613
`Filed: October 29, 2014
`USP 9,763,876 – Exhibit 1001
`Issued: Sept. 19, 2017
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`Serial No. 61/040,558
`Filed: March 28, 2008
`‘558 Provisional
`Exhibit 1008
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`Serial No. 12/413,439
`Filed: March 27, 2009
`US 2009/0258865
`Exhibit 1010
`(abandoned)
`Published: Oct. 15, 2009
`• FIRST DISCLOSURE OF ALKYL
`GLYCOSIDES
`• SUFFICIENT DISCLOSURE TO
`ANTICIPATE CLAIMS 8-10, 15, 30-
`33 UNDER § 102 AND INVALIDATE
`CLAIMS 34-36 UNDER § 103
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`Serial No. 61/497,017
`Filed: June 14, 2011
` ‘017 Provisional
`Exhibit 1005
`FIRST DISCLOSURE OF,
`INTER ALIA:
`1.SPECIFIC
`RANGES/AMOUNTS OF
`ETHANOL/BENZYL
`ALCOHOL
`2.UPPER RANGES OF
`DIAZEPAM;
`3.VITAMIN E RANGES;
`4.BIOAVAILABILITY
`DATA/RANGES
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`C-I-P
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`24
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`Serial. No. 61/570,110
`Filed: Dec. 13, 2011
`‘110 Provisional
`Exhibit 1006
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`Serial No. 13/495,942
`Filed: June 13, 2012
`USP 8,895,54