UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`
`
`
`COALITION FOR AFFORDABLE DRUGS VII LLC,
`Petitioner,
`
`v.
`
`HORIZON PHARMA USA, INC.,
`Patent Owner.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`IPR2015-01718
`Patent 8,945,621
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`DECLARATION OF LEON SHARGEL, PH.D., R.PH.
`
`
`
`CFAD EXHIBIT 1003
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`TABLE OF CONTENTS
`
`I. 
`
`Introduction and Bases for Opinions ........................................................... 1 
`
`A.  Qualifications ........................................................................................ 1 
`
`B.  Materials Reviewed ............................................................................... 4 
`
`C. 
`
`Legal Principles Used In Analysis ........................................................ 7 
`
`II. 
`
`Background .................................................................................................. 14 
`
`A. 
`
`B. 
`
`C. 
`
`State of the Art .................................................................................... 14 
`
`Overview of the ’621 Patent ................................................................ 26 
`
`Person of Ordinary Skill in the Art (POSA) ....................................... 27 
`
`III.  Claim Construction ..................................................................................... 28 
`
`A. 
`
`B. 
`
`C. 
`
`D. 
`
`“Low Dose Aspirin” and “LDA” ........................................................ 29 
`
`“Unit Dose Form” and “Unit Dosage Form” ...................................... 29 
`
`All Remaining Terms .......................................................................... 30 
`
`The Invalidity Grounds ....................................................................... 30 
`
`1. 
`
`2. 
`
`Ground 1: Claims 1-16 Are Obvious Under 35 U.S.C. §
`103(a) ........................................................................................ 30 
`
`Ground 2: Claims 1-16 Are Obvious Under 35 U.S.C. §
`103(a) ........................................................................................ 31 
`
`IV.  Ground 1: Plachetka in view of Graham and Goldstein Renders
`Obvious Claims 1-16 .................................................................................... 31 
`
`A.  A POSA Would Have Combined Plachetka, Graham, and
`Goldstein ............................................................................................. 31 
`
`B. 
`
`Claim 1: ............................................................................................... 34 
`
`i
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
`
`A method of reducing the incidence of NSAID-
`associated gastric ulcers in patients taking low dose
`aspirin who are at risk of developing such ulcers, .................... 34 
`
`wherein the method comprises administering to said
`patient in need thereof a pharmaceutical composition in
`unit dose form comprising: ....................................................... 35 
`
`(a) 20 mg of esomeprazole, or pharmaceutically
`acceptable salt thereof, .............................................................. 35 
`
`in a form and route sufficient to raise the gastric pH of
`said patient to at least 3.5 upon administration of one or
`more of said unit dose forms and .............................................. 36 
`
`(b) 500 mg of naproxen, or pharmaceutically acceptable
`salt thereof; ................................................................................ 36 
`
`wherein said unit dose form provides for coordinated
`release of the esomeprazole and the naproxen, ......................... 36 
`
`wherein at least a portion of said esomeprazole, or
`pharmaceutically acceptable salt thereof, is released
`independent of the pH of the surrounding medium, ................. 37 
`
`wherein the unit dosage form releases less than 10% of
`the naproxen or a pharmaceutically acceptable salt
`thereof after 2 hours when tested using the USP Paddle
`Method in 1000 ml of 0.1N HCl at 75 rpm at 37º C. +/-
`0.5º C., ....................................................................................... 37 
`
`wherein said pharmaceutical composition in unit dose
`form reduces the incidence of NSAID-associated ulcers
`in said patient and ..................................................................... 38 
`
`10.  wherein administration of the unit dose form is more
`effective at reducing the incidence of the NSAID-
`associated ulcers in patients taking LDA than in patients
`not taking LDA who are administered the unit dose form. ...... 39 
`
`ii
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`C. 
`
`D. 
`
`E. 
`
`F. 
`
`G. 
`
`H. 
`
`Claim 2: The method according to claim 1, wherein the risk is
`associated with chronic NSAID treatment. ......................................... 41 
`
`Claim 3: The method according to claim 1, wherein said patient
`is treated for a disease or disorder selected from pain and
`inflammation. ...................................................................................... 42 
`
`Claim 4: The method according to claim 1, wherein said patient
`is treated for a disease or disorder selected from osteoarthritis,
`rheumatoid arthritis, ankylosing spondylitis, and a combination
`thereof. ................................................................................................. 42 
`
`Claim 5: The method according to claim 1, wherein said unit
`dose form is at least about 95% free of sodium bicarbonate. ............. 42 
`
`Claim 6: The method according to claim 1, wherein said unit
`dose form begins to release said naproxen, or a
`pharmaceutically acceptable salt thereof, when the pH of the
`surrounding medium is at about 4.0 or greater. .................................. 43 
`
`Claim 7: The method according to claim 1, wherein said unit
`dose form begins to release said naproxen, or a
`pharmaceutically acceptable salt thereof, when the pH of the
`surrounding medium is at about 4.5 or greater. .................................. 44 
`
`I. 
`
`Claim 8: ............................................................................................... 44 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`A method of reducing the incidence of NSAID-
`associated gastric ulcers in patients taking low dose
`aspirin who are at risk of developing such ulcers, .................... 45 
`
`wherein the method comprises administering to the
`patient a pharmaceutical composition in unit dosage form
`suitable for oral administration comprising: ............................. 45 
`
`(a) 20 mg of esomeprazole or a pharmaceutically
`acceptable salt thereof, .............................................................. 45 
`
`that is immediately soluble when the dosage form is
`placed in an aqueous medium, independent of pH, .................. 45 
`
`iii
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
`
`in an amount effective to raise the gastric pH of the
`patient to at least 3.5 upon administration of one or more
`of the unit dosage forms, and .................................................... 46 
`
`(b) 500 mg of naproxen or pharmaceutically acceptable
`salt thereof, ................................................................................ 46 
`
`wherein the unit dosage form releases less than 10% of
`the naproxen or a pharmaceutically acceptable salt
`thereof after 2 hours when tested using the USP Paddle
`Method in 1000ml of 0.1N HCl at 75 rpm at 37º C. +/-
`0.5º C.; ....................................................................................... 46 
`
`wherein said pharmaceutical composition in unit dose
`form reduces the incidence of NSAID-related ulcers in
`said patient and .......................................................................... 46 
`
`wherein administration of the unit dose form is more
`effective at reducing the incidence of the NSAID-
`associated ulcers in patients taking LDA than in patients
`not taking LDA who are administered the unit dose form. ...... 47 
`
`J. 
`
`K. 
`
`L. 
`
`Claim 9: The method of claim 8, wherein the risk is associated
`with chronic NSAID treatment. .......................................................... 47 
`
`Claim 10: The method of claim 8, wherein the patient is treated
`for a disease or disorder selected from pain, inflammation,
`osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and
`combinations thereof. .......................................................................... 47 
`
`Claim 11: The method of claim 8, wherein the pharmaceutical
`composition is formulated to be administered to a patient twice
`daily. .................................................................................................... 48 
`
`M.  Claim 12: The method according to claim 8, wherein the unit
`dosage form further comprises a pharmacologically inert water
`soluble coating or film. ........................................................................ 48 
`
`N. 
`
`Claim 13: The method of claim 12, wherein the inert coating or
`film comprises a water soluble sugar. ................................................. 49 
`
`iv
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`O. 
`
`Claim 14: The method of claim 8, wherein administration of the
`unit dosage form is more effective at reducing the risk of ulcer
`than treatment with enteric coated naproxen or a
`pharmaceutically acceptable salt thereof. ........................................... 50 
`
`P. 
`
`Claim 15: ............................................................................................. 51 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`A method of reducing the incidence of NSAID-
`associated gastric ulcers in patients taking low dose
`aspirin (LDA) who are at risk of developing such ulcers, ........ 51 
`
`wherein the method comprises administering to said
`patient in need thereof twice a day for 1 month a
`pharmaceutical composition in unit dose form
`comprising: ................................................................................ 51 
`
`(a) 20 mg of esomeprazole, or pharmaceutically
`acceptable salt thereof, .............................................................. 52 
`
`in a form and route sufficient to raise the gastric pH of
`said patient to at least 3.5 upon administration of one or
`more of said unit dose forms, and ............................................. 52 
`
`(b) 500 mg of naproxen, or pharmaceutically acceptable
`salt thereof; ................................................................................ 52 
`
`wherein said unit dose form provides for coordinated
`release of the esomeprazole and the naproxen, ......................... 53 
`
`wherein at least a portion of said esomeprazole, or
`pharmaceutically acceptable salt thereof, is released
`independent of the pH of the surrounding medium, ................. 53 
`
`wherein the unit dosage form releases less than 10% of
`the naproxen or a pharmaceutically acceptable salt
`thereof after 2 hours when tested using the USP Paddle
`Method in 1000 ml of 0.1N HCl at 75 rpm at 37º C. +/-
`0.5º C., ....................................................................................... 53 
`
`v
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`9. 
`
`wherein administration of the unit dose form is more
`effective at reducing the incidence of the NSAID-
`associated gastric ulcers in patients taking LDA than in
`patients not taking LDA who are administered the unit
`dose form. .................................................................................. 53 
`
`Q. 
`
`Claim 16: ............................................................................................. 53 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`A method of reducing the incidence of NSAID-
`associated gastric ulcers in patients taking low dose
`aspirin (LDA) who are at risk of developing such ulcers, ........ 54 
`
`wherein the method comprises administering to said
`patient in need thereof twice a day for 3 months a
`pharmaceutical composition in unit dose form
`comprising: ................................................................................ 54 
`
`(a) 20 mg of esomeprazole, or pharmaceutically
`acceptable salt thereof, .............................................................. 55 
`
`in a form and route sufficient to raise the gastric pH of
`said patient to at least 3.5 upon administration of one or
`more of said unit dose forms, and ............................................. 55 
`
`(b) 500 mg of naproxen, or pharmaceutically acceptable
`salt thereof; ................................................................................ 55 
`
`wherein said unit dose form provides for coordinated
`release of the esomeprazole and the naproxen such that: ......... 55 
`
`wherein at least a portion of said esomeprazole, or
`pharmaceutically acceptable salt thereof, is released
`independent of the pH of the surrounding medium, ................. 56 
`
`wherein the unit dosage form releases less than 10% of
`the naproxen or a pharmaceutically acceptable salt
`thereof after 2 hours when tested using the USP Paddle
`Method in 1000 ml of 0.1N HCl at 75 rpm at 37º C. +/-
`0.5º C., ....................................................................................... 56 
`
`vi
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`9. 
`
`wherein administration of the unit dose form is more
`effective at reducing the incidence of said ulcers in
`patients taking LDA than in patients not taking LDA who
`are administered the unit dose form. ......................................... 56 
`
`R. 
`
`Conclusion ........................................................................................... 56 
`
`V.  Ground 2: Plachetka Renders Obvious Claims 1-16 ............................... 56 
`
`A. 
`
`Claim 1: ............................................................................................... 57 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`A method of reducing the incidence of NSAID-
`associated gastric ulcers in patients taking low dose
`aspirin who are at risk of developing such ulcers, .................... 57 
`
`wherein the method comprises administering to said
`patient in need thereof a pharmaceutical composition in
`unit dose form comprising: ....................................................... 58 
`
`(a) 20 mg of esomeprazole, or pharmaceutically
`acceptable salt thereof, .............................................................. 58 
`
`in a form and route sufficient to raise the gastric pH of
`said patient to at least 3.5 upon administration of one or
`more of said unit dose forms and .............................................. 59 
`
`(b) 500 mg of naproxen, or pharmaceutically acceptable
`salt thereof; ................................................................................ 59 
`
`wherein said unit dose form provides for coordinated
`release of the esomeprazole and the naproxen, ......................... 59 
`
`wherein at least a portion of said esomeprazole, or
`pharmaceutically acceptable salt thereof, is released
`independent of the pH of the surrounding medium, ................. 60 
`
`wherein the unit dosage form releases less than 10% of
`the naproxen or a pharmaceutically acceptable salt
`thereof after 2 hours when tested using the USP Paddle
`Method in 1000 ml of 0.1N HCl at 75 rpm at 37º C. +/-
`0.5º C., ....................................................................................... 60 
`
`vii
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`9. 
`
`wherein said pharmaceutical composition in unit dose
`form reduces the incidence of NSAID-associated ulcers
`in said patient and ..................................................................... 61 
`
`10.  wherein administration of the unit dose form is more
`effective at reducing the incidence of the NSAID-
`associated ulcers in patients taking LDA than in patients
`not taking LDA who are administered the unit dose form. ...... 62 
`
`Claim 2: The method according to claim 1, wherein the risk is
`associated with chronic NSAID treatment. ......................................... 63 
`
`Claim 3: The method according to claim 1, wherein said patient
`is treated for a disease or disorder selected from pain and
`inflammation. ...................................................................................... 64 
`
`Claim 4: The method according to claim 1, wherein said patient
`is treated for a disease or disorder selected from osteoarthritis,
`rheumatoid arthritis, ankylosing spondylitis, and a combination
`thereof. ................................................................................................. 64 
`
`Claim 5: The method according to claim 1, wherein said unit
`dose form is at least about 95% free of sodium bicarbonate. ............. 64 
`
`Claim 6: The method according to claim 1, wherein said unit
`dose form begins to release said naproxen, or a
`pharmaceutically acceptable salt thereof, when the pH of the
`surrounding medium is at about 4.0 or greater. .................................. 65 
`
`Claim 7: The method according to claim 1, wherein said unit
`dose form begins to release said naproxen, or a
`pharmaceutically acceptable salt thereof, when the pH of the
`surrounding medium is at about 4.5 or greater. .................................. 65 
`
`B. 
`
`C. 
`
`D. 
`
`E. 
`
`F. 
`
`G. 
`
`H. 
`
`Claim 8: ............................................................................................... 66 
`
`1. 
`
`A method of reducing the incidence of NSAID-
`associated gastric ulcers in patients taking low dose
`aspirin who are at risk of developing such ulcers, .................... 66 
`
`viii
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`7. 
`
`8. 
`
`9. 
`
`wherein the method comprises administering to the
`patient a pharmaceutical composition in unit dosage form
`suitable for oral administration comprising: ............................. 66 
`
`(a) 20 mg of esomeprazole or a pharmaceutically
`acceptable salt thereof, .............................................................. 66 
`
`that is immediately soluble when the dosage form is
`placed in an aqueous medium, independent of pH, .................. 66 
`
`in an amount effective to raise the gastric pH of the
`patient to at least 3.5 upon administration of one or more
`of the unit dosage forms, and .................................................... 67 
`
`(b) 500 mg of naproxen or pharmaceutically acceptable
`salt thereof, ................................................................................ 67 
`
`wherein the unit dosage form releases less than 10% of
`the naproxen or a pharmaceutically acceptable salt
`thereof after 2 hours when tested using the USP Paddle
`Method in 1000ml of 0.1N HCl at 75 rpm at 37º C. +/-
`0.5º C.; ....................................................................................... 67 
`
`wherein said pharmaceutical composition in unit dose
`form reduces the incidence of NSAID-related ulcers in
`said patient and .......................................................................... 68 
`
`wherein administration of the unit dose form is more
`effective at reducing the incidence of the NSAID-
`associated ulcers in patients taking LDA than in patients
`not taking LDA who are administered the unit dose form. ...... 68 
`
`I. 
`
`J. 
`
`Claim 9: The method of claim 8, wherein the risk is associated
`with chronic NSAID treatment. .......................................................... 68 
`
`Claim 10: The method of claim 8, wherein the patient is treated
`for a disease or disorder selected from pain, inflammation,
`osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and
`combinations thereof. .......................................................................... 68 
`
`ix
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`K. 
`
`L. 
`
`Claim 11: The method of claim 8, wherein the pharmaceutical
`composition is formulated to be administered to a patient twice
`daily. .................................................................................................... 68 
`
`Claim 12: The method according to claim 8, wherein the unit
`dosage form further comprises a pharmacologically inert water
`soluble coating or film. ........................................................................ 69 
`
`M.  Claim 13: The method of claim 12, wherein the inert coating or
`film comprises a water soluble sugar. ................................................. 70 
`
`N. 
`
`Claim 14: The method of claim 8, wherein administration of the
`unit dosage form is more effective at reducing the risk of ulcer
`than treatment with enteric coated naproxen or a
`pharmaceutically acceptable salt thereof. ........................................... 71 
`
`O. 
`
`Claim 15: ............................................................................................. 71 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`A method of reducing the incidence of NSAID-
`associated gastric ulcers in patients taking low dose
`aspirin (LDA) who are at risk of developing such ulcers, ........ 72 
`
`wherein the method comprises administering to said
`patient in need thereof twice a day for one month a
`pharmaceutical composition in unit dose form
`comprising: ................................................................................ 72 
`
`(a) 20 mg of esomeprazole, or pharmaceutically
`acceptable salt thereof, .............................................................. 73 
`
`in a form and route sufficient to raise the gastric pH of
`said patient to at least 3.5 upon administration of one or
`more of said unit dose forms, and ............................................. 73 
`
`(b) 500 mg of naproxen, or pharmaceutically acceptable
`salt thereof; ................................................................................ 73 
`
`wherein said unit dose form provides for coordinated
`release of the esomeprazole and the naproxen, ......................... 73 
`
`x
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`7. 
`
`8. 
`
`9. 
`
`wherein at least a portion of said esomeprazole, or
`pharmaceutically acceptable salt thereof, is released
`independent of the pH of the surrounding medium, ................. 73 
`
`wherein the unit dosage form releases less than 10% of
`the naproxen or a pharmaceutically acceptable salt
`thereof after 2 hours when tested using the USP Paddle
`Method in 1000 ml of 0.1N HCl at 75 rpm at 37º C. +/-
`0.5º C., ....................................................................................... 73 
`
`wherein administration of the unit dose form is more
`effective at reducing the incidence of the NSAID-
`associated gastric ulcers in patients taking LDA than in
`patients not taking LDA who are administered the unit
`dose form. .................................................................................. 74 
`
`P. 
`
`Claim 16: ............................................................................................. 74 
`
`1. 
`
`2. 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
`A method of reducing the incidence of NSAID-
`associated gastric ulcers in patients taking low dose
`aspirin (LDA) who are at risk of developing such ulcers, ........ 74 
`
`wherein the method comprises administering to said
`patient in need thereof twice a day for three months a
`pharmaceutical composition in unit dose form
`comprising: ................................................................................ 74 
`
`(a) 20 mg of esomeprazole, or pharmaceutically
`acceptable salt thereof, .............................................................. 75 
`
`in a form and route sufficient to raise the gastric pH of
`said patient to at least 3.5 upon administration of one or
`more of said unit dose forms, and ............................................. 75 
`
`(b) 500 mg of naproxen, or pharmaceutically acceptable
`salt thereof; ................................................................................ 75 
`
`wherein said unit dose form provides for coordinated
`release of the esomeprazole and the naproxen such that: ......... 76 
`
`xi
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`7. 
`
`8. 
`
`9. 
`
`wherein at least a portion of said esomeprazole, or
`pharmaceutically acceptable salt thereof, is released
`independent of the pH of the surrounding medium, ................. 76 
`
`wherein the unit dosage form releases less than 10% of
`the naproxen or a pharmaceutically acceptable salt
`thereof after 2 hours when tested using the USP Paddle
`Method in 1000 ml of 0.1N HCl at 75 rpm at 37º C. +/-
`0.5º C., ....................................................................................... 76 
`
`wherein administration of the unit dose form is more
`effective at reducing the incidence of said ulcers in
`patients taking LDA than in patients not taking LDA who
`are administered the unit dose form. ......................................... 76 
`
`Q. 
`
`Conclusion ........................................................................................... 76 
`
`VI.  Any Secondary Considerations of Nonobviousness Would Fail ............. 77 
`
`VII.  Conclusion .................................................................................................... 78 
`
`
`
`
`
`xii
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`
`
`
`
`TABLE OF APPENDICES
`
`Appendix A:
`
`Curriculum Vitae of Leon Shargel, Ph.D., R.Ph.
`
`Appendix B:
`
`Claim Chart for Ground 1: Plachetka in view of Graham and
`Goldstein Renders Claims 1-16 Obvious Under 35 U.S.C. §
`103(a)
`
`Appendix C:
`
`Claim Chart for Ground 2: Plachetka Renders Claims 1-16
`Obvious Under 35 U.S.C. § 103(a)
`
`
`
`xiii
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`I, Leon Shargel, Ph.D., R.Ph., declare and state as follows:
`I.
`
`Introduction and Bases for Opinions
`1. My name is Leon Shargel, and I reside in Raleigh, North Carolina. I
`
`have been retained by Conley Rose, P.C. on behalf of the Coalition for Affordable
`
`Drugs VII LLC (“CFAD” or “Petitioner”) and understand that I am submitting this
`
`declaration in connection with the above-referenced inter partes review (IPR)
`
`proceeding.
`
`2.
`
`Specifically, I have been requested to evaluate claims 1-16 of U.S.
`
`Patent No. 8,945,621 (“the ’621 Patent”) (Ex. 1001). As detailed in this
`
`declaration, it is my opinion that claims 1-16 are anticipated or rendered obvious
`
`by prior art references that predate the ’621 Patent. If requested by the parties to
`
`this proceeding or the Patent Trial and Appeal Board (“Board”), I will testify about
`
`my opinions expressed herein.
`
`3.
`
`I reserve the right to modify or supplement my opinions, as well as the
`
`bases for my opinions, based on the nature and content of the documentation, data,
`
`proof, and other evidence that other experts may present or based on any additional
`
`discovery or other information provided to me or found by me in this matter.
`
`A. Qualifications
`4.
`I have over 45 years of educational and work experience in the fields
`
`of pharmaceutics, pharmacology, and pharmacokinetics. Along with the
`
`1
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`experience listed in my curriculum vitae (CV), attached hereto as Appendix A, I
`
`note the following experience that is uniquely relevant to the subject matter at issue
`
`in this proceeding.
`
`5.
`
`I currently am the manager and founder of Applied Biopharmaceutics,
`
`LLC. I founded Applied Biopharmaceutics in 2007. Applied Biopharmaceutics
`
`provides scientific and technical consulting services for the pharmaceutical
`
`industry. For instance, Applied Biopharmaceutics assists clients in developing
`
`new dosage forms for Abbreviated New Drug Application (ANDA) and New Drug
`
`Application (NDA) submissions with the Food and Drug Administration (FDA).
`
`6.
`
`I have been an affiliate professor at the Virginia Commonwealth
`
`University School of Pharmacy in Richmond, Virginia since 2006. I have been an
`
`adjunct associate professor at the University of Maryland School of Pharmacy in
`
`Baltimore, Maryland since 1995.
`
`7.
`
`From 2001-2006, I was the Vice President, Biopharmaceutics, at
`
`Sandoz, Inc. (formerly Eon Labs) in Wilson, North Carolina. From 1997-2001, I
`
`was the Vice President and Technical Director at the National Association of
`
`Pharmaceutical Manufacturers in Ronkonkoma, New York. From 1996-1997, I
`
`was a Senior Research Pharmacist at Johns Hopkins Bayview Medical Center in
`
`Baltimore, Maryland.
`
`2
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`8.
`
`From 1995-1996, I was an Adjunct Visiting Associate Professor of
`
`Pharmacy at Howard University School of Pharmacy and Pharmacal Sciences in
`
`Washington, DC. In 1995, I served as the Vice President, Scientific Affairs, at
`
`Pharmakinetics Laboratories, Inc. in Baltimore, Maryland. From 1993-1994, I was
`
`the Director of Biochemistry and Pharmacokinetics at Forest Laboratories, Inc. in
`
`New York, New York. From 1991-1993, I was the Director of Pharmacokinetics
`
`at Chelsea Laboratories, Inc. in West Hempstead, New York.
`
`9.
`
`From 1982-1991, I was an Associate Professor of Pharmacy and
`
`Pharmacology and the Director of Pfeiffer Pharmaceutical Sciences Laboratory,
`
`Inc. at Massachusetts College of Pharmacy and Allied Health Sciences in Boston,
`
`Massachusetts. From 1975-1982, I was the Section Leader, Pharmaceutics, and an
`
`Associate Professor of Pharmacy and Pharmacology at Northeastern University
`
`College of Pharmacy and Allied Health Professions in Boston, Massachusetts.
`
`From 1969-1975, I was an Associate Research Biologist and Group Leader of
`
`Drug Metabolism and Disposition at Sterling-Winthrop Research Institute in
`
`Rensselaer, New York.
`
`10.
`
`I hold a Bachelor of Science in Pharmacy from the University of
`
`Maryland and a Doctor of Philosophy (Ph.D.) in Pharmacology (with minors in
`
`Physiology, Biochemistry, and Drug Metabolism) from the George Washington
`
`3
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`University Medical Center in Washington, D.C. I am a Registered Pharmacist in
`
`the state of Maryland, the state of Massachusetts, and the District of Columbia.
`
`11.
`
`I am an active member of several professional societies and have
`
`served on various national and international committees. I have organized and
`
`participated in many workshops and symposia, and have lectured widely on
`
`biopharmaceutics, generic drug development, bioequivalence, and
`
`pharmacokinetics.
`
`12.
`
`I have authored over 150 publications and several leading textbooks in
`
`pharmacy and the pharmaceutical industry, including Applied Biopharmaceutics
`
`and Pharmacokinetics, which will be published in its 7th edition by McGraw-Hill
`
`later this year.
`
`13.
`
`I am being compensated at a rate of $425 per hour for my non-
`
`testifying work and $500 per hour for my testifying work in this matter. My
`
`compensation is not conditioned on the outcome of this matter.
`
`B. Materials Reviewed
`14.
`In preparing this declaration, I reviewed the following materials:
`
`Exhibit No. Description
`
`1001
`
`1002
`
`U.S. Patent No. 8,945,621 (“the ’621 Patent”)
`
`File History of the ’621 Patent, U.S. Patent App. No. 12/822,612
`(“the ’612 Application”)
`
`4
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`Exhibit No. Description
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`U.S. Patent No. 6,926,907 (“Plachetka”)
`
`“Ulcer Prevention in Long-term Users of Nonsteroidal Anti-
`inflammatory Drugs,” David Y. Graham, et al., Archives of Internal
`Medicine, Vol. 162, January 28, 2002 (“Graham”)
`
`“Ulcer Recurrence in High-Risk Patients Receiving Nonsteroidal
`Anti-Inflammatory Drugs Plus Low-Dose Aspirin: Results of a Post
`Hoc Subanalysis,” Jay L. Goldstein, et al., Clinical Therapeutics,
`Vol. 26, No. 10, October 2004 (“Goldstein”)
`
`“Horizon Pharma Announces Agreement to Acquire U.S. Rights to
`VIMOVO(R) and Provides 2014 Guidance,” Horizon Pharma
`(Nov. 19, 2013)
`
`Horizon Pharma plc 2014 Irish Statutory Accounts, Horizon
`Pharma Public Limited Company (Apr. 9, 2015)
`
`“Pharmaceutical Companies Buy Rivals’ Drugs, Then Jack Up the
`Prices,” The Wall Street Journal (Apr. 26, 2015)
`
`U.S. Patent No. 4,757,060
`
`“The Mechanism of Action of Aspirin,” J.R. Vane, et al., Pergamon
`(June 15, 2003)
`
`G.B. Patent No. 1211134
`
`“Drug-Induced Peptic Ulcer Disease,” Valerie Vella, Journal of the
`Malta College of Pharmacy Practice, Issue 10 (2005)
`
`“Goodman & Gilman’s The Pharmacological Basis of
`Therapeutics,” Joel G. Hardman, et al., McGraw-Hill Publ’g Co.,
`Ninth Edition (1996)
`
`“Upper Gastrointestinal (GI) pH in Young, Healthy Men and
`Women,” Jennifer B. Dressman, et al., Pharmaceutical Research,
`Vol. 7, No. 7 (July 1990)
`
`5
`
`

`
`IPR2015-01718
`Patent 8,945,621
`
`
`Exhibit No. Description
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`“Effect of Orally Administered Prostaglandin E2 and its 15-Methyl
`Analogues on Gastric Secretion,” S. M. M. Karim, et al., British
`Med. Journal (Jan. 20, 1973)
`
`“Tagamet: The Discovery of Histamine H2-Receptor Antagon