UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`DR. REDDY’S LABORATORIES INC.,
`
`Petitioner
`
` v.
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`POZEN INC. and HORIZON PHARMA USA, INC.,
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`Patent Owners
`
`
`
`
`U.S. Patent No. 9,220,698 to Ault et al.
`
`
`
`Inter Partes Review No. Unassigned
`
`
`
`DECLARATION OF MEYER N. SOLNY, M.D.
`
`
`
`
`DRL EXHIBIT 1002
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`
`
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`DR. REDDY’S LABORATORIES INC.,
`
`Petitioner
`
` v.
`
`POZEN INC. and HORIZON PHARMA USA, INC.,
`
`Patent Owners
`
`
`
`
`U.S. Patent No. 9,220,698 to Ault et al.
`
`
`
`Inter Partes Review No. Unassigned
`
`
`
`DECLARATION OF MEYER N. SOLNY, M.D.
`
`
`
`
`DRL EXHIBIT 1002
`
`
`
`
`
`
`
`
`
`
`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`TABLE OF CONTENTS
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`I.
`
`Page
`QUALIFICATIONS AND BACKGROUND ................................................. 2
`A.
`Education and Experience ..................................................................... 2
`B. Materials Considered ............................................................................. 3
`C.
`Scope of Work ....................................................................................... 4
`II.
`SUMMARY OF OPINIONS ........................................................................... 4
`III. LEGAL STANDARDS ................................................................................... 5
`IV. PERSON OF ORDINARY SKILL IN THE ART .......................................... 7
`V. BACKGROUND ON NSAID-RELATED GASTRIC INJURY .................... 7
`VI. U.S. PATENT NO. 9,220,698 (Ex. 1001) ....................................................... 8
`VII. SCOPE AND CONTENT OF THE PRIOR ART REFERENCES ............... 13
`A. U.S. Patent No. 6,926,907 (Ex. 1004) ................................................. 13
`B. U.S. Patent No. 8,557,285 (Ex. 1005) ................................................. 17
`C. Howden 2005 (Ex. 1006) .................................................................... 19
`D.
`EC-Naprosyn Prescribing Information (Ex. 1009) ............................ 20
`E.
`Other Art that Informs Person of Ordinary Skill’s Knowledge .......... 21
`1.
`Zegerid (omeprazole) Powder for Oral Suspension
`Prescribing Information (2004) (Ex. 1010) .............................. 21
`2.
`Goldstein (Ex. 1011) ................................................................. 21
`3.
`Hochberg (Ex. 1012) ................................................................. 22
`VIII. UNPATENTABILITY OF THE ’698 PATENT ............................................. 23
`A.
`Claims 1-7 of the ’698 Patent Are Anticipated or Obvious
`over the ’285 Patent ............................................................................. 23
`
`i
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`
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`1.
`
`2.
`3.
`
`The method of claim 1 is anticipated by or obvious over the
`’285 patent ................................................................................. 23
`Claim 2 is anticipated by or obvious over the ’285 patent ....... 26
`Claims 3 and 4 are anticipated or obvious over the ’285
`patent ......................................................................................... 27
`4. Claims 5 and 6 are anticipated or obvious over the ’285
`patent .......................................................................................... 28
`5.
`Claim 7 is anticipated or obvious over the ’285 patent ............ 28
`B. All Claims of the ’698 Patent Are Obvious Over the ’285 patent
`in View of Howden 2005 and EC-Naprosyn ...................................... 29
`1.
`The method of claim 1 is obvious over the ’285 patent in view
`of Howden 2005 and EC-Naprosyn ......................................... 29
`Claim 2 is obvious over the ’285 patent in view of Howden
`and EC-Naprosyn ..................................................................... 30
`3.
`Claims 3 and 4 are obvious over the ’285 patent in view
`of Howden 2005 and EC-Naprosyn .......................................... 31
`
`4.
`Claims 5 and 6 are obvious over the ’285 patent in view
`of Howden 2005 and EC-Naprosyn .......................................... 31
`
`5.
`Claim 7 is obvious over the ’285 patent in view of
`Howden 2005 and EC-Naprosyn .............................................. 31
`
`IX. NO SUPPOSED SECONDARY CONSIDERATIONS OVERCOME
`THE OBVIOUSNESS ANALYSIS .............................................................. 32
`A.
`The ’698 Patent Does Not Demonstrate Any Unexpected Result ...... 32
`B.
`There Is No Evidence of Industry Skepticism of the ’698 Patent ........ 34
`C.
`The ’698 Patent Has Not Met Any Long-Felt, but Unmet Need ........ 34
`CONCLUSION .............................................................................................. 35
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`2.
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`X.
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`DRL EXHIBIT 1002
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`1.
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`I, Meyer N. Solny, M.D., have been retained by counsel for Petitioner
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`Dr. Reddy’s Laboratories Inc. (“DRL”). I understand that DRL is petitioning for
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`inter partes review (“IPR”) of U.S. Patent No. 9,220,698 to Ault et al. (“the ’698
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`patent”) (Ex. 1001), which is assigned to Pozen Inc. and Horizon Pharma USA, Inc.
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`(“Patent Owners”), to request that the United States Patent and Trademark Office
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`cancel certain claims of the ’698 patent as unpatentable. I submit this expert
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`declaration in support of DRL’s IPR petition for the ’698 patent. I have been
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`informed by counsel that DRL’s inter parte petition will be accompanied by a timely
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`motion for joinder under 37 C.F.R. §42.122(b) to the previously filed IPR2017-
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`01995 by Mylan Pharmaceuticals Inc. I have been further informed that on March
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`08, 2018 the Board instituted trial on Mylan’s IPR. Paper 18 in IPR2017-01995. I
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`have been also informed that Mylan’s IPR was supported by the expert declarations
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`of Drs. Michael Mayersohn, Ph.D. and David C. Metz, M.D. I have been further
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`informed by counsel that in order to facilitate resolution of substantially similar inter
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`parte petitions concerning the same patent claims and stating the same or
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`substantially similar grounds for invalidity, the Board accepts the use of the language
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`from the prior expert declarations, provided that the petitioner’s expert supports the
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`opinions stated in such prior declarations. Like Dr. Metz, I am a gastroenterologist.
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`I have reviewed the materials cited in this declaration, which are also the materials
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`cited in Dr. Metz’ declaration. In view of the above, I agree and adopt the opinions
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`1
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`stated in Dr. Metz’ declaration, which are reiterated below.
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`I.
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`QUALIFICATIONS AND BACKGROUND
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`A.
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`2.
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`Education and Experience
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`I am a Board Certified Gastroenterologist and Gastrointestinal
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`Endoscopist. I have been practicing medicine in the field of gastroenterology for
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`over 38 years with a special emphasis on upper gastrointestinal (GI) tract disease
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`states.
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`3.
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`I am board certified in gastroenterology and in internal medicine, and
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`listed as Top Doctor 2013-2017 (Castle Conolly).
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`4.
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`I received a Bachelor of Arts from the Yeshiva University, New York,
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`New York, in 1970. In 1974, I received a Medical Doctor (M.D.) degree from
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`Columbia University, College of Physicians & Surgeons and Masters of Business
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`Administration (MBA) from Columbia Business School in 2000.
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`5.
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`From 1974 to 1975, I interned in medicine at the New York Hospital –
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`Cornell Medical Center. From 1975 to 1977, I was a Junior and then Senior
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`Assistant Resident in Medicine at the New York Hospital – Cornell Medical Center.
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`6.
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`From 1977 to 1979, I was a Fellow at the Division of Gastroenterology
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`in the same center.
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`7.
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`For over 38 years, I have maintained an active and ongoing solo private
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`practice in internal medicine and gastroenterology, while practicing as an Assistant
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`2
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`Attending Physician in the Division of Gastroenterology and Hepatology at New
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`York Presbyterian Hospital and holding an academic appointment as a Clinical
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`Instructor in Medicine at the Weill Cornell College of Medicine. For the first ten
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`years of my career, my practice was evenly split between internal medicine and
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`gastroenterology.
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`8.
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`Thereafter, my practice increasingly focused on treating patients with
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`gastrointestinal disorders. Approximately 90% of my current practice is now focused
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`on consultative gastroenterology and gastrointestinal endoscopy.
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`9.
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`I am a member of several medical associations, including both the
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`American and New York Societies of Gastrointestinal Endoscopy.
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`10.
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`I am also a Fellow of the American College of Gastroenterology and a
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`Fellow of the American Gastroenterologic Association.
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`11. A copy of my curriculum vitae, which lists my publications and
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`describes my qualifications in detail is Exhibit A, attached hereto.
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`B. Materials Considered
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`12.
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`In forming my opinions set forth in this declaration, I considered and
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`relied upon my education, background, and years of experience in the practice of
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`medicine in the field of gastroenterology, including treating many patients, as well
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`as the materials listed on Exhibit B, or identified in this declaration, and cited herein.
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`3
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`C.
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`13.
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`Scope of Work
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`I have been retained by counsel for DRL in connection with this matter.
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`I am being compensated for my consulting work at the rate of $750 per hour. My
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`compensation in this case is in no way dependent on the outcome of the case.
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`II.
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`SUMMARY OF OPINIONS
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`14.
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`It is my opinion that the person of ordinary skill in the art would have
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`been motivated to administer a combination dosage form containing the NSAID
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`naproxen and the PPI esomeprazole, prior to the earliest patent application filing
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`date to which the ’698 patent claims priority, September 9, 2008, that results in the
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`pharmacokinetic and pharmacodynamic (or “PK / PD”) values recited in the claims.
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`The person having ordinary skill in the art would have known that the combination
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`of naproxen and esomeprazole at the claimed dosages had been patented in the same
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`multilayer structure as the dosage form described and claimed in the ’698 patent.
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`15. To the extent the Patent Owners argue that the precise PK / PD values
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`in the claims were not known prior to the ’698 patent was filed, it is my
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`understanding that DRL’s expert on PK / PD, Dr. Richard Bergstrom, explains in
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`his declaration supporting DRL’s petition (Ex. 1003), that a person having ordinary
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`skill in the art would have been motivated to target the claimed PK / PD values
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`recited in the claims because these values were known to be in the effective range.
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`Dr. Bergstrom also explains that the person having ordinary skill would have had a
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`4
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`reasonable expectation of success because it would have been routine to make and
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`test the prior art formulation at the claimed dosages of 500 mg naproxen and 20 mg
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`esomeprazole because the prior art formulation is already claimed for these dosages.
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`See Ex. 1003. Therefore, the method of administration recited in the claims is
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`anticipated or obvious over the prior art to the person having ordinary skill.
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`16.
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`It is also my opinion that there is no evidence of unexpected results or
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`industry skepticism for the claimed method of administration because the
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`formulation that results in the claimed pharmacokinetic and pharmacodynamic
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`values, and a method for administering it were already patented. And even if the
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`Patent Owners could establish that a long-felt, unmet need has been met, that need
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`would have been met by the prior art patents on the same drug.
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`III. LEGAL STANDARDS
`
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`17. Counsel has informed me of certain legal principles to guide me in my
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`analysis. Counsel has informed me that DRL carries the burden of proving
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`unpatentability by a preponderance of the evidence, and that this means DRL must
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`show that unpatentability is more probable than not.
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`18. Counsel has informed me that the question of whether the claims of a
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`patent are anticipated or obvious is to be considered from the perspective of the
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`person of ordinary skill in the art. Whether an invention would have been anticipated
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`or obvious is ascertained at the time the invention was made.
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`5
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`19. Counsel has informed me that an obviousness analysis involves
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`ascertaining the scope and content of the prior art, the level of the person of ordinary
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`skill in the pertinent art, the differences between the claimed invention and the prior
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`art and whether there are additional factors present that may nevertheless weigh
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`against obviousness such as unexpected results attributable to the invention or
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`whether the invention has met a long-felt, but unmet need.
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`20. Counsel has informed me that under the existing law an invention may
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`be found obvious:
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`When there is a design need or market pressure to solve a
`problem and there are a finite number of identified, predictable
`solutions, a person of ordinary skill has good reason to pursue
`the known options within his or her technical grasp. If this leads
`to the anticipated success, it is likely the product not of
`innovation but of ordinary skill and common sense. In that
`instance the fact that a combination was obvious to try might
`show that it was obvious under § 103.
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`21. Counsel has informed me that a prior art reference may anticipate a
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`claimed invention if the prior art reference discloses each of the claim elements
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`either expressly or inherently. A claim element is inherent in the anticipating
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`reference if that element, or characteristic, is the natural result that flows from the
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`reference’s explicit limitations.
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`22. Counsel has also informed me that when a composition is claimed in
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`6
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`terms of its function, property, or characteristics that it possesses, and that
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`composition is in the prior art, that the claimed invention may be anticipated or
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`obvious in view of the prior art reference.
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`IV. PERSON OF ORDINARY SKILL IN THE ART
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`23. The field of art here involves the knowledge of a medical doctor and
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`that of a pharmacologist or pharmacokineticist with experience in dosage form
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`design and evaluation. Thus, the hypothetical person of ordinary skill in the art is a
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`collaboration between a pharmacologist or pharmacokineticist having a Ph.D.
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`degree or equivalent training, or a M.S. degree with at least 2 years of some
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`experience in dosage form design and in in vitro and in vivo evaluation of dosage
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`form performance, and a medical doctor having at least 2 years of practical
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`experience treating patients in the gastroenterology field.
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`24. For the purposes of this report, I will be offering my opinion from the
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`perspective of the physician described above as of September 9, 2008, i.e., a medical
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`doctor in the field of gastroenterology with at least 2 years of experience treating
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`patients.
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`V. BACKGROUND ON NSAID-RELATED GASTRIC INJURY
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`25. Non-steroidal anti-inflammatory drugs, commonly referred to as
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`“NSAIDs,” are a class of drugs used to treat pain and inflammation, including pain
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`and inflammation associated with arthritis. The class includes aspirin, naproxen,
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`7
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`ibuprofen, and diclofenac. NSAIDs are among the most commonly prescribed
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`medications in the world and have been in use for a long time. Naproxen was first
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`approved by the FDA in 1976 under the trade name Naprosyn. Ex 1020, 1.
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`26. NSAIDs can cause a variety of side effects that vary in severity. Chronic
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`use of NSAIDs to treat chronic conditions such as arthritis can increase the risk of
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`more serious gastric (stomach) injury, such as stomach erosions and ulcers, and more
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`serious complications such as bleeding, perforation, or obstruction that can lead to
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`hospitalization or death. These NSAID-induced side effects are commonly called
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`NSAID-related injury or gastropathy.
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`27. Long-term NSAID use may cause systemic injury by reducing the
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`amount of prostaglandin in a patient’s body, which is a chemical required for proper
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`maintenance of the stomach’s protective mucosal layer. This reduction decreases the
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`stomach’s protective layer and increases the risk of gastric injury.
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`This injury can be reduced by controlling acid in the stomach through concomitant
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`administration of a prophylactic acid inhibitor with the NSAID.
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`VI. U.S. PATENT NO. 9,220,698 (Ex. 1001)
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`28.
`
`I have read U.S. Patent No. 9,220,698 (“the ’698 patent”), entitled
`
`“Method for Delivering a Pharmaceutical Composition to Patient in Need Thereof.”
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`The ’698 patent was filed on September 3, 2009, and claims priority to provisional
`
`application no. 61/095,584, filed on September 9, 2008. The inventors are listed as:
`
`8
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`Brian Ault, Mark Sostek, Everardus Orlemans, and John Plachetka.
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`29. The ’698 patent “is directed to a method for delivering a pharmaceutical
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`composition to a patient in need thereof, comprising: administering to said patient a
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`pharmaceutical composition in unit dose form comprising naproxen . . . and
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`esomeprazole.” Ex. 1001, 1:13-17.
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`30. The ’698 patent explains that “[o]ver 15 million Americans take
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`nonsteroidal anti-inflammatory drugs (NSAIDs) each day as a treatment for pain or
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`inflammation,” and that “NSAIDs are associated with a high incidence of
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`gastrointestinal complications, including gastritis, dyspepsia, gastroduodenal ulcers,
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`perforations, and bleeding.” Id. at 1:19-24.
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`31. The ’698 patent also explains that proton pump inhibitors (“PPI”), such
`
`as esomeprazole, are effective at improving NSAID tolerability, and work by
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`inhibiting stomach acid secretion. Id. at 1:27-37. Cited as one example is the prior
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`art U.S. Patent No. 6,926,907 (discussed in detail below), which “is directed to [a]
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`dosage form comprising a [PPI and] . . . an NSAID,” and “can be effective in
`
`improving NSAID tolerability through dosages of esomeprazole and naproxen that
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`produce the desired pharmacodynamic response and pharmacokinetic values.” Id.
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`32. According to the ’698 patent, “[t]here is a need for a clinically effective
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`therapy that delivers to a patient in need thereof . . . esomeprazole . . . for a duration
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`sufficient to achieve an intragastric pH of about 4 or greater and a plasma level of
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`9
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`naproxen that is efficacious.” Id. at 1:42-48.
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`33. The ’698 patent describes a series of embodiments in the form of
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`pharmacokinetic and pharmacodynamic values that result from administering a unit
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`dose form (i.e., a single tablet) containing naproxen and esomeprazole in the AM
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`and PM. Id. at 6:46-24:20.
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`34. The ’698 patent contains two examples. Example 1 describes a 9-day
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`study of “twice daily oral administration of three PN400 formulations (enteric coated
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`naproxen 500 mg combined with non-enteric coated esomeprazole 10, 20, or 30 mg)
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`versus the effect of twice daily oral administration of a separate 500 mg non-enteric
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`coated naproxen tablet and once daily oral administration of a separate EC[, i.e.,
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`enteric coated,] esomeprazole (20 mg) capsule (Nexium® 20 mg capsule).” Id. at
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`24:43-53. The study measured 24-hour intragastric pH and certain pharmacokinetic
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`parameters.
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`35. The ’698 patent states that “[t]he PN400 tablet is a multilayer tablet
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`comprising an inner core of naproxen surrounded by a first layer comprising an
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`enteric coating and a second layer comprising non-enteric coated esomeprazole.” Id.
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`at 24:56-59.
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`36. Example 2 describes a study that evaluated PN400 (delayed-release 500
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`mg/immediate release esomeprazole 20 mg) tablet to administrations of EC
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`naproxen (EC Naprosyn®) plus EC esomeprazole (Nexium®), or EC naproxen alone,
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`10
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`or EC esomeprazole alone. Id. at 46:26-33.
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`37. The ’698 patent contains seven (7) claims. Claim 1 is representative and
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`recites:1
`
`1.
`A method for treating osteoarthritis, rheumatoid
`arthritis, or ankylosing spondylitis comprising orally
`administering to a patient in need thereof an AM unit dose
`form and, 10 hours (±20%) later, a PM unit dose form,
`wherein:
`
`
`the AM and PM unit dose forms each comprises:
`naproxen, or a pharmaceutically acceptable salt thereof, in
`an amount to provide 500 mg of naproxen, and
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`esomeprazole, or a pharmaceutically acceptable salt
`thereof, in an amount to provide 20 mg of esomeprazole;
`
`said esomeprazole, or pharmaceutically acceptable salt
`thereof, is released from said AM and PM unit dose forms
`at a pH of 0 or greater,
`
`the AM and PM unit dose forms target:
`
`
`i)
`a pharmacokinetic (pk) profile for naproxen where:
`
`1 The ’698 patent contains a certificate of correction. The claim recitation above
`
`contains the corrections that appear on the certificate.
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`11
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`a)
`for the AM dose of naproxen, the mean Cmax is
`86.2 μg/mL (±20%) and the median Tmax is 3.0 hours
`(±20%); and
`b)
`for the PM dose of naproxen, the mean Cmax is 76.8
`μg/mL (±20%) and the median Tmax is 10 hours (±20%);
`and
`
`
`
`ii)
`a pharmacokinetic (pk) profile for esomeprazole
`where:
`a)
`for the AM dose of esomeprazole, the mean area
`under the plasma concentration-time curve from when the
`AM dose is administered to 10 hours (±20%) after the AM
`dose is administered (AUC0- 10,am) is 1216 hr*ng/mL
`(±20%),
`b)
`for the PM dose of esomeprazole, the mean area
`under the plasma concentration-time curve from when the
`PM dose is administered to 14 hours (±20%) after the PM
`dose is administered (AUC0- 14,pm) is 919 hr*ng/mL
`(±20%), and
`c)
`the total mean area under the plasma concentration-
`time curve for esomeprazole from when the AM dose is
`administered to 24 hours (±20%) after the AM dose is
`administered (AUC0-24) is 2000 hr*ng/ mL (±20%); and
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`the AM and PM unit dose forms further target a mean %
`time at which intragastric pH remains at about 4.0 or
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`12
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`greater for about a 24 hour period after reaching steady
`state that is at least about 60%.
`
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`38. Claims 2-7 recite additional elements that relate to the intragastric pH
`
`levels, the length of administration of the dosage forms, structural aspects of the
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`dosage form, and chemical makeup of the tablet.
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`VII.
`
`
`SCOPE AND CONTENT OF THE PRIOR ART REFERENCES
`A. U.S. Patent No. 6,926,907 (Ex. 1004)
`39. U.S. Patent No. 6,926,907 (“the ’907 patent,” Ex. 1004) issued on
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`August 9, 2005, from application no. 10/158,216, that was filed on May 31, 2002.
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`The ’907 patent claims priority to a provisional application filed on June 1, 2001.
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`Ex. 1004, cover page. John Plachetka is listed as the inventor.
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`40. The ’907 patent concerns treatments for the risks of gastrointestinal
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`ulcers and bleeding associated with long-term treatment with NSAIDs. Id. at 1:22-
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`40. The ’907 patent specification also recognizes that the problem of NSAID-
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`induced gastropathy (such as the development of gastroduodenal ulcers and other
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`gastric injury) was well known in the art. Id. at 1:22-40.
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`41. The ’907 patent notes that “more potent and longer lasting inhibitors,
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`such as proton pump inhibitors, are thought to be more protective during chronic
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`administration of NSAIDs than shorter acting agents” because gastric acidity was
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`known to play such a significant role in the development of gastroduodenal lesions.
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`13
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`Id. at 1:41-44, 1:26-34 (citing studies of effective treatment with acid inhibitors).
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`42. The ’907 patent goes on to note that it would have been well known to
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`the person of ordinary skill in the art, prior to the claimed priority date of June 1,
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`2001, that unit dosage forms combining NSAIDs and PPIs were present in the art
`
`and were effective at reducing NSAID-induced gastropathy, even in the absence of
`
`coordinated release:
`
`Recognizing the potential benefits of PPIs for the prevention of
`NSAID-induced gastroduodenal damage, others have disclosed
`strategies for combining the two active agents for therapeutic
`purposes.
`Id. at 2:21-24 (emphasis added).
`
`
`43. According to the ’907 patent applicant, however, the earlier-patented
`
`formulations had two drawbacks: (1) no coordinated release; and (2) no reduction in
`
`gastric acid levels before release of the NSAID:
`
`However, these suggestions do not provide for coordinated
`release or for reducing intragastric acid levels to a non-toxic
`level prior to the release of NSAID (U.S. Pat. Nos. 5,204,118;
`5,417,980; 5,466,436; 5,037,815).
`Id. at 2:24-28.
`
`
`
`44. According to the Detailed Description of the Invention in the ’907
`
`patent, the “present invention is based upon the discovery of improved
`
`pharmaceutical compositions for administering NSAIDs to patients.” Id. at 5:12-14.
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`14
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
`
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`The “compositions include acid inhibitors that are capable of raising the pH of the
`
`GI tract . . . and provide for the coordinated release of therapeutic agents, i.e., for the
`
`sequential release of acid inhibitor followed by [NSAID].” Id. at 5:15-19; see also,
`
`e.g., id. at Abstract, 1:11-18, 4:47-51.
`
`45. Regarding the mechanism for formulating the claimed dosage forms,
`
`the ’907 patent concedes that “[m]ethods for making appropriate formulations are
`
`well known in the art.” Id. at 5:40-43 (citing a leading treatise, Remington’s
`
`Pharmaceutical Sciences (16th ed. 1980)).
`
`46. Figure 2 of the ’907 patent depicts a schematic example of the claimed
`
`composition:
`
`
`
`47.
`
`“FIG. 2 illustrates a three layer dosage form. An acid inhibitor . . . is
`
`released immediately after ingestion by a patient in order to raise the pH of the [GI]
`
`tract to above a specific pH, e.g., above 4. The innermost layer contains naproxen.
`
`Thus, the dosage form has a naproxen core, an enteric film coat and an acid inhibitor
`
`film coat.” Id. at 5:1-7.
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`15
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`48. The ’907 patent also teaches the administration of the disclosed
`
`formulation to patients. In particular, the specification describes “administering [the]
`
`coordinated release . . . dosage form to achieve pain and symptom relief with a
`
`reduced risk of developing gastrointestinal damage . . . .” Id. at Abstract; see also,
`
`e.g., id. at 1:11-18, 3:5-7, 3:14-17, 4:18-20, 4:28-31, 4:53-60, claims 51 & 52.
`
`49. Claim 1 of the ’907 patent recites:
`
`1.
`A pharmaceutical composition in unit dosage form
`suitable for oral administration to a patient, comprising:
`(a)
`an acid inhibitor present in an amount effective to
`raise the gastric pH of said patient to at least 3.5 upon the
`administration of one or more of said unit dosage forms;
`
`(b)
`a nonsteroidal anti-inflammatory drug (NSAID) in
`an amount effective to reduce or eliminate pain or
`inflammation in said patient upon administration of one or
`more of said unit dosage forms; and
`wherein said unit dosage form provides for coordinated
`release such that:
`
`i)
`said NSAID is surrounded by a coating that, upon
`ingestion of said unit dosage form by said patient, prevents
`the release of essentially any NSAID from said dosage
`form unless the pH of the surrounding medium is
`3.5 or higher;
`
`ii)
`
`at least a portion of said acid inhibitor is not
`
`16
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`
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
`
`
`surrounded by an enteric coating and, upon ingestion of
`said unit dosage form by said patient, is released
`regardless of whether the pH of the surrounding medium
`is below 3.5 or above 3.5.
`50. Claim 5 recites:
`
`5. The pharmaceutical composition of claim 1, wherein
`said acid inhibitor is a proton pump inhibitor selected from
`the group consisting of: omeprazole, esomeprazole,
`lansoprazole, pantoprazole and rabeprazole.
`
`B. U.S. Patent No. 8,557,285 (Ex. 1005)
`
`51. U.S. Patent No. 8,557,285 (“the ’285 patent,” Ex. 1005) issued on
`
`October 15, 2013, from application no. 13/215,855, filed on August 23, 2011. The
`
`’285 patent claims priority to the same provisional application as the ’907 patent. Ex.
`
`1005, cover page. Like the ’907 patent, John Plachetka is the only named inventor.
`
`52. My review of the ’285 patent indicates that the specification of the ’285
`
`patent is nearly identical to the specification of the ’907 patent. Because the same
`
`language appears in the specification of the ’285 patent that is discussed above with
`
`respect to the ’907 patent (with some variation in the column and line numbers), that
`
`discussion will not be repeated here. Suffice it to say that the ’285 patent discloses
`
`the same pharmaceutical composition and methods of treatment disclosed in the ’907
`
`patent. See, e.g., Ex. 1005, 6:16-18 (“The present invention is based upon the
`
`discovery of improved pharmaceutical compositions for administering NSAIDs to
`
`17
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
`
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`patients.”); id. at 6:18-23 (“In addition to containing one or more NSAIDs, the
`
`compositions include acid inhibitors that are capable of raising the pH of the GI tract
`
`. . . and provide for the coordinated release of therapeutic agents, i.e., for the
`
`sequential release of acid inhibitor followed by [NSAID].”); id. at 6:44-45
`
`(“Methods for making appropriate formulations are well known in the art.”); id. at
`
`Fig. 2; id. at 6:5-10 (“FIG. 2 illustrates a three layer dosage form. An acid inhibitor
`
`. . . is released immediately after ingestion by a patient in order to raise the pH of the
`
`[GI] tract to above a specific pH, e.g., above 4. The innermost layer contains
`
`naproxen. Thus, the dosage form has a naproxen core, an enteric film coat and an
`
`acid inhibitor film coat.”); id. at Abstract (describing “administering [the]
`
`coordinated release . . . dosage form to achieve pain and symptom relief with a
`
`reduced risk of developing gastrointestinal damage . . . .”); id.at 3:14-20.
`
`53. The ’285 patent contains four (4) claims.
`
`54. Claim 1 recites:
`1.
`A pharmaceutical composition in unit dosage form
`comprising therapeutically effective amounts of:
`(a)
`esomeprazole, wherein at least a portion of said
`esomeprazole is not surrounded by an enteric coating; and
`(b)
`naproxen surrounded by a coating that inhibits its
`release from said unit dosage form unless said dosage form
`is in a medium with a pH of 3.5 or higher; wherein said
`unit dosage form provides for release of said esomeprazole
`
`18
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`such that upon introduction of said
`unit dosage form into a medium, at least a portion of said
`esomeprazole is released regardless of the pH of the
`medium.
`
`55. Claim 4 recites:
`
`The pharmaceutical composition of claim 1,
`4.
`wherein naproxen is present in said unit dosage form in an
`amount of between 200-600 mg and esomeprazole in an
`amount of from 5 to 100 mg per unit dosage form.
`
`
`C. Howden 2005 (Ex. 1006)
`
`56. Howden, C.W., “Review article: immediate-release proton-pump
`
`inhibitor therapy -- potential advantages” Aliment Pharmacol. Ther. 22(3): 25-30
`
`(2005) (Ex. 1006) (“Howden 2005”) was published in 2005, prior to the earliest
`
`priority date for the ’698 patent.
`
`57. Howden 2005 is a review article that states in the summary that it
`
`reports an overview of the PK and PD values of immediate-release omeprazole2 in
`
`
`2 Omeprazole is a PPI that contains a mixture of an R- and S-enantiomer (mirror
`
`images of the chemical compound). Esomeprazole is the S-enantiomer of
`
`omeprazole, and is also written as S-omeprazole, or (-)-omeprazole. See U.S. Patent
`
`No. 5,877,192, issued on March 2, 1999 (“the ’192 patent”) (Ex. 1007). The ’192
`
`19
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`EXHIBIT 1002 – DECLARATION OF MEYER N. SOLNY, M.D.
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`the form of Zegerid® powder for oral suspension and the potential advantages over
`
`delayed-release PPIs. Ex. 1006, 1. Howden 2005 reports that Zegerid® is available
`
`in two strengths, 40 mg or 20 mg omeprazole per unit dose. Id. at 2. Howden 2005
`
`discloses the PK data of Tmax, Cmax, and AUC on day 1 and day 7 of administration
`
`for Zegerid®. Id. at 2-3. Howden 2005 also discloses the results of PD studies with
`
`Zegerid®. Id. at 3-4.
`
`EC-Naprosyn Prescribing Information (Ex. 1009)
`
`D.
`
`58. EC-Naprosyn was approved in 1994, and
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