UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEALS BOARD
`
`
`AMNEAL PHARMACEUTICALS LLC
`Petitioner
`
`v.
`
`HOSPIRA, INC
`Patent Owner
`
`
`Inter Partes Review No. IPR2016-01578
`Patent 8,338,470
`
`
`DECLARATION OF JAMES GORDON CAIN, MD, MBA, FAAP
`
`
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEALS BOARD
`
`
`AMNEAL PHARMACEUTICALS LLC
`Petitioner
`
`v.
`
`HOSPIRA, INC
`Patent Owner
`
`
`Inter Partes Review No. IPR2016-01578
`Patent 8,338,470
`
`
`DECLARATION OF JAMES GORDON CAIN, MD, MBA, FAAP
`
`
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002
`
`
`
`TABLE OF CONTENTS
`
`INTRODUCTION .............................................................................................. 1
`
`
`I.
`
`II. QUALIFICATIONS & BACKGROUND ......................................................... 2
`
`III.
`
`INFORMATION CONSIDERED ................................................................... 3
`
`IV. THE ‘470 PATENT ......................................................................................... 4
`
`A.
`
`B.
`
`State of the Art ...................................................................................... 4
`
`Scope of the ‘470 Patent ........................................................................ 6
`
`V.
`
`CLAIM CONSTRUCTION ............................................................................ 7
`
`A. A Person of Ordinary Skill in the Art (POSA) ..................................... 7
`
`B.
`
`C.
`
`Broadest Reasonable Interpretation ...................................................... 7
`
`Claim Terms of the ‘470 Patent ............................................................ 8
`
`i.
`
`ii.
`
`“Ready To Use” .......................................................................... 8
`
`“Dexmedetomidine” .................................................................10
`
`VI. THE CLAIMED INVENTION IS WELL-KNOWN IN THE ART .............10
`
`VII. CONCLUDING STATEMENTS ..................................................................16
`
`i
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page i
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`I.
`
`INTRODUCTION
`
`I, James Gordon Cain, MD, MBA, FAAP, declare as follows:
`
`1.
`
`I am over 18 years of age. I have personal knowledge of the facts
`
`stated in this declaration and could testify competently to them if asked to do so.
`
`2.
`
`In this proceeding before the U.S. Patent and Trademark Office
`
`(“USPTO”), I have been retained by Amneal Pharmaceuticals LLC (“Amneal” or
`
`“Petitioner”) as an independent expert consultant. Although I am receiving
`
`compensation at my standard consulting rate for the time that I spend on this
`
`proceeding, I have no other interest in its result. I also expect to be reimbursed for
`
`reasonable expenses incurred in relation to my consulting. My compensation is
`
`independent of the opinions rendered or the outcome of this proceeding.
`
`3.
`
`I understand that this proceeding involves U.S. Patent No. 8,338,470
`
`(“the ‘470 patent”), Ex. 1001, issued on December 25, 2012, and that the ‘470
`
`patent issued from U.S. Patent Application Serial No. 13/541,524 (“the ‘524
`
`application”), Ex. 1048, filed on July 3, 2012. The ‘524 application is a
`
`continuation of U.S. Application No. 13/343,672, Ex. 1008, now U.S. Patent No.
`
`8,242,158 (“the ‘158 patent”), Ex. 1047, and claims priority to the ‘672
`
`application, which was filed on January 4, 2012. Accordingly, the earliest possible
`
`effective filing date of the ‘470 patent is January 4, 2012.
`
`4.
`
`I have been asked by counsel for Amneal to explain the technical
`
`
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`1
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 1
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`
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`subject matter of the ‘470 patent and its background. I have also been asked to
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`explain whether prior art discloses the compositions claimed in the ‘470 patent.
`
`My opinions are set forth below.
`
`II. QUALIFICATIONS & BACKGROUND
`5. My qualifications and credentials are fully set forth in my curriculum
`
`vitae, attached hereto as Exhibit A. I am an expert in the fields of clinical
`
`anesthesia and sedation, with significant experience with ready to use medications.
`
`In particular, I am knowledgeable about the use of dexmedetomidine for sedation
`
`purposes. For the past 24 years, I have accumulated significant training and
`
`experience in these and related fields.
`
`6.
`
`In 1987, I received a B.S. in Biology from the University of Scranton.
`
`In 1992, I received my M.D. from the School of Medicine at the University of
`
`Pittsburgh. From 1992-1993, I attended Yale University as a Primary-Care
`
`Internal Medicine intern. Through the Massachusetts General Hospital at Harvard
`
`University, I completed my Anesthesiology Residency from 1993-1996 and
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`Critical Care Medicine Fellowship in 1997 as well as my Adult and Pediatric
`
`Cardiac Anesthesiology Fellowship from 1995-1996 at the Massachusetts General
`
`Hospital and Boston Children’s Hospital.
`
`7.
`
`Subsequent to my postgraduate work, I held the position of Instructor
`
`at Harvard University in 1998 and as Assistant and Associate Professor at West
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`
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`2
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 2
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`Virginia University from 1998-2005. From 2005 to the present, I have held the
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`position as Visiting Associate Professor at the University of Pittsburgh.
`
`8.
`
`In addition to my academic appointments, I am currently the Director
`
`of Perioperative Medical Services, Transplant Anesthesiology and Trauma
`
`Anesthesiology as well as the Chief Charge Anesthesiologist at the Children’s
`
`Hospital of Pittsburgh of UPMC. I have been employed as an anesthesiologist
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`and/or intensivist since 1996 in a number of additional roles, as set forth in my CV,
`
`Ex. A.
`
`9.
`
`Further, from 2000 to the present, I have gained a significant amount
`
`of experience in the field of sedation by studying teaching the effect of
`
`dexmedetomidine on patients. In particular, I am published in the field of
`
`administration of dexmedetomidine and have given a multitude of invited lectures,
`
`as enumerated in my CV, Ex. A.
`
`10.
`
` I am not an attorney or patent agent and I offer no legal opinions
`
`herein. My opinions here are based on my professional experience, scientific
`
`expertise, and the materials I have reviewed.
`
`III.
`
`INFORMATION CONSIDERED
`
`11.
`
`In forming my opinions, I have reviewed the ‘470 patent, its
`
`prosecution history, and other prior art references cited in this declaration. In
`
`particular, I have reviewed the exhibits to Amneal’s petition listed in Exhibit B
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`
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`3
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 3
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`attached hereto.
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`IV. THE ‘470 PATENT
`
`A.
`
`State of the Art
`
`12.
`
`The medical field has recognized dexmedetomidine as a general
`
`sedation/analgesic agent since 1988- Ex. 1005, US. Pat. No. 4,910,214 (“the ‘214
`
`patent”), col. 3, 11. 55—59. Dexmedetomidine, (S)—4—[l-(2,3-dimethylphenyl)ethyl]—
`
`IH-imidazole, which
`
`is
`
`the S-enantiomer of medetomidine,
`
`4-[1-(2,3-
`
`dimethylphenyl)ethyl]-II-I—imidazole, has the following structure:
`
`13.
`
`Hm”
`
`Dexmedetomidine
`
`medetomidlne
`
`14. Medetomidine, a racemic mixture, was first disclosed in the prior art
`
`in 1985, Ex. 1004, US. Pat. No. 4,544,664 (“the ‘664 patent”), col. 19, l. 47 — col.
`
`20, l. 38, and separated into two enantiomers, one of which was dexmedetomidine,
`
`in 1988, Ex. 1005, col. 1, 11. 8-43.
`
`15. Additionally, no later than 1999 when dexmedetomidine entered the
`
`US market, articles such as Venn et al., Anaesthesia 54:1136-1142 (1999), Ex.
`
`1024, established that the prior art disclosed methods of sedating a patient while in
`
`an intensive care unit by administering dexmedetomidine, or a pharmaceutically
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`4
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC — Exhibit 1002 — Page 4
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`acceptable salt thereof, to the patient.
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`16. Thereafter, in 2004, U.S. Patent No. 6,716,867 likewise disclosed
`
`methods of sedating a patient. Ex. 1006, U.S. Pat. No. 6,716,867 (“the ‘867
`
`patent”). The ‘867 patent was issued on April 6, 2004, and therefore constitutes
`
`prior art under the relevant section of the patent code as I have been informed by
`
`counsel.
`
`17. The ‘867 patent specifically relates to a method of sedating a patient
`
`while in the intensive care unit by administering dexmedetomidine or a
`
`pharmaceutically acceptable salt thereof to the patient. Ex. 1006, abstract. The ‘867
`
`patent describes the use of dexmedetomidine that is diluted in 0.9% sodium
`
`chloride solution which is then ready for administration to patients. Id. at col. 7, ll.
`
`60-65.
`
`18. Administration of dexmedetomidine to a patient via parenteral
`
`(including intravenous infusion and intramuscular, Ex. 1021, Dyck et al.,
`
`Anesthesiology 78:813-820 (1993); Ex. 1022, Scheinin, et al., Anesthesiology
`
`78:1065-1075 (1993)), transmucosal (including buccal and intranasal, Ex. 1023,
`
`Yuen et al., Anesth. Analg. 105:374-80 (2007)) and oral routes was within the
`
`scope of the prior art. See also Ex. 1004 and Ex. 1005.
`
`19.
`
`In the prior art, dexmedetomidine was provided as a concentrate that
`
`directed the user to dilute prior to administration to a patient. See, e.g., Ex. 1007,
`
`
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`5
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`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 5
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`Sec. 2.4. Dexmedetomidine formulations for sedation were commercially available
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`in the U.S. as early as December 23, 1999, as PrecedexTM injection for intravenous
`
`infusion following dilution (or alternatively “PrecedexTM Concentrate”).
`
`20. The use of premix formulations of parental medications, particularly
`
`those for use in an intensive care unit setting was also well known prior to the
`
`filing date of the Patents-in-Suit. For example, Gerlach, Ex. 1020, proposes the use
`
`of standardized drug preparations to improve medication safety in the ICU. See
`
`also Giorgi, Ex. 1015 (most effective way to reduce microbial contamination in
`
`ICU setting is use of ready to use solution). Thus, from at least these prior art
`
`references, one of ordinary skill in the art would have been well aware of the
`
`properties of dexmedetomidine and the benefits of ready to use medications.
`
`Scope of the ‘470 Patent
`
`B.
`21. Generally, the ‘470 patent disclosure and claims are directed to a
`
`premixed pharmaceutical compositions of dexmedetomidine. Ex. 1001, col. 1, l.
`
`66 – col. 2, l. 5. The specification provides suitable containers including glass
`
`vials, ampoules, syringes, and plastic flexible containers, such as polyvinyl
`
`chloride (PVC), VisIV™, polypropylene and CR3 containers. Id. at col. 9, ll. 21-
`
`29. The specification also provides numerous suitable concentrations for the
`
`premixed concentrations, including the claimed concentration range of between
`
`about 0.005 to about 50 μg/mL. Id. at col. 7, l. 44 – col. 8, l. 19.
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`6
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 6
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`V. CLAIM CONSTRUCTION
`A. A Person of Ordinary Skill in the Art (POSA)
`I have been informed that construction of the terms of a patent claim
`22.
`
`is to be done from the point of view of a POSA at the time of the invention. For
`
`purposes of defining a POSA, I have assumed that the time of the invention is the
`
`date of filing of the ‘672 application, namely January 4, 2012.
`
`23.
`
`In formulating my opinions, I have relied upon my review of the
`
`references cited, my experience in the relevant art, and also considered the
`
`viewpoint of a POSA. In my opinion, the POSA at the time of invention would
`
`have held an advanced degree, such as a Ph.D. or M.D. in the field of drug
`
`development and formulation, or in the alternative would have significant clinical
`
`experience in anesthesia or sedation and would have familiarity with the use of
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`parenteral injection and/or familiarity with ready to use medications, as of January
`
`4, 2012.
`
`B.
`24.
`
`Broadest Reasonable Interpretation
`I have been advised by counsel that in an inter partes review
`
`proceeding before the USPTO, like this one, a patent claim term is to receive the
`
`“broadest reasonable interpretation” in light of the specification of the patent in
`
`which it appears. I have also been advised that, at the same time, patent claim
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`terms are generally given their ordinary and customary meanings as would be
`
`understood by a POSA.
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`7
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`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 7
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`25.
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`I have also been advised by counsel that patent claims are to be
`
`construed first in the context of the specification, including the plain meaning of
`
`the claims, of the patent. The prosecution history of the patent should also be
`
`considered to the extent that it provides clarification.
`
`26.
`
`I have kept in mind these claim construction principles in the analysis
`
`set forth below. In some cases, and where I have stated as such, my opinions have
`
`also been informed by specific portions of the prosecution history of the ‘470
`
`patent.
`
`C. Claim Terms of the ‘470 Patent
`i. “Ready To Use”
`‘470 patent discloses an embodiment of
`27. The
`
`the claimed
`
`pharmaceutical composition as being a “ready to use” liquid pharmaceutical
`
`composition. I have set forth my understanding, as a person of ordinary skill in the
`
`art, of what the term “ready to use” means below.1
`
`28. The claims of
`
`the ‘470 patent describe
`
`the claimed
`
`liquid
`
`pharmaceutical composition as being “ready to use” for parenteral administration.
`
`For example, independent claim 1 of the ‘470 patent reads:
`
`A ready to use liquid pharmaceutical composition for parenteral
`
`
`1 The dependent claims, in my opinion, do not introduce any terms that require
`
`construction.
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`
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`8
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`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 8
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`administration to a subject, comprising dexmedetomidine or a
`pharmaceutically acceptable salt thereof at a concentration of about
`0.005 to about 50 μg/mL disposed within a sealed glass container.
`
`Ex. 1001, col. 26, ll. 23-27.
`
`29. Also, the specification of the ‘470 patent discloses that the
`
`formulation of dexmedetomidine can be “ready to use.” In particular, the
`
`specification of the ’470 patent states:
`
`[i]n certain embodiments, the compositions of the present invention
`can be formulated as ‘ready to use’ compositions which refer to
`premixed compositions that are suitable for administration to a
`patient without dilution. For example, in certain embodiments, the
`compositions of the present invention are ‘ready to use’ upon
`removing the compositions from a sealed container or vessel.
`
`Ex. 1001, at col. 3, ll. 59-65 (emphasis added).
`
`30. Additionally, the term “ready to use” is a well-known term of art in
`
`the medical and pharmaceutical industry. See, e.g., Ex. 1044, “Injectable
`
`medicines,” WHO Collaborating Centre
`
`for Pharmaceutical Pricing and
`
`Reimbursement Policies, http://whocc.goeg.at/Glossary/PreferredTerms
`
`(last
`
`visited August 9, 2016). It is my opinion that one of skill in the art would
`
`understand the term “ready to use” to mean “requiring no further dilution or
`
`reconstitution before transfer to an administration device.” Id.
`
`31. Based on these descriptions, and my understanding of how this term is
`
`used by persons of ordinary skill in the art, it is my opinion that the broadest
`
`reasonable interpretation of “ready to use” must include a liquid pharmaceutical
`9
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`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 9
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`composition that requires no further dilution or reconstitution before administration
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`to a patient.
`
`ii. “Dexmedetomidine”
`‘470 patent discloses an embodiment of
`32. The
`
`the claimed
`
`pharmaceutical composition as comprising dexmedetomidine. The specification
`
`further defines “dexmedetomidine” as “(S)-4-[1-(2,3-dimethylphenyl) ethyl]-1H-
`
`imidazole,” and provides the following chemical formula:
`
`Ex. 1001, col. 3, ll. 24-50.
`
`
`
`33. The specification of the ‘470 patent defines dexmedetomidine as a
`
`“substantially pure, optically active dextrorotary stereoisomer of medetomidine, as
`
`the free base or pharmaceutically acceptable salt.” Ex. 1001, col. 3, ll. 24-27.
`
`Therefore, it is my opinion that the broadest reasonable interpretation of
`
`“dexmedetomidine” means “substantially pure, optically active dextrorotary
`
`stereoisomer of medetomidine, as the free base or pharmaceutically acceptable
`
`salt.” Id.
`
`VI. THE CLAIMED INVENTION IS WELL-KNOWN IN THE ART
`I understand that during prosecution of the ‘524 application,
`34.
`
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`10
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 10
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`Applicants submitted arguments to overcome an obviousness rejection over the
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`Precedex Draft Label. Ex. 1049, Office Action Response, mailed Sept. 17, 2012,
`
`U.S. Application No. 13/541,524.
`
`35. Specifically, the applicants argued that the Precedex Label failed to
`
`suggest or describe a premixture composition comprising about 0.005 to about 50
`
`μg/mL of dexmedetomidine disposed within a sealed glass container that is ready
`
`to use without dilution. Id. at p. 5.
`
`36. The applicants argued
`
`that “upon withdrawing
`
`the claimed
`
`composition from a sealed glass container, an artisan of ordinary skill can
`
`administer the composition directly to a subject” whereas the Precedex Label
`
`composition would be “not suitable for administering to a patient upon
`
`withdrawing the composition from a sealed container.” Id. at p. 6.
`
`37. Applicants further argued
`
`that
`
`the ready
`
`to use premixture
`
`composition in a sealed glass container is more stable over a prolonged period
`
`compared to, for example, the premixture composition in a plastic container. Id. at
`
`p. 8.
`
`38.
`
`In my opinion, one of skill in the art would have had a reasonable
`
`expectation of success of storing the diluted formulation for extended period of
`
`time. In fact, my own institution has been utilizing a pharmacy made under sterile
`
`conditions 4 mcg/cc (i.e., 4 μg/mL) dilution stored in acceptable syringes up to one
`
`
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`11
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 11
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`week with no apparent adverse events since at least 2007, Ex. 1035, Cain,
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`TraumaCare 13:3-5 (2007), and it appears from Anderson et al., Ex. 1038, Am. J.
`
`Health Syst. Pharm. 69:595-7 (2012), that Utah pharmacy had similar findings
`
`with minimal degradation in polyproylene syringes and references in document to
`
`such considerations in direct communication with Hospira in 2011.
`
`39. During prosecution of the ‘524 application, applicants relied upon an
`
`FDA Memorandum by Cynthia G. McCormick, M.D., dated November 30, 1999
`
`(“the McCormick FDA Memorandum”) to support their argument that the diluted 4
`
`μg/mL dexmedetomidine composition was known in the art to be stable for only 24
`
`hours. Ex. 1013, p. 8.
`
`40. Having reviewed Applicants’ arguments, I conclude that the results
`
`achieved with the claimed invention would not have been unexpectedly superior
`
`over the results that would be obtained by products already known in the prior art.
`
`41.
`
`In my opinion, the undiluted PrecedexTM solution disclosed in the
`
`2010 Label is ready to use for parenteral administration to a patient in some
`
`circumstances.
`
`42. Furthermore, and in contrast to some medications which require
`
`central venous administration unless diluted (e.g. dopamine, potassium, parenteral
`
`nutrition), insofar as I can ascertain there is no documented harm in administration
`
`of intravenous dexmedetomidine at 100mcg/ml other than the inconvenience of its
`
`
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`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 12
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`relatively small volume.
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`43. Based on my experience, dexmedetomidine is routinely administered
`
`parentally (primarily intramuscularly) and transmucosally to patients in the
`
`undiluted concentration of 100 mcg/mL directly from the vial as described in the
`
`2010 Precedex Label and demonstrates successful results. For example, undiluted
`
`intranasal administration has become a prime method of sedation for pediatric
`
`patients at the Children’s Hospital of Pittsburgh.
`
`44.
`
`In fact, as part of my usual practice, I, and our sedation team in
`
`general, administer PrecedexTM to patients at the provided, undiluted concentration
`
`of 100 μg/mL, directly from the glass vial. In my opinion, the undiluted
`
`concentration of PrecedexTM, is ready to use, just as effective as the diluted
`
`formulation and the preferred concentration for intramuscular and transmucosal
`
`administration. This 100mcg/cc concentration of ready to use dexmedetomidine is
`
`typically used for preoperative premedication and procedural sedation either as a
`
`solo agent or an adjunct with medications such as midazolam and ketamine. See
`
`also Ex. 1039, G. DiSilvio, M. Jacoby, D. Weiner, A. Broussard, P. Callahan, and
`
`J. Cain, “Intranasal Dexmedetomidine & Midazolam: A Novel Sedation Technique
`
`for Infant PFT,” Society for Pediatric Anesthesia, Phoenix, Arizona (March 2015).
`
`45. The 2010 Precedex Label directed a POSA to prepare a 4 μg/mL
`
`solution of PrecedexTM for parenteral administration via intravenous infusion by
`
`
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`13
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`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 13
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`diluting 2 mL of PrecedexTM in 48 mL of 0.9% sodium chloride injection to a total
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`of 50 mL.
`
`46. Dexmedetomidine is also routinely administered in the diluted
`
`concentration of 4 mcg/mL by following the dilution instructions set forth by the
`
`1999 Precedex package insert and the 2010 Precedex Label.
`
`47. Given the routine use and general acceptance of “ready to use” in the
`
`industry, and as shown in the prior art, a POSA would have been motivated to
`
`create an embodiment that falls within the scope of claims 1-7 based on available
`
`prior art.
`
`48.
`
`In my experience, dosages in “ready to use” form are commonly used
`
`and have been for a number of decades.
`
`49.
`
`In fact, differential dilution is routine and necessary in medical
`
`practice in order to tailor the appropriate amount and concentration of drug to be
`
`administered under particular sets of circumstances, such as for pediatric patients,
`
`to maintain osmolality, to avoid phlebitis and/or to avoid fluid overload. See Ex.
`
`1040, Neu et al., Crit. Care Med. 10:610-12 (1982); Ex. 1041, Potts et al.,
`
`Pediatrics 113:59-62 (2004); Ex. 1042, Merry et al., Pediatric Anesthesia 21:743-
`
`753 (2011); Ex. 1043, Rodriguez-Gonzalez et al., J. Am. Med. Info. Assoc. 1:72-
`
`78 (2012). Additionally, many locations, including Children’s Hospital of
`
`Pittsburgh, have discontinued nearly all ICU bedside differential dilutional
`
`
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`14
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`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 14
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`preparations and moved them to sterile preparation by pharmacy. See Ex. 1038.
`
`50.
`
`In fact, prior to January 4, 2012, I asked our pharmacy to prepare 10
`
`mL premixed syringes of dexmedetomidine at a diluted concentration of 4 mcg/mL
`
`for use as an anesthetic. Ex. 1035.
`
`51. Since 2005 our pharmacy has been preparing these syringes in a
`
`sterile environment. They determined that per their review of literature and
`
`customary treatment of other medications they routinely dilute, that a shelf life of 7
`
`days was acceptable. I am unaware of any adverse events attributable to this
`
`practice since it began.
`
`52. Additionally, Applicant’s reliance upon the FDA Memorandum by
`
`Cynthia G. McCormick, M.D. does not actually support their argument that the
`
`diluted 4 μg/mL dexmedetomidine composition was known in the art to be is stable
`
`for only 24 hours.
`
`53.
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`Instead, it is clear that the 24-hour limit was merely based on the FDA
`
`approved indications for use.
`
`54.
`
`In fact, Hospira itself sponsored studies in which the medication was
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`administered for more than 24 hours to pediatric patients. See, e.g., Ex. 1045,
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`Chrysostomou et al., Pediatric Crit. Care Med. 10:654-60 (2009). Indeed, there is
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`no mention of stability or instability in the documents relied upon by Applicants.
`
`55. A POSA would not understand stability of the dexmedetomidine to be
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`15
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 15
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`limited to 24 hours.
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`56. Therefore, it is my opinion that in view of the routine nature of
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`medical practice to choose the appropriate amount and concentration of drug to be
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`administered under particular sets of circumstances, it would have been obvious
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`for a POSA to prepare a ready to use solution of dexmedetomidine hydrochloride
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`within the scope of claims 1-7.
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`VII. CONCLUDING STATEMENTS
`In signing this declaration, I understand that the declaration will be
`57.
`
`filed as evidence in a contested case before the Patent Trial and Appeal Board of
`
`the United States Patent and Trademark Office. I acknowledge that I may be
`
`subject to cross-examination in this case and that cross-examination will take place
`
`within the United States. If cross-examination is required of me, I will appear for
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`cross-examination within the United States during the time allotted for cross-
`
`examination.
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`58.
`
`I declare that all statements made herein of my knowledge are true,
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`and that all statements made on information and belief are believed to be true, and
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`that these statements were made with the knowledge that willful false statements
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`and the like so made are punishable by fine or imprisonment, or both, under
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`Section 1001 of Title 18 of the United States Code.
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`16
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 16
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`17
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`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 17
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`EXHIBIT A
`
`Curriculum Vitae – James Gordon Cain
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 18
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`
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`CURRICULUM VITAE
`
`June 2016
`
`James Gordon Cain, MD, MBA, FAAP
`Director, Perioperative Medical Services, Children’s Hospital of Pittsburgh of UPMC
`Director, Transplant Anesthesiology, Children’s Hospital of Pittsburgh of UPMC
`Director, Trauma Anesthesiology, Children’s Hospital of Pittsburgh of UPMC
`Visiting Associate Professor, Department of Anesthesiology, University of Pittsburgh
`Past President, International Trauma Anesthesiology and Critical Care Society
`Past President, West Virginia Society of Anesthesiologists
`
`BIOGRAPHICAL
`
`
`
`
`
`Birth Date
`February 25
`
`
`
`
`
`
`
`
`
`
`
`
`
`Name
`James Gordon Cain, MD, MBA, FAA P
`
`
`
`Home Address
`
`107 Sherborne Drive
`McMurray, Pennsylvania 15317
`
`
`Cell Phone
`724.506.3141
`
`
`
`
`Business Address
`
`Department of Anesthesiology
`Children’s Hospital of Pittsburgh of UPMC
`4401 Penn Avenue
`
`
`
`Pittsburgh, Pennsylvania 15224
`
`Business Phone
`412.692.5260
`
`
`
`
`
`
`
`
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`
`
`
`
`
`
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`
`
`
`
`
`
`
`
`
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`
`
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`
`
`
`
`
`
`
`
`Birth Place
`Towanda, Pennsylvania
`
`Citizenship
`United States of America
`
`
`
`Hospital: cainj@upmc.edu
`University: jgc13@pitt.edu
`Personal: jamesgcain@gmail.com
`
`
`
`Business Fax
`412.692.8685
`
`
`
`
`
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`
`
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`
`
`
`EDUCATION AND TRAINING
`
`POSTGRADUATE
`1997
`
`Massachusetts General Hospital
`Harvard University
`
`
`
`
`
`
`James Gordon Cain, MD, MBA, FAAP
`
`
`Critical Care Medicine Fellowship
`William Hurford, MD
`
`1
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 19
`
`
`
`CURRICULUM VITAE
`
`Boston, Massachusetts
`
`
`1995-1996 Massachusetts General Hospital
`Boston Children’s Hospital
`
`Harvard University
`
`
`Boston, Massachusetts
`
`
`1993-1996 Massachusetts General Hospital
`Harvard University
`
`
`
`
`Yale University
`New Haven, Connecticut
`
`
`
`
`
`1992-1993
`
`
`
`
`
`
`PROFESSIONAL
`1987-1992
`University of Pittsburgh
`School of Medicine
`Pittsburgh, Pennsylvania
`
`
`
`
`GRADUATE
`Katz Graduate School of Business
`2014-2018
`Anticipated University of Pittsburgh
`
`Pittsburgh, Pennsylvania
`
`
`Katz Graduate School of Business
`University of Pittsburgh
`Pittsburgh, Pennsylvania
`
`
`2011-2012
`
`
`
`
`
`2001-2003
`
`
`
`UNDERGRADUATE
`1983-1987
`University of Scranton:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Adult and Pediatric Cardiac
`Anesthesiology Fellowship
`Michael D’Ambra, MD
`
`Anesthesiology Residency
`Warren Zapol, MD
`
`Primary-Care Internal Medicine
`Internship
`Stephen Huot, MD, PhD
`
`MD, 1992
`
`PhD, Organization Behavior and
`Human Resource Management
`Minor: Strategic Management
`
`MBA, International, 2012
`
`Business Administration
`Courses
`
`Auburn University/Southern Medical
`Association
`
`
`
`
`
`James Gordon Cain, MD, MBA, FAAP
`
`
`
`
`
`
`BS, 1987, Biology
`
`2
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 20
`
`
`
`CURRICULUM VITAE
`
`
`
`
`
`A Jesuit Institution
`Scranton, Pennsylvania
`
`
`
`
`
`
`
`Minor, History
`Cognate, Chemistry
`
`
`
`
`
`APPOINTMENTS AND POSITIONS
`ACADEMIC APPOINTMENTS
`2005-present University of Pittsburgh
`School of Medicine
`Pittsburgh, Pennsylvania
`
`
`
`
`
`Visiting Associate Professor
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Harvard University
`School of Medicine
`
`Harvard University
`School of Medicine
`
`
`
`
`
`
`2004-2005 West Virginia University
`
`
`School of Medicine
`
`1998-2004 West Virginia University
`
`
`School of Medicine
`
`1998
`
`
`1993-1997
`
`
`
`NON-ACADEMIC APPOINTMENTS AND POSITIONS
`2014-present Children’s Hospital of Pittsburgh of UPMC Director
`Pittsburgh, Pennsylvania
`
`
`Transplant Anesthesiology
`
`
`
`
`
`
`
`
`
`
`2014-present Children’s Hospital of Pittsburgh of UPMC Founding Member
`Pittsburgh, Pennsylvania
`
`
`Radiology Anesthesiology Team
`
`Associate Professor
`
`Assistant Professor
`
`Instructor
`
`Clinical Fellow
`
`
`
`
`
`2012-present Children’s Hospital of Pittsburgh of UPMC Founding Member
`Pittsburgh, Pennsylvania
`
`
`Transplant Anesthesiology Team
`
`
`2008-present Children’s Hospital of Pittsburgh of UPMC Director
`Pittsburgh, Pennsylvania
`
`
`Perioperative Medical Services
`
`James Gordon Cain, MD, MBA, FAAP
`
`
`
`
`3
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 21
`
`
`
`CURRICULUM VITAE
`
`
`2008-present Children’s Hospital of Pittsburgh of UPMC Chief Charge Anesthesiologist
`Pittsburgh, Pennsylvania
`
`
`
`
`2005-present Children’s Hospital of Pittsburgh of UPMC Director
`Pittsburgh, Pennsylvania
`
`
`Trauma Anesthesiology
`
`
`2005-present Children’s Hospital of Pittsburgh of UPMC Pediatric Transplant
`Pittsburgh, Pennsylvania
`
`
`Anesthesiologist
`
`
`2005-present Children’s Hospital of Pittsburgh of UPMC Pediatric Anesthesiologist
`Pittsburgh, Pennsylvania
`
`
`2005-2011
`
`
`2007-2008
`
`2008
`
`
`2008
`
`
`
`
`
`2005-2008
`
`
`1998-2005
`
`
`
`UPMC Presbyterian Hospital
`Pittsburgh, Pennsylvania
`
`
`
`Anesthesiologist
`
`Children’s Hospital of Pittsburgh of UPMC Charge Anesthesiologist
`Pittsburgh, Pennsylvania
`
`
`
`
`Children’s Hospital of Pittsburgh of UPMC Pediatric Pain Physician
`Pittsburgh, Pennsylvania
`
`
`
`
`Children’s Hospital of Pittsburgh of UPMC
`Pittsburgh, Pennsylvania
`
`
`
`Children’s Hospital of Pittsburgh of UPMC Pediatric Cardiac Anesthesiologist
`Pittsburgh, Pennsylvania
`
`
`
`Interim Associate Director
`Perioperative Medical Services
`
`
`
`Ruby Memorial Hospital
`Robert C. Byrd Health Sciences Center
`West Virginia University
`Morgantown, West Virginia
`
`Charge Anesthesiologist
`
`James Gordon Cain, MD, MBA, FAAP
`
`
`4
`
`Petition for Inter Partes Review of US 8,338,470
`Amneal Pharmaceuticals LLC – Exhibit 1002 – Page 22
`
`
`
`CURRICULUM VITAE
`
`1998-2005
`
`
`1998-2005
`
`
`
`Ruby Memorial Hospital
`Robert C. Byrd Health Sciences Center
`West Virginia University
`Morgantown, West Virginia
`
`
`
`Ruby Memorial Hospital
`Robert C. Byrd Health Sciences Center
`West Virginia University
`Morgantown, West Virginia
`
`Cardiac Anesthesiologist
`
`Anesthesiologist
`
`
`1998-2005
`
`Anesthesiologist
`
`
`
`Chestnut Ridge Hospital
`Robert C. Byrd Health Sciences Center
`West Virginia University
`Morgantown, West Virginia
`
`1998-2005 West Virginia University Children’s Hospital Pediatric Anesthesiologist
`Robert C. Byrd Health Sciences Center
`West Virginia University
`
`
`2003-2005
`
`
`2003-2004
`
`
`2003-2004
`
`
`2003-2004
`
`
`
`
`
`Ruby Memorial Hospital
`Robert C. Byrd Health Scie
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