Attorney Docket No.
`IPR2016-01370
`110670-0009-651
`U.S. Patent No. 8,664,231
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`KOIOS PHARMACEUTICALS LLC,
`Petitioner
`
`v.
`
`MEDAC GESELLSCHAFT FLIER KLINISCHE
`SPEZIALPRAPARATE MBH,
`Patent Owner
`
`Case No. IPR2016-01370
`Patent Number 8,664,231
`
`Before JACQUELINE WRIGHT BONILLA, TONI R. SCHEINER,
`and ERICA A. FRANKLIN, Administrative Patent Judges
`
`EXPERT DECLARATION OF THOMAS ZIZIC, M.D.
`
`June 9, 2017
`
`Medac Exhibit 2092
`Koios Pharmaceuticals v. Medac
`IPR2016-01370
`Page 00001
`
`
`IPR2016-01370
`110670-0009-651
`U.S. Patent No. 8,664,231
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`KOIOS PHARMACEUTICALS LLC,
`Petitioner
`
`v.
`
`MEDAC GESELLSCHAFT FLIER KLINISCHE
`SPEZIALPRAPARATE MBH,
`Patent Owner
`
`Case No. IPR2016-01370
`Patent Number 8,664,231
`
`Before JACQUELINE WRIGHT BONILLA, TONI R. SCHEINER,
`and ERICA A. FRANKLIN, Administrative Patent Judges
`
`EXPERT DECLARATION OF THOMAS ZIZIC, M.D.
`
`June 9, 2017
`
`Medac Exhibit 2092
`Koios Pharmaceuticals v. Medac
`IPR2016-01370
`Page 00001
`
`
`
`Attorney Docket No.
`IPR2016-01370
`1 10670-0009-651
`U.S. Patent No. 8,664,231
`I, Thomas Zizic, M.D., have been retained as an expert by counsel for medac
`
`Gesellschaft Fur Klinische Spezialpraparate Mbh, Inc. ("Medac") in the above-
`
`captioned Inter Partes Review ("IPR")
`
`I. QUALIFICATIONS
`I am a rheuinatology physician and Associate Professor of Medicine
`1.
`
`at The Johns Hopkins University ("Johns Hopkins"). I have treated arthritis since
`
`the 1970s and published extensively on the progression of treatment options. I
`
`routinely treat inflammatory autoimmune disease patients with methotrexate,
`
`including using oral, intramuscular, and subcutaneous administration, and have
`
`done so throughout my clinical experience. I have treated thousands of patients
`
`with rheumatoid arthritis since 1971.
`
`2.
`
`I graduated from The Johns Hopkins University School of Medicine
`
`in 1965. I completed my internship and residency at Johns Hopkins between 1965
`
`and 1967. I also completed apost-doctoral fellowship at Johns Hopkins from 1969
`
`to 1971.
`
`3.
`
`I am board qualified in Rheumatology. I am a founding fellow of the
`
`American College of Rheumatology. I am also a member of multiple professional
`
`societies related to inflammatory autoimmune diseases, including the American
`
`Rheumatism Association and the District of Columbia Rheumatism Association.
`
`2
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`Page 00002
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`Attorney Docket No.
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`1 1 0670-0009-65 1
`U.S. Patent No. 8,664,231
`From 1971 to the present, I have held teaching and academic positions
`4.
`
`at Johns Hopkins. I was first an Instructor in Medicine from 1971 to 1975, and
`
`then became an Assistant Professor of Medicine from 1975 to 1981, when I
`
`became an Associate Professor of Medicine, a position I have held continuously
`
`since then.
`
`5.
`
`Among my other publications, since 1980, I have authored multiple
`
`publications on the diagnosis and treatment of rheumatoid arthritis. These include
`
`three articles on methotrexate, nine articles and abstracts on rheumatoid arthritis,
`
`six book chapters on rheumatoid arthritis (including three that discuss
`
`methotrexate), and 13 clinical studies involving methotrexate.
`
`6. My educational background, work experience, and a list of my
`
`publications are set forth in my curriculum vitae, which is attached as Tab A to this
`
`Declaration. A list of the cases in which I have testified as an expert at trial or by
`
`deposition over the previous 4 years is attached at Tab B.
`
`II. SCOPE OF ASSIGNMENT AND SUMMARY OF MY OPINIONS
`I am informed and understand that Koios Pharmaceuticals LLC
`7.
`
`("Koios") has petitioned for an IPR of Medac's U.S. Patent No. 8,664,231 (Ex.
`
`1001, "the `231 Patent") and has requested the cancellation of claims 1-22 of the
`
``231 Patent. I am informed and understand that in the IPR, Koios has relied on
`
`(among other documents) U.S. Patent No. 6,544,504 (Ex. 1003, "Grim") and a
`
`3
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`Page 00003
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`Attorney Docket No.
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`110670-0009-651
`U.S. Patent No. 8,664,231
`Wyeth product label "Methotrexate Sodium for Injection" (Ex. 1021, "Wyeth"). I
`
`also understand that the Patent Trial and Appeal Board ("Board") has instituted
`
`trial on claims 1-22 in view of Grint and Wyeth, among other documents. See Feb.
`
`8, 2017 Decision Granting Institution ("Decision").
`
`8.
`
`I am instructed that the challenged claims have a priority date of July
`
`21, 2006. I have been asked to assess the knowledge of the skilled artisan at that
`
`date, how physicians used methotrexate to treat inflammatory autoimmune
`
`diseases at that date, and what the skilled artisan would have understood from
`
`Grint and Wyeth at that date.
`
`9.
`
`In forming my opinions, I have relied upon my education, experience,
`
`and various written materials. A list of the written materials that I considered in
`
`rendering my opinions is attached to this declaration as Tab C. Each of these
`
`materials is a type of document that experts in my field would reasonably rely
`
`upon when forming their opinions.
`
`10. I hereby declare that all statements made herein of my own
`
`knowledge are true and that all statements made on information and belief are
`
`believed to be true; and further that these statements were made with the
`
`knowledge that willful false statements and the like so made are punishable by fine
`
`or imprisonment, or both, under 18 U.S.C. § 1001. If called to testify as to the
`
`truth of the matters stated herein, I could and would testify competently.
`
`0
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`Page 00004
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`IPR2016-01370
`U.S. Patent No. 8,664,231
`III. LEVEL OF SKILL IN THE ART
`1 1. I have been instructed, for the purposes of this Declaration, to opine
`
`Attorney Docket No.
`110670-0009-651
`
`on the knowledge and understanding of a person having ordinary skill in the art
`
`("POSITA") as of July 21, 2006.
`
`12. I understand that the factors considered in determining the ordinary
`
`level of skill in the art include: (i) the levels of education and experience of persons
`
`working in the field; (ii) the types of problems encountered in the field; and (iii)
`
`the sophistication of the technology. I understand that a person having ordinary
`
`skill in the art is not a real person, but rather a hypothetical individual with the
`
`qualities based on the factors above.
`
`13. I understand that Medac has previously stated that a POSITA with
`
`respect to the `231 Patent as of July 21, 2006 would have the understanding of: a) a
`
`person with an M.D. and experience using methotrexate to treat inflammatory
`
`autoimmune diseases; or b) a person with a Ph.D. or Pharm.D. in pharmacology,
`
`pharmaceutics, or chemistry; or c) a person with a lesser degree but with at least
`
`several years of additional experience in methotrexate preparation (e.g., a
`
`pharmacy technician or nurse) in either an academic or industrial setting.
`
`14. Based on over 40 years of experience in treating inflammatory
`
`autoimmune diseases, using (among other things) oral, intramuscular, and
`
`5
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`Page 00005
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`Attorney Docket No.
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`U.S. Patent No. 8,664,231
`subcutaneous administration of rnethotrexate, I agree with this definition of the
`
`level of ordinary skill in the art.
`
`15. I understand that Koios has taken the position that a POSITA would
`
`have either a Pharm.D. or a Ph.D. in pharmacy, pharmacology, or a related
`
`discipline; an M.D. or D.O. with experience in using methotrexate; or a B.S. in
`
`pharmacy with at least two years of experience formulating active pharmaceutical
`
`ingredients for injection. A POSITA would collaborate with others having
`
`expertise in, for- example, methods of treating disease and administering medicines.
`
`While I believe that the M.D. or D.O. in Koios's definition should have experience
`
`in using MTX to treat inflammatory autoimmune diseases, and that the B.S. in the
`
`Koios definition should have experience in formulating methotrexate for injection,
`
`my opinions are the same regardless of which of these levels of skill in the art I
`
`apply.
`
`IV. USE OF METHOTREXATE FOR THE TREATMENT OF
`INFLAMMATORY AUTOIMMUNE DISEASES
`16. Oral methotrexate has been used to treat inflammatory autoimmune
`
`diseases (like rheumatoid arthritis) since the 1950s. As noted above, I have treated
`
`thousands of patients with rheumatoid arthritis since 1971. In the 1980s, I was
`
`among the first rheumatologists to promote the use of methotrexate for rheumatoid
`
`arthritis. This was even before the FDA formally approved the drug for that
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`indication. I also participated in a number of studies in the 1990s and 2000s on the
`
`use of biologics, with and without methotrexate, for the treatment of rheumatoid
`
`arthritis. Accordingly, I have familiarity with methotrexate treatments over the
`
`past four decades, including those involving oral, intramuscular, and subcutaneous
`
`administration.
`
`17. Based on my experience, before the July 21, 2006 priority date of the
`
``231 Patent, and including until Medac introduced its RASUVOTM product in
`
`2014, the highest concentration of methotrexate that I ever used for subcutaneous
`
`injection, in treating inflammatory autoimmune diseases like rheumatoid arthritis,
`
`was 25 mg/ml. I am also not aware of other physicians using any higher
`
`concentrations subcutaneously for the treatment of inflammatory autoimmune
`
`diseases before RASUVOTM was introduced.
`
`18. In my experience, most rheumatoid arthritis patients using
`
`methotrexate start with a weekly dose of 7.5 or 10 mg, which may then increase to
`
`weekly doses of 20 or 25 mg, as necessary.
`
`19. Methotrexate is a cytotoxic or chemotherapeutic agent, meaning that it
`
`is harmful to living cells. Generally, cytotoxic agents pose a substantial risk of
`
`local toxicity to the patient near the point of injection.
`
`20. During intravenous injection, cytotoxic agents can leak into
`
`surrounding areas and damage soft tissue.
`
`This occurrence is known as
`
`fll
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`Page 00007
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`Attorney Docket No.
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`110670-0009-651
`U.S. Patent No. 8,664,231
`extravasation. When extravasation occurs, cytotoxic agents are known to cause
`
`necrosis and sloughing of soft tissues, such as skin. Ex. 2095 ("Gaze") at 2
`
`("[C]hemotherapeutic agents can cause severe and widespread tissue destruction if
`
`they are extravasated during treatment and thus remain undiluted at the site of
`
`injection."). As a cytotoxic agent, methotrexate was known to have the potential to
`
`cause irritation or tissue damage, if extravasated. Id. (Case 13, noting "infusion of
`
`methotrexate 100 mg" and resulting sloughing). The damage to soft tissue that
`
`occurs during extravasation may be predictive of potential damage during direct
`
`injection of the active agent into soft tissue such as muscle or subcutaneous tissue.
`
`Given that the concentration of the methotrexate will generally be higher in those
`
`methods (intramuscular and subcutaneous injection) than in IV injection, there
`
`could be a greater chance of local toxicity in them.
`
`21.
`
`Irritation or tissue damage at the injection site depends on the total
`
`dose, volume, and concentration of the drug administered. See, e.g., Ex. 2098
`
`("Schulmeister") at 5 ("[t]he severity of vesicant extravasation injuries generally is
`
`influenced by the type of vesicant that extravasates ... the concentration. and
`
`amount of the vesicant in the tissue); see also Ex. 2025 ("Boyle") at 3
`(extravasation "tissue injury depends on the drug as well as its dose, concentration,
`of the
`. and other irritant properties
`
`physiochemical characteristics
`infusate"). As one example, the literature reports that for cisplatin (another
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`Page 00008
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`Attorney Docket No.
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`110670-0009-651
`U.S. Patent No. 8,664,231
`cytotoxic agent), reducing concentrations can reduce the risk of injury: "The
`
`paucity of injection site problems with cisplatin may relate to its routine dilution in
`
`large volume parenteral saline solutions. This practice dramatically lessens
`
`cisplatin infusion concentrations and thereby diminishes the likelihood that a large
`
`ulcerogenic cisplatin dose could be extravasated in typical clinical settings." Ex.
`
`2097 ("Dorr") at 13. This routine dilution prior to injection is likely the reason that
`
`Ignoffo (Ex. 2096; 1980) lists cis-platinum (cisplatin) among "irritants or non-
`
`vesicants." Dorr agrees that cisplatin is generally an irritant. Ex. 2097 at 12-13 .
`
`However, Dorr also reports ulcerations due to extravasations when cisplatin is used
`
`in higher concentrations. Id.
`
`22. Even after July 2006, it was known that drugs for subcutaneous
`
`injection could cause local irritation and tissue damage: "These drugs must be
`
`highly soluble, low volume (less than 2 mL in a good-sized adult), and
`
`nonirritating (to prevent tissue damages, tissue necrosis, and sterile abscess
`
`formation)."
`
`Ex. 2005 ("Aschenbrenner") at 16-17.
`
`Subcutaneous or
`
`intramuscular injection could also cause more irritation than IV administration,
`
`which "[a]voids tissue irritation or injury resulting from IM or SC administration
`
`(e.g., with chemotherapeutic drugs .. .)." Id. at 18.
`
`23. Brooks (Ex. 1008), cited by Koios, reports that subcutaneous injection
`
`of methotrexate may be less painful than intramuscular injection. Ex. 1008 at 1, 3.
`
`G'
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`Page 00009
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`In my experience, other drugs such as antibiotics can be injected intramuscularly
`
`without pain. Accordingly, in my view, Brooks demonstrates that methotrexate is
`
`an irritant in that it can cause pain at the injection site, whether the injection is
`
`subcutaneous or intramuscular, although subcutaneous injection causes less pain.
`
`24. Much like cis-platinum, methotrexate has also been differently
`
`classified. For example, some literature (around 1980) classified methotrexate as a
`
`non-vesicant, or a drug that is not generally associated with severe necrosis. E.g.,
`
`Ex. 2096 at 2, Tbl. 1 (classifying methotrexate among "[d]rugs uncommonly
`
`associated with severe local necrosis"). However, even if the local reaction upon
`
`extravasation was not "severe," there was a potential for local toxicity to the
`
`patient using methotrexate, particularly in higher concentrations. Accordingly, the
`
`categorization of various cytotoxic agents has varied, which led to some
`
`uncertainty about the danger of drugs like methotrexate, particularly when used in
`
`high doses or concentrations.
`
`25. Even after July 2006, methotrexate has been classified as a drug that
`
`can cause local tissue damage after extravasation. For example, certain hospital
`
`guidelines classified methotrexate as both an "exfoliant" ("capable of causing
`
`inflammation and shedding of the skin but less likely to cause tissue death") and
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`"irritant" ("capable of causing inflammation and irritation, rarely proceeding to
`
`breakdown of tissue"). Ex. 2024 at 3-4.
`
`10
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`26. Based on this literature and my experience, physicians were generally
`
`cautious about increasing the amount and concentration of cytotoxic or
`
`chemotherapeutic agents, including inethotrexate, for injection, out of the concern
`
`for increased risk of injury at the soft tissue sites of injection. Ex. 2028 a~ 30
`
`("Any agent extravasated in high enough concentration may be an irritant."). Di .
`
`Schiff testified that any toxicity associated with methotrexate is dose-dependent,
`
`not concentration-dependent. Ex. 1034 ¶¶ 107-10. This testimony, however, is
`
`contrary to the knowledge in the art at the July 21, 2006 priority date of the `231
`
`Patent. For example, it was reported in April 2006 that methotrexate "causes dose-
`
`and serum concentration-related
`
`nephrotoxicity, hepatotoxicity, and
`
`myelosuppression." Ex. 2031 ("Parshuram") at 1 (emphasis added); see also Ex.
`
`2055 (Stoller) at 1 ("[d]etermination of methotrexate concentration in plasma
`
`thus identified patients at high risk of toxicity") (emphasis added). Accordingly,
`
`the concentration of inethotrexate in the blood can affect systemic toxicity, and
`
`similarly, the concentration of methotrexate in soft tissue following subcutaneous
`
`injection could affect local toxicity.
`
`V. THE PRIOR ART ON WHICH KOIOS AND THE BOARD RELY
`A. Grint
`27. I understand that Koios and the Board have relied on Grint (Ex. 1003)
`
`as prior art in this IPR I also understand that Koios and the Board (Decision at 16-
`
`11
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`17) argue that Grint discloses subcutaneous injections of methotrexate at
`
`concentrations above 30 mg/ml because Grint says that methotrexate should be
`
`"compounded for convenient and effective administration in effective amounts."
`
`Ex. 1003 at 6:60-7:1.
`
`28. In my opinion, the mere statement that a drug should be "compounded
`
`for convenient and effective administration in effective amounts" does not inform a
`
`POSITA of any particular doses or concentrations for that drug. In the context of
`
`concentration, Grint's broad methotrexate concentration range of "about 0.1 to
`
`about 40 mg/ml" makes that lack of teaching even more pronounced. For these
`
`reasons, a POSITA would not know what specific concentrations of methotrexate
`
`are "convenient and effective" for any particular type of administration or
`
`treatment of any particular type of disease. A physician would have to consult
`
`other sources to determine the proper concentration; i.e., which is conventionally
`
`believed to be convenient and effective, for a given administration and a given
`
`disease. In my experience, the highest concentration of methotrexate that was used
`
`to treat inflammatory autoimmune diseases before the July 2006 priority date was
`
`25 mg/ml. Thus, in my view, the POSITA reading Grint would not understand that
`
`it was referring to any higher concentrations than 25 mg/ml for the treatment of
`
`inflammatory autoimmune diseases using subcutaneous administration.
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`iF~
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`29. Grint's single illustrative example, Example 1, does not change my
`
`view. Ex. 1003 at 7:40-44. Example 1 does not recite the concentration of the
`
`methotrexate. Id. at 7:55-59. It provides only the dose "12.5-25 mg" and states
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`that patients had received the therapeutic dose for at least four months prior to the
`
`study and that the amount remained constant throughout the study. Id. In my
`
`experience, the POSITA would understand that disclosure to mean that the
`
`methotrexate was being delivered in concentrations of 25 mg/ml or less. Those
`
`were the only concentrations being used to treat rheumatoid arthritis at Grint's July
`
`1998 priority date.
`
`30. In the context of the amount of methotrexate, Grint's disclosure is also
`
`lacking. Grint states: "A unit dosage form can, for example, contain methotrexate
`
`in amounts ranging from 0.1 to 400 mg." Id. at 6:64-65. Again, Grint, by
`
`specifying such a broad dose range, has not provided any information to the
`
`POSITA about what dose is "convenient and effective" for a given disease.
`
`Further sources of information and conventional practice would have to be
`
`consulted. In my experience, the highest weekly dose of methotrexate used to treat
`
`rheumatoid arthritis was 25 mg. The lowest weekly dose was 5 mg. Accordingly,
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`no physician would administer a unit dose as low as 0.1-4 mg or as high as 100-
`
`400 mg to treat rheumatoid arthritis.
`
`13
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`31. In the context of mode of administration, Grint refers to
`
`"subcutaneous" only once: in Example 1 ("oral, subcutaneous or intramuscular
`
`dosing"). Id. at 7:56-57. As noted above, Grint does not correlate any such
`
`administration to a concentration or dose. It says only that a dose of 12.5-25 mg
`
`was used. Again, in my view, the POSITA would take from this disclosure that the
`
`standard, conventional dose and concentration we1-e being used: up to 25 mg/week
`
`using up to 25 mg/ml. Furthermore, in Example 1, methotrexate was used as a
`
`comparator, with IL-10 therapy as the primary treatment under evaluation. Id. at
`
`8:14-22. The Example 1 study also did not report any statistical significance for its
`
`results, only "trends," and did not demonstrate that IL-10 in combination with
`
`methotrexate had any beneficial effects on rheumatoid arthritis. Id. at 8:50-58.
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`Therefore, Example 1 did not show that methotrexate (even subcutaneously, at
`
`undisclosed concentrations) was "convenient and effective," even in combination
`
`with IL-10.
`
`32. For these reasons, a POSITA would not have understood Grint to
`
`teach that any specific methotrexate concentration for subcutaneous administration,
`and certainly not a concentration of more than 30 mg/ml, was "convenient and
`effective" for treating inflammatory autoimmune diseases, like rheumatoid
`
`arthritis.
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`f[!
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`B. Wyeth
`33. I understand that Koios and the Board (Decision at 28-30) also rely on
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`Attorney Docket No.
`1 1 0670-0009-65 1
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`Wyeth (Ex. 1021), a product label for "Methotrexate Sodium for Injection," as
`
`prior art against the `231 Patent.
`
`34. Wyeth contains the following statement:
`
`Methotrexate Sodium for Injection should be reconstituted with an
`appropriate sterile, preservative free medium such as 5% Dextrose
`Solution, USP, or Sodium Chloride Injection, USP. Reconstitute the
`20 mg vial to a concentration no greater than 25 mg/mL. The 1 gram
`vial should be reconstituted with 19.4 mL to a concentration of 50
`mg/mL. When high doses of methotrexate are administered by IV
`infusion, the total dose is diluted in 5%Dextrose Solution.
`
`Ex. 1021 at 79.
`
`35. In my opinion, this disclosure in Wyeth does not teach the use of
`
`methotrexate at 50 mg/ml for subcutaneous injection for the treatment of
`
`rheumatoid arthritis. First, read in context with the other sections of Wyeth, these
`
`statements in Wyeth teach a person of ordinary skill in the art only that a 1 gram
`
`vial reconstituted to a concentration of 50 mg/ml would be used (with substantial
`
`further dilution) for IV infusion. Second, as I explained above, I and no one I
`
`know used 50 mg/ml methotrexate concentration to treat rheumatoid arthritis by
`
`subcutaneous administration.
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`36. For example, Wyeth teaches that acute lymphoblastic leukemia
`
`patients "were treated with intermediate-dose intravenous methotrexate
`
`(1 gm/m2)." Ex. 1021 at 66, 69. Further, Wyeth teaches that for osteosarcoma
`
`"[t]he starting dose for high dose methotrexate treatment is 12 grams/m2 ... [and]
`
`the dose may be escalated to 15 grams/m2." Id. at 75. It further indicates that this
`
`12 gram/m2 methotrexate is administered "IV as 4 hour infusion (starting dose)."
`
`Id. at 76. The average adult body surface area is 1.7 m2. See, e.g., Ex. 2005
`
`(Aschenbrenner) at 24. Accordingly, these examples show that multiple grams are
`
`required for these treatments. Wyeth therefore is saying that the 1 gram
`
`methotrexate vials are to be used in those high-dose IV treatments. It is not for the
`
`low-dose treatment of rheumatoid arthritis or other inflammatory autoimmune
`
`diseases.
`
`37. Conversely, Wyeth refers to a 20 mg vial. I believe that the POSITA
`
`would understand, as I understand, Wyeth to be saying that this vial was for use in
`
`treating rheumatoid arthritis and other inflammatory autoimmune diseases. There
`
`are sound reasons for this. First, generally, rheumatoid arthritis patients would be
`
`prescribed a weekly methotrexate dose no higher than 20 or 25 mg. Only using a
`
`Wyeth 20 mg vial would make sense for that application. Second, for that vial,
`
`Wyeth says to use "no greater than 25 mg/ml." That was the highest concentration
`
`being used at that time for the treatment of rheumatoid arthritis. Third, the
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`i['!
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`110670-0009-651
`U.S. Patent No. 8,664,231
`resulting 0.8 ml volume would also be consistent with subcutaneous injection; i.e.,
`
`more than 1 ml is disfavored as painful. By contrast, the Wyeth 1 gram vial would
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`be many times greater than the maximum single dose for rheumatoid arthritis (or
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`any other inflammatory autoiminune disease). The resulting 20 ml volume of the
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`19.4 ml diluted 1 gram vial also far exceeds any possible volume for subcutaneous
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`injection, and would make sense only for IV infusion. In my experience, a
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`physician would not use a 1 gram vial to prepare a single dose of 25 mg, and then
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`throw away the remaining drug (975 mg). Wyeth also states that each vial,
`
`whether 20 mg or 1 gram, was for "Single Use Only." Id. at 80.
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`VI. COMPENSATION AND PREVIOUS TESTIMONY
`38. The cases for which I have testified as an expert at trial or by
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`deposition within the preceding four years are listed in Tab B to this report. As
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`compensation for my time spent working and testifying in connection with this
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`IPR, I receive $670.00 per hour for all consulting work and $920.00 per hour for
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`all testimony in deposition and/or at trial. My compensation is not dependent on
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`the outcome of this case.
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`VII. SUPPLEMENTAL OR AMENDED OPINION
`39. I reserve the right to supplement or amend my opinions in response to
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`the opinions expressed by Koios or its experts, or in light of any additional
`
`17
`
`Page 00017
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`
`
`Attorney Docket No.
`IPR2416-01370
`1 1 0670-0009-65 1
`U.S. Patent No. 8,664,231
`evidence, testimony, discovery or other information that may be provided to me
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`after the date of this report.
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`*
`
`~
`
`I declare under penalty of perjury under the laws of the United States of
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`America that the foregoing is true and correct to the best of my knowledge.
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`Dated: June 9, 2017
`
`~_
`
``'3 ~ ~~
`'~"``"~
`Thomas Zizic, .D.
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` ~
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`Page 00018
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`TAB A
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`TAB ATAB ATAB A
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`Page 00019
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`THOMAS M. ZIZIC, M.D. March 2017
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`Physician, The Johns Hopkins Hospital
`Baltimore, Maryland
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`Physician, Good Samaritan Hospital
`Baltimore, Maryland
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`Associate Professor of Medicine
`Johns Hopkins University School of Medicine
`Baltimore, Maryland
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`CURRE NT APPOINTMENTS
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`HOSPITAL:
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`UNIVERSITY:
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`OFFICE ADDRESS:
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` Primary Rheumatology Office
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`4014 Philadelphia Rd.
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`Abingdon, Md. 21009
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`P - 410-734-4290
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`F - 410-734-4273
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`Cell-410-340-7819
`tzizic@aol.com
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`
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`HOME ADDRESS
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`EDUCATION:
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`1954 - 1958
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`1958 - 1961
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`1961 – 1965
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`1965 – 1966
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`8415 Bellona Ave. #811
`Baltimore, Md. 21204
`443-895-4829
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`Bay View High School
`Milwaukee, Wisconsin
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`University of Wisconsin, B.S.
`Madison, Wisconsin
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`The Johns Hopkins University
`School of Medicine, M.D.
`Baltimore, Maryland
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`The Johns Hopkins Hospital
`Baltimore, Maryland
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`6/7/2017
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`Page 00020
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`1966 – 1967
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`1967 – 1969
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`1969 – 1971
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`1971 – 1973
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`1971 – 1973
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`1973 – 1981
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`1975 - 1981
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`Intern in Medicine, Marburg Medical Service
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`The Johns Hopkins Hospital
`Baltimore, Maryland
`Assistant Resident, Marburg Medical Service
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`Military Service
`San Antonio, Texas
`School of Aerospace Medicine
`
`The Johns Hopkins University
`School of Medicine
`Baltimore, Maryland
`Fellow in Internal Medicine,
`Connective Tissue Division
`
`The Arthritis Foundation
`Post-Doctoral Fellow
`
`The Johns Hopkins University
`School of Medicine
`Baltimore, Maryland
`Instructor in Medicine
`
`The University of Maryland
`School of Medicine
`Baltimore, Maryland
`Assistant Professor of Medicine
`
`Assistant Professor Medicine
`The Johns Hopkins University School of Medicine
`Baltimore, Maryland
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`Associate Professor of Medicine
`The Johns Hopkins University School of Medicine
`Baltimore, Maryland
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`1981 - Present
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`BOARD CERTIFICATIONS:
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`1965
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`State of Maryland, Medical Examiners
`Physicians and Surgeons
`1971 Qualified -Rheumatology
` (Boards nonexistent- Grandfathered)
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`HONORS:
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`Phi Eta Sigma
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`6/7/2017
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`Page 00021
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`Phi Kappa Phi
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`Phi Beta Kappa
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`Founding Fellow, American College of Rheumatology
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`1961
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`1961
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`1986
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`MEMBERSHIP IN PROFESSIONAL SOCIETIES:
`1971 - Present
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`American Rheumatism Association
`1975 - 1985
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`District of Columbia Rheumatism Association
`1971 - Present
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`The Johns Hopkins Hospital Medical Society
`1971 – Present
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`The Johns Hopkins University Alumni Association
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`Arthritis Foundation (Maryland Chapter)
`1976 - 1977
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`Vice President
`1977 - 1979
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`Medical & Scientific Committee
`1977 - 1979
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`Professional Education Committee
`1975 - 1976
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`Maryland Society of Rheumatic Diseases, President
`1974 - 1976
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`Arthritis Alert, State of Maryland, Chairman
`1986 - 1992
`State Commission on Arthritis and Related Disease,
`Chairman
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`CONSULTANT APPOINTMENT:
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`1975 - 1978
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`Rheumatology Consultant, United States Public
`Administration Hospital, Baltimore, Maryland
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`1978 - 1980
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`Rheumatology Consultant, United States Public Health
`Services Hospital, Baltimore, Maryland
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`SELECTED COMMITTEES/ACTIVITIES:
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`1971 – 1972
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`1972 – 1975
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`1973 – 1975
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`1974 – 1976
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`Library Committee
`Good Samaritan Hospital
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`Faculty Steering Committee
`Johns Hopkins University/Good Samaritan Hospital
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`Medical Planning and Developmental Committee
`Johns Hopkins Medical Institutions
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`Arthritis Alert, State of Maryland
`Chairman
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`6/7/2017
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`Page 00022
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`1974 – 1975
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`1974 – 1975
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`1975 – 1976
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`1975 – 1976
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`1975 – 1976
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`1975 – 1985
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`1976 – 1977
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`1976 – 1979
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`1977 – 1987
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`1976 – 1977
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`1977 – 1978
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`1977 – 1980
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`1978 – 1983
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`1978 – 1979
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`Pharmacy and Therapeutic Committee
`Good Samaritan Hospital
`Chairman
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`Credentials Committee
`Good Samaritan Hospital
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`Admissions Committee
`Johns Hopkins University
`School of Medicine
`
`Utilization Review Committee
`Good Samaritan Hospital
`
`Maryland Society of Rheumatic Disease
`President
`
`Associate Director
`Rheumatic Disease Unit
`Good Samaritan Hospital
`
`Update in Rheumatology I
`Johns Hopkins University/University of Maryland
`Course Director
`
`Education Committee
`Arthritis Foundation, Maryland Chapter
`Chairman
`
`
`Board of Directors
`Courseware, Inc.
`
`
`
`Arthritis Foundation, Maryland Chapter
`Vice-President
`
`Medical Audit Committee
`Good Samaritan Hospital
`
`Medical and Scientific Committee
`Arthritis Foundation, Maryland Chapter
`
`Associate Director
`NIAMDD Multipurpose Arthritis Center
`Johns Hopkins University School of Medicine
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`Board of Directors
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` 4
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`6/7/2017
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`Page 00023
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`1978 –1979
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`1978 – 1981
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`1979 – 1980
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`1979 – 1980
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`1979 – 1984
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`1980 – 1981
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`1980 – 1982
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`1982 – 1986
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`1985 – 1989
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`1991 - 1993
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`1991 – 1998
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`1991 - 1994
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`1993 – 1996
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`Maryland Lupus Foundation
`
`Medical Executive Committee
`Good Samaritan Hospital
`
`Medical Records Committee
`Good Samaritan Hospital
`Chairman
`
`Update in Rheumatology II
`Johns Hopkins University/University of Maryland
`Course Director
`
`National Arthritis Foundation Committee on
`Health Services Administration
`
`National Arthritis Foundation Committee on
`Governmental Affairs
`
`Update in Rheumatology III
`Johns Hopkins University/University of Maryland
`Course Director
`
`Arthritis Foundation, Maryland Chapter
`Vice-President
`
`Arthritis Information Clearinghouse
`Advisory Group
`
`The Arthritis Society, Toronto, Canada
`
`Southeast Region Council
`American College of Rheumatology
`External Reviewer for Research Grant Applications
`
`President
`Chesapeake Osteoporosis Center, Inc.
`Baltimore, Maryland
`
`National Medical Advisory Board
`Protocare, Inc.
`
`Director of Medical Affairs
`Murray Electronics
`Hunt Valley, Maryland
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`6/7/2017
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`Page 00024
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