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`I, the undersigned. Dr. Leonard J. Chyall, U.S. Passport No. 432624896, with a business
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`address of Chyall Pharmaceutical. Consulting LLC, 3000 Kent Avenue. Suite Dl-105, West
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`Lafayette, Indiana 47906, USA, having been, warned that I must state the truth and that I
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`shall be liable to the penalties prescribed by law should I fail to do so, hereby declare in
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`writing as follows:
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`1. 1 am the same Leonard J. Chyall who submitted a declaration dated August 3, 2010
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`(the "First Chyall Declaration") and a declaration dated March 7, 2012 (the
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`"Second Chyall Declaration"), in support of the position of Teva Pharmaceutical
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`Industries Ltd. ("Teva") in the proceedings before the Honorable Deputy Registrar
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`of Patents regarding Israel Patent Application No. 172563, filed by Merck & Co.
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`Inc., U.S.A ("Merck").
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`2. This declaration was prepared in response to the Affidavit of Prof. Jerry L. Atwood
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`submitted on behalf of Merck regarding an experiment that Prof. Atwood conducted
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`in August 2012 (the "Second Atwood Affidavit"). I was advised by Teva's
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`counsel that Merck does not rely on paragraphs 3, 6, 7, 8 and 9 of the Second
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`Atwood Affidavit.
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`3. The fact that I have not commented on any particular point in the Second Atwood
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`Affidavit does not mean that I accept or agree with that point. There is nothing in
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`the Second Atwood Affidavit that causes me to change the views that I expressed in
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`the First and Second Chyall Declarations.
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`1
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`Merck Sharp & Dohme Corp. Exhibit 2031
`Dr. Reddy’s Laboratories Inc. v. Merck Sharp and Dohme Corp.
`IPR2020-01060
`Page 1
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`byproducts and/or unreacted sitagliptin base dissolved in the reaction solvent
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`and trapped inside the recovered solids, would make it more difficult to
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`remove those now solidified impurities, byproducts and/or unreacted
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`sitagliptin base through subsequent washing.
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`F. Prof. Atwood states that he used 3x3 mL of isopropanol solvent to wash and
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`filter the solids that he recovered. See Atwood Exhibit HH. This is a very
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`small amount of solvent for washing Prof. Atwood,s recovered solids when
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`using a Buchner funnel with a diameter of approximately 7 cm. Using too
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`little solvent for washing would result in ineffective removal of impurities,
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`byproducts and unreacted starting materials.
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`9. Prof. Atwood's laboratory notebook, Exhibit HH of his Second Affidavit, by itself,
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`does not provide enough detail to determine whether one or more of the above steps
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`rendered Prof. Atwood's washing steps inadequate. Therefore, unlike my criticism of
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`Prof. Atwood's previous experiments - which did not include any filtration and
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`washing and therefore did not require that I conduct experiments to conclude that
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`Prof. Atwood's assertions regarding the solids that he recovered were unreliable and
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`without scientific merit -1 could only prove- the misleading nature of Prof. Atwood,s
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`New Experiment, which included a "filtration and washing" step, by conducting
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`experiments.
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`My Experiments Prove That Prof. Atwood,s "Filtration And Washing" Was
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`Ineffective
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`10. I received from Teva a sample container labeled lot no. D6655070112, which I
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`understand to contain Sitagliptin Free Base. The sample was assigned LIMS No.
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`308390, and I characterized the material using XPRD (see Exhibit A). The XRPD
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`5
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`Merck Sharp & Dohme Corp. Exhibit 2031
`Dr. Reddy’s Laboratories Inc. v. Merck Sharp and Dohme Corp.
`IPR2020-01060
`Page 2
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`
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`pattern obtained for the material confirmed that the material was crystalline sitagliptin
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`base as disclosed in PCT Publication No. WO 2009/070314 A2.
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`11. I first replicated as closely as possible the New Experiment described in the Second
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`Atwood Affidavit. I conducted this replication to ensure that it was possible, based
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`on the procedure described in Prof. Atwood's laboratory notebook, Exhibit HH, to
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`obtain crystalline solids with the characteristic XRPD pattern of Prof. Atwood's
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`alleged "2:1 salt".
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`12. However, my solution did not solidify overnight like Prof. Atwood,s solution. In
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`order to precipitate the reaction product, I cooled the reaction mixture using an ice
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`bath with stirring. I filtered and washed my recovered solids using the same
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`"filtration and washing" protocol that Prof. Atwood used to filter and wash his
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`recovered solids. I analyzed the recovered solids by XRPD. The recovered solids
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`had the same characteristic XRPD pattern as that of Prof. Atwood,s solids
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`(Exhibit B), which demonstrates that my use of an ice bath to precipitate solids did
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`not affect the final product and was not a material deviation from Prof. Atwood's
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`procedure. I refer to the solids that I recovered from this experiment as "the
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`Replicated Atwood Wash Solids". A detailed description of how I obtained the
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`Replicated Atwood Wash Solids is set forth in my laboratory notebooks, (Exhibit C).
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`13. I next conducted an experiment to see the effect of progressively more thorough
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`washings than employed by Prof. Atwood,s "filtration and washing" protocol. To do
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`so, I again replicated Prof. Atwood's New Experiment, except at double the scale, so
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`as to obtain a sufficient amount of material. This time the solution solidified
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`overnight, like Prof. Atwood's solution. I analyzed the recovered solids by XRPD.
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`The solids recovered on the Biichner funnel after washing once with isopropanol had
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`Merck Sharp & Dohme Corp. Exhibit 2031
`Dr. Reddy’s Laboratories Inc. v. Merck Sharp and Dohme Corp.
`IPR2020-01060
`Page 3
`
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