THIRD DECLARATION OF LEONARD X CHYALL, PH.D.
`
`I, the undersigned. Dr. Leonard J. Chyall, U.S. Passport No. 432624896, with a business
`
`address of Chyall Pharmaceutical. Consulting LLC, 3000 Kent Avenue. Suite Dl-105, West
`
`Lafayette, Indiana 47906, USA, having been, warned that I must state the truth and that I
`
`shall be liable to the penalties prescribed by law should I fail to do so, hereby declare in
`
`writing as follows:
`
`1. 1 am the same Leonard J. Chyall who submitted a declaration dated August 3, 2010
`
`(the "First Chyall Declaration") and a declaration dated March 7, 2012 (the
`
`"Second Chyall Declaration"), in support of the position of Teva Pharmaceutical
`
`Industries Ltd. ("Teva") in the proceedings before the Honorable Deputy Registrar
`
`of Patents regarding Israel Patent Application No. 172563, filed by Merck & Co.
`
`Inc., U.S.A ("Merck").
`
`2. This declaration was prepared in response to the Affidavit of Prof. Jerry L. Atwood
`
`submitted on behalf of Merck regarding an experiment that Prof. Atwood conducted
`
`in August 2012 (the "Second Atwood Affidavit"). I was advised by Teva's
`
`counsel that Merck does not rely on paragraphs 3, 6, 7, 8 and 9 of the Second
`
`Atwood Affidavit.
`
`3. The fact that I have not commented on any particular point in the Second Atwood
`
`Affidavit does not mean that I accept or agree with that point. There is nothing in
`
`the Second Atwood Affidavit that causes me to change the views that I expressed in
`
`the First and Second Chyall Declarations.
`
`1
`
`Merck Sharp & Dohme Corp. Exhibit 2031
`Dr. Reddy’s Laboratories Inc. v. Merck Sharp and Dohme Corp.
`IPR2020-01060
`Page 1
`
`
`
`I, the undersigned. Dr. Leonard J. Chyall, U.S. Passport No. 432624896, with a business
`
`address of Chyall Pharmaceutical. Consulting LLC, 3000 Kent Avenue. Suite Dl-105, West
`
`Lafayette, Indiana 47906, USA, having been, warned that I must state the truth and that I
`
`shall be liable to the penalties prescribed by law should I fail to do so, hereby declare in
`
`writing as follows:
`
`1. 1 am the same Leonard J. Chyall who submitted a declaration dated August 3, 2010
`
`(the "First Chyall Declaration") and a declaration dated March 7, 2012 (the
`
`"Second Chyall Declaration"), in support of the position of Teva Pharmaceutical
`
`Industries Ltd. ("Teva") in the proceedings before the Honorable Deputy Registrar
`
`of Patents regarding Israel Patent Application No. 172563, filed by Merck & Co.
`
`Inc., U.S.A ("Merck").
`
`2. This declaration was prepared in response to the Affidavit of Prof. Jerry L. Atwood
`
`submitted on behalf of Merck regarding an experiment that Prof. Atwood conducted
`
`in August 2012 (the "Second Atwood Affidavit"). I was advised by Teva's
`
`counsel that Merck does not rely on paragraphs 3, 6, 7, 8 and 9 of the Second
`
`Atwood Affidavit.
`
`3. The fact that I have not commented on any particular point in the Second Atwood
`
`Affidavit does not mean that I accept or agree with that point. There is nothing in
`
`the Second Atwood Affidavit that causes me to change the views that I expressed in
`
`the First and Second Chyall Declarations.
`
`1
`
`Merck Sharp & Dohme Corp. Exhibit 2031
`Dr. Reddy’s Laboratories Inc. v. Merck Sharp and Dohme Corp.
`IPR2020-01060
`Page 1
`
`
`
`byproducts and/or unreacted sitagliptin base dissolved in the reaction solvent
`
`and trapped inside the recovered solids, would make it more difficult to
`
`remove those now solidified impurities, byproducts and/or unreacted
`
`sitagliptin base through subsequent washing.
`
`F. Prof. Atwood states that he used 3x3 mL of isopropanol solvent to wash and
`
`filter the solids that he recovered. See Atwood Exhibit HH. This is a very
`
`small amount of solvent for washing Prof. Atwood,s recovered solids when
`
`using a Buchner funnel with a diameter of approximately 7 cm. Using too
`
`little solvent for washing would result in ineffective removal of impurities,
`
`byproducts and unreacted starting materials.
`
`9. Prof. Atwood's laboratory notebook, Exhibit HH of his Second Affidavit, by itself,
`
`does not provide enough detail to determine whether one or more of the above steps
`
`rendered Prof. Atwood's washing steps inadequate. Therefore, unlike my criticism of
`
`Prof. Atwood's previous experiments - which did not include any filtration and
`
`washing and therefore did not require that I conduct experiments to conclude that
`
`Prof. Atwood's assertions regarding the solids that he recovered were unreliable and
`
`without scientific merit -1 could only prove- the misleading nature of Prof. Atwood,s
`
`New Experiment, which included a "filtration and washing" step, by conducting
`
`experiments.
`
`My Experiments Prove That Prof. Atwood,s "Filtration And Washing" Was
`
`Ineffective
`
`10. I received from Teva a sample container labeled lot no. D6655070112, which I
`
`understand to contain Sitagliptin Free Base. The sample was assigned LIMS No.
`
`308390, and I characterized the material using XPRD (see Exhibit A). The XRPD
`
`5
`
`Merck Sharp & Dohme Corp. Exhibit 2031
`Dr. Reddy’s Laboratories Inc. v. Merck Sharp and Dohme Corp.
`IPR2020-01060
`Page 2
`
`
`
`pattern obtained for the material confirmed that the material was crystalline sitagliptin
`
`base as disclosed in PCT Publication No. WO 2009/070314 A2.
`
`11. I first replicated as closely as possible the New Experiment described in the Second
`
`Atwood Affidavit. I conducted this replication to ensure that it was possible, based
`
`on the procedure described in Prof. Atwood's laboratory notebook, Exhibit HH, to
`
`obtain crystalline solids with the characteristic XRPD pattern of Prof. Atwood's
`
`alleged "2:1 salt".
`
`12. However, my solution did not solidify overnight like Prof. Atwood,s solution. In
`
`order to precipitate the reaction product, I cooled the reaction mixture using an ice
`
`bath with stirring. I filtered and washed my recovered solids using the same
`
`"filtration and washing" protocol that Prof. Atwood used to filter and wash his
`
`recovered solids. I analyzed the recovered solids by XRPD. The recovered solids
`
`had the same characteristic XRPD pattern as that of Prof. Atwood,s solids
`
`(Exhibit B), which demonstrates that my use of an ice bath to precipitate solids did
`
`not affect the final product and was not a material deviation from Prof. Atwood's
`
`procedure. I refer to the solids that I recovered from this experiment as "the
`
`Replicated Atwood Wash Solids". A detailed description of how I obtained the
`
`Replicated Atwood Wash Solids is set forth in my laboratory notebooks, (Exhibit C).
`
`13. I next conducted an experiment to see the effect of progressively more thorough
`
`washings than employed by Prof. Atwood,s "filtration and washing" protocol. To do
`
`so, I again replicated Prof. Atwood's New Experiment, except at double the scale, so
`
`as to obtain a sufficient amount of material. This time the solution solidified
`
`overnight, like Prof. Atwood's solution. I analyzed the recovered solids by XRPD.
`
`The solids recovered on the Biichner funnel after washing once with isopropanol had
`
`Merck Sharp & Dohme Corp. Exhibit 2031
`Dr. Reddy’s Laboratories Inc. v. Merck Sharp and Dohme Corp.
`IPR2020-01060
`Page 3
`
`
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
