`
`Filed: August 1, 2017
`
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`ACRUX DDS PTY LTD. & ACRUX LIMITED
`Petitioners,
`
`v.
`
`KAKEN PHARMACEUTICAL CO., LTD. and
`VALEANT PHARMACEUTICALS INTERNATIONAL, INC.
`Patent Owner and Licensee
`
`
`
`Case: IPR2017-00190
`U.S. Patent No. 7,214,506
`
`
`
`
`
`
`DECLARATION OF YOSHIYUKI TATSUMI, PH.D.
`
`
`
`
`
`
`
`
`
`
`
`
`I, Yoshiyuki Tatsumi, hereby declare and state:
`
`Case IPR2017-00190
`
`1.
`
`I am an inventor of the subject matter described and claimed in U.S.
`
`Patent No. 7,214,506 (“the ’506 patent”). I submit this Declaration on behalf of
`
`Kaken Pharmaceutical Co., Ltd. (“Kaken”) in Inter Partes Review No. 2017-
`
`00190.
`
`2.
`
`I am a Group Manager of the Pharmacology Department of the Drug
`
`Discovery Center at Kaken Pharmaceutical Co., Ltd. (“Kaken”). I am also the
`
`Chairman of
`
`the Biosafety Committee and Chairman of
`
`the Genetic
`
`Recombination Experiment Safety Committee at Kaken.
`
`3.
`
`I graduated with a degree in Pharmaceutical Sciences from Kindai
`
`University in 1990 before gaining a master’s degree in pharmaceutical science
`
`from Kindai University Graduate School. I obtained a Ph.D. in Pharmaceutics
`
`from Kindai University Graduate School in 2003.
`
`4.
`
`In 1992, I joined the Chemotherapy Group of Pharmaceutical Science
`
`in the Research Center of Kaken. In general, from 1992-1995, I worked on
`
`antibacterial agents, including cephalosporins and quinolones. From 1994-2000, I
`
`worked on the treatment of athlete’s foot (also known as tinea pedis) using KP-
`
`103. I have extensive experience in researching and evaluating the therapeutic
`
`effects of KP-103, including for the topical treatment of tinea pedis and
`
`onychomycosis.
`
`1
`
`
`
`
`
`
`Case IPR2017-00190
`
`5.
`
`I have been asked to explain the research and development Kaken
`
`conducted on KP-103 and to explain the contents of several internal laboratory
`
`notebooks, and activity reports relating to that research. This Declaration describes
`
`my personal knowledge of each of the events and documents described below.
`
`6.
`
`Kaken discovered the compound KP-103 in the early-1990’s during
`
`its research on a new antifungal agent that could be commercialized to treat tinea
`
`pedis. In particular, Kaken hoped to discover an antifungal agent that could be
`
`used to treat mycosis and specifically, tinea pedis (commonly called athlete’s foot).
`
`7.
`
`Kaken considered various topical antifungal agents and focused its
`
`attention on triazole derivatives to develop a broad spectrum antifungal agent. We
`
`evaluated the differences between triazole and imidazole derivatives and studied
`
`the in vitro activities of the agents against various microorganisms commonly
`
`found in tinea pedis. In the course of this research, KP-103 was discovered.
`
`8.
`
`Exhibit 2030 and Exhibit 2033 are pages from lab notebooks during
`
`our research. Exhibit 2030 is a laboratory notebook labeled “Fungus” and is dated
`
`September 8, 1992 through September 17, 1993. Exhibit 2033 is titled “Antifungal
`
`activity of triazole-based compound in vitro” and is dated April 26, 1993. I have
`
`knowledge of the work recorded on these pages. The compound labeled either “S-
`
`32282” or “32282” corresponds to KP-103. See Ex. 2030, 2; Ex. 2033, 1. It was
`
`the regular practice at Kaken to maintain contemporaneous laboratory notebooks
`
`2
`
`
`
`
`
`documenting the research we conducted and the results of those experiments, as
`
`Case IPR2017-00190
`
`reflected in these appendices. To the best of my knowledge, these reports are
`
`accurate and reflect data generated during the experiments that led to the discovery
`
`of KP-103. Because Kaken was interested in commercializing an antifungal agent,
`
`none of the data resulting from the research in the 1992-1993 period was published
`
`or otherwise made publicly available at that time. Instead, Kaken continued
`
`experimenting with KP-103 and other antifungal agents.
`
`9.
`
`Kaken then decided to publish its internal data to determine third-
`
`party interest in licensing KP-103 as a treatment for tinea pedis. In September
`
`1996, licensing representatives from Kaken and I attended the 36th Interscience
`
`Conference on Antimicrobial Agents and Chemotherapy (ICAAC). At the
`
`ICAAC, we presented the Kaken Abstracts that are shown in Exhibit 1015 and
`
`related Abstracts 790, 792, and 793, which are shown in Exhibit 2036, Exhibit
`
`2037, and Exhibit 2038, respectively. I located Abstracts 790, 792, and 793 in my
`
`corporate files. Those were the only materials relating to the conference that I
`
`found. I have personal knowledge of the information presented in the Abstracts
`
`and personal knowledge of Kaken’s commercialization efforts for KP-103.
`
`10. The Kaken Abstracts explained that KP-103 was a novel antifungal
`
`that had been developed for topical treatment of tinea pedis and that KP-103
`
`showed broad spectrum antifungal activity and positive cure rates against that
`
`3
`
`
`
`
`
`fungal infection. The progression of in vitro experiments in the Kaken Abstracts
`
`Case IPR2017-00190
`
`from MIC activity testing, to testing in stripped horny layer, and then on guinea pig
`
`skin illustrates our research focus on tinea pedis and the direction of that work.
`
`11. Kaken began phase I clinical trials related to using KP-103 to treat
`
`tinea pedis in November 1996. Following the conclusion of the phase I trial in
`
`November 1997, the company decided to stop any additional clinical trials or
`
`research on KP-103 and the project was subsequently put aside.
`
`12. To my knowledge, the clinical significance of KP-103 for treating
`
`onychomycosis had not yet been recognized by Kaken or by anyone at the ICAAC
`
`meeting, nor had I heard of anyone else suggesting at that time to use KP-103 for
`
`that indication. Once the KP-103 project was put aside, we were permitted to
`
`publish the data from our 1992-1993 research evaluating KP-103’s efficacy in
`
`tinea pedis.
`
`13. We published the data in 1999 in an article entitled “Synthesis and
`
`Antifungal Activities of (2R,3R)-2-Aryl-1-azolyl-3-(substituted amino)-2-butanol
`
`Derivatives as Topical Antifungal Agents” by Ogura et al. I understand the article
`
`has been cited in the Inter Partes Review as Exhibit 1012. The article was based
`
`in part on the data in Exhibits 2030, 2033, 2036, 2037, and 2038. I am listed as an
`
`author on this publication and I have personal knowledge of its contents. To the
`
`best of my knowledge, this article accurately describes experiments from 1992-
`
`4
`
`
`
`
`
`1993 that Kaken conducted in the course of discovering KP-103 and evaluating
`
`Case IPR2017-00190
`
`KP-103 as a possible antifungal agent useful for the treatment of tinea pedis.
`
`14. Later, I returned to KP-103 and tested it for effectiveness against
`
`onychomycosis. Prior to this research, to my knowledge, no one at Kaken believed
`
`KP-103 would be an effective topical treatment for onychomycosis. A summary of
`
`the testing that took place at that time is embodied in the Research and
`
`Development Activity Report dated May 28, 1999 (“the May 1999 Report”) as
`
`shown in Exhibit 2039. I have personal knowledge of the contents of this May
`
`1999 Report. To the best of my knowledge, this May 1999 Report is an accurate
`
`description of the experiments described therein. It therefore reflects a full and
`
`complete summary of the experiments relating to topical KP-103, as applied to the
`
`nail for treating onychomycosis, conducted up to the May 1999 time period.
`
`15.
`
` Based on my work at Kaken, I have personal knowledge of Kaken’s
`
`record keeping practices in or around 1999. Research and Development Activity
`
`Reports like the May 1999 Report were produced in Kaken’s normal course of
`
`business to report on a research group’s activities from the previous month. This
`
`particular May 1999 Report (Ex. 2039) includes work from April 1999 to May
`
`1999 when I was directly involved in the underlying research. I am not aware of
`
`any earlier reports relevant to this study other than the materials enclosed with this
`
`declaration.
`
`5
`
`
`
`
`
`
`Case IPR2017-00190
`
`16.
`
`I am indicated as one of the “Responsible parties” on the Report. The
`
`data produced during our testing is shown in Exhibit 2042 and is dated May 21,
`
`1999. I drafted a summary of our testing, which is shown in Exhibit 2045 and is
`
`dated May 26, 1999. I drafted the document in Exhibit 2045 according to the
`
`normal procedure in our Research Group, which required me to provide the Team
`
`Leader of the Pharmacology Department, who at that time was Dr. Hisato Senda,
`
`with a summary of our ongoing projects. Dr. Senda then reviewed my summary
`
`and used it to prepare the May 1999 Report. I later received and reviewed that
`
`May 1999 Report. The May 1999 Report bears a stamp with the seal of Dr. Senda.
`
`17. The May 1999 Report describes the development of a guinea pig
`
`model of onychomycosis and treatment efficacy of KP-103 using this model. It
`
`explains that as part of our research program, our team at Kaken devised a new
`
`method to evaluate the effects of antimicrobial agents on onychomycosis. At that
`
`time, we had discovered that existing methods did not reliably evaluate the
`
`efficacy of an agent for onychomycosis. For instance, existing methods applied
`
`an antifungal agent to an infected animal but then conducted culture tests without
`
`removing the drug remaining in the skin or nails. This caused the drug to have a
`
`lasting effect in the removed sample and hindered the ability to detect fungus in the
`
`samples. Our method removed the antifungal agent from the infected site,
`
`allowing us to accurately evaluate the antifungal agent’s effect in order to
`
`6
`
`
`
`
`
`accurately detect fungus in the tissue in culture tests, without the influence of any
`
`Case IPR2017-00190
`
`remaining agent.
`
`18. The May 1999 Report describes the use of Kaken’s guinea pig model
`
`to test topical administration of KP-103 to treat onychomycosis. Guinea pigs were
`
`infected with a fungal solution of T. mentagrophytes SM-110, and the infection by
`
`this species of fungus in toenails was confirmed. Ex. 2039, 1. Test compounds
`
`included KP-103, lanoconazole, terbinafine, and control. We tested two treatment
`
`frequencies, 15 days and 20 days. Animals were euthanized, and the nails were
`
`excised and evaluated for the presence of fungus.
`
`19. The May 1999 Report indicates that topical application of KP-103,
`
`administered 20 times, was therapeutically effective and significantly reduced the
`
`average number of fungi in nails compared to base control (1.82 ± 0.91 versus 3.23
`
`± 0.74 respectively, p <0.05). Ex. 2039, Table. Furthermore, KP-103 increased
`
`the number of fungus-negative toe nails, thus completely curing the nails of three
`
`out of ten toenails. Ex. 2039, Table. Significant fungus reduction efficacy was not
`
`confirmed with 20 topical applications of lanoconazole or terbinafine. Ex. 2039,
`
`Table.
`
`20. Based on the results of this experiment, we “conjectured that because
`
`KP-103 [has] low affinity with keratin, it exhibited good penetration in the nail
`
`plate and demonstrated excellent efficacy.” Ex. 2039, 1. In addition, based on the
`
`7
`
`
`
`
`
`results of this experiment, we knew that topical (or “local”) administration of
`
`Case IPR2017-00190
`
`KP103 was effective against onychomycosis. That is, that KP-103 would be
`
`suitable for the purpose of topically treating onychomycosis. This was in contrast
`
`to existing topical treatments, which did not exhibit efficacy.
`
`21. Thus, as of May 1999, we concluded that we had invented a method
`
`of treating a subject having onychomycosis by topically administering a
`
`therapeutically effective amount of KP-103 to the nail of the subject. Ex. 2039, 2.
`
`22.
`
`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 the statements were made with the knowledge
`
`that willful false statements and the like so made are punishable by fine or
`
`imprisonment, or both, under Section 1001 of Title 18 of the United States Code,
`
`and that such willful false statements may jeopardize the validity of the application
`
`or any patents issuing thereon.
`
`Dated:
`
`
`
`
` By:
`
`
`
`8
`
`
`
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
