Case IPR2022-00722
`U.S. Patent No. 7,041,786
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
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`MYLAN PHARMACEUTICALS INC.,
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`Petitioner,
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`v.
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`BAUSCH HEALTH IRELAND LIMITED,
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`Patent Owner.
`
`__________________
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`Case IPR2022-00722
`U.S. Patent No. 7,041,786
`__________________
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`DECLARATION OF KUNWAR SHAILUBHAI
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`Bausch Health Ireland Exhibit 2023, Page 1 of 18
`Mylan v. Bausch Health Ireland - IPR2022-00722
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`U.S. Patent No. 7,041,786
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`MYLAN PHARMACEUTICALS INC.,
`
`Petitioner,
`
`v.
`
`BAUSCH HEALTH IRELAND LIMITED,
`
`Patent Owner.
`
`__________________
`
`Case IPR2022-00722
`U.S. Patent No. 7,041,786
`__________________
`
`DECLARATION OF KUNWAR SHAILUBHAI
`
`Bausch Health Ireland Exhibit 2023, Page 1 of 18
`Mylan v. Bausch Health Ireland - IPR2022-00722
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`Case IPR2022-00722
`U.S. Patent No. 7,041,786
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`I.
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`I, Kunwar Shailubhai, under penalty of perjury, declare as follows:
`INTRODUCTION
`I am of legal age and otherwise competent to make this declaration.
`1.
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`2.
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`I am the first named inventor on U.S. Patent No. 7,041,786 (Ex. 1001,
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`“the ’786 patent”). I have been asked to submit a declaration attesting to how the
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`data disclosed in Table 4 in the specification of the ’786 patent and other relevant
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`data related to the peptides disclosed in the ’786 patent were generated.
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`II.
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`EDUCATION AND WORK EXPERIENCE
`3.
`I graduated from the Maharaja Sayajirao University of Baroda with a
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`Ph.D. in Microbiology in 1984 and from the University of Missouri-Saint Louis
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`with an M.B.A. in 2002.
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`4.
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`I am currently employed by the Pennsylvania Biotechnology Center
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`and Baruch S. Blumberg Institute as a Senior Advisor and Professor.
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`III. BIOLOGICAL ACTIVITY DATA IN TABLE 4 OF THE ’786 PATENT
`I was involved in synthesizing and testing of guanylate cyclase (“GC-
`5.
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`C”) receptor agonists that enhance intracellular production of cyclic guanosine
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`monophosphate (“cGMP”), including the peptides of the experimental examples
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`reported in the ’786 patent. As such, I have first-hand knowledge of how the
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`peptides reported below were made and tested.
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`1
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`Bausch Health Ireland Exhibit 2023, Page 2 of 18
`Mylan v. Bausch Health Ireland - IPR2022-00722
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`Case IPR2022-00722
`U.S. Patent No. 7,041,786
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`6.
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`I directed the synthesis and testing of the GC-C receptor agonist
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`peptides in order to examine biological activity as disclosed in Table 4 of the ’786
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`patent.
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`7.
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`Human T84 colon carcinoma cells were obtained from the American
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`Type Culture Collection. (Id. at 15:27-29). Cells were grown in a 1:1 mixture of
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`Ham’s F-12 medium and Dulbecco’s modified Eagle’s medium (“DMEM”)
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`supplemented with 10% fetal bovine serum, 100 U penicillin/ml, and 100 μg/ml
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`streptomycin. (Id. at 15:29-32). The cells were fed fresh medium every third day
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`and split at a confluence of approximately 80%. (Id. at 15:32-34).
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`8.
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`Peptides were custom synthesized by Multiple Peptide Systems, San
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`Diego, California, and by Princeton Biomolecules, Langhorne, Pennsylvania. (Id.
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`at 15:36-38). Biological activity of the synthetic peptides was assayed. (Id. at
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`15:38-39). The confluent monolayers of T84 cells in 24-well plates were washed
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`twice with 250 μl of DMEM containing 50 mM HEPES (pH 7.4), pre-incubated at
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`37°C for 10 minutes with 250 μl DMEM containing 50 mM HEPES (pH 7.4) and 1
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`mM isobutylmethylxanthine (“IBMX”), followed by incubation with peptides (0.1
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`nM to 10 μM) for 30 minutes. (Id. at 15:40-46). The medium was aspirated, and
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`the reaction was terminated by the addition of 3% perchloric acid. (Id. at 15:46-
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`47). Following centrifugation, and neutralization with 0.1 N NaOH, the
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`2
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`Bausch Health Ireland Exhibit 2023, Page 3 of 18
`Mylan v. Bausch Health Ireland - IPR2022-00722
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`Case IPR2022-00722
`U.S. Patent No. 7,041,786
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`supernatant was used directly for measurements of cGMP using an ELISA kit
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`(Caymen Chemical, Ann Arbor, Michigan). (Id. at 15:47-50).
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`9.
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`As indicated in the following table, the peptides were custom
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`synthesized and purified (>95% purity) using a published procedure (procedure
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`from Klodt, et al., J. Peptide Res. 50:222-230 (1997)). (Id. at 15:53-54, 18:32).
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`Peptides were evaluated in the T84 cell-based assay for their ability to enhance
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`intracellular levels of cGMP. (Id. at 15:55-56). The results of this test are shown
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`in Table 4 below.
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`(Id. at 16:1-19). I note that the p value below Table 4 contains a typographical
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`error and should say p < 0.05. (Id. at 16:19).
`3
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`Bausch Health Ireland Exhibit 2023, Page 4 of 18
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`U.S. Patent No. 7,041,786
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`IV. DATA IN STUDY NUMBER SP-PH-001
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`Bausch Health Ireland Exhibit 2023, Page 5 of 18
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`Case IPR2022-00722
`U.S. Patent No. 7,041,786
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`Bausch Health Ireland Exhibit 2023, Page 6 of 18
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`U.S. Patent No. 7,041,786
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`Bausch Health Ireland Exhibit 2023, Page 7 of 18
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`U.S. Patent No. 7,041,786
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`7
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`Bausch Health Ireland Exhibit 2023, Page 8 of 18
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`U.S. Patent No. 7,041,786
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`V. DATA IN STUDY NUMBER SP-PH-004
`A.
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`Bausch Health Ireland Exhibit 2023, Page 9 of 18
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`Bausch Health Ireland Exhibit 2023, Page 10 of 18
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`Case IPR2022-00722
`U.S. Patent No. 7,041,786
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`Bausch Health Ireland Exhibit 2023, Page 11 of 18
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`Bausch Health Ireland Exhibit 2023, Page 12 of 18
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`U.S. Patent No. 7,041,786
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`Bausch Health Ireland Exhibit 2023, Page 13 of 18
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`Case IPR2022-00722
`U.S. Patent No. 7,041,786
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`Bausch Health Ireland Exhibit 2023, Page 14 of 18
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`Bausch Health Ireland Exhibit 2023, Page 15 of 18
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`Case IPR2022-00722
`U.S. Patent No. 7,041,786
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`VI. DATA DISCLOSED IN TABLE 4 OF THE ’786 PATENT, STUDY NO.
`SP-PH-001, AND STUDY NO. SP-PH-004
`30. Based on my involvement with the synthesis and testing of GC-C
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`receptor agonist peptides in order to examine their isomerization, biological
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`activity, and heat stability as disclosed in Table 4 of the ’786 patent, Study No. SP-
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`PH-001, and Study No. SP-PH-004, I have first-hand knowledge of how these test
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`data disclosed were generated.
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`31.
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`I hereby certify that each of the records for Study No. SP-PH-001 and
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`Study No. SP-PH-004 (i.e., Ex. 2027 and Ex. 2028):
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`(A) were made or obtained at or near the time of occurrence of the matters
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`set forth in the records, by, or from information transmitted by, a person
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`with personal knowledge of those matters;
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`(B) were kept in the course of regularly conducted business activity;
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`(C) were created or obtained as a regular business practice; and
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`(D) are the types of information created, obtained, and used in the ordinary
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`course of business.
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`32.
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`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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`further, that these statements were made with knowledge that willful false
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`15
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`Bausch Health Ireland Exhibit 2023, Page 16 of 18
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`statements and the like so made are punishable by fine or imprisonment, or both,
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`Case IPR2022-00722
`U.S. Patent No. 7,041,786
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`under 18 U.S.C. § 1001.
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`Bausch Health Ireland Exhibit 2023, Page 17 of 18
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`Bausch Health Ireland Exhibit 2023, Page 18 of 18
`Mylan v. Bausch Health Ireland - IPR2022-00722
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