IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`AMERIGEN PHARMACEUTICALS LIMITED
`
`and
`
`ARGENTUM PHARMACEUTICALS LLC
`
`Petitioners
`
`v.
`
`JANSSEN ONCOLOGY, INC.,
`
`Patent Owner
`_______________
`
`Case IPR2016-002861
`
`Patent 8,822,438 B2
`_______________
`
`
`
`PETITIONERS’ RESPONSE TO PATENT OWNER’S
`
`MOTION FOR OBSERVATIONS ON CROSS-EXAMINATION
`
`
`
`
`
`
`
`1 Case IPR2016-01317 has been joined with this proceeding.
`
`
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`AMERIGEN PHARMACEUTICALS LIMITED
`
`and
`
`ARGENTUM PHARMACEUTICALS LLC
`
`Petitioners
`
`v.
`
`JANSSEN ONCOLOGY, INC.,
`
`Patent Owner
`_______________
`
`Case IPR2016-002861
`
`Patent 8,822,438 B2
`_______________
`
`
`
`PETITIONERS’ RESPONSE TO PATENT OWNER’S
`
`MOTION FOR OBSERVATIONS ON CROSS-EXAMINATION
`
`
`
`
`
`
`
`1 Case IPR2016-01317 has been joined with this proceeding.
`
`
`
`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`1. Response to Observation No. 1
`
`
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the testimony does not
`
`address the manner or extent in which the targets are in common and in which the
`
`targets are different. In particular, the answer also does not address the targets in
`
`common which inhibit the key components of the cortisol (glucocorticoid)
`
`synthesis pathway.
`
`2. Response to Observation No. 2
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the testimony does not
`
`conflict with any opinions in his declaration. Paragraphs 30, 37, 39 of Dr. Ratain’s
`
`declaration address evidence of adrenal toxicity and O’Donnell’s (Exh. 1003)
`
`disclosure of administration of glucocorticoids with ketoconazole to treat prostate
`
`cancer. Further, it is not relevant as to whether both ketoconazole and abiraterone
`
`acetate were known to reduce cortisol (a glucocorticoid) levels, thereby requiring
`
`administration of prednisone (replacement glucocorticoid).
`
`3. Response to Observation No. 3
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the testimony does not
`
`2
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`
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`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`
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`contradict that ketoconazole was known to treat prostate cancer. For example,
`
`O’Donnell (Exh. 1003) states: “A direct antitumour effect of ketoconazole in vitro
`
`has also been demonstrated (Eichenberger and Trachtenberg, 1988). . . . In clinical
`
`trials, both agents [ketoconazole and aminoglutethimide] have shown some activity
`
`as second-line agents (measured by clinical benefit as well as reduction in PSA), .
`
`. . .”
`
`4. Response to Observation No. 4
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the testimony does not
`
`contradict that prednisone was known to treat prostate cancer, which the answer
`
`does not address. In this regard, in Ex. 2124, at p. 65, l. 11-18, the witness
`
`testified:
`
`Q. To a person of ordinary skill in the art, would they consider reduced PSA
`
`sufficient to reflect an anti-cancer effect or would the person of ordinary skill
`
`require evidence of enhanced life expectancy?
`
`A. A person of ordinary skill would not require evidence of life expectancy
`
`nor would the FDA.
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`Further it does not contradict that prednisone was known to be used in
`
`combination with other drugs for the treatment of prostate cancer. See for example
`
`3
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`
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`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`
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`AMG 1091, paragraph 36, and O’Donnell (Exh. 1003) states: “A direct antitumour
`
`effect of ketoconazole in vitro has also been demonstrated (Eichenberger and
`
`Trachtenberg, 1988). . . . In clinical trials, both agents [ketoconazole and
`
`aminoglutethimide] have shown some activity as second-line agents (measured by
`
`clinical benefit as well as reduction in PSA), . . .”
`
`5. Response to Observation No. 5
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the testimony does not
`
`conflict with any opinions in his declaration. The cited testimony is not relevant
`
`because the testimony does not contradict that dexamethasone was known to treat
`
`prostate cancer, which the answer does not address. In this regard, in Ex. 2124, at
`
`p. 65, l. 11-18, the witness testified:
`
`Q. To a person of ordinary skill in the art, would they consider reduced PSA
`
`sufficient to reflect an anti-cancer effect or would the person of ordinary skill
`
`require evidence of enhanced life expectancy?
`
`A. A person of ordinary skill would not require evidence of life expectancy
`
`nor would the FDA.
`
`6. Response to Observation No. 6
`
`4
`
`
`
`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`
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`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the question is completely
`
`vague and ambiguous. It is unclear what “this sentence” is or what quote in the
`
`declaration is being referred to. Further, Patent Owner’s explanation of relevance
`
`is attorney argument and speculation because the question is so incomprehensible.
`
`7. Response to Observation No. 7
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the question is vague as to
`
`whether Dr. Ratain regularly treats patients with prostate cancer now or has ever
`
`regularly treated patients with prostate cancer. In fact, in Ex. 2124, at p. 24, l. 23-
`
`p. 25, l. 4, the witness testified:
`
`Q. Has there ever been a time in your professional career where you've
`
`regularly treated patients with prostate cancer?
`
`MR. CASIERI: Object to form.
`
`BY THE WITNESS:
`
`A. Yes.
`
`8. Response to Observation No. 8
`
`5
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`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`
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`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the answer does not
`
`contradict the opinion of Dr. Dorin that one would consider the delta or change in
`
`cortisol in response to the Synacthen test to be a useful parameter for diagnosing
`
`adrenal insufficiency but that the Δ-cortisol is more informative than peak cortisol
`
`concentration for the physiologic question addressed in Study C. Exh. AMG 1093
`
`at ¶ 59.
`
`9. Response to Observation No. 9
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the testimony does not
`
`quantify just how little glucocorticoid activity that corticosterone has as compared
`
`to the glucocorticoid activity of cortisol.
`
`10. Response to Observation No. 10
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because Dr. Dorin’s opinion
`
`addressed what would be appropriate, not what was actually done. “Based on the
`
`promising data of Barrie (AMG 1005) and O’Donnell (AMG 1003), it is evident
`
`that further clinical trials assessing safety and efficacy of long-term AA in men
`
`with mCRPC would be appropriate.” Exh. AMG 1093 at ¶ 31.
`
`6
`
`
`
`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`11. Response to Observation No. 11
`
`
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`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the testimony does not
`
`address the risks versus the benefits of Patent Owner’s views concerning
`
`concomitant administration of glucocorticoids. “I disagree with Dr. Auchus’
`
`discussion that the risks of concomitant administration of replacement
`
`glucocorticoid would be so great that POSA would be discouraged from using that
`
`management strategy in men with mCRPC treated with long term AA. Auchus’
`
`argument is detached from the clinical context of the treatment population of
`
`metastatic prostate cancer. . . ” Exh. AMG 1093 at ¶ 29.
`
`12. Response to Observation No. 12
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the question is vague and
`
`ambiguous. It is unclear what “those deficiencies” are being referred to in the
`
`question. Further it is unclear the extent and manner of that the clinical symptoms
`
`are variable.
`
`13. Response to Observation No. 13
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. Even Patent Owner failed to point out the relevancy of this testimony.
`
`7
`
`
`
`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`
`
`Regardless, there is nothing on the record to require expertise of
`
`P450c17deficiency syndrome by one of ordinary skill in the art.
`
`14. Response to Observation No. 14
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. There is nothing on the record to require expertise of P450c17
`
`deficiency syndrome by one of ordinary skill in the art. Further, the testimony
`
`does not address whether Dr. Dorin knows the clinical presentation of P450c17
`
`deficiency syndrome. Finally, Patent Owner inappropriately presents attorney
`
`argument in an attempt to create relevancy.
`
`15. Response to Observation No. 15
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. Dr. Dorin did not claim to be an expert in prostate cancer. Rather Dr.
`
`Dorin is an expert in endocrinology and metabolism engaged to rebut the opinion
`
`of Patent Owner’s endocrinologist, Dr. Auchus. Exh. AMG 1093 at ¶ 7.
`
`16. Response to Observation No. 16
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony does not contradict the testimony of Dr. Dorin
`
`explaining that a POSA would not have questioned the data or conclusions of
`
`O’Donnell that all patients in Study C had abnormal Synacthen results but that an
`
`8
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`
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`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`
`
`expert in endocrinology would recognize the Δ-cortisol values after AA to be “so
`
`low as to be readily identified as ‘abnormal.’” Exh. AMG 1093 at ¶ 62.
`
`17. Response to Observation No. 17
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the testimony does not
`
`contradict Dr. Serel’s explanation that “the common inhibitory effect on cortisol
`
`production and resulting increase in ACTH as a consequence of administering
`
`either abiraterone acetate or ketoconazole would have plainly and sufficiently
`
`suggested to a POSA the use of a glucocorticoid, such as prednisone, with both
`
`compounds as glucocorticoid replacement therapy.” Exh. AMG 1095 at ¶ 7.
`
`18. Response to Observation No. 18
`
`Petitioners respond that the cited testimony is not relevant to this
`
`proceeding. The cited testimony is not relevant because the testimony does not
`
`address the terms that were used in the 2004 article of Chodak concerning benefit
`
`provided by ketoconazole.
`
`Dated: February 3, 2017
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`Respectfully Submitted,
`
`/William D. Hare/
`William D. Hare
`Reg. No. 44,739
`McNeely Hare & War, LLP
`12 Roszel Road, Suite C104
`Princeton, NJ 08540
`
`9
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`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`
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`(202) 640-1801
`bill@miplaw.com
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`10
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`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`CERTIFICATE OF SERVICE
`
`The undersigned hereby certifies that the foregoing Petitioners’ Response to
`
`
`
`
`
`Patent Owner’s Motion for Observations was served on February 3, 2017 by
`
`delivering copies via electronic mail on the following attorneys of record for the
`
`Patent Owner:
`
`Dianne B. Elderkin
`Barbara L. Mullin
`Ruben H. Munoz
`delderkin@akingump.com
`bmullin@akingump.com
`rmunoz@akingump.com
`JANS-ZYTIGA@akingump.com
`AKIN GUMP STRAUSS HAUER & FELD LLP
`
`David T. Pritikin
`Bindu Donovan
`Paul J. Zegger
`Todd Krause
`Isaac Olson
`Alyssa B. Monsen
`dpritikin@sidley.com
`bdonovan@sidley.com
`pzegger@sidley.com
`tkrause@sidley.com
`iolson@sidley.com
`amonsen@sidley.com
`ZytigaIPRTeam@sidley.com
`SIDLEY AUSTIN LLP
`
`Jennifer H. Roscetti
`Anthony C. Tridico
`jennifer.roscetti@finnegan.com
`anthony.tridico@finnegan.com
`FINNEGAN HENDERSON FARABOW GARRETT & DUNNER
`
`11
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`
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`Petitioners’ Response To Patent Owner’s Motion For Observations
`Petition for Inter Partes Review 2016-00286
`
`
`Teresa Stanek Rea
`Shannon M. Lentz
`TRea@Crowell.com
`SLentz@Crowell.com
`CROWELL & MORING LLP
`
`
`
`
`
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`Date: February 3, 2017
`
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`
`
`/William D. Hare/
`William D. Hare
`
`12
`
`
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