`U.S. Patent No. 7,049,328
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`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
`
`TARO PHARMACEUTICALS U.S.A., INC.,
`Petitioners,
`
`v.
`
`APOTEX TECHNOLOGIES, INC.,
`Patent Owner.
`________________
`
`Case IPR2017-01446
`U.S. Patent No. 7,049,328
`
`Title: USE FOR DEFERIPRONE
`________________
`
`
`PATENT OWNER’S OBSERVATIONS ON THE CROSS EXAMINATION
`OF DR. JAYESH MEHTA
`
`LEGAL\36966684\1
`
`
`
`Pursuant to the Scheduling Order (Paper 8), Patent Owner Apotex
`
`IPR2017-01446
`U.S. Patent No. 7,049,328
`
`
`Technologies, Inc. (“Apotex”) submits the following observations on cross-
`
`examination of Dr. Jayesh Mehta.
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`I.
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`Inherent Anticipation
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`1.
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`In Exhibit 2040, at 18:6-17 and 20:2-16, Dr. Mehta testified that
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`practicing the prior art methods of dosing deferiprone to blood transfusion-
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`dependent patients will not achieve the claimed results of the ’328 patent in every
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`single patient and that a possibility or probability of something happening would
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`meet the standard for inherent anticipation. This testimony is relevant to Dr.
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`Mehta’s opinions in paragraphs 20, 67, 74, 75, and 77 of his Declaration (Ex.
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`1002) and paragraphs 35 and 41 of his Reply Declaration (Ex. 1060) that “prior art
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`may still anticipate if that element is ‘inherent’ in its disclosure, that is, if it is
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`necessarily found in the prior art” (Ex. 1002 at ¶ 20), and that the administration of
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`75 mg/kg/day of deferiprone in Hoffbrand 1998, Olivieri Abstract 1995, and
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`Olivieri 1995 inherently anticipates the claims of the ’328 patent. The testimony is
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`relevant because Dr. Mehta uses an improper legal standard for inherent
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`anticipation to conduct his analysis of the prior art. The testimony is also
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`inconsistent with Dr. Mehta’s opinions that the administration of 75 mg/kg/day of
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`deferiprone in the prior art inherently anticipates the claims of the ’328 patent.
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`2.
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`In Exhibit 2040, at 8:1 – 9:4, 10:8 – 12:7, and 24:24 – 27:7, Dr. Mehta
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`1
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`testified that the claims of the ’328 patent require a therapeutically effective
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`amount to achieve a specific outcome in individual patients, that the ability of
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`deferiprone to bind iron and remove it from the body depends on the dose, and that
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`75 mg/kg/day will not bind and reduce cardiac iron in each and every patient at
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`that dose. This testimony is relevant to Dr. Mehta’s opinions in paragraphs 37, 61,
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`66, 67, 74, 75, and 77 of his Declaration (Ex. 1002) and paragraphs 15, 20, 27, 38,
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`and 41 of his Reply Declaration (Ex. 1060) that “clinical experience has shown
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`that treatment with 75/mg/kg/day of deferiprone is effective at maintaining a non-
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`toxic level of iron in the blood of transfusion-dependent patients, thereby treating
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`iron overload.” (Ex. 1002 at ¶ 37.) This testimony is relevant because it is
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`inconsistent with Dr. Mehta’s opinions that the administration of 75 mg/kg/day of
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`deferiprone in the prior art inherently anticipates the claims of the ’328 patent.
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`II. Claim Construction
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`3.
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`In Exhibit 2040, at 8:1 – 9:4, 10:8 – 12:7, and 16:16 –18:4, Dr. Mehta
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`testified that, under the district court’s claim construction, the “sufficient to”
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`clauses in the claims of the ’328 patent and the like define the therapeutically
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`effective dose in the claims. This testimony is relevant because it is inconsistent
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`with Dr. Mehta’s opinions in paragraphs 55, 56, 66 and 71 of his Declaration (Ex.
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`1002) and paragraph 18 of his Reply Declaration (Ex. 1060) that the “sufficient to”
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`language in the claims of the ’328 patent “adds nothing to the claimed method”
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`2
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`and does not require a person attempting to practice the claims to, for example,
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`change the dose administered to the patient being treated. This testimony is also
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`relevant because it is inconsistent with Dr. Mehta’s opinions that the “sufficient to”
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`language in the claims of the ’328 patent is “not limiting because the method is
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`performed in the identical manner of whether the particular results are achieved.”
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`(Ex. 1002 at ¶ 66.)
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`4.
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`In Exhibit 2040, at 24:24 – 27:7, Dr. Mehta testified that physicians
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`would adjust a chelation regimen based on an individual patient’s response to
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`treatment, and that a physician attempting to practice the claims of the ’328 patent
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`would look at the results achieved in an individual patient in order to know if the
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`claimed methods were successfully practiced. This testimony is relevant because it
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`is inconsistent with Dr. Mehta’s opinion that “the term ‘therapeutically effective
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`amount’ must be understood to mean an amount that is in general successful, even
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`if not successful in each and every patient treated.” (Ex. 1060 at ¶ 15.) This
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`testimony is also relevant because it also is inconsistent with Dr. Mehta’s opinions
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`that the “sufficient to” language in the claims of the ’328 patent is “not limiting
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`because the method is performed in the identical manner of whether the particular
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`results are achieved.” (Ex. 1002 at ¶ 66.)
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`III. MRI T2 Relaxation Time (“TRT”)
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`5.
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`In Exhibit 2040, at 40:15 – 46:5 and 49:16 – 55:3, Dr. Mehta
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`3
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`confirmed that Liu et al. (Ex. 1062) disclosed that serum ferritin does not
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`accurately reflect the differential iron storage between the organs in the body, that
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`in the 1994-1996 timeframe, the authors were still evaluating the usefulness of
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`MRI TRT measurements of tissue iron, and that there were caveats to MRI TRT
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`that required independent validation of the process in humans before wide
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`application. This testimony is relevant because it is inconsistent with Dr. Mehta’s
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`opinions in paragraph 26 of his Reply Declaration (Ex. 1060) that the “prior art
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`shows that clinicians in the field of iron overload treatment recognized that cardiac
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`MRI TRT was a reliable measure of heart iron concentration.”
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`IV. The Clinical Study Described in the ’328 Patent
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`6.
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`In Exhibit 2040, at 6:6 – 7:25, Dr. Mehta testified that the study
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`described in column 14, line 43 through column 26, line 5 of the ’328 patent was a
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`retrospective study and thus it was not possible to adjust the deferiprone dose in
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`such a study. This testimony is relevant to Dr. Mehta’s opinions in paragraph 15
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`of his Reply Declaration (Ex. 1060) because it explains why the inventors did not
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`adjust the dose of deferiprone in the study described in column 14, line 43 through
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`column 26, line 5 of the ’328 patent.
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`V. Anticipation by Hoffbrand 1998
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`7.
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`In Exhibit 2040, at 35:7-13, Dr. Mehta testified that Hoffbrand and his
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`coauthors determined that for the 5 patients that died of cardiac disease, treatment
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`4
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`with deferoxamine would have been better than deferiprone. This testimony is
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`relevant to Dr. Mehta’s opinions in paragraphs 37-41 of his Reply Declaration (Ex.
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`1060) that the patients described in Hoffbrand 1998 that died of cardiac disease
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`were successfully treated with deferiprone. This testimony is relevant because
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`Hoffbrand and coauthors determined that treatment with deferiprone is an
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`inappropriate therapy for patients with iron-induced cardiomyopathy. (Ex. 1007
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`at 5.)
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`Date: June 28, 2018
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` Respectfully submitted,
`
` By: /s/ W. Blake Coblentz
`W. Blake Coblentz
`Reg. No. 57,104
`COZEN O’CONNOR
`1200 Nineteenth Street, N.W.
`Washington, D.C. 20036
`(202) 912-4837
`
`5
`
`
`
`IPR2017-01446
`U.S. Patent No. 7,049,328
`
`CERTIFICATE OF SERVICE
`
`I hereby certify that on June 28, 2018, I caused a true and correct copy of
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`Patent Owner’s Observations on the Cross-Examination of Dr. Jayesh Mehta
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`to be served via electronic mail on the following attorneys of record:
`
`Huiya Wu
`Sarah Fink
`GOODWIN PROCTER LLP
`The New York Times Building
`620 Eighth Avenue
`New York, NY 10018-1405
`HWu@goodwin.law.com
`SFink@goodwinlaw.com
`
`Date: June 28, 2018
`
`/s/ W. Blake Coblentz
`W. Blake Coblentz
`Reg. No. 57,104
`COZEN O’CONNOR
`1200 Nineteenth Street, N.W.
`Washington, DC 20036
`(202) 912-4837
`
`