Paper 7
`Trials@uspto.gov
`Entered: November 28, 2017
`Tel: 571-272-7822
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`TARO PHARMACEUTICALS U.S.A., INC.,
`Petitioner,
`v.
`APOTEX TECHNOLOGIES, INC.,
`Patent Owner.
`
`Case IPR2017-01446
`Patent 7,049,328 B2
`
`
`Before LORA M. GREEN, JEFFREY N. FREDMAN, and
`ZHENYU YANG, Administrative Patent Judges.
`
`FREDMAN, Administrative Patent Judge.
`
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`
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`IPR2017-01446
`Patent 7,049,328 B2
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`I. INTRODUCTION
`A. Background
`Taro Pharmaceuticals U.S.A., Inc. (“Petitioner”) filed a Petition
`(Paper 2, “Pet.”) requesting an inter partes review of claims 1–17 and 19
`(the “challenged claims”) of U.S. Patent No. 7,049,328 B2 (Ex. 1001, “the
`’328 patent”). See 35 U.S.C. §§ 311–319. Apotex Technologies, Inc.
`(“Patent Owner”) filed a Preliminary Response. Paper 6 (“Prelim. Resp.”).
`
`Institution of an inter partes review is authorized by statute when “the
`information presented in the petition . . . and any response . . . shows that
`there is a reasonable likelihood that the petitioner would prevail with respect
`to at least 1 of the claims challenged in the petition.” 35 U.S.C. § 314; see
`37 C.F.R. §§ 42.4, 42.108. For the reasons set forth below, we conclude that
`Petitioner has established a reasonable likelihood that it would prevail in
`showing the unpatentability of at least one of the challenged claims of the
`’328 patent. Therefore, we institute an inter partes review for claims 1, 2,
`and 4–17 and 19 of the ’328 patent. 1
`
`B. Related Proceedings
`Petitioner indicates that the ’328 patent was asserted in ApoPharma
`Inc. v. Taro Pharmaceutical Industries, Ltd., No. 2:16-cv-00528 (E.D.Tx.)
`Pet. 2.
`
`
`1 We note that “Apotex has filed a Statutory Disclaimer under 35 U.S.C.
`§ 253(a) in compliance with 37 C.F.R. § 1.321(a) with the United States
`Patent and Trademark Office for the ’328 patent to statutorily disclaim claim
`3.” Prelim Resp. 8. Therefore, because claim 3 is disclaimed, we dismiss
`the Petition for inter partes review as to claim 3 pursuant to 37 C.F.R.
`§ 42.107(e).
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`C. The ’328 Patent (Ex. 1001)
`The ’328 patent addresses patients who require “regular transfusions
`of red blood cells” that can result in “widespread iron overload in the
`patient.” Ex. 1001, 1:27–30. “Iron overload is dangerous since the
`excessive iron can cause toxic degenerative changes in the heart, liver and
`endocrine organs.” Id. at 1:30–32.
`The ’328 patent teaches: “Iron chelators are drugs that enhance the
`iron excretion. Iron overload is most often treated by the use of the iron
`chelator desferrioxamine.” Id. at 1:52–54. “Recently another iron chelator,
`deferiprone by oral administration, has been used successfully for removal
`of iron in thalassemia patients who could not comply with desferrioxamine.”
`Id. at 1:63–66.
`The ’328 patent teaches
`data now reveal that iron-induced heart disease occurs even in
`patients who are compliant with desferrioxamine, and even
`some of those who do not have high levels of total body iron as
`assessed by serum ferritin or liver iron concentrations. It has
`thus become evident that lowering of the total body iron alone
`is insufficient to protect against iron-induced heart damage.
`Id. at 2:48–54. The ’328 patent teaches: “Nowhere is there taught the cardio
`selective/preferred function of deferiprone in relation to desferrioxamine
`and/or other chelating agents when administered to patients having iron
`overload.” Id. at 9:40–43.
`The ’328 patent teaches the inventors “unexpectedly discovered that
`deferiprone has a cardio selective/preferred function when compared to
`desferrioxamine or alternative chelating agents utilized in patients suffering
`iron overload.” Id. at 10:2–5.
`
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`D. Illustrative Claims
`Of the challenged claims, claims 1, 2, and 4–10 are independent
`claims of the ’328 patent. The remaining challenged claims 11–17 and 19
`depend directly from claims 1, 2, and 4‒10.2 Claims 1 and 15 are illustrative
`of the challenged claims and recite:
`
`1. A method of treating iron induced cardiac disease in a
`blood transfusion dependent patient experiencing an iron
`overload condition of the heart, said method comprising
`administering to the patient a therapeutically effective
`amount of deferiprone or a physiologically acceptable salt
`thereof sufficient to stabilize/reduce iron accumulation in
`the heart resulting from being transfusion dependent.
`15. The method of claims 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 wherein
`the administration frequency to the patient of a dosage
`amount of deferiprone or a physiologically acceptable salt
`thereof is daily in the range of 25 mg to 75 mg per kilogram
`of body weight.
`
`
`Ex. 1001, 27:3–9, 28:33–37.
`E. The Asserted Grounds of Unpatentability
`Petitioner contends that the challenged claims are unpatentable based
`on the following grounds. Pet. 9–10.
`
`
`
`Reference
`MIMS 19983
`
`Basis
`§ 102(b)
`
`Claims Challenged
`1, 2, 4–11, 13–17, 19
`
`
`2 Claims 18 and 20 were not challenged in this proceeding.
`3 Monthly Index of Medical Specialties, Vol. 18, No. 12, December 1998
`(“MIMS 1998,” Ex. 1009).
`
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`Hoffbrand 19984
`Olivieri Abstract 19955
`Agarwal 20006
`Olivieri 19957
`MIMS 1998
`Hoffbrand 1998
`Olivieri Abstract 1995
`Agarwal 2000
`Olivieri 1995
`
`§ 102(b)
`§ 102(b)
`§ 102(b)
`§ 102(b)
`§ 103(a)
`§ 103(a)
`§ 103(a)
`§ 103(a)
`§ 103(a)
`
`1, 2, 4–11, 13–17, 19
`1, 2, 4–11, 13–17, 19
`1, 2, 4–11, 13–17, 19
`1, 2, 4–11, 13–17, 19
`1, 2, 4–17, 19
`1, 2, 4–17, 19
`1, 2, 4–17, 19
`1, 2, 4–17, 19
`1, 2, 4–17, 19
`
`Petitioner relies on the Declaration of Jayesh Mehta, M.D. Ex. 1002.
`Patent Owner relies upon two Declarations, that of Dr. Thomas D. Coates,
`M.D., Ex. 2001, and of Dr. Dudley J. Pennell, M.D., Ex. 2003.
`
`II. ANALYSIS
`A. Claim Interpretation
`In an inter partes review, claim terms in an unexpired patent are given
`their broadest reasonable construction in light of the specification of the
`patent in which they appear. 37 C.F.R. § 42.100(b); Cuozzo Speed Techs.,
`
`
`4 Hoffbrand et al., Long-Term Trial of Deferiprone in 51 Transfusion-
`Dependent Iron Overloaded Patients, BLOOD, 91(1):295–300, 1998
`(“Hoffbrand 1998,” Ex. 1007).
`5 Olivieri et al., First Prospective Randomized Trial of the Iron Chelators
`Deferiprone (L1) And Deferoxamine, Abstract 983: Hemoglobinopathies and
`Thalassemias II, 249a, PROGRAM OF THE 37TH ANNUAL MEETING OF THE
`AMERICAN SOCIETY OF HEMATOLOGY, December 1995 (“Olivieri Abstract
`1995,” Ex. 1010).
`6 Agarwal, Deferiprone (Kelfer): A Report of 22 Patients Who Have Taken It
`for over a Decade, 10TH INTERNATIONAL CONFERENCE ON ORAL
`CHELATORS IN THE TREATMENT OF THALASSEMIA AND OTHER DISEASES
`AND BIOMED MEETING, March 2000 (“Agarwal 2000,” Ex. 1011).
`7 Olivieri et al., Iron-Chelation Therapy with Oral Deferiprone in Patients
`with Thalassemia Major, N. ENGL. J. MED., 332:918–22, 1995 (“Olivieri
`1995,” Ex. 1012).
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`LLC v. Lee, 136 S. Ct. 2131, 2144–46 (2016). Under the broadest
`reasonable interpretation approach, claim terms are given their ordinary and
`customary meaning as would be understood by one of ordinary skill in the
`art in the context of the entire disclosure. In re Translogic Tech., Inc., 504
`F.3d 1249, 1257 (Fed. Cir. 2007). We determine that the following claim
`language needs to be discussed.
`
`1. “a blood transfusion dependent patient experiencing an iron
`overload condition of the heart”
`Petitioner offers an interpretation of the preamble as limiting “the
`patient who is to be treated” “as patients with a condition on the spectrum of
`cardiac disease that includes patients with minor cardiac dysfunction due to
`iron overload on one end, and patients with severe congestive heart failure
`due to iron overload on the other.” Pet. 20, 23 (citing Ex. 1002 ¶ 60). Patent
`Owner agrees “the preambles of claims 1–10 should be considered
`limitations of the claims.” Prelim. Resp. 11.
`We agree with the parties that the preamble language gives life and
`meaning to the claims by limiting the patient population being treated to
`patients dependent on blood transfusions who are “experiencing an iron
`overload condition of the heart” (Ex. 1001 27:4–5, claim 1). See Griffin v.
`Bertina, 285 F.3d 1029, 1033 (Fed. Cir. 2002) (“Diagnosis is thus the
`essence of this invention; its appearance in the [claim] gives ‘life and
`meaning’ to the manipulative steps.”). In both Griffin and the instant claims,
`the manipulative steps are directly related to the preamble limitations.
`
`2. “therapeutically effective amount”
`Petitioner interprets “‘therapeutically effective amount’ recited in
`each of claims 1–10 . . . [to] necessarily include the ranges recited in each of
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`claims 13, 14, and 15. Claims 1–10 therefore each include a daily dose of,
`for example, 75 mg of deferiprone per kg of body weight.” Pet. 24.
`Patent Owner disagrees, and contends “the ‘therapeutically effective
`amount of deferiprone’ required by claims 1, 2, and 4–10 varies depending
`on the desired result.” Prelim. Resp. 13. Patent Owner contends the
`“dosages required by claims 1, 2, and 4–10 can necessarily be broader than
`those required by claims 13–15. For at least this reason, the disputed
`limitations are material to their respective claims, and without them there
`would be no way to assess what amount of deferiprone is required by these
`claims.” Id. at 14.
`
`We agree with both Petitioner and Patent Owner’s proposed
`constructions, which overlap in scope and are therefore not mutually
`exclusive, at this stage of the proceeding on the record before us. The
`independent claims 1, 2, and 4–10 do not recite a specific “therapeutically
`effective amount” as noted by Patent Owner and, therefore, reasonably
`encompass any amounts that are “therapeutically effective” consistent with
`the remaining limitations of the claims. We also agree with Petitioner,
`however, that because dependent claims cannot be broader than the claims
`from which they depend under 35 U.S.C. § 112, fourth paragraph, the
`recitation of 75 mg per kilogram of body weight in claim 15 necessarily
`constitutes a value that is a “therapeutically effective amount” as recited in
`claims 1, 2, and 4–10.
`
`
`3.
`Intended results
`
`Petitioner contends the “recitations that the administration of
`deferiprone is ‘sufficient’ to treat the conditions stated in the preambles
`(claims 1, 2, 4, and 5) or is intended to produce a particular result (claims 6–
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`10) do not have patentable weight because they do not alter the steps of the
`method.” Pet. 24. Petitioner relies on Bristol-Myers for the proposition
`“that a recitation of an intended result, ‘reduced hematologic toxicity,’ was
`not limiting because the expression ‘does not result in a manipulative
`difference in the steps of the claim.’” Pet. 25, citing Bristol-Myers Squibb
`Co. v. Ben Venue Labs., 246 F.3d 1368, 1376 (Fed. Cir. 2001). Petitioner
`contends: “Neither the doctrine of claim differentiation, nor an alleged
`newly discovered result of a known process, directed to the same purpose as
`taught by the prior art— to treat iron-overload conditions—render these
`intended results limitations of the claims.” Pet. 27.
`
`Patent Owner contends “the claimed invention is not the mere
`administration of deferiprone to blood transfusion-dependent patients, but
`instead the discovery of methods for using deferiprone to selectively reduce
`the iron burden on the hearts of blood transfusion patients, in particular
`compared to other available iron chelators (e.g., desferrioxamine).” Prelim.
`Resp. 14–15. Patent Owner contends they “overcame prior art and
`enablement rejections by explaining at length how the specific results
`required by claims 1, 2, 4–10, and 19 distinguished the invention over the
`prior art.” Id. Patent Owner contends
`the disputed phrase in Bristol-Myers was unnecessary to
`patentability and was only voluntarily added to the claims after
`the Examiner allowed the claims. ([citing Bristol-Myers, 246
`F.3d at 1375]) This stands in direct contrast to the allegedly
`“intended results” of the challenged claims, which, as discussed
`above, were essential for the claims of the ’328 patent to
`distinguish over the cited prior art.
`
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`Id. at 18. Patent Owner contends “under the “new use of a known process”
`standard in Bristol-Myers, the disputed claim terms are properly limitations
`of the claims.” Id. at 18.
`
`We agree with Petitioner’s proposed interpretation that claim
`language reciting intended results are not limiting at this stage of the
`proceeding based on the preliminary record currently before us. In
`particular, claim 1 of the ’328 patent recites the intended result of treatment
`of blood transfusion dependent patients with therapeutically effective
`amounts of deferiprone “sufficient to stabilize/reduce iron accumulation in
`the heart.” Ex. 1001, 27:8–9.
`
`We compare these facts to the simpler hypothetical in Catalina, where
`the Federal Circuit explained:
`Inventor A receives a patent having composition claims for
`shoe polish. . . . Suppose Inventor B discovers that the polish
`also repels water when rubbed onto shoes. Inventor B could
`not likely claim a method of using the polish to repel water on
`shoes because repelling water is inherent in the normal use of
`the polish to shine shoes. . . . In other words, Inventor B has
`not invented a “new” use by rubbing polish on shoes to repel
`water.
`Catalina Mktg., Int’l v. Coolsavings.com, 289 F.3d 801, 809–10 (Fed. Cir.
`2002). Just as the intended result of repelling water is not a new limiting use
`of shoe polish on shoes in Catalina, the intended results recited in claims 1–
`10 of treating or reducing iron burden in the heart do not, based on the
`record currently before us, appear to impose limitations on methods of
`treatment of blood transfusion patients with deferiprone relative to prior art
`methods of treatment of the same patient population with the same drug in
`the same amounts.
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`B. Principles of Law
`A claim is unpatentable under 35 U.S.C. § 102 if a single prior art
`reference expressly or inherently describes each and every limitation as set
`forth in the claim. See Perricone v. Medicis Pharm. Corp., 432 F.3d 1368,
`1375 (Fed. Cir. 2005); Verdegaal Bros., Inc. v. Union Oil Co., 814 F.2d 628,
`631 (Fed. Cir. 1987). “A single prior art reference may anticipate without
`disclosing a feature of the claimed invention if such feature is necessarily
`present, or inherent, in that reference.” Allergan, Inc. v. Apotex Inc., 754
`F.3d 952, 958 (Fed. Cir. 2014) (citing Schering Corp. v. Geneva Pharm.,
`339 F.3d 1373, 1377 (Fed. Cir. 2003)).
`A patent claim is unpatentable under 35 U.S.C. § 103(a) if the
`differences between the claimed subject matter and the prior art are such that
`the subject matter, as a whole, would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which said
`subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
`(2007). The question of obviousness is resolved on the basis of underlying
`factual determinations including: (1) the scope and content of the prior art;
`(2) any differences between the claimed subject matter and the prior art;
`(3) the level of ordinary skill in the art; and (4) objective evidence of
`nonobviousness. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
`In that regard, an obviousness analysis “need not seek out precise
`teachings directed to the specific subject matter of the challenged claim, for
`a court can take account of the inferences and creative steps that a person of
`ordinary skill in the art would employ.” KSR, 550 U.S. at 418. In KSR, the
`Supreme Court also stated that an invention may be found obvious if trying a
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`course of conduct would have been obvious to a person having ordinary
`skill:
`
`When there is a design need or market pressure to solve a
`problem and there are a finite number of identified, predictable
`solutions, a person of ordinary skill has good reason to pursue
`the known options within his or her technical grasp. If this
`leads to the anticipated success, it is likely the product not of
`innovation but of ordinary skill and common sense. In that
`instance the fact that a combination was obvious to try might
`show that it was obvious under § 103.
`KSR, 550 U.S. at 421. “KSR affirmed the logical inverse of this statement
`by stating that § 103 bars patentability unless ‘the improvement is more than
`the predictable use of prior art elements according to their established
`functions.’” In re Kubin, 561 F.3d 1351, 1359−60 (Fed. Cir. 2009) (citing
`KSR, 550 U.S. at 417).
`We are mindful that the level of ordinary skill in the art also is
`reflected by the prior art of record.8 See Okajima v. Bourdeau, 261 F.3d
`1350, 1355 (Fed. Cir. 2001); See In re GPAC Inc., 57 F.3d at 1579; In re
`Oelrich, 579 F.2d 86, 91 (CCPA 1978).
`
`8 Patent Owner states that the level of skill in the art at the time of the
`invention “would include physicians who treated iron overload in patients
`requiring chronic blood transfusions. . . . Such a person would have had a
`medical degree and some experience in hematology, cardiology, or a related
`field.” Prelim. Resp. 10, citing Ex. 2001 ¶ 26, Ex. 2003 ¶ 29. Petitioner also
`states person with ordinary skill in the art “would have had an M.D. and
`several years of clinical work experience in hematology, and would have
`had research, clinical, and/or testing experience with iron chelators to treat
`iron overload in the body, including iron overload of the heart.” Pet. 11,
`citing Ex. 1002 ¶ 41. We, therefore, agree with both parties that the level of
`ordinary skill in the art includes M.D.’s with clinical experience with iron
`chelators in treatment of transfusion patients with iron overload. See Prelim.
`Resp. 10, Pet. 11. In re GPAC Inc., 57 F.3d 1573, 1579 (Fed. Cir. 1995).
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`We analyze the asserted grounds of unpatentability in accordance with
`the above-stated principles.
`
`C. Anticipation over Mims 1998
`Petitioner contends that claims 1, 2, 4–11, 13–17 and 19 are
`unpatentable under 35 U.S.C. § 102(b) as anticipated by MIMS 1998. Pet.
`32–33.
`Petitioner asserts that “MIMS 1998 discloses that deferiprone is used
`to treat transfusion haemosiderosis (Ex. 1009 (MIMS 1998) at 256), which,
`as Dr. Mehta explains, is iron overload due to blood transfusions”; that
`“MIMS 1998 also discloses that deferiprone is administered at a dose of 75
`mg/kg per day”; and that “MIMS 1998 discloses that deferiprone is used to
`treat ‘iron-storage disease’ . . . a broad term that includes iron overload due
`to transfusion dependency and also includes the entire spectrum of cardiac
`disease caused by iron overload.” Pet. 33–34.
`Patent Owner asserts that this ground fails, among other reasons,
`because “a POSA would have understood ‘iron-storage disease’ to mean
`excess total body iron, or excess hepatic iron—not excess iron in the heart.”
`Prelim. Resp. 34 (citing Ex. 2001 ¶ 46). Patent Owner asserts:
`Ex. 1017 refers to cardiac disease (among numerous other
`conditions) as a “sequelae of iron overload” []—meaning that
`cardiac disease may result from iron overload, not that cardiac
`disease is an iron storage disease. Further, when discussing
`haemochromatosis, which is synonymous with “iron storage
`disease,” Ex. 1017 refers to total body iron or hepatic iron, and
`what, at the time, were general upper limits of hepatic iron that
`could result in “an increased risk of cardiac disease and early
`death.” (Ex. 1017 at 565.) Thus, while an “iron-storage
`disease” may eventually lead to excess iron in the heart, the
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`treatment of “iron-storage disease” does not inevitably result in
`treating a patient having an iron overload condition of the heart.
`Id. at 34–35. Patent Owner asserts “Taro has not provided any evidence that
`administering 75 mg/kg of deferiprone yields the claimed results (i.e., is a
`‘therapeutically effective amount’) or that MIMS discloses any dose of
`deferiprone that necessarily yields the claimed results.” Id. at 36.
`
`1. MIMS 1998 (Ex. 1009)
`MIMS 1998 teaches, in the context of a pharmacopeia, treatment of
`diseases including: “Transfusion haemosiderosis, acute iron poisoning, iron
`overload in liver cirrhosis, diagnosis of iron-storage disease” with
`deferiprone at doses of “50–100mg/kg body wt. Daily in 2-4 divided doses.”
`Ex. 1009 3, col. 2.
`
`Petitioner’s Declarant, Dr. Mehta, states, relying on Exhibit 1017, that
`a “person of ordinary skill in the art would have known that cardiac disease
`is an iron storage disease, and is the most common cause of death for
`untreated iron overload.” Ex. 1002 ¶ 73 (citing Ex. 1017, 557–58).
`Specifically, Exhibit 1017 states:
`
`The sequelae of iron overload include hepatic fibrosis and
`cirrhosis, multiple endocrinopathies (diabetes mellitus,
`hypogonadism, hypoparathyroidism, hypothyroidism),
`immunological dysfunction, growth and bone abnormalities,
`short stature, cardiac disease (congestive heart failure,
`arrhythmias), pulmonary dysfunction and hyperpigmentation of
`the skin. Progressive organ dysfunction, affecting the heart,
`liver and endocrine system in particular, ultimately leads to
`death in the second or third decade of life if left untreated.
`Ex. 1017, 557.
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`Patent Owner’s Declarant, Dr. Coates, “disagree[s] with Dr. Mehta
`that a POSA would understand the terms ‘iron-storage disease’ and ‘cardiac
`disease’ (or iron overload condition of the heart) to be synonymous.” Ex.
`2001 ¶ 46. Dr. Coates explains “Ex. 1017 teaches that cardiac disease is one
`of many different conditions that may result from iron overload. (Ex. 1017,
`557–58.) Therefore, a POSA would not understand Ex. 1017 to teach that a
`patient with iron-storage disease necessarily has an iron overload condition
`of the heart.” Ex. 2001 ¶ 47. Patent Owner’s Declarant, Dr. Pennell, states
`“a POSA would have understood the term iron-storage disease to refer to
`liver disease resulting from excess iron.” Ex. 2003 ¶ 35.
`
`2. Analysis
`We find, based on the current evidence of record, MIMS 1998, as
`supported by Drs. Coates and Pennell, better supports Patent Owner’s
`position that MIMS 1988 does not anticipate claims 1, 2, 4–11, 13–17, and
`19 because the evidence does not support Petitioner’s position that patients
`with “iron-storage disease” as discussed in MIMS 1988 necessarily
`encompasses patients with “an iron overload condition of the heart” or “iron-
`induced cardiac disease” as required by independent claims 1, 2, and 4–10.
`“Inherency . . . may not be established by probabilities or possibilities. The
`mere fact that a certain thing may result from a given set of circumstances is
`not sufficient.” MEHL/Biophile Int’l. Corp. v. Milgraum, 192 F.3d 1362,
`1365 (Fed. Cir. 1999).
`Exhibit 1017 identifies a number of different diseases associated with
`iron storage, and the evidence of record does not demonstrate that any
`particular patient necessarily experiences iron overload of the heart rather
`than liver, endocrine or other tissues. See Ex. 1017, 557. Moreover, both of
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`Patent Owner’s Declarants persuasively explain that the term “iron-storage
`disease” as used by MIMS 1998 is not necessarily coextensive with cardiac
`disease. See Ex. 2001 ¶ 47, Ex. 2003 ¶ 35. Even Petitioner’s Declarant, Dr.
`Mehta, states that cardiac disease “is the most common cause of death for
`untreated iron overload,” reasonably supporting the position that other, less
`common, causes of death based on overload of other tissues are
`encompassed by the phrase “iron-storage disease” in MIMS 1998. See Ex.
`1002 ¶ 73.
`
`Accordingly, we find that Petitioner has not sufficiently demonstrated
`a reasonable likelihood that it would prevail on one of claims 1, 2, 4–11, 13–
`17, and 19 as anticipated by MIMS 1998.
`
`D. Anticipation over Hoffbrand 1998
`Petitioner contends that claims 1, 2, 4–11, 13–17 and 19 are
`unpatentable under 35 U.S.C. § 102(b) as anticipated by Hoffbrand 1998.
`Pet. 34–36. See Prelim Resp. 38–41.
`Petitioner asserts “Hoffbrand 1998 discloses the treatment of ‘fifty-
`one iron-overloaded regularly transfused patients’ with deferiprone” and
`“Hoffbrand 1998 discloses administration of deferiprone at a dose of 75
`mg/kg per day.” Pet. 35 (citing Ex. 1007, 296 and Ex. 1002 ¶ 74).
`Petitioner further states “Hoffbrand 1998 discloses that ten patients had a
`liver iron content above 15.0 mg/g dry weight, due to iron overload.”
`Id. at 35–36 (citing Ex. 1007, 297 and Ex. 1002 ¶¶ 74–75).
`Patent Owner asserts that this ground fails, among other reasons,
`because “there is a discordance between liver iron content and heart iron
`content—indeed, heart iron content cannot be predicted from liver iron
`concentration and heart function (e.g., left-ventricular ejection fraction) is
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`unrelated to liver iron or serum ferritin concentrations.” Prelim. Resp. 39
`(citing Ex. 2003 ¶ 51). Patent Owner asserts that:
`Hoffbrand 1998 states that the death of four patients due to
`cardiac disease implies that “deferiprone is inappropriate
`therapy for patients with iron-induced cardiomyopathy in whom
`continuous intravenous DFX [deferoxamine] is needed to cause
`continuous removal of toxic, nontransferrin-bound iron from
`plasma.” (Ex. 1007 at 299.) A POSA reading this statement
`would understand that Hoffbrand 1998 is teaching the use of
`intravenous DFX (not deferiprone) for patients having an iron
`overload condition of the heart (e.g., iron-induced
`cardiomyopathy).
`
`Id. at 39–40. Patent Owner further notes Hoffbrand 1988 “was not designed
`to assess whether deferiprone could reduce cardiac iron levels.” Id. at 40.
`Patent Owner also contends “Hoffbrand 1998 was expressly
`considered, on numerous occasions, by the Examiner during prosecution of
`the ’328 Patent” and, therefore, “the Office has fully considered the
`patentability of the ’328 patent in view of Hoffbrand 1998.” Id. at 42.
`
`1. Hoffbrand 1998 (Ex. 1007)
`Hoffbrand 1998 teaches: “Fifty-one iron-overloaded regularly
`transfused patients who were unable to take DFX or not compliant with
`DFX were included in the trial.” Ex. 1007, 295. Hoffbrand 1998 teaches
`“Deferiprone was administered orally in a total daily dose of 75 mg/kg/body
`weight (range, 50 to 79 mg/kg) at least an hour before food every 8 to 12
`hours.” Id.
`Hoffbrand 1998 identifies three types of patients, i) “Patients
`withdrawn from long-term therapy,” “Fatalities during the study,” and
`“Patients continuing to take deferiprone.” Regarding fatalities, Hoffbrand
`1998 teaches:
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`Five patients died, but in none could this be attributed a toxic
`effect of the drug. In four previously, poorly chelated patients,
`death was due to cardiac disease induced by iron overload.
`However, these findings imply that deferiprone is inappropriate
`therapy for patients with iron-induced cardiomyopathy in whom
`continuous intravenous DFX is needed to cause continuous
`removal of toxic, nontransferrin-bound iron from plasma.
`
`
`Id. at 299.
`Regarding patients continuing to take deferiprone, Hoffbrand 1998
`teaches: “Five patients had liver iron content between 7.9 and 14.1 mg/g dry
`weight and the remaining 10 patients had a liver iron content above 15.0
`mg/g dry weight, ie, falling within the range that has been associated with
`cardiac disease.” Id. at 297.
`Petitioner’s Declarant, Dr. Mehta, states “Hoffbrand 1998 discloses
`that ten patients had a liver iron content above 15.0 mg/g dry weight, which
`falls in the range of iron content that has been associated with cardiac
`disease due to iron overload,” thereby anticipating claims 1, 2, 4–11, 13–17,
`and 19. Ex. 1002 ¶ 74.
`Patent Owner’s Declarant, Dr. Coates, states “Hoffbrand 1998 could
`not have assessed whether 75 mg/kg/day of deferiprone is a therapeutically
`effective amount . . . because Hoffbrand did not measure cardiac iron
`levels.” Ex. 2001 ¶ 55. Dr. Coates states because “patients died of iron-
`induced cardiac disease despite deferiprone treatment . . . a POSA would
`have viewed Hoffbrand 1998 as disparaging the use of deferiprone to
`stabilize, reduce, or treat iron overload in the heart, including iron-induced
`heart disease.” Id. ¶ 56.
`Patent Owner’s Declarant, Dr. Pennell, states “Hoffbrand 1998 did not
`measure cardiac iron levels” and “four deaths occurred as a result of
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`congestive heart failure—despite treatment with 75 mg/kg/day of
`deferiprone.” Ex. 2003 ¶ 36. Dr. Pennell concludes “a POSA would
`understand that Hoffbrand 1998 teaches the use of desferrioxamine as
`opposed to deferiprone in patients with cardiac disease.” Id.
`
`2. Section 325(d) – Discretion to Decline to Institute
`Patent Owner urges us to decline to institute this asserted ground
`under 35 U.S.C. § 325(d) because “Hoffbrand 1998 was expressly
`considered, on numerous occasions, by the Examiner during prosecution of
`the ’328 Patent” and, therefore, “the Office has fully considered the
`patentability of the ’328 patent in view of Hoffbrand 1998.” Prelim. Resp.
`42.
`
`Under § 325(d), we have discretion to “reject the petition or request
`because[] the same or substantially the same prior art or arguments
`previously were presented to the Office.” 35 U.S.C. § 325(d). Considering
`all of the relevant facts and circumstances, Patent Owner’s argument is
`insufficient to persuade us to exercise our discretion to deny the Petition.
`Petitioner relies on a declaration from Dr. Mehta, which Patent Owner does
`not allege is duplicative of evidence previously presented to the Office. See
`Tandus Flooring, Inc. v. Interface, Inc., Case IPR2013-00333, 2013 WL
`8595289, at *2 (PTAB Dec. 9, 2013) (Paper 16) (declining to deny petition
`under § 325(d) where petitioner presented new declaration evidence).
`
`3. Analysis
`We find that the current evidence of record in Hoffbrand 1998, as
`supported by Dr. Mehta, provides a reasonable likelihood that Hoffbrand
`1998 anticipates claims 1, 2, 4–11, 13–17, and 19 because the evidence
`currently of record supports Petitioner’s position that at least ten patients
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`discussed in Hoffbrand 1988 necessarily satisfy the requirement for patients
`treated with a therapeutically effective amount of deferiprone who had “an
`iron overload condition of the heart” or “iron-induced cardiac disease” as
`required by independent claims 1, 2, and 4–10.
`In particular, Hoffbrand 1998 teaches patients who continued
`deferiprone treatment including “10 patients [who] had a liver iron content
`above 15.0 mg/g dry weight, ie, falling within the range that has been
`associated with cardiac disease.” Ex. 1007, 297. This disclosure evidences
`that the patients in Hoffbrand 1998 necessarily had iron levels sufficient for
`iron overload conditions of the heart. Id. Hoffbrand 1998 further teaches
`treatment of those patients with 75 mg/kg of body weight, a dose directly
`falling within the therapeutically effective range required by dependent
`claims 13–15. Id. at 295, Ex. 1001, 28:23–37. Dr. Mehta affirms that “a
`liver iron content above 15.0 mg/g dry weight . . . falls in the range of iron
`content that has been associated with cardiac disease due to iron overload.”
`Ex. 1002 ¶ 74.
`These facts align with Montgomery, where the Federal Circuit found
`that a claim to a method for treatment of stroke to a diagnosed patient by
`administration