Trials@uspto.gov
`571-272-7822
`
`
` Paper 9
`Entered: February 13, 2017
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`ROXANE LABORATORIES, INC.,
`Petitioner,
`
`v.
`
`NOVARTIS AG,
`Patent Owner.
`
`____________
`
`Case IPR2016-01461
`Patent 9,006,224 B2
`____________
`
`
`
`
`
`Before LORA M. GREEN, CHRISTOPHER L. CRUMBLEY, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`
`CRUMBLEY, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a) and 37 C.F.R. § 42.108
`
`
`
`
`
`
`
`
`571-272-7822
`
`
` Paper 9
`Entered: February 13, 2017
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`
`ROXANE LABORATORIES, INC.,
`Petitioner,
`
`v.
`
`NOVARTIS AG,
`Patent Owner.
`
`____________
`
`Case IPR2016-01461
`Patent 9,006,224 B2
`____________
`
`
`
`
`
`Before LORA M. GREEN, CHRISTOPHER L. CRUMBLEY, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`
`CRUMBLEY, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a) and 37 C.F.R. § 42.108
`
`
`
`
`
`
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`I. INTRODUCTION
`
`Roxane Laboratories, Inc. filed a Petition requesting an inter partes
`
`review of claims 1 and 2 of U.S. Patent No. 9,006,224 B2 (Ex. 1001, “the
`
`’224 patent”). Paper 2 (“Pet.”). Novartis AG, the owner of the ’224 patent,
`
`filed a Preliminary Response to the Petition. Paper 6 (“Prelim. Resp.”).
`
`Pursuant to 35 U.S.C. § 314(a), an inter partes review may not be
`
`instituted unless the information presented in the Petition and any
`
`Preliminary Response shows “there is a reasonable likelihood that the
`
`petitioner would prevail with respect to at least 1 of the claims challenged in
`
`the petition.” Taking into account the information presented, we conclude
`
`that the record does not establish a reasonable likelihood that Roxane will
`
`prevail in proving that claims 1 and 2 of the ’224 patent are unpatentable.
`
`Accordingly, we do not institute an inter partes review.
`
`A. Related Matters
`
`We are informed that the ’224 patent has been asserted in two patent
`
`infringement actions in the United States District Court for the District of
`
`Delaware: Novartis Pharm. Corp. et al. v. Roxane Labs., Inc., No. 15-474-
`
`RGA, and Novartis Pharm. Corp. et al. v. Par Pharm., Inc., No. 15-475-
`
`RGA. Pet. 4–5; Paper 4, 2. Claims 1–3 of the ’224 patent have been
`
`challenged by a different petitioner in IPR2016-01479, currently pending
`
`before the Board.
`
`B. The ’224 Patent
`
`The ’224 patent, titled “Neuroendocrine Tumor Treatment,” issued
`
`April 14, 2015, from U.S. Patent Application No. 12/094,173. Ex. 1001,
`
`
`
`2
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`(54), (45), (21). Specifically, the patent describes treating neuroendocrine
`
`tumors using mTOR (mammalian target of rapamycin) inhibitors, including
`
`rapamycin and its derivatives. Id. at 1:2–5, 1:17–43. One specifically listed
`
`rapamycin derivative is 40-O-(2-hydroxyethyl)-rapamycin, also known as
`
`everolimus. Id. at 1:46–47; 11:50.
`
`The ’224 patent discloses that mTOR inhibitors have activity as
`
`immunosuppressants, and have also been found useful for the treatment of
`
`solid tumors, particularly advanced solid tumors, including pancreatic
`
`neuroendocrine tumors (PNETs). Id. at 2:35–67. PNETs are particularly
`
`lethal, having a 5-year patient survival rate of 55.3%; the ’224 patent states
`
`that most are malignant at the time of diagnosis, and 60% or more present
`
`with liver metastases. Id. at 3:1–10. The ’224 patent concludes that there is
`
`an unmet need for treatment of PNETs in patients whose disease has
`
`progressed following one or more courses of chemotherapy. Id. at 3:10–12.
`
`The ’224 patent describes a method of treatment using mTOR
`
`inhibitors, specifically with everolimus (“compound A”). Id. at 11:66–67.
`
`The patent proposes a clinical study in which patients with advanced PNETs
`
`are treated with 10 mg/day of everolimus after failure of cytotoxic
`
`chemotherapy. Id. at 26:56–60.
`
`C. Illustrative Claim
`
`
`
`Of the challenged claims, claims 1 is independent and illustrative of
`
`the challenged claims:
`
`1. A method for treating pancreatic neuroendocrine tumors,
`comprising administering to a human subject in need thereof a
`therapeutically effective amount of 40-0-(2-hydroxyethyl)-
`
`
`
`3
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`rapamycin as a monotherapy and wherein the tumors are
`advanced tumors after failure of cytotoxic chemotherapy.
`
`Ex. 1001, 26:66–27:4.
`
`D. Asserted Grounds of Unpatentability
`
`
`
`Roxane challenges claims 1 and 2 of the ’224 patent on the following
`
`grounds of unpatentability:
`
`References
`
`Lane2 and Tabernero3
`
`von Wichert,4 Dutcher,5 Cottens,6 and
`Tabernero
`
`Basis1
`
`Challenged Claims
`
`§ 103(a) 1 and 2
`
`§ 103(a) 1 and 2
`
`
`
`1 The relevant sections of the Leahy-Smith America Invents Act (“AIA”),
`Pub. L. No. 112–29, took effect on March 16, 2013. Because the application
`from which the ’224 patent issued was filed before that date, our citations to
`Title 35 are to its pre-AIA version.
`
`2 U.S. Published Patent Application 2004/0147541 A1 to Lane et al.
`(published July 29, 2004) (Ex. 1005).
`
`3 J. Tabernero et al., A phase I study with tumor molecular
`pharmacodynamics (MPD) evaluation of dose and schedule of the oral
`mTOR-inhibitor Everolimus (RAD001) in patients (pts) with advanced solid
`tumors, DEVELOPMENTAL THERAPEUTICS: MOLECULAR THERAPEUTICS,
`Abstract 3007, 193s (2005) (Ex. 1006).
`
`4 Götz von Wichert et al., Insulin-like Growth Factor-I is an Autocrine
`Regulator of Chromogranin A Secretion and Growth in Human
`Neuroendocrine Tumor Cells, 60 CANCER RES. 4573–4581 (Aug. 15, 2000)
`(Ex. 1007).
`
`5 Janice P. Dutcher, Mammalian Target of Rapamycin (mTOR) Inhibitors, 6
`CURRENT ONCOLOGY REP. 111–115 (2004) (Ex. 1008).
`
`6 U.S. Patent 5,665,772 to Cottens et al. (Sept. 9, 1997) (Ex. 1009).
`
`
`
`4
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`
`
`Roxane contends that all asserted references are prior art to the ’224
`
`patent under 35 U.S.C. § 102(b). Pet. 27–32. Novartis does not, at this
`
`stage of the proceeding, challenge the prior art status of any reference.
`
`II. ANALYSIS
`
`A. Claim Construction
`
`In an inter partes review, we construe claims by applying the broadest
`
`reasonable interpretation in light of the specification. 37 C.F.R. § 42.100(b);
`
`see also In re Cuozzo Speed Techs., LLC, 136 S. Ct. 2131, 2144–46 (2016).
`
`Under the broadest reasonable interpretation standard, and absent any
`
`special definitions, 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). Any special definitions for claim terms or phrases
`
`must be set forth with reasonable clarity, deliberateness, and precision. In re
`
`Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
`
`Roxane does not set forth an explicit construction for any claim term,
`
`asserting instead that all terms should be “accorded their broadest reasonable
`
`interpretation as understood by” a person of ordinary skill in the art. Pet. 17.
`
`In response, Novartis asks that we construe the claim term “advanced,”
`
`alleging that Roxane’s arguments in the Petition are based on an improper
`
`interpretation of the term. Prelim. Resp. 6. Novartis asks that we construe
`
`an “advanced” tumor, as used in claim 1, to mean a tumor that is metastatic
`
`or unresectable. Id. at 6–8. Furthermore, Novartis contends, “advanced” is
`
`not synonymous with “after failure of cytotoxic chemotherapy.” Id. at 8–13.
`
`
`
`5
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`We agree with Novartis that the broadest reasonable interpretation of
`
`“advanced” tumors, when viewed in light of the ’224 patent specification, is
`
`“metastatic or unresectable.” Novartis correctly points out that the
`
`specification refers to “patients with measurable advanced (metastatic or
`
`unrese[c]table) pancreatic neuroend[o]crine tumors,” suggesting that
`
`metastatic and unresectable tumors are subsets within advanced tumors.
`
`Ex. 1001, 26:57–58. We also note that the specification discusses the use of
`
`mTOR inhibitors for cancer chemotherapy “particularly for the treatment of
`
`solid tumors, especially of advanced solid tumors,” implying that not all
`
`solid tumors are “advanced.” Id. at 2:39–40. Novartis’ proffered
`
`construction is also consistent with the evidence of ordinary and customary
`
`usage, such as the Cancer Glossary published by the American Cancer
`
`Society. Ex. 2005, 3 (“advanced cancer” definition).
`
`We also agree with Novartis that “advanced,” in the usage of claim 1,
`
`is different than “after failure of cytotoxic chemotherapy.” The language of
`
`the claim itself, by including both terms, supports this conclusion. In other
`
`words, were we to interpret “advanced” tumors to mean those “after failure
`
`of cytotoxic chemotherapy,” then there would be no reason to include the
`
`latter phrase in the claim. Furthermore, as Novartis points out, the
`
`specification of the ’224 patent refers to patients with advanced tumors who
`
`had not yet undergone any treatment. Ex. 1001, 3:2–4 (60% or more of
`
`patients present with metasteses [advanced tumors] at the time of diagnosis).
`
`These advanced tumors, therefore, are present prior to the failure of any
`
`chemotherapy, as treatment has not yet begun.
`
`
`
`6
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`For these reasons, we adopt Novartis’ proposed construction for
`
`“advanced,” meaning “metastatic or unresectable,” and distinguishable from
`
`“after failure of cytotoxic chemotherapy.”
`
`B. Obviousness over Lane and Tabernero
`
`Roxane contends that claims 1 and 2 are unpatentable under 35 U.S.C.
`
`§ 103(a) as having been obvious over the combined teachings of Lane and
`
`Tabernero. Pet. 35–39. Roxane relies upon the Declaration of Kenneth Ho-
`
`Ming Yu, M.D., M.Sc. (Ex. 1003) to support its positions.
`
`Lane discloses that rapamycin derivatives have “interesting effects in
`
`the treatment of solid tumo[]rs,” including tumors of the pancreas. Ex.
`
`1005, Abstract, ¶ 17. In one instance, Lane describes an experiment in
`
`which rats bearing CA20948 pancreatic tumors were treated using
`
`everolimus (“Compound A”), and concludes that the treatment “significantly
`
`and consistently decreases . . . the rate of CA20948 pancreatic tumor
`
`growth.” Id. ¶¶ 9, 88. According to Dr. Yu, a person of ordinary skill in the
`
`art would have understood that the CA20948 pancreatic cell line was used as
`
`a model for evaluating PNETs. Ex. 1003 ¶ 29.
`
`Tabernero is the abstract of a presentation regarding a Phase I study of
`
`the use of everolimus in patients with advanced solid tumors. Ex. 1006,
`
`193s. According to Dr. Yu, “[t]ypically, patients who present with advanced
`
`solid tumors have tumors which are surgically refractory and which have not
`
`responded to cytotoxic chemotherapy.” Ex. 1003 ¶ 37. Tabernero discloses
`
`that everolimus inhibits mTOR, a protein kinase involved in “the regulation
`
`of cell growth, proliferation, and survival.” Ex. 1006, 193s. Tabernero
`
`
`
`7
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`recommends further Phase II–III development of everolimus, at a dosage of
`
`10 mg daily, as a single agent tumor treatment. Id.
`
`In view of Lane, Roxane asserts that a person of ordinary skill in the
`
`art seeking to develop a treatment for PNET would have had reason “to
`
`select everolimus and would have reasonably expected that everolimus,
`
`which had been shown to be efficacious against the CA20948 pancreatic cell
`
`line, a model for evaluating PNETs, would be effective as an anticancer
`
`monotherapy agent for treating PNETs.” Pet. 37. Furthermore, Roxane
`
`contends that in view of Tabernero, a person of ordinary skill would have
`
`understood that “everolimus monotherapy is a safe and effective treatment
`
`for advanced solid tumors which have not responded to cytotoxic
`
`chemotherapy.” Id. at 38. Combining these disclosures, according to
`
`Roxane, a person of ordinary skill would have been motivated to use 10mg
`
`daily of everolimus as a monotherapy antitumor agent for human patients
`
`with advanced PNET after failure of cytotoxic chemotherapy, leading to
`
`claims 1 and 2 of the ’224 patent. Id. at 38–39.
`
`Novartis argues that neither Lane nor Tabernero teaches or suggests
`
`the treatment of advanced PNETs after failure or cytotoxic chemotherapy, as
`
`required by the claims. Prelim. Resp. 13–17. Furthermore, Novartis
`
`contends that a person of ordinary skill in the art would have not had a
`
`reasonable expectation of success in treating advanced PNETs with
`
`everolimus after failure of cytotoxic chemotherapy. Id. at 17–24. Novartis
`
`supports these arguments with the Declaration of Matthew H. Kulke, M.D.
`
`(Ex. 2001).
`
`
`
`8
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`Novartis observes that Roxane’s Petition only relies on Tabernero to
`
`teach or suggest treatment of advanced tumors after failure of cytotoxic
`
`chemotherapy. Prelim. Resp. 14. Tabernero, however, does not contain an
`
`explicit reference to either advanced PNETs or the failure of cytotoxic
`
`chemotherapy. Rather, as Novartis notes, Roxane argues that Tabernero’s
`
`disclosure of “advanced solid tumors” would have been understood to refer
`
`to tumors that have not responded to advanced cytotoxic chemotherapy. Id.
`
`Novartis challenges this assertion as unsupported, as it is based only on the
`
`conclusory testimony of Dr. Yu, and also inconsistent with the prior art. Id.
`
`at 14–15.
`
`Novartis cites the testimony of Dr. Kulke that a person of ordinary
`
`skill in the art would have understood Tabernero’s use of the term
`
`“advanced solid tumors” to refer to metastatic or unresectable tumors, not
`
`those which have failed to respond to cytotoxic chemotherapy. Ex. 2001
`
`¶ 33. According to Novartis, patients could have been enrolled in the
`
`Tabernero study without having been treated previously with cytotoxic
`
`chemotherapy. Prelim. Resp. 15.
`
`Above, we concluded that in the context of the ’224 patent,
`
`“advanced” tumors refer to metastatic or unresectable tumors, and not to
`
`those which have previously undergone treatment with cytotoxic
`
`chemotherapy, and found that this usage is consistent with the ordinary and
`
`customary meaning of the term. We see no reason to conclude that
`
`Tabernero intended to depart from this ordinary and customary usage, and
`
`cannot conclude that Tabernero’s reference to “advanced solid tumors”
`
`
`
`9
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`would have been understood by a person of ordinary skill in the art as
`
`describing tumors that have failed to respond to cytotoxic chemotherapy.
`
`Roxane has not presented us with evidence sufficient to persuade us
`
`otherwise. The sole evidence relied upon to link Tabernero’s “advanced
`
`solid tumors” to the failure of cytotoxic chemotherapy is Dr. Yu’s testimony
`
`that “[t]ypically, patients who present with advanced solid tumors have
`
`tumors which are surgically refractory and which have not responded to
`
`cytotoxic chemotherapy.” Ex. 1003 ¶ 37. But Dr. Yu cites no evidence to
`
`support this association, leaving us only with his bare conclusion. As the
`
`Board has stated repeatedly, conclusory expert testimony is entitled to little
`
`or no weight. See Monsanto Co. v. Pioneer Hi-Bred Int’l, Inc., Case
`
`IPR2013-00022, 6–7 (PTAB Apr. 11, 2013) (Paper 43); 37 C.F.R.
`
`§ 42.65(a); see also Velander v. Garner, 348 F.3d 1359, 1371 (Fed. Cir.
`
`2003) (Board has discretion to accord appropriate weight to broad
`
`conclusory statements from expert witness). Where, as here, the conclusory
`
`testimony is the sole basis for establishing that a claim limitation is taught or
`
`suggested by the prior art, we find it insufficient to establish a reasonable
`
`likelihood of prevailing regarding that claim.
`
`For these reasons, we cannot conclude that Roxane has established
`
`sufficiently that it would prevail in proving that claims 1 and 2 of the ’224
`
`patent would have been obvious over Lane and Tabernero. Because we find
`
`that the asserted prior art does not teach or suggest treatment of advanced
`
`PNET after failure of cytotoxic chemotherapy, we do not address Novartis’
`
`remaining argument regarding expectation of success.
`
`
`
`10
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`C. Obviousness over von Wichert, Dutcher, Cottens, and Tabernero
`
`Roxane also contends that claims 1 and 2 would have been obvious
`
`over the combined disclosures of von Wichert, Dutcher, Cottens, and
`
`Tabernero. Pet. 40–45. We need not set forth in detail the proposed ground,
`
`because it suffers from the same fault as the prior one. Specifically, the
`
`ground only relies on Tabernero—and Dr. Yu’s conclusory, unsupported
`
`testimony—to disclose treatment of a tumor after failure of cytotoxic
`
`chemotherapy. Id. at 43. Roxane’s reliance on von Wichert, Dutcher, and
`
`Cottens do not remedy the deficiency of Tabernero discussed above, as
`
`Roxane does not contend that any of these references teach or suggest
`
`treatment after failure of cytotoxic chemotherapy. We, therefore, conclude
`
`that Roxane has not established a reasonable likelihood of prevailing on this
`
`asserted ground of unpatentability.
`
`III. CONCLUSION
`
`For the foregoing reasons, we conclude that the information presented
`
`in the Petition and Preliminary Response does not establish a reasonable
`
`likelihood that Roxane will prevail in proving that claims 1 and 2 of the ’224
`
`patent are unpatentable.
`
`Accordingly, it is
`
`IV. ORDER
`
`ORDERED that pursuant to 35 U.S.C. § 314(a) the petition is denied,
`
`and no inter partes review is instituted.
`
`
`
`11
`
`
`
`IPR2016-01461
`Patent 9,006,224 B2
`
`
`For PETITIONER:
`
`Keith A. Zullow
`Marta E. Delsignore
`GOODWIN PROCTER LLP
`kzullow@goodwinprocter.com
`mdelsignore@goodwinprocter.com
`
`
`
`For PATENT OWNER:
`
`Nicholas N. Kallas
`Raymond R. Mandra
`FITZPATRICK, CELLA, HARPER & SCINTO
`nkallas@fchs.com
`rmandra@fchs.com
`
`12
`
`
`
`
`
`
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