Trials@uspto.gov
`571-272-7822
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` Paper 12
`Entered: January 3, 2018
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`BRECKENRIDGE PHARMACEUTICAL, INC.,
`Petitioner,
`
`v.
`
`NOVARTIS PHARMACEUTICALS CORP.,
`Patent Owner.
`____________
`
`Case IPR2017-01592
`Patent 8,410,131 B2
`____________
`
`
`
`Before SHERIDAN K. SNEDDEN, ROBERT A. POLLOCK, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`POLLOCK, Administrative Patent Judge.
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`571-272-7822
`
`
`
`
`
` Paper 12
`Entered: January 3, 2018
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`BRECKENRIDGE PHARMACEUTICAL, INC.,
`Petitioner,
`
`v.
`
`NOVARTIS PHARMACEUTICALS CORP.,
`Patent Owner.
`____________
`
`Case IPR2017-01592
`Patent 8,410,131 B2
`____________
`
`
`
`Before SHERIDAN K. SNEDDEN, ROBERT A. POLLOCK, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`POLLOCK, Administrative Patent Judge.
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`IPR2017-01592
`Patent 8,410,131 B2
`
`
`INTRODUCTION
`I.
`Breckenridge Pharmaceutical, Inc. (“Petitioner”) filed a Petition for an inter
`partes review of claims 1–3 and 5–9 of U.S. Patent No. 8,410,131 B2 (“the ’131
`patent,” Ex. 1001). Paper 1 (“Pet.”). Novartis Pharmaceuticals Corp. (“Patent
`Owner” or “Novartis”) timely filed a Preliminary Response. Paper 9 (“Prelim.
`Resp.”). We review the Petition, Preliminary Response, and accompanying
`evidence under 35 U.S.C. § 314.
`For the reasons provided below, we determine Petitioner has satisfied the
`threshold requirement set forth in 35 U.S.C. § 314(a). Because Petitioner has
`demonstrated a reasonable likelihood that at least claim 1 of the ’131 patent is
`unpatentable, we institute an inter partes review of the challenged claims.
`
` Related Proceedings
`According to the parties, the ’131 Patent is at issue in Novartis Pharm. Corp.
`v. West-Ward Pharm. Int’l. Ltd., C.A. No. 15-0474-RGA (D. Del.); Novartis
`Pharm. Corp. v. Breckenridge Pharm., Inc., C.A. No. 16-0431-RGA (D. Del.);
`Novartis Pharm. Corp. v. Teva Pharm. USA, Inc., C.A. No. 17-0393-RGA (D.
`Del.); and Novartis Pharm. Corp. v. Breckenridge Pharm., Inc., C.A. No. 17-0420-
`RGA (D. Del.). Pet. 4; Paper 3; Paper 6.
`
` The ’131 Patent and Relevant Background
`The ’131 patent relates to “a new use” for the macrolide antibiotic
`rapamycin and derivatives thereof, including compounds of formula I:
`
`2
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`wherein
`R1 is CH3 or C3-6alkynyl, R2 is H or -CH2-CH2OH, and
`X is =0, (H, H) or (H, OH)
`provided that R2 is other than H when X is =0 and R1 is CH3.
`
`
`Ex. 1001, 1–36. A preferred compound within the genus of formula I is 40-O-(2-
`hydroxyethyl)-rapamycin, also known as everolimus, which is depicted in claim 1
`of the ’131 Patent (subject to the Certificate of Correction dated October 20, 2015).
`See id. at 1:42–48; Pet. 14, 33; Prelim. Resp. 13.1
`According to the Specification:
`Compounds of formula I have, on the basis of observed activity, e.g.
`binding to macrophilin-12 (also known as FK-506 binding protein or
`FKBP-12) . . . been found to be useful e.g. as immunosuppressant, e.g.
`in the treatment of acute allograft rejection. It has now been found that
`Compounds of formula I have potent antiproliferative properties which
`
`
`1 Petitioner notes, and Patent Owner does not dispute, that 40-O-(2-hydroxyethyl)-
`rapamycin is variously referred to as “Compound A” of the ’131 Patent, “SDZ
`RAD, RAD, RAD001, and Certican®.” Pet. 6, n.4. For consistency, we refer to
`this compound as everolimus.
`
`3
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`make them useful for cancer chemotherapy, particularly of solid
`tumors, especially of advanced solid tumors.
`Id. at 1:49–58. The Specification defines “solid tumors” as “tumors and/or
`metastasis (wherever located) other than lymphatic cancer,” including excretory
`system tumors (e.g. kidney, renal pelvis, ureter, bladder, and unspecified urinary
`organs). Id. at 2: 20–29.
`
` Challenged Claims
`Petitioner challenges claims 1–3 and 5–9 of the ’131 Patent, of which only
`claim 1 is independent. Claim 1 recites:
`1. A method for inhibiting growth of solid excretory system tumors in
`a subject, said method consisting of administering to said subject a
`therapeutically effective amount of [everolimus].
`Depending from claim 1, claims 2 and 3, respectively, specify that the solid
`excretory system tumor is “an advanced solid excretory system tumor,” or “a
`kidney tumor.” Claim 5 specifies that the everolimus is administered orally.
`Claims 6–9 recite amounts of everolimus administered, most narrowly specified in
`claim 9 as “a unit dosage form of 10 mg.
`
`
`Asserted Grounds of Unpatentability
`Petitioner asserts the following grounds of unpatentability (Pet. 6–7):
`Ground Claim(s)
`Basis
`Reference(s)
`1
`1–3 and 5–9
` § 102(a)/102(e)(1) Wasik2
`2
`1–3 and 5–9
` § 103(a)
`Wasik alone or in
`combination with Navarro3
`
`
`2 WO 01/51049 A1, published July 19, 2001. Ex. 1002.
`3 WO 00/33878 A2, published Dec. 6, 1999. Ex. 1003.
`4
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`Ground Claim(s)
`3
`1–3 and 5–9
`
`Basis
` § 103(a)
`
`4
`
`5
`
`1–3 and 5–9
`
` § 103(a)
`
`1–3 and 5–9
`
` § 103(a)
`
`Reference(s)
`Wasik, Navarro, Crowe,4
`and Luan5
`Alexandre,6 Crowe,
`Hidalgo,7 Schuler,8
`Neumayer, and Navarro, 9
`Alexandre, Crowe, Hidalgo,
`Schuler, Neumayer,
`Navarro, and Luan
`
`In support of its patentability challenges, Petitioner relies on the Declaration
`of Allan J. Pantuck, M.D. Ex. 1010. Patent Owner relies on the Declaration of
`Howard A. Burris, III, M.D. Ex. 2001.
`
`
`4 Crowe et al., Absorption and Intestinal Metabolism of SDZ-RAD and Rapamycin
`in Rats, 27(5) Drug Metab. Disp. 627-632 (1999). Ex. 1004.
`5 Luan et al., Sirolimus Prevents Tumor Progression: mTOR Targeting for the
`Inhibition of Neoplastic Progression, 1 Suppl. 1 Am. J. Transplant. 243, Abstr. No.
`428 (2001). Ex. 1005.
`6 Alexandre et al., CCI-779, A new Rapamycin Analog, Has Antitumor Activity at
`Doses Including Only Mild Cutaneous Effects and Mucositis: Early Results of an
`Ongoing Phase I Study, 5(suppl.), Clin. Cancer Res. 3730s, Abstr. No. 7 (1999).
`Ex. 1007.
`7 Hidalgo et al., The Rapamycin-sensitive Signal Transduction Pathway as a
`Target for Cancer Therapy, 19(56) Oncogene 6680-6686 (2000). Ex. 1006.
`8 Schuler et al., SDZ RAD, A New Rapamycin Derivative, 64(1) Transplantation
`36–42 (1997). Ex. 1008.
`9 Neumayer et al., Entry-into-human Study with the Novel Immunosuppressant SDZ
`RAD in Stable Renal Transplant Patients, 48(5) Br. J. Clin. Pharmacol. 694–703
`(1999). Ex. 1009.
`
`
`5
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`II. ANALYSIS
`“In an [inter partes review], the petitioner has the burden from the onset to
`show with particularity why the patent it challenges is unpatentable.” Harmonic
`Inc. v. Avid Tech., Inc., 815 F.3d 1356, 1363 (Fed. Cir. 2016) (citing 35 U.S.C. §
`312(a)(3) (requiring inter partes review petitions to identify “with particularity . . .
`the evidence that supports the grounds for the challenge to each claim”)). This
`burden of persuasion never shifts to Patent Owner. See Dynamic Drinkware, LLC
`v. Nat’l Graphics, Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015) (discussing the
`burden of proof in inter partes review).
`To anticipate a claim under 35 U.S.C. § 102, “a single prior art reference
`must expressly or inherently disclose each claim limitation.” Finisar Corp. v.
`DirecTV Group, Inc., 523 F.3d 1323, 1334 (Fed. Cir. 2008). That “single
`reference must describe the claimed invention with sufficient precision and detail
`to establish that the subject matter existed in the prior art.” Verve, LLC v.
`Crane Cams, Inc., 311 F.3d 1116, 1120 (Fed. Cir. 2002). While the elements must
`be arranged in the same way as is recited in the claim, “the reference need not
`satisfy an ipsissimis verbis test.” In re Gleave, 560 F.3d 1331, 1334 (Fed. Cir.
`2009). “[I]t is proper to take into account not only specific teachings of the
`reference but also the inferences which one skilled in the art would reasonably be
`expected to draw therefrom.” In re Preda, 401 F.2d 825, 826 (CCPA 1968). The
`dispositive question is whether one skilled in the art would reasonably understand
`or infer from a prior art reference that every claim element is disclosed in that
`reference. Eli Lilly v. Los Angeles Biomedical Research Inst. at Harbor-UCLA
`Med. Ctr, 849 F.3d 1073, 1074–75 (Fed. Cir. 2017).
`
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`A claim is unpatentable under 35 U.S.C. § 103(a) if the differences between
`the subject matter sought to be patented 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 that subject matter pertains. KSR
`Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). In analyzing the obviousness
`of a combination of prior art elements, it can be important to identify a reason that
`would have prompted one of skill in the art “to combine . . . known elements in the
`fashion claimed by the patent at issue.” Id. at 418.
`A precise teaching directed to the specific subject matter of a challenged
`claim is not necessary to establish obviousness. Id. Rather, “any need or problem
`known in the field of endeavor at the time of invention and addressed by the patent
`can provide a reason for combining the elements in the manner claimed.” Id.
`at 420. Accordingly, a party that petitions the Board for a determination of
`unpatentability based on obviousness must show that “a skilled artisan would have
`been motivated to combine the teachings of the prior art references to achieve the
`claimed invention, and that the skilled artisan would have had a reasonable
`expectation of success in doing so.” In re Magnum Oil Tools Int’l, Ltd., 829 F.3d
`1364, 1381 (Fed. Cir. 2016) (internal quotations and citations omitted).
`
` Person of Ordinary Skill in the Art
`Petitioner proposes that a person of ordinary skill in the art as of the relevant
`date(s)10 would possess:
`
`
`10 Although the parties disagree as to the relevant priority date with respect to
`whether Luan qualifies as prior art, this controversy does not otherwise affect our
`analysis. See section II(E)(c), below.
`
`7
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`(i) a medical degree (e.g., M.D.) with several years of specific
`experience in medical or surgical oncology, which may include board
`certification, as well as knowledge oncological drug development and
`clinical pharmacology; or
`(ii) a Ph.D. in cancer biology, molecular biology, medicinal chemistry,
`or a related field with several years of experience in oncological drug
`development and clinical pharmacology, including evaluating cancer
`therapeutics in in vitro and/or in vivo assays, as well as familiarity with
`the practice of medical oncology.
`Pet. 14 (citing Ex. 1010 ¶ 20) (paragraphing added). Patent Owner adopts
`Petitioner’s definition. Prelim. Resp. 3. The undisputed proposed definition is not
`inconsistent with the cited prior art, and we adopt it for the purposes of this
`Decision. See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001)
`(explaining that specific findings regarding ordinary skill level are not required
`“where the prior art itself reflects an appropriate level and a need for testimony is
`not shown” (quoting Litton Indus. Prods., Inc. v. Solid State Sys. Corp., 755 F.2d
`158, 163 (Fed. Cir. 1985)).
`
` Claim Construction
`In an inter partes review, claim terms in an unexpired patent are interpreted
`according to 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., LLC
`v. Lee, 136 S. Ct. 2131, 2144–46 (2016) (upholding the use of the broadest
`reasonable interpretation standard). Under that standard, we presume that a claim
`term carries its “ordinary and customary meaning,” which “is the meaning that the
`term would have to a person of ordinary skill in the art in question” at the time of
`the invention. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007);
`see also Trivascular, Inc. v. Samuels, 812 F.3d 1056, 1062 (Fed. Cir. 2016)
`8
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`(“Under a broadest reasonable interpretation, words of the claim must be given
`their plain meaning, unless such meaning is inconsistent with the specification and
`prosecution history.”). Any special definition for a claim term must be set forth in
`the specification with reasonable clarity, deliberateness, and precision. In re
`Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994). Limitations, however, may not be
`read from the specification into the claims (In re Van Geuns, 988 F.2d 1181, 1184
`(Fed. Cir. 1993)), nor may the Board “construe claims during [an inter partes
`review] so broadly that its constructions are unreasonable under general claim
`construction principles” (Microsoft Corp. v. Proxyconn, Inc., 789 F.3d 1292, 1298
`(Fed. Cir. 2015) (overruled on other grounds by Aqua Products, Inc. v. Matal, 872
`F.3d 1290 (Fed. Cir. 2017)).
`Petitioner proposes definitions for the terms “inhibiting growth,” “solid
`excretory system tumors,” and “a subject,” in the claim phrase “inhibiting growth
`of solid excretory system tumors in a subject.” Pet. 15–16. Petitioner further
`proposes definitions for “advanced solid excretory system tumor,” “kidney tumor,”
`and “unit dosage form.” Id. at 16–18. Patent Owner proposes definitions for
`“solid excretory system tumors,” “advanced solid excretory system tumors,” and
`“kidney tumor.” Prelim. Resp. 4–10. We agree with Patent Owner that the latter
`three terms require express construction. See id. at 10.
`
`a. “solid excretory system tumors”
`According to Petitioner, the “solid excretory system tumors” of claim 1 refer
`to “benign or malignant tumors of the excretory system, including kidney, renal
`pelvis, ureter, bladder, other and unspecified urinary organs.” Pet. 16 (citing
`Ex. 1010 ¶¶ 71–75; Ex. 1001, 2:20–21, 28–29). Patent Owner contends that
`Petitioner’s proposed definition “reads the ‘solid’ limitation out of the claim” in
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`that it fails to limit the term to tumors (or their metastasis) arising from cells of the
`urinary excretory system. Prelim. Resp. 7–8. For the reasons set forth on pages 4–
`8 of the Preliminary Response, which we adopt, we agree with Patent Owner that
`“solid excretory system tumors” means “tumors and/or metastases, other than
`tumors and/or metastases of the blood or lymphatic system, which arise from the
`cells of the urinary excretory system.”
`Briefly, the Specification defines “solid tumors” as “tumors and/or
`metastasis (wherever located),” including excretory system tumors, but expressly
`excluding lymphatic cancer. Id. at 2:20–29. The Specification further defines
`“lymphatic cancer” as “tumors of [the] blood and lymphatic system,” exemplified
`by leukemias, lymphomas, and “unspecified malignant neoplasms of lymphoid,
`haematopoletic [sic] and related tissues.” Id. at 4:20–30. As Patent Owner notes,
`lymphatic cancers are non-solid, “liquid tumors” and, thus, expressly excluded by
`the language of claim 1. See Prelim. Resp. 5 (citations omitted). With respect to
`the cell type of origin, the Specification makes clear that “excretory system
`tumors” refers to tumors (or their metastasis) arising from cells of the urinary
`excretory system. Ex. 1001, 2:20–21, 28–29, 58–62; see Ex. 2001 ¶ 42.
`Accordingly, for the purpose of this Decision, we define “solid excretory
`system tumors” to mean “tumors and/or metastases, other than tumors and/or
`metastases of the blood or lymphatic system, which arise from the cells of the
`urinary excretory system.” Prelim. Resp. 9.
`
`b. “advanced solid excretory system tumors”
`Petitioner notes that “[a] solid tumor can be localized (confined to the organ
`from which it arose), locally advanced (spread beyond the tissue from which it
`arose to nearby tissues or lymph nodes), or metastatic (spread to distant sites or
`10
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`tissues in the body).” Pet. 17 (citing Ex. 1010 ¶ 84). The parties agree that
`“advanced” solid excretory system tumors, as set forth in claim 2, indicates locally
`advanced or metastatic tumors. See Pet. 16–17; Prelim. Resp. 8–9. In the interest
`of clarity, we define “advanced solid excretory system tumor[s]” to mean: “locally
`advanced or metastatic tumors, other than tumors and/or metastases of the blood or
`lymphatic system, which arise from the cells of the urinary excretory system.” Id.
`
`c. “kidney tumors”
`Claim 3 of the ’131 patent limits the “solid excretory system tumors” of
`claim 1 to “kidney tumors.” Consistent with our definition of “solid excretory
`system tumors,” we understand the term “kidney tumors” as referring to “solid
`excretory system tumors arising from kidney cells.” Id. at 9.
`
` Anticipation by Wasik (Ground 1)
`Petitioner provides arguments and evidence purporting to show that Wasik
`anticipates claims 1–3 and 5–9 of the ’131 Patent. Pet. 32–38. Patent Owner
`opposes. Prelim. Resp. 21–32. Having considered the arguments and evidence
`before us, for the reasons set forth below, we find that the record establishes a
`reasonable likelihood that Petitioner will prevail on this asserted ground.
`Wasik discloses the treatment of lymphoproliferative disorders (e.g., post-
`transplant lymphoproliferative disorders (“PLTDs”), lymphatic tumors,
`lymphomas, and leukemias), including the inhibition of their metastases by
`administering rapamycin, or an O-methylated derivative of rapamycin, preferably
`everolimus (SDZ RAD or 40-0-(2-hydroxy)ethyl-rapamycin). See e.g., Ex. 1002,
`
`11
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`Abstract, 2:23–3:2, 10:16–22, 12:5–13, 19:17–20, 30:3–35:17, 39:19–40:16.11
`Wasik teaches unit dosages of these compounds, including in the range of “from
`about 500 micrograms to about 10 milligrams” and “1 to 10 milligrams per day.”
`Id. at 16:21–24, 18:18–24.
`Petitioner relies, most particularly, on the statement at page 17, lines 19–29
`of Wasik that:
`In another embodiment, the invention includes a method of using an
`O-alkylated rapamycin derivative such as [everolimus] or rapamycin to
`inhibit the establishment of a tumor in a mammal. This method
`involves administering to a mammal having a first tumor, an amount of
`the rapamycin derivative sufficient to inhibit establishment of a second
`tumor derived from the first tumor in the mammal. A mammal to be
`treated with an O-alkylated rapamycin derivative for this purpose can
`have substantially any type of first tumor such as a tumor of the brain,
`kidney, liver, breast, or ovary. Other representative anti-tumor activities
`that can be exhibited by an O-alkylated rapamycin derivative such as
`[everolimus]
`include
`inhibition of
`tumorigenesis,
`inhibition of
`metastasis, inhibition of tumor cell growth, inhibition of tumor cell
`proliferation, and induction of tumor cell death.
`See Pet. 35.
`Patent Owner argues that Wasik fails to anticipate because it does not
`disclose the treatment of solid tumors, but is solely directed to the treatment of
`non-solid tumors, specifically lymphomas, which are expressly excluded from the
`scope of the challenged claims. Prelim. Resp. 21–29. Relying largely on the
`testimony of its expert, Dr. Burris, Patent Owner argues that Wasik uses the terms
`tumor and “lymphoma” interchangeably, such that “[a]ll references to “tumor[s]”
`
`
`11 Where possible, we refer to the native page number of cited references rather
`than to the pagination added by parties.
`
`12
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`in Wasik referred to lymphomas.” See id. at 22–24. Patent Owner further relies on
`Dr. Burris’s testimony in arguing that Wasik fails to disclose a method for
`inhibiting growth of advanced solid excretory tumors as required by claim 2 (id. at
`30–32),12 or the treatment of “kidney tumors” as the term is used in claim 3 (id. at
`26–27).
`Although Wasik is generally directed to treating tumors of lymphatic origin,
`page 17, lines 19–29 of the reference may be read as teaching “another
`embodiment,” wherein everolimus may be used to treat, not only lymphatic
`tumors, but “substantially any type of first tumor,” specifically including those of
`the kidney. Moreover, Dr. Burris’s opinions as to what Wasik discloses are
`directly contradicted by those of Petitioner’s expert, Dr. Pantuk. See Ex. 1010 ¶¶
`195–217, 225. Such disputed issues of material fact are best resolved on a full trial
`record; furthermore, at this stage of the proceeding, “a general issue of material
`fact created by [Patent Owner’s] testimonial evidence will be viewed in the light
`most favorable to the petitioner.” See 37 C.F.R. § 42.108(c).
`Patent Owner also appears to argue that, during prosecution of the ’131
`patent and related U.S. applications, both the Applicant and the Examiner
`understood Wasik as limited to lymphatic cancers. Prelim. Resp. 24–25. Patent
`Owner merely points to instances where Wasik was cited with respect to lymphatic
`
`
`12 Patent Owner argues that although page 19, lines 19–29 of Wasik discloses
`preventing metastasis, it fails to disclose inhibiting the growth of advanced tumors.
`See Pet. 30; see also Ex. 1010 ¶¶ 69–70 (asserting that the ordinary and customary
`meaning of “inhibiting growth” of a tumor refers to slowing growth or progression
`of a tumor). But as we discern nothing in Wasik limiting the “first tumor” to a
`primary tumor, the passage may also be read as encompassing the inhibition of
`locally advanced or metastatic tumors.
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`cancers, which is hardly affirmative evidence that Wasik is limited to those
`conditions. In short, we do not find these arguments persuasive in light of the
`other evidence of record. See discussion, above, regarding page 17, lines 19–29 of
`Wasik.
`Patent Owner also points to a Communication pursuant to Article 96(2) from
`the Wasik applicant to the European Patent Commission as evidence that “the
`[Wasik] applicant distinguished Cottens . . . by explaining that the tumors in
`Cottens . . . which are solid tumors, are ‘significantly different from a
`lymphoproliferative disorder since they affect only non-lymphocytic cells or
`tissues.’” Id. at 25 (quoting Ex. 2019, 7). To the extent the Wasik applicant was
`distinguishing Cottens from claims to “alleviating a lymphoproliferative disorder”
`(see Ex. 1002, 1–2), the statement says nothing about what Wasik discloses. To
`the extent Wasik incorporates Cottens by reference, as discussed below, the
`statement underscores Petitioner’s contention that Wasik discloses non-lymphatic
`solid tumors.
`Accordingly, on the present record, we find that Petitioner demonstrates a
`reasonable likelihood of showing that Wasik anticipates the challenged claims.
`Although not necessary for our Decision to institute inter partes review,
`Petitioner further argues that Wasik incorporates by reference the subject matter of
`Cottens.13 Pet. 28; see also Ex. 1001, 8:3–6 (incorporating by reference “methods
`for making” O-alkylated rapamycin derivatives); id. at 34:20–21 (incorporating by
`reference “[t]he disclosure of every patent, patent application, and publication cited
`herein . . . in its entirety”). According to Petitioner, “Cottens . . . describes
`
`
`13 WO 94/09010, published April 28, 1994. Ex. 1026.
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`everolimus and its use in the treatment of tumors.” Pet. 28–29 (citing Ex. 1026 at
`5, 8; Ex. 1010 ¶¶ 26, 47). Petition further argues that Novartis admitted during
`prosecution that Cottens encompassed solid tumors. See Pet. 28–29 (citing
`Ex. 1027, Applicant’s statement that Cottens “is not limited to solid tumors and
`can therefore include liquid tumors”). Petitioner reasonably interprets this portion
`of the prosecution history as an admission that one of ordinary skill in the art
`would have understood “that methods of treating lymphoma (or liquid) tumors may
`also be used to treat solid tumors, and vice versa.” Id. at 29.
`Patent Owner responds that Wasik incorporates only those teachings of
`Cottens disclosing O-alkylated rapamycin derivatives and methods of making
`those compounds. Prelim. Resp. 28 (citing Ex. 1002, 6:3–6). In attempting to
`exclude the remaining portions of Cottens, Patent Owner argues that Wasik’s
`declaration that “[t]he disclosure of every patent, patent application, and
`publication cited herein . . . in its entirety,” is a “[v]ague catch-all phrase[],” which
`does not “clearly indicat[e] the specific material for incorporation,” as required
`under Federal Circuit precedent. Id. (citing Kyocera Wireless Corp. v. Int’l Trade
`Comm’n, 545 F.3d 1340, 1351–52 (Fed. Cir. 2008)). We do not agree.
`In Kyocera, the Court addressed whether the collection of documents
`(specifications) collectively known as the “GSM standard,” qualified as single
`anticipatory reference. 545 F.3d 1350–52. With respect to whether each document
`in the collection incorporates the others by reference, the Court found that “[a]t
`most, each relevant GSM specification identifies itself as a part of the greater GSM
`standard; specifications at times cross-reference other specifications. This vague
`referencing practice is hardly sufficient to meet this court’s legal requirements for
`incorporation,” which requires that “the incorporating document . . . identify the
`15
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`IPR2017-01592
`Patent 8,410,131 B2
`
`incorporated document with detailed particularity, clearly indicating the specific
`material for incorporation.” Id. at 1351–52. In contrast, Wasik’s statement that
`“[t]he disclosure of every patent, patent application, and publication cited herein is
`incorporated in its entirety,” clearly specifies that the entire disclosure of cited
`patent documents, including Cotten, is incorporated into the Wasik specification.
`See Ex. 1001, 34:20–21; see also Harari v. Lee, 656 F.3d 1331, 1335 (2011)
`(holding that a blanket statement in the host document that “[t]he disclosures of the
`two applications are hereby incorporate[d] by reference” was sufficient to
`incorporate two applications in their entirety).
`Accordingly, Applicant’s assertions regarding Cottens further support our
`view that Petitioner demonstrates a reasonable likelihood of showing that Wasik
`anticipates the challenged claims.
`
` Obviousness in view of Wasik, and optionally, Navarro (Ground 2)
`Petitioner asserts that claims 1–3 and 5–9 are obvious in view of Wasik
`alone or in combination with Navarro’s “teach[ing] that everolimus in dosages up
`to 10 mg is useful for the treatment of tumors.” Pet. 39–42; see Ex. 1003, 2, 4
`(disclosing that everolimus is useful both for its immunosuppressant properties and
`in the treatment and prevention of “proliferative disorders, e.g. tumors”).
`Patent Owner disagrees for the reasons discussed above with respect to
`anticipation over Wasik and further argues that “Navarro[] does not remedy
`Wasik’s deficiencies”. Prelim. Resp. 32–33. For the reasons set forth in section
`II(C), we find that Petitioner demonstrates a reasonable likelihood of showing that
`Wasik, and thus, the combination of Wasik and Navarro, render the challenged
`claims obvious. See In re McDaniel, 293 F.3d 1379, 1385 (Fed. Cir. 2002) (“It is
`
`16
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`IPR2017-01592
`Patent 8,410,131 B2
`
`well settled that ‘anticipation is the epitome of obviousness.’”) (quoting Connell v.
`Sears, Roebuck & Co., 722 F.2d 1542, 1548 (Fed. Cir. 1983)).
`
` Obviousness in view of Wasik, Navarro, Crowe, and Luan (Ground 3)
`Petitioner asserts that claims 1–3 and 5–9 are obvious in view of Wasik in
`combination with Navarro, Crowe, and Luan. Patent Owner disagrees. Prelim.
`Resp. 32–40, 45–52. Having considered the arguments and evidence before us, for
`the reasons set forth below, we find that the record establishes a reasonable
`likelihood that Petitioner will prevail on its asserted ground.
`Having discussed Wasik and Navarro in sections II(C) and II(D), above, we
`proceed with an overview of Crowe and Luan.
`
`a. Overview of Crowe
`Citing Schuler (Ex. 1008), Crowe teaches that “[everolimus] is a structural
`analog of rapamycin, sharing the same mechanisms of action.” Ex. 1004, 630.
`Upon comparing the absorption, intestinal metabolism, and bioavailability of
`everolimus as compared to rapamycin in an animal model, Crowe concludes that
`“[everolimus] has a better absorption profile that rapamycin in this study, which
`counteracts its high rate of intestinal metabolism and systemic elimination so that
`both rapamycin and [everolimus] have similar blood levels after oral application.”
`Id. at 632.
`
`b. Overview of Luan
`The Luan abstract, titled, “Sirolimus Prevents Tumor Progression: mTOR
`Targeting for the Inhibition of Neoplastic Progression,” explores the effect of
`sirolimus, also known as rapamycin and tacrolimus in a mouse model of
`
`17
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`IPR2017-01592
`Patent 8,410,131 B2
`
`immunosuppressive-induced tumor progression. Ex. 1005, 1;14 see Ex. 1010 ¶ 24
`(confirming that “sirolimus” is synonymous with “rapamycin”). The title and text
`of Luan reflects the understanding of one of ordinary skill in the art that rapamycin
`acts via the mTOR signaling pathway whereas tacrolimus (i.e., FK506) is a
`calcineurin inhibitor. See e.g., id. (“Our studies demonstrate that sirolimus has a
`diametrically opposite effect to that of calcineurin inhibitors on tumor
`progression.”); Ex. 1030, 808, Abstract;15 Ex. 1057, 239;16 Ex. 1058, 3.17
`Luan reports that, in contrast to tacrolimus, rapamycin had a statistically
`significant effect on preventing metastases of renal carcinoma cells in non-
`immunocompromised BALB/c mice, as well as in immunocompromised SCID-
`beige mice—a “highly malignant intrarenal cancer model.” Id. Luan reports that
`rapamycin increased survival in both models, and resulted in “reversal of the
`invasive phenotype of renal cancer cells . . . reduction in cell-division . . . and . . .
`“promotion of apoptosis.” Id. Luan posits that these results “open[] new avenues
`for the prevention and/or management of post-transplant neoplasia.” Id.
`
`
`14 As discussed in section II(b), below, Exhibit 1005 is a multi-document exhibit,
`the first page of which contains the Luan abstract. For ease of reference, we refer
`to the pagination that Petitioner has added to the exhibit.
`15 Alexandre et al., La rapamycine et Ie CCI-779, 86(10) Bull Cancer 808–11
`(1999);
`16 Choi et a., Structure of the FKB12-Rapamycin Complex Interacting with the
`Binding Domain of Human FRAP, 273 Science 239–42 (1996).
`17 Rapamune Approved Draft Labeling as of August 2000.
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`Patent 8,410,131 B2
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`
`c. Prior art effect of Luan
`i. Priority date of the ’131 Patent
`The ’131 patent issued from application No. 10/468,520, which is based on
`International Patent Application No. PCT/EP02/01714, filed February 18, 2002,
`and claiming benefit of foreign priority to GB 014072.4 (“GB ’072” (Ex. 1012)
`and GB 012957.2 (“GB ’957” (Ex. 1013)), dated February 19, 2001, and October
`17, 2001, respectively.
`Petitioner contends that, although Luan has a publication date of May 2001
`(i.e., after the date of GB ’072), it qualifies as prior art because the ’131 Patent is
`only entitled to the February 18, 2002, priority date of PCT/EP02/01714 because
`GB ’072 and GB ’957 lack written descriptive support for the full breadth of the
`claims. Pet. 11–13, 26.
`GB ’07218 discloses the use of everolimus (40-0-(2-hydroxyethyl)-
`rapamycin) as a preferred compound for the treatment of “solid tumors, especially
`advanced solid tumors.” Ex. 1012, 1–2. GB ’072 defines “solid tumors” as
`“tumors and/or metastasis (wherever located) other than lymphatic cancer,”
`including “renal-cell carcinomas” and “genitourinary cancer, e.g. cervical, uterine,
`ovarian, prostate or bladder cancer.” Id. at 2. GB ’072 further discloses: “Where .
`. . a tumor, a tumor disease, a carcinoma or a cancer is mentioned, also metastasis
`in the original organ or tissue and/or in any other location are implied alternatively
`or in addition, whatever the location of the tumor and/or metastasis is.” Id. at 3.
`
`
`18 We henceforth refer only to GB ’072 because only this earlier-filed document is
`critical to whether Luan qualifies as prior art, and th
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