Paper No. 10
`Trials@uspto.gov
`Entered: May 8, 2018
`Tel: 571-272-7822
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`CIPLA LTD.,
`Petitioner,
`v.
`ABRAXIS BIOSCIENCE, LLC,
`Patent Owner.
`
`Case IPR2018-00163
`Patent 7,923,536 B2
`
`Before JEFFREY N. FREDMAN, RAMA G. ELLURU, and
`SUSAN L. C. MITCHELL, Administrative Patent Judges.
`
`ELLURU, Administrative Patent Judge.
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a)
`
`Dismissing Petitioner’s Motion for Joinder
`37 C.F.R. § 42.122(b)
`
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`IPR2018-00163
`Patent 7,923,536 B2
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`
`I. INTRODUCTION
`A. Background
`Petitioner Cipla Ltd. (“Petitioner”) filed a Petition (Paper 1, “Pet.”)
`requesting an inter partes review of claims 1–16 (the “challenged claims”)
`of U.S. Patent No. 7,923,536 B2 (Ex. 1001, “the ’536 patent”). Patent
`Owner Abraxis Bioscience, LLC (“Patent Owner”) filed a Preliminary
`Response. Paper 8 (“Prelim. Resp.”).
`Concurrently with the Petition, Petitioner filed a Motion for Joinder
`(Paper 3, “Joinder Motion”). The Joinder Motion seeks to join this
`proceeding with Actavis LLC v. Abraxis Biosciences, IPR 2017-01103
`(“2017-01103 IPR”). Joinder Motion 1.
`At the time Petitioner filed the instant Petition and Joinder Motion, the
`Board had instituted inter partes review of the ’536 patent in the 2017–
`01103 IPR. Subsequent to that institution, the parties in the 2017–01103
`IPR submitted a Joint Motion to Terminate Inter Partes Review under
`35 U.S.C. § 317(a) and 37 C.F.R. §§ 42.72 and 42.74. Because we grant the
`motion to terminate, there is no instituted inter partes review for Petitioner
`to join, and thus, Petitioner’s Joinder Motion is dismissed as moot.
`However, because the instant Petition is not statutorily barred, a separate
`inter partes review may be instituted. 35 U.S.C. § 315(b). Pet. 7.
`
`We have authority to determine whether to institute an inter partes
`review under 35 U.S.C. § 314 and 37 C.F.R. § 42.4(a). To institute an inter
`partes review, we must determine that the information presented in the
`Petition shows “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(a). For the reasons set forth below, we conclude that Petitioner has
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`not established a reasonable likelihood that it would prevail in showing the
`unpatentability of at least one of the challenged claims of the ’536 patent.
`Therefore, we deny institution of an inter partes review for claims 1–16 of
`the ’536 patent.
`
`B. Related Proceedings
`Petitioner indicates that the ’536 patent was asserted in Abraxis
`BioScience, LLC v. Actavis LLC, C.A. No. 16-1925-JMV-MF; and Abraxis
`BioScience, LLC v. Cipla Ltd., C.A. No. 16-9074-JMV-MF. Pet. 5. In
`addition to the 2017-01103 IPR, additional requests for inter partes review
`of other patents related to the ’536 patent have been filed: U.S. Patent Nos.
`8,138,229 (“the ’229 patent”), 7,820,788 (“the ’788 patent”), and 8,853, 260.
`Id. at 5. Petitioner contemporaneously filed petitions for inter partes review
`of the ’788 and ’229 patents. Id. at 6.
`
`C. The ’536 Patent (Ex. 1001)
`The ’536 patent involves methods of formulating pharmaceuticals
`with carriers to “reduce one or more side effects.” Ex. 1001, 3:57–63. Such
`methods specifically involve formulating taxol (paclitaxel), an agent active
`against carcinomas, (id. at 4:8–34), with albumin, a protein found in human
`plasma (id. at 4:66–5:64).
`The ’536 patent specifically prefers that the composition “have a
`particle or droplet size less than about 200 nanometers” (id. at 9:51–9:53)
`and a “ratio of albumin to pharmaceutical agent in the pharmaceutical
`composition [that] is about 18:1 or less” (id. at 3:39–45). It is also stated in
`the ’536 patent that:
`While the ratio of protein to pharmaceutical agent will have to be
`optimized for different protein and pharmaceutical agent
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`combinations, generally the ratio of protein, e.g., albumin, to
`pharmaceutical agent is about 18:1 or less (e.g., about 15:1, about
`10:1, about 5:1, or about 3:1). More preferably, the ratio is about
`0.2:1 to about 12:1. Most preferably, the ratio is about 1:1 to
`about 9:1.
`Id. at 11:61–67. The ’536 patent also prefers a formulation “essentially free
`of cremophor” because “cremophor typically is used as a solvent for
`paclitaxel, and is associated with side effects that can be severe” (id. at
`11:66–12:6).
`
`D. Illustrative Claims
`Of the challenged claims, claim 1 is the sole independent claim of the
`’536 patent. The remaining challenged claims 2–16 depend directly or
`indirectly from claim 1. Claim 1 is illustrative of the challenged claims and
`recites:
`
`1. A method of treating cancer in a human individual,
`comprising injecting into the individual an effective amount
`of a pharmaceutical composition comprising paclitaxel and a
`pharmaceutically
`acceptable
`carrier, wherein
`the
`pharmaceutically acceptable carrier comprises albumin,
`wherein the albumin and the paclitaxel in the composition are
`formulated as particles, wherein
`the particles
`in
`the
`composition have a particle size of less than about 200 nm,
`and wherein the weight ratio of albumin to paclitaxel in the
`composition is about 1:1 to about 9:1.
`Ex. 1001, 37:20.
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`Patent 7,923,536 B2
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`
`Desai2
`Desai
`Desai, Kadima,3 and
`Liversidge4
`
`E. The Asserted Grounds of Unpatentability
`Petitioner contends that the challenged claims are unpatentable based
`on the following grounds. Pet. 7–8.1
`References
`
`Basis
`§ 102(b)
`§ 103(a)
`§ 103(a)
`
`Claims Challenged
`1–16
`1–16
`1–16
`
`Petitioner relies also on the Declaration of Cory Berkland, Ph.D. See
`Ex. 1002.
`
`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.,
`LLC v. Lee, 136 S. Ct. 2131, 2144–46 (2016). Under this standard, we
`interpret claim terms using “the broadest reasonable meaning of the words in
`their ordinary usage as they would be understood by one of ordinary skill in
`the art, taking into account whatever enlightenment by way of definitions or
`otherwise that may be afforded by the written description contained in the
`applicant’s specification.” In re Morris, 127 F.3d 1048, 1054 (Fed. Cir.
`1997). “Under a broadest reasonable interpretation, words of the claim must
`
`
`1 Unless otherwise noted, we refer to the original page numbers of an exhibit
`as opposed to the page numbers added by a party.
`2 WO 99/00113 A1, published Jan. 7, 1999 (Ex. 1006, “Desai”).
`3 WO 00/06152 A1, published Feb. 10, 2000 (Ex. 1004, “Kadima”).
`4 US 5,399,363, issued Mar. 21, 1995 (Ex. 1005, “Liversidge”).
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`be given their plain meaning, unless such meaning is inconsistent with the
`specification and prosecution history.” Trivascular, Inc. v. Samuels, 812
`F.3d 1056, 1062 (Fed. Cir. 2016). Only terms in controversy must be
`construed and only to the extent necessary to resolve the controversy. Vivid
`Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999).
`We determine that the following claim language needs to be discussed.
`
`1. “the weight ratio of albumin to paclitaxel in the composition”
`Petitioner offers an interpretation of the claim phrases “the weight
`ratio of albumin to paclitaxel in the composition” and “ratio (w/w) of
`albumin to the paclitaxel in the pharmaceutical composition” as at least “the
`albumin-paclitaxel ratio in the starting ingredients used to make the
`composition.” Pet. 19–20 (citing Ex. 1002 ¶ 48) (emphasis omitted).
`Petitioner states a “skilled artisan reading [the ’536 patent’s] examples
`would understand that the ‘ratio of albumin to paclitaxel’ was based on the
`amounts used to make the composition.” Id. at 20 (citing Ex. 1002 ¶ 37).
`Patent Owner disagrees, and offers an interpretation that the term
`should be construed as “the weight ratio of albumin-to-paclitaxel in the
`finished pharmaceutical composition, not the ratio of the starting materials.”
`Prelim. Resp. 11 (emphasis omitted). Patent Owner states:
`The claim requires that the ratio concerns albumin and paclitaxel
`“in the composition,” and that “composition” is plainly the
`claimed “pharmaceutical composition for injection”— i.e., the
`finished pharmaceutical product. (EX1001, claim 1.) . . . Thus,
`based on the plain claim language, the ratio refers to the claimed
`finished pharmaceutical product, not the albumin and paclitaxel
`starting materials prior to the formation of the nanoparticles.
`
`Id. at 12. Patent Owner notes “the specification and prosecution history
`make clear that the claimed weight ratio must be directed to the finished
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`pharmaceutical composition.” Id. at 12–13. For example, Patent Owner
`notes, the “Examiner referred to a vial of a finished product . . . as having
`the claimed ‘weight ratio of 9:1 of albumin-to-paclitaxel.’” Id. at 13
`(quoting Ex. 1021, 4).
`
`We agree with Patent Owner’s proposed construction on the record
`before us. Claim 1 of the ’536 patent uses the definite article “the” in
`providing antecedent basis for “the composition” in the claim phrase “the
`weight ratio of albumin to paclitaxel in the composition.” See ’536 patent,
`claim 1. The article “the” refers to “a pharmaceutical composition” that is
`injected into an individual with cancer. See ’536 patent, claim 1 (“[a]
`method of treating cancer in a human . . . comprising injecting into the
`individual an effect amount of a pharmaceutical composition”). Therefore,
`the reasonable interpretation based on the intrinsic use in the claim requires
`“the composition” to be the “pharmaceutical composition.” See Warner–
`Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1356 (Fed. Cir. 2003) (“[I]t is
`a rule of law well established that the definite article ‘the’ particularizes the
`subject which it precedes. It is a word of limitation as opposed to the
`indefinite or generalizing force of ‘a’ or ‘an.’”). Furthermore, based on the
`express claim language, the broadest reasonable interpretation of the
`“pharmaceutical composition” is that it refers to the final product because it
`is injected into the patient.
`Thus, we agree with Patent Owner on this record that “the weight
`ratio of albumin to paclitaxel in the composition” in claim 1 of the ’536
`patent means the ratio of albumin to paclitaxel in the final composition, i.e.,
`the composition injected into the patient. Patent Owner also argues that the
`Specification of the ’536 patent and the prosecution history support this
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`interpretation, but we need not reach that determination because the plain
`language of the claim supports our interpretation. See Prelim. Resp. 12–14.
`See DSW, Inc. v. Shoe Pavilion, Inc., 537 F.3d 1342, 1347 (Fed. Cir. 2008)
`(“[A]bsent contravening evidence from the specification or prosecution
`history, plain and unambiguous claim language controls the construction
`analysis.”).
`
`2. “a particle size of less than about 200 nm”
`Petitioner offers an interpretation of the claim phrase “a particle size
`of less than about 200 nm.” See Pet. 22–23. Patent Owner states that only
`“one term requires construction in deciding whether to institute IPR,” the
`“weight ratio” term, and does not address Petitioner’s claim interpretation of
`this claim language. See Prelim. Resp. 10–14.
`Because our decision does not require an express construction of this
`claim phrase to resolve any dispute, we do not need to interpret expressly the
`claim term “a particle size of less than about 200 nm.” See, e.g., Wellman,
`Inc. v. Eastman Chem. Co., 642 F.3d 1355, 1361 (Fed. Cir. 2011) (“[C]laim
`terms need only be construed ‘to the extent necessary to resolve the
`controversy.’”) (quoting Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc.,
`200 F.3d 795, 803 (Fed. Cir. 1999)).
`
`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
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`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
`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.
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`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).
`Petitioner, supported by the testimony of Dr. Berkland, states that the
`level of skill in the art at the time of the invention is a person who has an
`“advanced degree in chemistry, chemical engineering, pharmaceutics,
`pharmacy, or a related discipline, and/or having experience formulating
`compounds for use in pharmaceutical compositions, including nanoparticle
`suspensions, for several years.” Pet. 8 (citing Ex. 1002 ¶ 20). Patent Owner
`“does not dispute Petitioner’s definition of a POSA.” Prelim. Resp. 10. We,
`therefore, apply Petitioner’s stated level of ordinary skill in the art because
`of the sophistication of the technology and the educational level of those
`who work in this area. See In re GPAC, 57 F.3d at 1579. Furthermore, the
`prior art itself demonstrates the level of skill in the art at the time of the
`invention. 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)).
`We analyze the asserted grounds of unpatentability in accordance with
`the above-stated principles.
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`
`C. Anticipation by Desai
`Petitioner asserts that claims 1–16 are unpatentable under 35 U.S.C.
`§ 102(b) as anticipated by Desai. Pet. 23–34. Patent Owner opposes this
`ground. Prelim. Resp. 15–30.
`
`1. Desai (Ex. 1006)
`Desai teaches “relates to methods for the production of particulate
`vehicles for the intravenous administration of pharmacologically active
`agents, as well as novel compositions produced thereby.” Ex. 1006, 1:6–9.
`“The invention provides, in a particular aspect, a composition of anti-cancer
`drugs, e.g., Taxol, in the form of nanoparticles in a liquid dispersion or as a
`solid which can be easily reconstituted for administration.” Id. at 24:11–14.
`Desai discloses the following with respect to the pharmaceutical Capxol.
`
`Capxol™ is a novel, cremophor-free formulation of the
`anticancer drug paclitaxel . . . . Capxol™ is a lyophilized powder
`for reconstitution and intravenous administration.
` When
`reconstituted with a suitable aqueous medium such as 0.9%
`sodium chloride injection or 5% dextrose injection, Capxol™
`forms a stable colloidal solution of paclitaxel. The size of the
`colloidal suspension may range from 20nm to 8 microns with a
`preferred range of about 20-400 nm. The two major components
`of Capxol™ are unmodified paclitaxel and human serum
`albumin (HSA).
`Id. at 25:29 to 26:13. Desai teaches “Capxol™ is merely a shorthand means
`of reference to protein-coated paclitaxel nanoparticles produced by the
`method of Example 1” and that “[e]ach vial of Capxol™ contains 30 mg of
`paclitaxel and approximately 400 mg of human serum albumin.” Id. at
`36:17–29. Example 1 of Desai teaches:
`30 mg paclitaxel is dissolved in 3.0 ml methylene chloride. The
`solution was added to 27.0 ml of human serum a[l]bumin
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`solution (1% w/v). The mixture was homogenized for 5 minutes
`at low RPM (Vitris homogenizer, model: Tempest I.Q.) in order
`to form a crude emulsion, and then transferred into a high
`pressure homogenizer (Avestin). The emulsification was
`performed at 9000-40,000 psi while recycling the emulsion for
`at least 5 cycles. The resulting system was transferred into a
`Rotary evaporator, and methylene chloride was rapidly removed
`at 40°C, at reduced pressure (30 mm Hg), for 20-30 minutes. The
`resulting dispersion was translucent, and the typical diameter of
`the resulting paclitaxel particles was 160-220 (Z-average,
`Malvern Zetasizer).
`Id. at 60:25 to 61:6.
`In Example 4, Desai teaches the “dispersion is filtered through a 0.22
`micron filter (Millipore), without any significant change in turbidity, or
`particle size. HPLC analysis of the Taxol content revealed that more than
`97% of the Taxol was recovered after filtration.” Id. at 63:24–27. Example
`16 of Desai summarizes a preferred manufacturing process with 1 gram of
`paclitaxel and 431 ml of a 3% albumin solution that is filtered during the
`manufacturing process. Id. at 73:17 to 74:24.
`
`2. Analysis
`Petitioner asserts that Desai discloses each limitation of the
`challenged claims. See Pet. 21–31. Patent Owner asserts that the
`anticipation ground fails “because Desai does not expressly or inherently
`meet the albumin-paclitaxel weight ratio limitation of the claims.”5 Prelim.
`Resp. 15. Thus, the anticipation issue focuses on whether Desai inherently
`or expressly teaches the requirement in claim 1 that a “weight ratio of
`
`
`5 Patent Owner erroneously identifies the challenged claims as claims 1–19
`and 21–48, as opposed to claims 1–16. See Prelim. Resp. 15.
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`albumin to paclitaxel in the composition is about 1:1 to about 9:1.” On this
`record, we agree with Patent Owner.
`Petitioner refers to Desai’s Example 1 as expressly and inherently
`disclosing the “about 1:1 to about 9:1” albumin to paclitaxel weight ratio
`limitation of claim 1. Pet. 27–30. Specifically, Petitioner asserts the
`following:
`Example 1 of Desai discloses an albumin-paclitaxel ratio of
`about 9:1 by providing that “30 mg paclitaxel is dissolved in 3.0
`ml methylene chloride,” which “was added to 27.0 ml of human
`serum albumin solution (1% w/v).” EX1006, 62. A skilled artisan
`would have known that 27 ml of 1% (w/v) albumin contains 270
`mg of albumin, which, when combined with 30 mg of paclitaxel,
`necessarily results in a composition with an albumin-paclitaxel
`weight ratio of 270:30—i.e., a ratio of exactly 9:1. EX1002 ¶98.
`That is an express disclosure of the claimed 9:1 ratio. Even if
`Patent Owner were to argue that it is not expressly disclosed
`because the language “9:1” does not appear, the listing of the
`ingredients and their amounts in the example is still an inherent
`disclosure of the claimed ratio.
`Id. at 27 (emphasis added).
`In addition to its “expressly disclosed” position, Petitioner makes
`several arguments as to why Example 1 inherently discloses the weight ratio
`limitation. Petitioner argues that even if we limit the claims to a “‘final’”
`ratio, “there is no evidence that Example 1 results in any loss of paclitaxel
`during manufacturing that would affect the composition’s albumin-paclitaxel
`ratio.” Id. at 32. Petitioner avers that “[t]here is no mention in Desai of any
`paclitaxel loss, and no reason why any of Example 1’s steps would result in
`such loss.” Id. (citing Ex. 1002, ¶ 106). Petitioner also argues that
`“[a]lthough Desai indicates that ‘CapxolTM is merely a shorthand reference
`to protein-coated paclitaxel nanoparticles produced by the method of
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`Example 1,’ (EX1006, 38), Example 1’s method is not limited to making
`CapxolTM.” Id. According to Petitioner, Example 1’s method can produce
`“multiple different embodiments of Desai’s albumin-paclitaxel formulation,
`including one with an albumin-paclitaxel ratio of 9:1.” Id. Petitioner
`concludes that “a skilled artisan would have understood that Example 1
`provides a method of making an albumin-paclitaxel composition like
`Capxol™—but does not necessarily result in Capxol™ itself, which has an
`albumin-paclitaxel ratio of 13.3:1.” Id. at 33.
`Petitioner argues that Example 16 “more specifically describes the
`production of Capxol ™.” Id. Petitioner contends that the initial albumin-
`paclitaxel ratio of Example 16 is 12.93:1, and the filtration step in Example
`16 results in a ratio of 13,3:1. Id. According to Petitioner, Example 4,
`which describes a similar step of sterile filtration as Example 16, results in
`approximately 97% of Taxol recovery after filtration. Id. at 33–34. Thus,
`asserts Petitioner, “a skilled artisan would expect to recover approximately
`97% of the paclitaxel after sterile filtration, thereby raising the 12.93:1 ratio
`of albumin to paclitaxel in the starting materials of Example 16 to 13.3:1—
`the exact ratio for Capxol™ disclosed in Desai.” Id. at 34 (citing Ex. 1002
`¶ 65). Petitioner concludes that “a skilled artisan would have understood
`that the precise method of obtaining Capxol™’s 13.3:1 ratio was disclosed in
`Example 16—not Example 1—which instead results in a 9:1 ratio.” Id.
`(citing Ex. 1002 ¶ 111).
`Patent Owner makes multiple arguments as to why Desai does not
`expressly or inherently disclose the recited “about 1:1 to about 9:1” weight
`ratio of albumin to paclitaxel. Patent Owner argues that Desai’s Example 1
`does not expressly disclose the “about 1:1 to about 9:1” weight ratio
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`limitation of claim 1, under the proper claim construction of the term (i.e.,
`the “final composition”). Prelim. Resp. 15. In further support, Patent
`Owner asserts that the remainder of Desai is “silent” about the weight ratio
`of albumin to paclitaxel in the final composition. Id. at 16.
`Patent Owner also argues that Desai does not inherently disclose the
`required weight ratio of claim 1. Id. at 16–18. As a preliminary matter, in
`response to Petitioner’s argument that there is no evidence that Example 1
`results in a loss of paclictaxel during manufacturing that would affect the
`starting albumin-paclitaxel ratio, Patent Owner argues that Petitioner is
`asserting an inherency argument, and thus, carries the burden of establishing
`inherency. Id. at 16–17. Patent Owner next argues that “the deposition
`testimony of Dr. Berkland and the Declaration of Dr. Oupicky demonstrate
`that the argument lacks merit.” Id. at 17. Patent Owner further argues that
`Desai’s other examples (Examples 1, 4 and 16) do not support Petitioner’s
`position that the starting ratio of Example 1 would not change. Id. Rather,
`Patent Owner argues that Desai’s teachings, other than those found in
`Example 1, show that a “starting albumin-to-paclitaxel weight ratio of 9:1
`would not remain the same for the final composition” and that “additional
`evidence not presented in the prior IPRs confirms that Petitioner cannot
`prove that the 9:1 weight ratio of the final composition is inherently
`anticipated by Desai.” Id. at 17–18.
`Petitioner has not sufficiently persuaded us that Desai expressly
`discloses the “weight ratio of albumin to paclitaxel in the composition is
`about 1:1 to about 9:1” limitation of claim 1. Our previous decision on
`institution in the 2017-01103 IPR instituting a review of the challenge
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`claims in the ’536 patent relied upon Dr. Berkland’s interpretation of Desai’s
`examples to support the position that:
`the combination of teachings in Example 1 of Desai of a 9:1
`starting ratio of albumin to paclitaxel combined with the teaching
`in Example 4 that 97% of the Taxol was recovered after filtration
`reasonably supports Petitioner’s position that Desai teaches a
`cancer treatment using final pharmaceutical composition with a
`ratio of albumin to paclitaxel that is “about 9:1” as required by
`claim 1 of the ’536 patent.
`2017-01103 IPR, Paper 7, 17 (citing Ex. 1002 ¶ 74).
`In this proceeding, Patent Owner provides evidence showing that
`Dr. Berkland’s opinion on Desai’s disclosure is not reliable. Specifically,
`Patent Owner has submitted a deposition of Dr. Berkland, during which
`Dr. Berkland testifies that “the only thing that’s disclosed [in Desai] is the
`starting ingredients.” Ex. 2070, 133:7–14. Specifically, with respect to
`Example 1, Dr. Berkland responded to the question “Example 1, it doesn’t
`tell you what the final ratio is, right?” with “[t]hat’s correct.” Id. at 133:14–
`17. Dr. Berkland further responds to a question “of the ratios you cite in
`paragraph 145, 9:1, 9.8:1 and 12.9:1, those are all starting ratios, right?”
`with “[y]es, that’s my recollection.” Id. at 195:16–19. Dr. Berkland also
`could not confirm that the 97% recovery rate disclosed in Desai’s Example 4
`was based on the entire manufacturing process, from start through filtration,
`as opposed to, for example, based on only the process immediately before
`filtration to immediately after filtration. Id. at 174:24–178:1. That is,
`Dr. Berkland acknowledged that Example 4 does not necessarily
`demonstrate 97% recovery of the complete Example 1 production process.
`See id. Furthermore, Dr. Berkland testifies that Desai does not disclose
`explicit measurements of the final ratios of albumin-paclitaxel compositions.
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`Ex. 2070, 195:16–196:2. Therefore, based on the record in this case, we are
`not sufficiently persuaded that under our claim construction, Desai’s
`Example 1 expressly discloses the “weight ratio of albumin to paclitaxel in
`the composition is about 1:1 to about 9:1” limitation of claim 1.
`Petitioner also has not sufficiently persuaded us that Desai inherently
`discloses the “weight ratio of albumin to paclitaxel in the composition is
`about 1:1 to about 9:1” limitation of claim 1. “[A] prior art reference may
`anticipate without disclosing a feature of the claimed invention if that
`missing characteristic is necessarily present, or inherent, in the single
`anticipating reference.” Schering Corp. v. Geneva Pharmaceuticals, Inc.,
`339 F.3d 1373, 1377 (Fed. Cir. 2004). However, “[i]nherency . . . 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).
`As a preliminary matter, Petitioner has not sufficiently persuaded us
`that Example 1 is not limited to producing Capxol, but can produce multiple
`different embodiments, including one with an albumin to paclitaxel ratio of
`9:1. See Pet. 32. Desai expressly states that Example 1 produces Capxol
`having a final albumin to paclitaxel ratio of 13.3:1. Ex. 1006, 36:16–19, 28–
`29; Ex. 2066 ¶ 49. Indeed as Patent Owner further notes (Prelim. Resp. 18),
`in a 2014 proceeding before the Indian patent office, Dr. Desai, the inventor,
`stated that Example 1 [of Desai6] produces Capxol with a final ratio of
`
`
`6 The declaration refers to WO00/71079. WO00/71079 shares substantially
`the same text and examples as Desai (WO 99/00113) and claims priority to
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`13.3:1. Ex. 2069 ¶ 5. Dr. Desai explains that “[t]aking into account loss of
`paclitaxel during the nanoparticle preparation process, the estimated
`albumin/paclitaxel ratio in the resulting nanoparticle albumin-bound
`paclitaxel composition was about 13.3:1.”7 Id.
`The disclosure in Example 5 of Desai further supports the finding that
`Example 1 produces Capxol, with a final ratio of 13.3:1. Example 5 states
`that “HPLC analysis of the Taxol content typically revealed that 70-100% of
`the Taxol could be recovered after filtration, depending on the conditions
`employed.” Ex.1006, 64:25–28. As Patent Owner further asserts, “a POSA
`could take Example 5’s 70% recovery rate and apply it to Example 1’s 9:1
`starting ratio, arriving at a final ratio of 12.86:1, which is consistent with
`Capxol’s 13.3:1 final ratio. 8 Prelim. Resp. 24 (citing Ex. 2066 ¶ 63).
`
`
`U.S. application 09/316,642 that matured into U.S. patent 6,749,868. See
`Ex. 2066 ¶ 66.
`7 Petitioner’s argument that a skilled artisan would not have interpreted
`Example 1 as producing Capxol because Capxol contains 400 mg of
`albumin, more than the starting amount of 270 mg of albumin in Example 1
`is unavailing. Pet. 32–33. Petitioner has not accounted for the loss of
`paclitaxel during manufacturing. See Prelim. Resp. 19 (Patent Owner
`asserting “Given the loss of paclitaxel during nanoparticle preparation, either
`a larger batch would need to be made, or more than one batch would need to
`be combined, to ensure that each vial of Capxol had the necessary fill
`volume to obtain the full 30 mg of paclitaxel that is intended for the
`patient.”).
`8 Patent Owner also persuasively shows that Petitioner’s argument that
`Example 16, as opposed to Example 1, produces Capxol is not adequately
`supported. See Prelim. Resp. 19–25. For example, Dr. Desai stated in the
`2014 proceeding before the Indian patent office that Example 16 of Desai
`was used to manufacture an “old formulation,” which had a final ratio of
`albumin to paclitaxel of 12.93:1. Ex. 2069 ¶¶ 9–10; see Ex. 2066 ¶¶ 64–73.
`Further, Petitioner argues that the 97% recovery rate of paclitaxel, disclosed
`in Example 4, applied to the 12.93:1 starting albumin to paclitaxel ratio in
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`
`In addition, we credit Dr. Desai’s testimony that neither Example 1
`nor Example 16 in WO00/71079 inherently results in an “about 1:1 to about
`9:1” weight ratio of albumin to paclitaxel. Dr. Desai states that “[e]xample 1
`of WO00/71079 discloses a lab-scale preparation method of nanoparticle
`albumin bound paclitaxel composition by high pressure homogenization
`method. . . . Taking into account loss of paclitaxel during the nanoparticle
`preparation process, the estimated albumin/paclitaxel ratio in the resulting
`nanoparticle albumin-bound paclitaxel co