Paper No. 9
`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 IPR2018-00162
`Patent 7,820,788 B2
`
`
`Before JEFFREY N. FREDMAN, RAMA G. ELLURU, and
`SUSAN L. C. MITCHELL, Administrative Patent Judges.
`
`FREDMAN, 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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`IPR2018-00162
`Patent 7,820,788 B2
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`
`I. INTRODUCTION
`A. Background
`Petitioner Cipla Ltd. (“Petitioner”) filed a Petition (Paper 2, “Pet.”)
`requesting an inter partes review of claims 1–12 (the “challenged claims”)
`of U.S. Patent No. 7,820,788 B2 (Ex. 1001, “the ’788 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 2017-01101
`(“2017-01101 IPR”). Joinder Motion 1.
`At the time Petitioner filed the instant Petition and Joinder Motion, the
`Board had instituted inter partes review of the ’788 patent in the 2017–
`01101 IPR. Subsequent to that institution, the parties in the 2017–01101
`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 granted
`the motion to terminate, there is no instituted inter partes review for
`Petitioner to join, and the Joinder Motion is moot.
`However, because the instant Petition is not statutorily barred, a
`separate inter partes review may be instituted. 35 U.S.C. § 315(b).
`
`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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`IPR2018-00162
`Patent 7,820,788 B2
`
`not established a reasonable likelihood that they would prevail in showing
`the unpatentability of at least one of the challenged claims of the ’788
`patent. Therefore, we deny institution of an inter partes review for claims
`1–12 of the ’788 patent.
`
`B. Related Proceedings
`Petitioner indicates that the ’788 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 2017-01101 IPR, Actavis filed three additional requests for
`inter partes review of other patents owned by Abraxis that are related to the
`’788 patent: IPR2017-01100 (involving U.S. Patent No. 8,853,260);
`IPR2017-01103 (involving U.S. Patent No. 7,923,536); and IPR2017-01104
`(involving U.S. Patent No. 8,138,229). Id.
`Petitioner indicates they also filed petitions for inter partes review of
`related U.S. Patent Nos. 8,138,229 (IPR2018-00164), and 7,923,536
`(IPR2018-00163). Pet. 6. U.S Patent 8,138,229 and U.S. Patent 7,923,536
`are both continuations of the ’788 patent.
`
`C. The ’788 Patent (Ex. 1001)
`The ’788 patent involves methods of formulating pharmaceuticals
`with carriers to “reduce one or more side effects.” Ex. 1001, 3:55–61. Such
`methods specifically involve formulating taxol (paclitaxel), an agent active
`against carcinomas, (id. at 4:31–39), with albumin, a protein found in human
`plasma (id. at 5:8–18).
`The ’788 patent specifically prefers that the composition “have a
`particle or droplet size less than about 200 nanometers” (id. at 9:52) and a
`“ratio of albumin to pharmaceutical agent in the pharmaceutical composition
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`[that] is about 18:1 or less” (id. at 3:27–28). It is also stated in the ’788
`patent that:
`While the ratio of protein to pharmaceutical agent will have to be
`optimized for different protein and pharmaceutical agent
`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 ’788 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 12:1–
`6).
`
`D. Illustrative Claims
`Of the challenged claims, claim 1 is the sole independent claim of the
`’788 patent. The remaining challenged claims 2–12 depend directly or
`indirectly from claim 1. Claim 1 is illustrative of the challenged claims and
`recites:
`
`1. A pharmaceutical composition for injection 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 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, 38:17–24.
`
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`IPR2018-00162
`Patent 7,820,788 B2
`
`
`Desai1
`Desai
`Desai, Kadima,2 and
`Liversidge3
`
`E. The Asserted Grounds of Unpatentability
`Petitioner contends that the challenged claims are unpatentable based
`on the following grounds. Pet. 7–8.
`References
`
`Basis
`§ 102(b)
`§ 103(a)
`§ 103(a)
`
`Claims Challenged
`1–9, 11, 12
`1–12
`1–12
`
`Petitioner relies also on the Declaration of Cory Berkland, Ph.D. Pet.
`1–75; 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
`be given their plain meaning, unless such meaning is inconsistent with the
`
`
`1 WO 99/00113 A1, published Jan. 7, 1999 (Ex. 1006, “Desai”).
`2 WO 00/06152 A1, published Feb. 10, 2000 (Ex. 1004, “Kadima”).
`3 US 5,399,363, issued Mar. 21, 1995 (Ex. 1005, “Liversidge”).
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`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 phrase “the weight ratio
`of albumin to paclitaxel in the composition” as at least “the albumin-
`paclitaxel ratio in the starting ingredients used to make the composition.”
`Pet. 19 (citing Ex. 1002 ¶ 53). Petitioner states a “skilled artisan reading
`[the ’788 patent’s] examples would understand that the ‘ratio of albumin to
`paclitaxel’ was based on the amounts used to make the composition.” Pet.
`20 (citing Ex. 1002 ¶ 36).
`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. 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.
`
`Prelim. Resp. 12. Patent Owner notes “the specification and prosecution
`history make clear that the claimed weight ratio must be directed to the
`finished pharmaceutical composition.” Prelim. Resp. 12–13. Specifically,
`Patent Owner notes, the “Examiner referred to a vial of a finished product
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`. . . as having the claimed ‘weight ratio of 9:1 of albumin-to-paclitaxel.’”
`Prelim. Resp. 13 (citing Ex. 1021, 4).
`
`We agree with Patent Owner’s proposed construction on the record
`before us. The ’788 patent claims use 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 ’788 patent, claim 1. The
`article “the” refers to “a pharmaceutical composition” that is injected into an
`individual with cancer. See ’788 patent, claim 1 (“[a] pharmaceutical
`composition for injection”). 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 ’788
`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 ’788 patent and the prosecution history support this
`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
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`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 term “a particle size of
`less than about 200 nm” to “include[] particle sizes of 220 nm or less,
`measured as the Z-average diameter using a Malvern Zetasizer.” Pet. 22
`(citing Ex. 1002 ¶ 54). Petitioner points out that “every example in the ʼ788
`patent that mentions particle size refers to “the typical average diameter” of
`the particles and discloses a particle size range of ‘50–220 nm (Z-average,
`Malvern Zetasizer).’” Pet. 22 (citing Ex. 1002 ¶ 39; Ex. 1001, Examples 1,
`2, 4–14, 47–49).
`
`Patent Owner states that only “one term requires construction in
`deciding whether to institute IPR,” the “weight ratio” term, and does not
`dispute Petitioner’s claim interpretation. Prelim. Resp. 10.
`Because our decision does not require an express construction 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,
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`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
`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
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`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).
`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 ¶ 16). Patent Owner
`“does not dispute Petitioner’s definition of a POSA.” See 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 1–9, 11, and 12 are unpatentable under
`35 U.S.C. § 102(b) as anticipated by Desai. Pet. 21–33. Patent Owner
`opposes this ground. Prelim. Resp. 15–30.
`
`1. Desai (Ex. 1006)
`Desai teaches using “anti-cancer drugs, e.g., Taxol, in the form of
`nanoparticles.” Ex. 1006, 24:12–13. 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).
`Ex. 1006, 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.”
`Ex. 1006, 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
`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 30 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
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`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).
`
`Ex. 1006, 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.” Ex. 1006, 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. Ex. 1006, 73:17 to 74:24.
`
`2. Analysis
`Petitioner asserts that Desai teaches each limitation of the challenged
`claims. See Pet. 23–34. Patent Owner asserts that this ground fails “because
`Desai does not expressly or inherently meet the albumin-paclitaxel weight
`ratio limitation of the claims.” 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 albumin to paclitaxel in the
`composition is about 1:1 to about 9:1.” We agree with Patent Owner.
`Petitioner asserts that “Desai as a whole is directed to ‘particulate
`vehicles for the intravenous administration of pharmacologically active
`agents’”; that “Example 1 of Desai discloses a method of producing
`albumin-paclitaxel nanoparticles with a typical average diameter of 160–220
`nm”; and that “Example 1 of Desai discloses an albumin-paclitaxel ratio of
`about 9:1.” Pet. 24–26.
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`Petitioner asserts with regard to the albumin-paclitaxel ratio that:
`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 ¶100. 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.
`
`Pet. 26.
`In support of its position, Petitioner asserts “the fact that Example 1 of
`Desai discloses quantities of paclitaxel and albumin in a 9:1 ratio is
`sufficient to establish a reasonable likelihood of anticipation.” Pet. 30.
`Petitioner asserts “there is no evidence that Example 1 results in any loss of
`paclitaxel during manufacturing that would affect the composition’s
`albumin-paclitaxel ratio. There is no mention in Desai of any paclitaxel
`loss, and no reason why any of Example 1’s steps would result in such loss.”
`Pet. 31 (citing Ex. 1002 ¶ 113). In support of its position that Desai’s
`Example 1 does not result in loss of paclitaxel, Petitioner contrasts Example
`1 with Example 16, which includes a filtration step. Petitioner asserts
`a skilled artisan would have understood that Example 16 is
`consistent with Example 1 but more specifically describes the
`production of Capxol™ . . . Example 16 uses 1 g (i.e., 1,000 mg)
`of paclitaxel, which results initially in an albumin-paclitaxel ratio
`of 12.93:1. Id.; EX1002 ¶¶ 68–70, 118. The resulting
`suspension is sterile filtered using a 200 nm filter before being
`filled into vials containing 30 mg of paclitaxel, and then
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`lyophilized. EX1006, 76–66. That filtration step in Example 16
`results in a ratio of 13.3:1. . . . Thus, 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.
`
`Pet. 33–34(citing Ex. 1002 ¶ 118).
`Petitioner further supports the argument that the manufacturing
`process in Desai’s Example 1 does not result in loss of paclitaxel by
`referring to the manufacturing process disclosed in the ’788 patent
`specification. Specifically, Petitioner’s Declarant, Dr. Berkland, states
`regarding Example 49 of the ’788 patent that: “135 mg of paclitaxel was
`combined with 1,350 mg of albumin (27 ml of 5% w/v solution),
`corresponding to a 10:1 ratio.” Ex. 1002 ¶ 37. Dr. Berkland concludes
`“therefore, the albumin-paclitaxel ratio of Example 49 was either
`‘calculated’ based on the starting materials, or measured after the process
`steps were completed, at which point the ratio remained the same as the ratio
`of starting materials.” Id. Dr. Berkland also points out that: “There is no
`suggestion in the ʼ788 patent that the ratio of albumin to paclitaxel
`materially changes during the manufacturing process. Nor is there any
`disclosed assay or discussion of how to measure or predict the ratio of
`albumin to paclitaxel in the final pharmaceutical composition.” Id. ¶ 38.
`As noted above, Patent Owner argues that this ground fails because
`“Desai does not expressly disclose the claimed albumin-paclitaxel weight
`ratio limitations.” Prelim. Resp. 15. Patent Owner makes multiple
`arguments as to why Desai does not teach the claimed range.
`As a preliminary matter, Patent Owner argues that there is insufficient
`evidence that the 9:1 albumin-paclitaxel ratio in Desai’s Example 1 is for the
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`final formulation. Patent Owner asserts “Dr. Berkland admitted that
`Example 1’s 9:1 ratio concerns the starting ingredients only.” Prelim. Resp.
`16 (citing Ex. 2070, 132:15–133:17). Patent Owner further notes that “in a
`2014 proceeding before the Indian patent office, Dr. Desai himself testified
`that Example 1 [of Desai] produces Capxol with a final ratio of 13.3:1.”
`Prelim. Resp. 18 (citing Ex. 2069 ¶ 5). Patent Owner, to address the
`question of whether any of the examples suggests the claimed ratio, also
`asserts Example 16 doesn’t suggest the final ratio, stating “Dr. Desai
`confirmed that Example 16 [of Desai], with its 12.93:1 starting ratio, was
`used to manufacture the old formulation, which had a final ratio of 19:1.”
`Prelim. Resp. 20 (citing Ex. 2069 ¶¶ 9–10; 2066 ¶¶ 64–73).
`Patent Owner also argues that Desai’s other examples do not provide
`sufficient evidence as to the loss of paclitaxel during Example 1’s
`manufacturing process. Desai’s Example 4 teaches a 97% recovery rate in
`the final product. Ex. 1006, 63:26–28. However, Patent Owner asserts that
`As Dr. Berkland admitted,
`there
`is no
`indication
`that
`[paclitaxel’s] 97% recovery “after filtration” reflects total loss of
`paclitaxel during processing; that value may account only for
`loss of paclitaxel during the filtration step, and not paclitaxel loss
`leading up to filtration. (EX2070, 176:24-178:1; EX2066 ¶ 54.)
`As Dr. Oupicky likewise explained, the 97% recovery value may
`be substantially understated for the final product because it does
`not account for the total amount lost during the entire process,
`including loss prior to filtration. (EX2066 ¶¶ 54-55.).
`
`Prelim. Resp. 21.
`Patent Owner also argues that the 97% recovery rate disclosed in
`Example 4 cannot be applied to Example 1. Patent Owner points to Dr.
`Berkland’s acknowledgement that “the processing parameters for [Examples
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`4 and 16] are markedly different, which could lead to different recovery
`rates.” Prelim. Resp. 21 (citing Ex. 2070, 182:17–189:4). Patent Owner
`asserts: “Given these differences, the POSA could not conclude that
`Example 16 necessarily leads to the same 97% recovery after filtration
`disclosed in Example 4, and it is thus unfounded to apply Example 4’s
`recovery to Example 16.” Prelim. Resp. 22 (citing Ex. 2066 ¶ 58).
`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. (EX2066 ¶ 63.) According to Patent Owner, this ratio is
`consistent with Capxol’s 13.3:1 final ratio.” Prelim. Resp. 24. Patent
`Owner, thus, concludes that “based on Desai’s disclosure that Example 1
`produces Capxol, a POSA would have logically assumed that the recovery
`rate of Example 5, not Example 4, applied” to Example 1. Prelim. Resp. 24–
`25.
`
`Lastly, Patent Owner also argues that the “loss of paclitaxel can occur
`as a result of phenomena, processes, or mechanisms during manufacture,
`including epimerization or other degradation or transformations, binding to
`processing vessels and other equipment, and precipitation.” Prelim. Resp.
`26 (citing Ex. 2001 ¶ 28; Ex. 2028 1224, 1231–35; Ex. 2029 3106–08; Ex.
`2030, 1295–97).
`
`We agree with Patent Owner that the current evidence of record, as
`supported by the admissions of Dr. Berkland and explained by Dr. Desai,
`supports the position that none of the Desai examples necessarily result in a
`final about 1:1 to about 9:1 ratio of albumin to paclitaxel as required by
`claim 1 of the ’788 patent.
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`Our previous decision on institution in the 2017-01101 IPR instituting
`a review of the challenge claims in the ’788 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”
`2017-01101 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, where Dr. Berkland
`acknowledges that in Example 1, “the only thing that’s disclosed is the
`starting ingredients.” Ex. 2070, 133. Dr. Berkland responded to the
`question “Example 1, it doesn’t tell you what the final ratio is, right?” with
`“[t]hat’s correct.” Ex. 2070, 133. Dr. Berkland 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.” Ex. 2070, 195.
`Dr. Berkland also responds “[t]hat’s correct” in response to a question
`expressing ambiguity about whether the 97% recovery discussed in
`Example 4 of Desai was addressed solely to a filtration step or to the entire
`production process. Ex. 2070, 174–175. That is, Dr. Berkland
`acknowledged that Example 4 does not necessarily demonstrate 97%
`recovery of the complete Example 1 production process. See Ex. 2070, 176.
`Therefore, Dr. Berkland’s testimony is reasonably interpreted as
`demonstrating ambiguity as to whether a final about 1:1 to about 9:1 ratio of
`albumin to paclitaxel in Example 1 of Desai inherently results from
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`performance of the manufacturing process disclosed in Desai. In contrast,
`the testimony of Dr. Desai, the inventor in Desai, confirms that the
`manufacturing steps disclosed in Desai do not necessarily result in a final
`about 1:1 to about 9:1 ratio of albumin to paclitaxel. See Ex. 2069 ¶ 5.
`In addition, we credit Dr. Desai’s testimony that neither Example 1
`nor Example 16 in WO00/710794 inherently results in an about 1:1 to about
`9:1 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 composition was about 13.3:1.” Ex.
`2069 ¶ 5. Dr. Desai also states that
`Example 16 of W099/00113 provides a “Summary of the
`Presently Preferred Manufacturing Process: Starting with 1 gram
`Paclitaxel as the BDS.” 51. 7 ml of 25% albumin was added to
`379.3 ml water to make a total of 431 ml of 3% albumin. The
`starting ratio of albumin to paclitaxel was about 13:1.
`Ex. 2069 ¶ 9.
`Dr. Desai’s statements expressly rebut any reading of either of Desai’s
`Examples 1 or 16 as necessarily resulting in a final composition with an
`about 1:1 to about 9:1 ratio of albumin to paclitaxel. “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.”
`
`
`4 WO00/71079 shares substantially the same text and examples as Desai
`(WO 99/00113) and claims priority to U.S. application 09/316,642 that
`matured into U.S. patent 6,749,868. See Ex. 2066 ¶ 66.
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`MEHL/Biophile Int’l. Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir.
`1999).
`Therefore, on the current record, the evidence based on Desai’s
`disclosure in its entirety, when read in light of the statements by Dr.
`Berkland and Dr. Desai, does not reasonably support Petitioner’s position
`that Desai inherently teaches a final pharmaceutical composition with a ratio
`of albumin to paclitaxel that is “about 9:1” as required by claim 1 of the ’788
`patent.
`
`Accordingly, we find that Petitioner has not shown that there is a
`reasonable likelihood that they would prevail on one of claims 1–9, 11, and
`12 of the ’788 patent as anticipated by Desai.
`
`D. Obviousness over Desai alone or in combination with
`