Trials@uspto.gov
`Tel.: 571-272-7822
`
`
`
`
`Paper No. 9
`Entered: March 10, 2016
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`COALITION FOR AFFORDABLE DRUGS XI LLC,
`Petitioner,
`
`v.
`
`INSYS PHARMA, INC.,
`Patent Owner.
`______________
`
`Case IPR2015-01799
`Patent 8,835,460 B2
`_______________
`
`
`
`Before DEBORAH KATZ, GRACE KARAFFA OBERMANN,
`and SUSAN L. C. MITCHELL, Administrative Patent Judges.
`
`OBERMANN, Administrative Patent Judge.
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
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`

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`IPR2015-01799
`Patent 8,835,460 B2
`
`
`I. INTRODUCTION
`Petitioner requests an inter partes review of claims 1–5 of U.S.
`Patent 8,835,460 B2 (“the ’460 patent”). Paper 1 (“Pet.”). Patent Owner filed a
`Preliminary Response. Paper 8 (“Prelim. Resp.”). We have statutory authority
`under 35 U.S.C. § 314(a), which provides that an inter partes review may not be
`instituted unless the Petition demonstrates “a reasonable likelihood that the
`petitioner would prevail with respect to at least 1 of the claims challenged in the
`petition.” Taking account of the information presented in the Preliminary
`Response, we conclude that the Petition fails to make that showing. On this
`record, we deny the Petition and decline to institute review.
`
`Related Proceedings
`A.
`Petitioner identifies no related district court proceedings. Pet. 2–3. With
`this decision, we issue decisions denying inter partes review in IPR2016-01797
`and IPR2016-01800, which involve the same parties and related patents.
`
`The ’460 Patent
`B.
`The ’460 patent relates to a sublingual formulation of fentanyl, an opioid
`receptor agonist with analgesic potency up to 100 times that of morphine.
`Ex. 1001, 1:13–14. Sublingual delivery is achieved through the mucosal
`membranes lining the floor of the mouth. Id. at 8:27–28. The ’460 patent
`describes a sublingual formulation of fentanyl useful for relieving “breakthrough
`pain” in cancer patients almost immediately after administration. Id. at 6:29–42.
`The ’460 patent distinguishes sublingual (floor of the mouth) administration
`from other routes of delivery, for example, buccal (lining of the cheeks)
`administration. Id. at 7:49–8:33. The ’460 patent discloses a fentanyl formulation
`delivered “to the sublingual mucosa via spray,” which “results in a rapid onset of
`therapeutic effect of” the active agent. Id. at 9:46–49. The formulations are
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`“delivered as liquid droplets having a mean diameter of at least about 10 microns,”
`with a preferred distribution “from about 30 microns to about 70 microns.” Id.
`at 9:36–45.
`The Challenged Claims
`C.
`Petitioner challenges claims 1–5 of the ’460 patent. Critical to our analysis,
`each challenged claim relates to a sublingual fentanyl formulation in the form of
`liquid “droplets having a mean diameter” that falls within specified ranges.
`Claim 1 is illustrative and reads as follows (emphasis added):
`1. A sublingual formulation comprising discrete liquid droplets
`of an effective amount of fentanyl or a fentanyl derivative
`selected from the group consisting of sufentanil, carfentanil,
`lofentanil and alfatenil,1 a free base or a pharmaceutically
`acceptable salt thereof, in a pharmaceutically acceptable liquid
`carrier, said droplets having a mean diameter of from about 30
`to about 70 microns.
`Claims 2 and 3 require a non-propellant sublingual fentanyl formulation
`comprising discrete liquid “droplets having a mean diameter of at least about 10
`microns.” Claim 4 requires liquid “droplets having a mean diameter of from
`about 30 to about 70 microns.” Claim 5 depends from claim 1 and, thus, inherits
`the limitation that requires discrete liquid “droplets having a mean diameter of
`from about 30 to about 70 microns.”
`D.
`The Asserted Prior Art
`The Petition asserts the following references in the grounds of
`unpatentability:
`1. UK Patent Pub. No. GB 2399286 A, pub. Sept. 15, 2004. (Ex. 1003)
`(“Ross GB”).
`
`
`1 The ’460 patent specification discloses that the fentanyl derivative intended
`is alfentanil. Ex. 1001, 6:26–28; 18:29, 40.
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`Patent 8,835,460 B2
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`2. US Patent Pub. No. 2002/0055496 A1, pub. May 9, 2002 (Ex. 1005)
`(“McCoy”).
`3. US Patent No. 5,370,862, issued Dec. 6, 1994 (Ex. 1004) (“Klokkers-
`Bethke”).
`4. US Patent No. 6,946,150 B2, issued Sept. 20, 2005 (Ex. 1007)
`(“Whittle”).
`Asserted Grounds of Unpatentability
`D.
`The Petition asserts the following grounds of unpatentability:
`
`References
`
`Ross GB and McCoy
`
`Ross GB, Klokkers-Bethke,
`and McCoy
`Ross GB and Whittle
`
`Ross GB, Klokkers-Bethke,
`and Whittle
`McCoy
`
`Basis
`
`§ 103
`
`§ 103
`
`§ 103
`
`§ 103
`
`§ 102(b)
`
`Claim(s)
`Challenged
`1, 4, 5
`
`2, 3
`
`1, 4, 5
`
`2, 3
`
`1, 4, 5
`
`
`In addition to the asserted prior art references, the Petition advances
`declaration testimony of Dr. Kinam Park. Ex. 1002.
`
`II. ANALYSIS
`
`A. Claim Construction
`In an inter partes review, we construe claim terms of an unexpired patent
`according to their broadest reasonable interpretation in light of the patent
`specification. 37 C.F.R. § 42.100(b). Under that standard, we assign terms their
`ordinary and customary meaning as understood by one of ordinary skill in the art
`in the context of the entire patent disclosure. In re Translogic Tech., Inc., 504 F.3d
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`1249, 1257 (Fed. Cir. 2007). 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). We construe only those terms
`necessary to resolve the controversy. Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc.,
`200 F.3d 795, 803 (Fed. Cir. 1999).
`The broadest reasonable interpretation of “discrete liquid droplets” requires
`express construction. That term is not defined, but is closely associated with the
`term “spray,” in the ’460 patent specification. Ex. 1001, 3:17–20 (invention is
`directed to “a liquid spray formulation in the form of discrete liquid droplets”).
`Based on the information presented, we accept Petitioner’s view that the broadest
`reasonable interpretation of “discrete liquid droplets” is “water or other liquid
`broken up into minute droplets and blown, ejected into, or falling through the air.”
`Pet. 14 (quoting Ex. 1008) (dictionary definition of “spray”). That interpretation is
`reasonable in view of the claim wording, the specification, and the dictionary
`definition of “spray” advanced by Petitioner. No other claim term requires express
`construction for the purposes of this decision.
`
`B. Grounds Based on Obviousness
`The Petition states four grounds of obviousness based on various
`combinations of asserted prior art references. Pet. 5–6. We focus on a single
`dispositive issue; namely, whether the information presented shows sufficiently
`that the asserted prior art references would have recommended, to one of ordinary
`skill in the art, modifying Ross GB’s “spray” formulation to provide “droplets
`having a mean diameter” within the specified ranges of the challenged claims.
`We first address whether Ross GB’s reference to a “spray” formulation
`constitutes disclosure of “discrete liquid droplets.” Id. at 19. We then turn to
`whether Petitioner shows sufficiently that an ordinary artisan would have been led
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`to modify Ross GB’s “spray” to provide “droplets having a mean diameter” that
`falls within the specified ranges of the claims. Id. at 20–21 (argument as to
`claim 1). For the purposes of this decision, the prior art, itself, demonstrates the
`appropriate level of ordinary skill in the art at the time of the invention. See
`Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (the prior art, itself,
`can reflect the level of skill in the art).
`
`i. Ross GB’s Reference to a “Spray” Formulation
` Constitutes Disclosure of “Discrete Liquid Droplets”
`Each challenged claim requires a fentanyl formulation comprised of liquid
`droplets. Ex. 1001, 57:37–58:55 (claims 1–5). Claims 1–3 and 5 specify “discrete
`liquid droplets,” whereas claim 4 specifies “liquid droplets.” Id. The Petition
`directs us to Ross GB’s disclosure of a “spray” formulation, which according to
`Petitioner, satisfies those liquid droplet limitations. Pet. 19–20 (quoting Ex. 1003,
`3:29–33). Patent Owner responds that Ross GB’s “spray” formulation is not
`shown adequately to comprise “discrete liquid droplets” or “liquid droplets” within
`the meaning of the claims. Prelim. Resp. 15–17.
`Taking account of the information presented in the Petition and Preliminary
`Response, we determine that Ross GB’s disclosure of a “spray” refers to a
`formulation that comprises “discrete liquid droplets.” Pet. 19–20. Patent Owner
`aptly observes that Ross GB “does not use the words ‘droplet,’ ‘discrete,’ or any
`variant thereof.” Prelim. Resp. 16. Notwithstanding that observation, the
`reference repeatedly refers to the administration of a fentanyl formulation “by
`means of a pump spray device.” Ex. 1003, Abstract; see id. at 1:3–4 (Ross GB,
`disclosing “pump spray formulations” of fentanyl suitable for sublingual delivery);
`id. at 8:15 (packaging “multiple doses” of fentanyl preparations “in a pump spray
`system comprising a sealed container fitted with a metering pump”).
`
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`The Petition directs us to Dr. Park’s opinion that a person of ordinary skill in
`the art “would have understood that the spray disclosed in [Ross GB] comprises
`discrete liquid droplets.” Pet. 19 (quoting Ex. 1002 ¶ 16). The Petition also
`identifies objective support for that opinion; specifically, a dictionary definition,
`which indicates that a “spray” would have been understood at the time of the
`invention to mean “water or other liquid broken up into minute droplets and blown,
`ejected into, or falling through the air.” Id. at 14, 20 (quoting Ex. 1008).
`Patent Owner suggests that Ross GB’s “spray” reasonably refers to “a
`singular ‘jet’ of liquid” as demonstrated by two other definitions of “spray” set
`forth in the dictionary advanced by Petitioner. Prelim Resp. 15–16 (citing
`Ex. 1008). One definition refers to “a jet of fine particles of liquid.” Ex. 1008.
`The next-stated definition refers to “a liquid to be discharged or applied in such a
`jet”—which reasonably refers back to the “jet of fine particles of liquid”
`referenced in the immediately prior definition. Id. (emphasis added). Both
`definitions advanced by Patent Owner, in fact, support Petitioner’s view that a
`spray comprises “fine particles of liquid.” Id. Neither refers to a “singular” jet of
`liquid. Prelim. Resp. 16; see Ex. 1008 (dictionary definitions). On this record, we
`determine that Ross GB’s reference to a fentanyl “spray” would have conveyed to
`an ordinary artisan a liquid formulation broken up into minute droplets, within the
`meaning of the term “discrete liquid droplets” in claim 1.
`We next turn to whether Petitioner shows sufficiently that one would have
`been prompted to modify the mean diameter of the droplets in Ross GB’s spray
`formulation to provide a mean diameter within the ranges specified in the
`challenged claims.
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`ii. The Prior Art Is Not Shown to Recommend
` Modifying Ross GB’s Spray to Provide “Droplets
` Having a Mean Diameter” Within the Claimed Ranges
`Each challenged claim requires liquid “droplets having a mean diameter”
`that falls within specified ranges. Ex. 1001, 57:37–58:55 (claims 1–5). Claims 1,
`4, and 5 specify “droplets having a mean diameter of from about 30 to about 70
`microns.” Id. Claims 2 and 3, by contrast, specify “droplets having a mean
`diameter of at least about 10 microns.” Id. In Petitioner’s view, the asserted prior
`art references would have recommended modifying Ross GB’s spray formulation,
`in view of McCoy or Whittle, to provide “droplets having a mean diameter” within
`the claimed ranges. Pet. 19–51.
`McCoy discloses a formulation and system for intra-oral delivery of
`pharmaceutical agents, including fentanyl, that are mixed with an oral-absorption
`enhancer. Ex. 1005, Abstract, ¶¶ 5, 17. McCoy discloses liquid droplets “sized
`within the range of about 1 to 200 microns, more preferably within the range of
`10–100 microns.” Id. ¶ 19. Whittle, by contrast, relates to a formulation of
`cannabinoids administered “via a pump action spray.” Ex. 1007, Abstract. The
`Petition directs us to Whittle’s disclosure of a cannabinoids-containing formulation
`delivered as a “spray in which the particles have a mean aerodynamic particle size
`of between 15 and 45 microns, more particularly between 20 and 40 microns and
`an average of about 33 microns.” Pet. 41–42 (quoting Ex. 1007, 4:46–52).
`The Petition includes no adequate rationale why a person of ordinary skill in
`the art would have been prompted to modify Ross GB’s spray formulation to
`provide droplets sized according to McCoy or Whittle. Ross GB is not shown to
`be concerned with the size, much less the mean diameter, of liquid droplets in the
`spray formulation. Id. at 21–22. Even if we accept that McCoy or Whittle would
`have suggested liquid droplets having the specified mean diameter, institution of
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`review is not warranted, because the Petition does not explain adequately why one
`would have been led to import the droplet sizing disclosed in McCoy or Whittle
`into the spray formulation of Ross GB.
`“[A] patent composed of several elements is not proved obvious merely by
`demonstrating that each of its elements was, independently, known in the prior
`art.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). “If identification of
`each claimed element in the prior art were sufficient to negate patentability, very
`few patents would ever issue.” In re Rouffet, 149 F.3d 1350, 1357 (Fed. Cir.
`1998). Obviousness can be established when the prior art, itself, would have
`suggested the claimed subject matter. In re Rinehart, 531 F.2d 1048, 1051
`(CCPA 1976). But the Petition identifies no persuasive reason why the prior art
`would have recommended modifying Ross GB’s spray to alter the size, or mean
`diameter, of the droplets. Instead, the Petition selects elements from
`compositionally-different formulations and, without addressing those differences,
`argues that it would have been obvious to combine the selected elements in the
`manner that is specified in the challenged claims.
`Petitioner first argues that reducing the droplet size in Ross GB’s spray, to a
`size comparable to the droplets disclosed in McCoy or Whittle, would have been
`understood to provide “a higher surface area to be absorbed by the mucosa of the
`intra-oral cavity.” Pet. 22 (discussing McCoy) (quoting Ex. 1002 ¶ 22); see id.
`at 42 (discussing Whittle) (quoting Ex. 1002 ¶ 67). The Petition, however, fails to
`direct us to any disclosure in the asserted prior art, or any other credible evidence,
`from which we can reasonably conclude that an “ordinary artisan would have
`perceived the droplet sizes disclosed in” McCoy or Whittle to be smaller than those
`in Ross GB’s spray. Prelim. Resp. 20. That deficiency, standing alone, warrants
`denial of the obviousness grounds stated in the Petition.
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`The Petition also fails to direct us to persuasive information that the mean
`diameter of droplets was of any concern in Ross GB’s spray—much less that one
`would have understood that Ross GB’s sublingual fentanyl spray would benefit
`from a modification to droplet surface area for the purpose of providing “a higher
`surface area to be absorbed by the mucosa of the intra-oral cavity.” Pet. 22, 42. In
`that regard, McCoy’s disclosure of droplet sizes is presented in the context of an
`intra-oral formulation that comprises an oral-absorption enhancer. Ex. 1005 ¶ 19.
`Whittle’s disclosure of droplet sizes is presented in the context of a formulation
`containing cannabinoids, and is not shown on this record to address increasing the
`surface area for absorption by mucosa. Pet. 42; see Ex. 1007, Abstract, 4:40–53
`(disclosure of preferred range of particle sizes for “delivering cannabinoids”).
`The Petition directs us to no credible information that links a concern—
`about droplet size, mean diameter, or droplet surface area—to Ross GB’s spray,
`which includes no absorption enhancer and no cannabinoid. See Pet. 21–22, 42–43
`(failing to establish that link, and directing us to no disclosure in Ross GB of a
`formulation comprising an absorption enhancer or a cannabinoid). That aspect of
`the Petition rests on bare opinion testimony that is not tethered adequately to
`objective evidence, tending to show that one would have combined the teachings
`of the references. Id. (citing Ex. 1002 ¶¶ 22–24, 67–68).
`The Petition also includes argument that utilizing a smaller droplet size in
`Ross GB’s spray would have been understood to decrease “any discomfort to the
`patient from administration of the drug.” Id. at 22, 26 (quoting Ex. 1002 ¶ 23).
`Here again, the Petition directs us to no suggestion in the asserted prior art that one
`would have perceived the droplet sizes in Ross GB’s spray to be larger than the
`droplets disclosed in McCoy or Whittle. See Prelim. Resp. 20. Nor does the
`Petition direct us to any disclosure sufficient to show that patient discomfort was a
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`concern in Ross GB. Pet. 22, 26, 35–36, 43, 49; see Prelim. Resp. 20–21 (pointing
`out that deficiency in the Petition).
`On that point, Petitioner again rests on bare opinion testimony to make out
`its challenge. Pet. 22, 26, 35–36, 43, 49. Under our rules, however, an opinion
`that does not disclose underlying facts “is entitled to little or no weight.” 37 C.F.R.
`§ 42.65(a); see Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d
`281, 294 (Fed. Cir. 1985) (lack of objective support for opinion testimony “may
`render the testimony of little probative value in a validity determination”); see also
`Prelim. Resp. 19–22 (explaining why neither of the two asserted reasons for the
`proposed combination are adequately supported). Because the Petition rests on
`opinion testimony untethered to adequate objective proof—for example,
`disclosures in the prior art—institution of review is not warranted.
`The obviousness grounds based on McCoy are deficient for another reason,
`which we discuss below in the context of the ground based on anticipation. In a
`nutshell, the Petition ignores that McCoy nowhere refers to the “mean diameter” of
`liquid particles. Pet. 25, 35, 54, 58; see Prelim. Resp. 17–19 (identifying that
`deficiency in the Petition). The Petition does not explain adequately how or why
`McCoy would have suggested the “mean diameter” limitations of the challenged
`claims. Ex. 1001, 57:37–58:55 (claims 1–5).
`On this record, the Petition fails to show sufficiently that McCoy or Whittle
`would have recommended modifying the droplets in Ross GB’s spray to satisfy the
`“mean diameter” limitations of claims 1–5. For that reason, the Petition fails to
`establish a reasonable likelihood of prevailing on the obviousness grounds.
`
`C. The Ground Based on Anticipation by McCoy
`The Petition asserts also that McCoy anticipates claims 1, 4, and 5. Pet. 51–
`60. Each of those claims requires liquid “droplets having a mean diameter of from
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`about 30 to about 70 microns.” Ex. 1001, 57:37–58:55. The Petition fails to direct
`us to disclosure in McCoy that anticipates that specified range. Pet. 51–60.
`The Petition directs us to McCoy’s teaching that the liquid droplets will be
`“sized within the range of about 1 to 200 microns, more preferably within the
`range of 10–100 microns.” Id. at 54 (quoting Ex. 1005 ¶ 19). Significantly, the
`Petition ignores that McCoy does not teach a “mean diameter” value or range for
`liquid droplets. Id. As Patent Owner points out, the Petition does not “explain
`how one of ordinary skill [in the art] would identify a particular range for mean
`diameter of droplets from a spectrum of possible droplet sizes that is about 2–5
`times broader” than the mean diameter range “of from about 30 to about 70
`microns” that is specified in claims 1, 4, and 5. Prelim. Resp. 51. In that regard,
`the Petition directs us to conclusory opinion testimony that McCoy’s preferred
`droplet sizes encompass the claimed “mean diameter” range of claim 1. Pet. 54
`(citing Ex. 1002 ¶ 21).
`Patent Owner responds, and we agree, that the Petition fails to adequately
`explain how McCoy’s preferred droplet sizes correspond to a mean diameter value,
`which “would require information regarding distribution of droplet diameters
`across the broad spectrum of droplet sizes” disclosed in McCoy. Prelim. Resp. 51.
`Critically lacking is a cogent explanation of how an ordinary artisan “would have
`predicted a particular range for mean diameter of droplets from a spectrum of
`possible droplet sizes” disclosed in McCoy. Id. at 17. We agree with Patent
`Owner that Dr. Park’s sweeping, but unsupported, opinion that “there is no
`reasonable difference in how the claimed range operates over the range” disclosed
`in McCoy is insufficient to support a successful anticipation challenge. Id. at 18–
`19 (quoting Ex. 1002 ¶ 21).
`
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`III. CONCLUSION
`Taking account of the information in the Petition and Preliminary Response,
`we decline to institute review because the information presented does not
`demonstrate a reasonable likelihood that Petitioner would prevail with respect to at
`least one of the claims challenged in the Petition. 35 U.S.C. § 314(a).
`
`IV. ORDER
`
`For the reasons given, it is
`ORDERED that the Petition is denied.
`
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`IPR2015-01799
`Patent 8,835,460 B2
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`FOR PETITIONER:
`Gregory J. Gonsalves
`gonsalves@gonsalveslawfirm.com
`
`Christopher Casieri
`MCNEELY, HARE & WAR LLP
`chris@miplaw.com
`
`FOR PATENT OWNER:
`Gerald Flattmann
`Naveen Modi
`PAUL HASTINGS LLP
`CFAD-Insys@paulhastings.com
`CFAD-Insys@paulhastings.com
`
`
`
`
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