Coalition for Affordable Drugs XI LLCv.Insys Pharma, Inc.

Patent Trial and Appeal Board

Mar 10, 2016

13895124 (P.T.A.B. Mar. 10, 2016)

Trials@uspto.gov Paper No. 9
Tel.: 571-272-7822 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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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.
A. Related Proceedings
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.
B. The ’460 Patent
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.
C. The Challenged Claims
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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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”).
D. Asserted Grounds of Unpatentability
The Petition asserts the following grounds of unpatentability:
References Basis Claim(s)
Challenged
Ross GB and McCoy § 103 1, 4, 5
Ross GB, Klokkers-Bethke,
and McCoy
§ 103 2, 3
Ross GB and Whittle § 103 1, 4, 5
Ross GB, Klokkers-Bethke,
and Whittle
§ 103 2, 3
McCoy § 102(b) 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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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