Paper No. ______
`Filed: December 11, 2015
`
`Filed on behalf of: Insys Pharma, Inc
`
`By: Gerald J. Flattmann (CFAD-Insys@paulhastings.com)
`
`Naveen Modi (CFAD-Insys@paulhastings.com)
`
`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
`
`______________________
`
`Patent Owner’s Preliminary Response
`to Petition for Inter Partes Review
`of U.S. Patent No. 8,835,460
`
`
`
`
`
`
`
`

`
`TABLE OF CONTENTS
`
`Page
`Introduction ...................................................................................................... 1
`
`Background ...................................................................................................... 2
`
`I.
`
`
`
`II.
`
`III. The Board Should Exercise Its Discretion Under 35 U.S.C. § 325(d) ............ 4
`
`A.
`
`B.
`
`C.
`
`D.
`
`E.
`
`Substantially the Same Information as That Contained in Ross_GB
`(Ex. 1003) Was Considered by the Office ............................................ 5
`
`The ’496 Publication (Ex. 1005) Was Considered by the Office ....... 10
`
`The ’150 Patent (Ex. 1007) Was Considered by the Office ................ 11
`
`CFAD’s Newly Presented References Are Deficient ......................... 12
`
`Conclusion ........................................................................................... 13
`
`IV. CFAD Advances Flawed Obviousness Analyses .......................................... 13
`
`A. Ground 1: Claims 1, 4, and 5 Are Not Obvious Over Ross_GB
`(Ex. 1003) and the ’496 Publication (Ex. 1005) ................................. 14
`
`B.
`
`1.
`
`2.
`
`1.
`
`2.
`
`3.
`
`CFAD Fails to Explain How the References Disclose or Suggest
`the Features of Claims 1, 4, and 5 .................................................. 15
`
`CFAD Fails to Explain Why One of Ordinary Skill Would Have
`Combined the Asserted References ............................................... 19
`
`Ground 2: Claims 2 and 3 Are Not Obvious Over Ross_GB
`(Ex. 1003), the ’496 Publication (Ex. 1005), and the ’862 Patent
`(Ex. 1004) ............................................................................................ 22
`
`CFAD Fails to Explain How the References Disclose or Suggest
`the Features of Claims 2 and 3 ....................................................... 23
`
`CFAD Fails to Explain Why One of Ordinary Skill Would Have
`Combined the Asserted References ............................................... 28
`
`CFAD Resorts to Non-Analogous Art and Conclusory Allegations
`of Obviousness ............................................................................... 33
`
`i
`
`

`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`C.
`
`
`
`Ground 3: Claims 1, 4, and 5 Are Not Obvious Over Ross_GB
`(Ex. 1003) and the ’150 Patent (Ex. 1007) .......................................... 37
`
`D. Ground 4: Claims 2 and 3 Are Not Obvious Over Ross_GB
`(Ex. 1003), the ’150 Patent (Ex. 1007), and the ’862 Patent (Ex. 1004)
` ............................................................................................................. 39
`
`E.
`
`F.
`
`CFAD’s Grounds Rely on Improper Hindsight .................................. 42
`
`CFAD Fails to Adequately Address Evidence of Secondary
`Considerations ..................................................................................... 43
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`Commercial Success ...................................................................... 44
`
`Failure of Others ............................................................................ 45
`
`Long-Felt Need .............................................................................. 46
`
`Skepticism ...................................................................................... 47
`
`Unexpected Results ........................................................................ 48
`
`V.
`
`CFAD Advances Flawed Anticipation Analyses .......................................... 49
`
`A. Ground 5: Claims 1, 4, and 5 Are Not Anticipated by the ’496
`Publication (Ex. 1005) ......................................................................... 50
`
`VI. CFAD’s Claim Construction Analysis Is Deficient ...................................... 51
`
`VII. CFAD Advances Redundant Grounds of Rejection ...................................... 53
`
`VIII. Conclusion ..................................................................................................... 56
`
`ii
`
`

`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`CASES
`Apple Inc. v. ITC,
`725 F.3d 1356 (Fed. Cir. 2013) .......................................................................... 43
`
`
`
`Ariosa Diagnostics v. Verinata Health, Inc.,
`IPR2013-00276, Paper 43 (Oct. 23, 2014) ......................................................... 41
`
`In re Baxter Travenol Labs.,
`952 F.2d 388 (Fed. Cir. 1991) ............................................................................ 49
`
`Cheese Sys., Inc. v. Tetra Pak Cheese & Powder Sys., Inc.,
`725 F.3d 1342 (Fed. Cir. 2013) .......................................................................... 42
`
`Circuit Check Inc. v. QXQ Inc.,
`795 F.3d 1331 (Fed. Cir. 2015) .......................................................................... 33
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
`Patent Litig.,
`676 F.3d 1063 (Fed. Cir. 2012) .......................................................................... 13
`
`Excelsior Med. Corp. v. Lake,
`IPR2013-00494, Paper 10 (Feb. 6, 2014) ............................................................. 4
`
`In re Fay,
`347 F.2d 597 (C.C.P.A. 1965) ............................................................................ 36
`
`Graham v. John Deere Co. of Kan. City,
`383 U.S. 1 (1966) ................................................................................................ 13
`
`Helifix Ltd. v. Blok-Lok, Ltd.,
`208 F.3d 1339 (Fed. Cir. 2000) .......................................................................... 49
`
`Hulu LLC v. Intertainer, Inc.,
`IPR2014-01456, Paper 8 (Mar. 6, 2015) .............................................................. 4
`
`Intri-Plex Techs., Inc. v. Saint-Gobain Performance Plastics Rencol
`Ltd.,
`IPR2014-00309, Paper 83 (Mar. 23, 2015) .................................................. 13, 43
`
`iii
`
`

`
`TABLE OF AUTHORITIES
`(continued)
`
`Jiawei Tech. (HK) Ltd. et al. v. Richmond,
`
`IPR2014-00938, Paper 20 (Dec. 16, 2014)................................................... 51, 52
`
`Page(s)
`
`In re Kahn,
`441 F.3d 977 (Fed. Cir. 2006) ............................................................................ 14
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ................................................................................ 13, 14, 32
`
`Leo Pharm. Prods., Ltd. v. Rea,
`726 F.3d 1346 (Fed. Cir. 2013) .......................................................................... 36
`
`Liberty Mut. Ins. Co. v. Progressive Cas. Ins. Co.,
`CBM2012-00003, Paper 7 (Oct. 25, 2012) .................................................. 54, 55
`
`Metrics, Inc. et al. v. Senju Pharm. Co., Ltd., et al.,
`IPR2014-01041, Paper 19 (Feb. 19, 2015) ......................................................... 41
`
`Monarch Knitting Mach. Corp. v. Sulzer Moral GmbH,
`139 F.3d 877 (Fed. Cir. 1998) ............................................................................ 47
`
`Motorola, Inc. v. Interdigital Tech. Corp.,
`121 F.3d 1461 (Fed. Cir. 1997) .......................................................................... 49
`
`Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc.,
`520 F.3d 1358 (Fed. Cir. 2008) .................................................................... 35, 48
`
`Panduit Corp. v. Dennison Mfg. Co.,
`774 F.2d 1082 (Fed. Cir. 1985) .......................................................................... 45
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) .................................................................... 35, 36
`
`Prism Pharma Co. v. Choogwae Pharma Corp.,
`IPR2014-00315, Paper 14 (July 8, 2014) ............................................................. 4
`
`Schering Corp. v. Geneva Pharm., Inc.,
`339 F.3d 1373 (Fed. Cir. 2003) .......................................................................... 49
`
`iv
`
`

`
`TABLE OF AUTHORITIES
`(continued)
`
`Schott Gemtron Corp. v. SSW Holding Co., Inc.,
`
`IPR2014-00367, Paper 62 (May 26, 2015) ......................................................... 33
`
`Page(s)
`
`Standard Oil Co. v. Am. Cyanamid Co.,
`774 F.2d 448 (Fed. Cir. 1985) ............................................................................ 36
`
`Star Sci., Inc. v. R.J. Reynolds Tobacco Co.,
`655 F.3d 1364 (Fed. Cir. 2011) .......................................................................... 43
`
`Syntex (USA) LLC v. Apotex, Inc.,
`407 F.3d 1371 (Fed. Cir. 2005) .......................................................................... 45
`
`In re Wright,
`999 F.2d 1557 (Fed. Cir. 1993) .......................................................................... 49
`
`STATUTES
`
`35 U.S.C.
`§ 102 .................................................................................................................... 14
`§ 103(a) ......................................................................................................... 13, 14
`§ 312(a)(3) .......................................................................................................... 41
`§ 313 ...................................................................................................................... 1
`§ 325(d) ....................................................................................................... 4, 5, 13
`§ 326(b) ............................................................................................................... 54
`
`OTHER AUTHORITIES
`
`37 C.F.R.
`§ 42.1(b) .............................................................................................................. 54
`§ 42.65 ..................................................................................................... 17, 19, 25
`§ 42.65(a) ............................................................................................................ 50
`§ 42.100(b) .......................................................................................................... 53
`§ 42.104(b)(3) ..................................................................................................... 51
`§ 42.104(b)(3)–(5) .............................................................................................. 52
`§ 42.107 ................................................................................................................. 1
`
`Office Patent Trial Practice Guide,
` 77 Fed. Reg. 48756 (Aug. 14, 2012) ..................................................... 17, 19, 25
`
`
`
`v
`
`

`
`Case IPR2015-01799
`
`LIST OF EXHIBITS
`
`
`2001. Allen et al., Disperse Systems, in ANSEL’S PHARMACEUTICAL DOSAGE
`FORMS AND DRUG DELIVERY SYSTEMS (L. Allen & H. Ansel, eds., 2014).
`
`2002. U.S. Food & Drug Admin. Oral Solutions and Suspensions, in FDA GUIDE
`TO INSPECTIONS OF ORAL SOLUTIONS AND SUSPENSIONS (August 1994).
`
`2003. U.S. Food & Drug Admin. Metered Dose Inhaler (MDI) and Dry Powder
`Inhaler (DPI) Drug Products (Draft Guidance Document) Center for Drug
`Evaluation and Research (October 1998).
`
`2004. U.S. Food & Drug Admin. Bioavailability and Bioequivalence Studies for
`Nasal Aerosols and Nasal Sprays for Local Action (Draft Guidance
`Document) Center for Drug Evaluation and Research (June 1999).
`
`2005. U.S. Food & Drug Admin. Summary Review for Regulatory Action
`(NDA # 202788, Insys Therapeutics, Inc.) Center for Drug Evaluation and
`Research (January 4, 2012).
`
`2006. Feierman & Lasker, 1996. “Metabolism of fentanyl, a synthetic opioid
`analgesic, by human liver microsomes. Role of CYP3A4.” Drug Metab
`Dispos 24(9):932–39.
`
`2007. Graff & Pollack, 2005. “Nasal drug administration: potential for targeted
`central nervous system delivery.” J Pharm Sci. 94(6):1187–95.
`
`2008.
`[Reserved]
`2009. Subsys® Highlights of Prescribing Information. Revised: 01/2012.
`2010. Murthy & Kar, Disperse Systems, in PHARMACEUTICAL TECHNOLOGY
`VOLUME I (NEW AGE INTERNATIONAL (P) LTD., PUBLISHERS, 2013).
`
`2011. Ross et al., 2004. “Novel Compositions.” (WO 2004/080382).
`
`2012. Ross et al., 2006. “Novel Compositions.” U.S. Patent Application
`Publication (US 2006/0062812 A1).
`
`2013. Sakane et al., 1991. “The transport of a drug to the cerebrospinal fluid
`directly from the nasal cavity: the relation to the lipophilicity of the drug.”
`Chem Pharm Bull (Tokyo) 39(9):2456–68.
`
`vi
`
`

`
`Case IPR2015-01799
`
`LIST OF EXHIBITS
`(continued)
`2014. Sarkar, 1992. “Drug metabolism in the nasal mucosa.” Pharm Res 9(1):1–
`9.
`
`2015. Watts et al., 2015. “Intranasal Spray Device Containing Pharmaceutical
`Composition.” U.S. Patent Application Publication 2015/0283123 A1.
`
`2016. Bredenberg. Copy of Ex. 1006 from Coal. For Affordable Drugs XI LLC v.
`Insys Pharma, Inc., IPR2015-01797.
`
`2017. Declaration of Dr. Larry Dillaha, M.D., signed Sept. 17, 2012, in U.S.
`Patent Application No. 11/698,739.
`
`2018. U.S. Patent No. 8,835,459 to Kottayil et al., issued on Sept. 16, 2014.
`
`2019. McCoy et al., 2001. “Formulation and system for intra-oral delivery of
`pharmaceutical agents.” (WO 00/47203 A1).
`
`2020.
`
`[Reserved]
`
`2021.
`
`[Reserved]
`
`2022.
`
`[Reserved]
`
`2023.
`
`[Reserved]
`
`2024.
`
`[Reserved]
`
`2025.
`
`[Reserved]
`
`2026.
`
`[Reserved]
`
`2027. Chen et al., 2002. “Identification of the enzymatic mechanism of
`nitroglycerin bioactivation.” PNAS 99(12): 8306–8311.
`
`2028.
`
`Information Disclosure Sheet, filed July 22, 2013, in U.S. Patent
`Application No. 13/895,124. (Initialed by Examiner).
`
`2029.
`
`[Reserved]
`
`2030. Coal. For Affordable Drugs XI LLC v. Insys Pharma, Inc., IPR2015-
`01797, Paper 1 (Aug. 24, 2015).
`
`vii
`
`

`
`
`I.
`
`Introduction
`
`Case IPR2015-01799
`
`U.S. Patent No. 8,835,460 (“the ’460 patent”) is one of four U.S. patents
`
`directed to Subsys®, the first and only fentanyl sublingual spray, developed by
`
`Patent Owner Insys Pharma, Inc. (“Patent Owner” or “Insys”). Subsys is the most-
`
`prescribed brand-name drug of its class for treating breakthrough cancer pain.
`
`Petitioner Coalition For Affordable Drugs XI, LLC (“Petitioner” or “CFAD”), a
`
`subsidiary of an investment fund managed by Kyle Bass, filed the petition for inter
`
`partes review (“the Petition”). CFAD also has filed petitions against two related
`
`patents directed to Subsys®: U.S. Patent Nos. 8,486,972 (at issue in IPR2015-
`
`01800) and 8,835,459 (at issue in IPR2015-01797).
`
`This Preliminary Response, submitted in accordance with 35 U.S.C. § 313
`
`and 37 C.F.R. § 42.107, explains the many reasons why the Patent Trial and
`
`Appeal Board (“the Board”) should not institute a trial. As demonstrated below,
`
`CFAD has asserted grounds based on information the Examiner already considered
`
`and in fact applied during prosecution. In addition, CFAD’s obviousness
`
`arguments do not address each and every claim feature, and they fail to explain
`
`why one of ordinary skill would have arrived at the claimed invention. CFAD
`
`makes hindsight-driven attempts to plug the holes in each ground, relying on bald
`
`assertions that some claim elements could have been discovered through routine
`
`optimization and that others would have been known from non-analogous art.
`
`1
`
`

`
`
`CFAD’s anticipation arguments similarly fail to address each and every claim
`
`Case IPR2015-01799
`
`feature. They instead rely on CFAD’s expert to disclose what the allegedly
`
`anticipatory reference does not. To make matters worse, CFAD sidesteps its
`
`obligation to construe critical claim terms. In sum, CFAD simply has not shown a
`
`reasonable likelihood that it would prevail on any ground. Therefore, Patent
`
`Owner respectfully submits that the Board should decline to institute a trial.
`
`II. Background
`Many cancer patients suffer periodic flares of pain, varying in intensity and
`
`duration, that come quickly and without warning. Every second is agony, and
`
`patients need convenient, strong, and fast-acting medication. To fill that need,
`
`Insys developed Subsys®, the first and only FDA-approved sublingual spray for
`
`treating breakthrough cancer pain.
`
`Unlike the breakthrough pain medications marketed before it (e.g., Actiq®
`
`lozenges and Abstral® tablets), Subsys® conveniently provides significant pain
`
`relief as soon as five minutes after dosing. See, e.g., Ex. 2017. Doctors and
`
`patients have overwhelmingly accepted this benefit such that within three years of
`
`entering the market, Subsys® has achieved nearly 50% market share, surpassing all
`
`five pre-existing competitors (including Actiq® and its generic counterpart) to
`
`become the most prescribed branded drug of its kind. See infra at 44–45 (sales
`
`data).
`
`2
`
`

`
`
`
`Case IPR2015-01799
`
`Developing Subsys® was no easy task. Its solid-form competitors (e.g.,
`
`lozenges and buccal tablets) require release and dispersal before absorption from
`
`dissolved form—a relatively slow process that increases the likelihood of
`
`swallowing the drug, which decreases bioavailability and relief of breakthrough
`
`pain. See, e.g., Ex. 1001, col. 2, ll. 1–11. Insys set out to create a faster, more
`
`reliable alternative: liquid sublingual formulations. This new path was fraught
`
`with technical challenges. Among other things, the ’460 patent’s inventors were
`
`concerned with optimizing the in vivo permeability profile for faster onset of
`
`action; stability in solution; sufficient solubility; palatability; preventing microbial
`
`growth without creating unwanted chemical reactions; and creating a liquid
`
`capable of being dispersed in a fine mist comprising droplets with high surface
`
`area, but without being prone to inhalation and deposition in the airways. See, e.g.,
`
`Ex. 2010, pp. 4, 13; Ex. 2002, p. 1.
`
`After years of research and development—which CFAD now dismisses as a
`
`“matter of routine”—Insys created and developed Subsys® through clinical trials.
`
`Claim 1 of the ’460 patent recites a sublingual formulation comprising liquid
`
`droplets of a specific size, an effective amount of fentanyl (or a derivative thereof)
`
`and a pharmaceutically acceptable liquid carrier. Claim 5 recites a method of
`
`using that formulation to treat pain in humans. Claims 2 and 3 are directed to
`
`specific, non-propellant combinations of fentanyl free base, ethanol, and propylene
`
`3
`
`

`
`
`glycol. Claim 4 recites a multi-dose device for sublingual administration,
`
`Case IPR2015-01799
`
`comprising both (1) a reservoir containing fentanyl (or a derivative thereof) and a
`
`pharmaceutically acceptable liquid carrier and (2) an actuator that delivers a
`
`therapeutically effective dose of liquid droplets of a specific size. Extensive
`
`clinical trials have shown that the claimed inventions provide, among other things,
`
`significant pain relief in as few as five minutes. See, e.g., Ex. 2017.
`
`III. The Board Should Exercise Its Discretion Under 35 U.S.C. § 325(d)
`Under 35 U.S.C. § 325(d), “the Director may take into account whether, and
`
`reject the petition or request because, the same or substantially the same prior art or
`
`arguments previously were presented to the Office.” The Board has exercised that
`
`authority to deny institution of IPRs based on art or arguments presented during
`
`prosecution. See e.g., Hulu LLC v. Intertainer, Inc., IPR2014-01456, Paper 8 at 7–
`
`8 (Mar. 6, 2015); Prism Pharma Co. v. Choogwae Pharma Corp., IPR2014-00315,
`
`Paper 14 at 12–13 (July 8, 2014); Excelsior Med. Corp. v. Lake, IPR2013-00494,
`
`Paper 10 at 20 (Feb. 6, 2014).
`
`References asserted in all grounds of the Petition, or references disclosing
`
`the same or substantially the same information, were considered by and discussed
`
`with the Office during prosecution of the ’460 patent. To the extent allegedly new
`
`secondary references were not expressly considered, they are deficient for other
`
`reasons (e.g., they are not analogous art or involve solid-form fentanyl
`
`4
`
`

`
`
`preparations, which present different challenges than those faced by the inventors
`
`Case IPR2015-01799
`
`at least with respect to formulation, desired pharmacokinetic profile, and efficacy).
`
`As explained in detail below, and pursuant to 35 U.S.C. § 325(d), the Board should
`
`deny the Petition in its entirety.
`
`A.
`
`Substantially the Same Information as That Contained in Ross_GB
`(Ex. 1003) Was Considered by the Office
`
`Grounds 1–4 of the Petition rely on Ross_GB (Ex. 1003). (Pet. at 5–6.)
`
`Ross_GB is a Great Britain patent publication by Calvin Ross, et al. (Pet. at 3–4.)
`
`CFAD alleges that it discloses aspects of sublingual fentanyl formulations as
`
`recited in claims 1–5 of the ’460 patent, the multi-dose device recited in claim 4
`
`and the method recited in claim 5. (Pet. at 18–51.) The Examiner considered the
`
`content of Ross_GB at least twice. First, the Examiner considered International
`
`Patent Application Publication WO 2004/080382 (“the ’382 publication”;
`
`Ex. 2011), the disclosure of which is identical to Ross_GB. See Ex. 2028, p. 5.
`
`Second, the Examiner considered U.S. Patent Application Publication
`
`2006/0062812 by Calvin Ross, et al. (“Ross_US2006”; Ex. 2012). See Ex. 2028,
`
`p. 4. In fact, Ross_US2006 served as the basis of multiple rejections during
`
`prosecution of the ’460 patent. See, e.g., Ex. 1018, p. 9 (item C); Ex. 1020, pp. 4–
`
`5 (item 7). Indeed, CFAD’s arguments hinge on disclosures in Ross_GB that also
`
`appear in Ross_US2006:
`
`5
`
`

`
`
`
`Case IPR2015-01799
`
` Ross_GB recites a “pharmaceutical formulation comprising
`
`(i) fentanyl.” Ex. 1003 (Abstract). Ross_US2006 discloses a
`
`“pharmaceutical formulation compris[ing]: (a) fentanyl.” Ex. 2012,
`
`¶¶ [0018]–[0019].
`
` Ross_GB recites a product “preferably administered sublingually as a
`
`spray.” It further states, “The formulations are well tolerated when
`
`administered to the sensitive sublingual mucosa and the sublingual
`
`spray administration will result in rapid onset of the therapeutic effect
`
`of the fentanyl.” Ex. 1003, p. 3, ll. 29–32. Ross_US2006 recites the
`
`same. Ex. 2012, ¶ [0022].
`
` Ross_GB states that “a therapeutically effective amount of a
`
`formulation for the treatment of pain according to the invention is
`
`used.” Ex. 1003, p. 8, ll. 10–11. Ross_US2006 recites the same.
`
`Ex 2012, ¶ [0063].
`
` Ross_GB recites “(a) fentanyl or a pharmaceutically acceptable salt
`
`thereof; (b) water as carrier; and (c) a polar organic solvent in
`
`sufficient amount to enhance the solubility of the fentanyl or
`
`pharmaceutically acceptable salt thereof in the water.” Ex. 1003, p. 3,
`
`ll. 24–27. Ross_US2006 recites the same. Ex 2012, ¶ [0019]–[0021].
`
`6
`
`

`
`
`
`Case IPR2015-01799
`
` Ross_GB contains Example 1, as a formulation comprising fentanyl
`
`base (0.0280g), saccharin (0.0177g), absolute ethanol (2.8336g),
`
`menthol (0.0531g), and citrate buffer (4.1516g). Ex. 1003, p. 11,
`
`ll. 1–9. Ross_US2006 discloses an Example 1 formulation
`
`comprising the same. Ex 2012, ¶ [0096].
`
` Ross_GB states, “The concentration of polar organic solvent is in the
`
`range preferably of between 6 and 50%, more preferably 20-45%[,]
`
`especially 35-42%.” Ex. 1003, p. 5, ll. 22–23. Ross_US2006 recites
`
`the same. Ex. 2012, ¶ [0042].
`
` Ross_GB states, “The preferred polar organic solvent is ethanol.”
`
`Ex. 1003, p. 5, ll. 7–8. Ross_US2006 recites the same. Ex. 2012,
`
`¶ [0038].
`
` Ross_GB states, “Examples of polar organic solvents that may be
`
`used to enhance the solubility of fentanyl, or the physiologically
`
`acceptable salt thereof in the water, include: lower alcohols (e.g. C2-4
`
`alcohols) such as ethanol; lower polyols (e.g. C2-4 polyols) such as
`
`glycerol and propylene glycol.” Ex. 1003, p. 5, ll. 1–4.
`
`Ross_US2006 recites the same. Ex. 2012, ¶ [0037].
`
` Ross_GB states, “Suitable moisturizing agents include, for example,
`
`the polar organic solvents such as glycols, especially propylene
`
`7
`
`

`
`
`
`Case IPR2015-01799
`
`glycol.” Ex. 1003, p. 7, ll. 11–14. Ross_US2006 recites the same.
`
`Ex. 2012, ¶ [0057].
`
` Ross_GB states that “single or multiple use devices comprising a
`
`single or multiple dose of the formulation of the invention [are]
`
`envisaged.” Ex. 1003, p. 8, ll. 25–26. Ross_US2006 recites the same.
`
`Ex. 2012, ¶ [0066].
`
` Ross_GB states, “The invention relates to formulations of fentanyl,
`
`especially pump spray formulations suitable for sublingual delivery.”
`
`Ex. 1003, p. 1, ll. 3–4. Ross_US2006 recites the same. Ex. 2012,
`
`¶ [0002].
`
` Ross_GB states, “Formulations according to the invention are
`
`preferably packaged as a bulk solution containing multiple doses in a
`
`pump spray system comprising a sealed container fitted with a
`
`metering pump. Thus as an aspect of the invention we provide a
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`sealed container containing a plurality of doses of a formulation
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`according to the invention.” Ex. 1003, p. 8, ll. 13–17. Ross_US2006
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`recites the same. Ex. 2012, ¶ [0064].
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` Ross_GB states, “Another aspect of the invention is a metered dose
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`dispensing system comprising a sealed container containing a
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`formulation of the invention fitted with a metering pump, an actuator
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`and a channelling device.” Ex. 1003, p. 9, ll. 4–6. Ross_US2006
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`recites the same. Ex. 2012, ¶ [0072].
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` Ross_GB states that “[p]referably the actuator will be designed to
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`deliver a sublingually effective dose.” Ex. 1003, p. 9, ll. 26.
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`Ross_US2006 recites the same. Ex. 2012, ¶ [0076].
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` Ross_GB states, “Formulations of the invention are useful in
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`analgesia and in the treatment of pain.” Ex. 1003, p. 8, l. 5.
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`Ross_US2006 recites the same. Ex. 2012, ¶ [0063].
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` Ross_GB states that “[f]entanyl is a narcotic alkaloid, which has been
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`used for many years as an anaesthetic and an analgesic, especially in
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`the treatment of moderate to severe pain.” Ex. 1003, p. 1, ll. 6–7.
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`Ross_US2006 recites the same. Ex. 2012, ¶ [0006].
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` Ross_GB recites “formulations of fentanyl, especially pump spray
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`formulations suitable for sublingual delivery.” Ex. 1003, p. 1, ll. 3–4.
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`Ross_US2006 discloses “formulations of opioid analgesics and in
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`particular fentanyl, especially pump spray formulations suitable for
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`sublingual delivery.” Ex. 2012, ¶ [0002].
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` Ross_GB states, “[T]he formulations of the invention are preferably
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`administered sublingually as a spray.” Ex. 1003, p. 3, ll. 29–30.
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`Ross_US2006 discloses “[t]he formulations of the invention may be
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`used in analgesia and for the treatment of pain. They are preferably
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`administered sublingually as a spray.” Ex. 2012, ¶ [0022].
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` Ross_GB recites “monitor[ing] patients for evidence of
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`self[-]medication.” Ex. 1003, p. 1, l. 15. Ross_US2006 recites the
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`same. Ex. 2012, ¶ [0007].
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`Though CFAD concedes that aspects of Ross_US2006 and Ross_GB “are
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`very similar” (IPR2015-01797, Pet. at 32; IPR2015-01800, Pet. at 36), and that
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`“Ross_GB is a foreign priority document US2006/0062812, which was cited by
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`the examiner during the prosecution of the application that led to the ‘460 patent”
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`(Pet. at 5 n.1), it fails to acknowledge that information cited in Ross_GB also exists
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`in the already-considered-and-applied Ross_US2006.
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`B.
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`The ’496 Publication (Ex. 1005) Was Considered by the Office
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`Grounds 1, 2, and 5 of the Petition rely on the ’496 publication (Ex. 1005).
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`(Pet. at 5–6.) The ’496 publication is a published U.S. patent application by
`
`Randall McCoy et al. (Pet. at 4.) CFAD alleges that it discloses discrete liquid
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`droplets having a mean diameter of from about 30 to about 70 microns (as recited
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`in claims 1, 4, and 5 of the ’460 patent) and discrete liquid droplets having a mean
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`diameter of at least about 10 microns (as recited in claims 2 and 3 of the ’460
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`patent). (See, e.g., Pet. at 21–22 (claim 1), 25–27 (claims 4 and 5), 35–36
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`10
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`(claim 2), 40 (claim 3).) However, the Examiner already considered the ’496
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`Case IPR2015-01799
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`publication. Ex. 2028, p. 2.
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`In addition to considering the ’496 publication itself, the Examiner
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`considered a related application by McCoy et al. (International Publication Number
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`WO 00/47203 (“the ’203 publication”; Ex. 2019)), which contains language
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`identical to that which CFAD cites in the ’496 publication. Ex. 2028, p. 5. More
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`specifically, CFAD cites to eight particular paragraphs in the ’496 publication:
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`[0041], [0019], [0002], [0017], [0014], [0022], [0008],1 and [0031]. (Pet. at 21, 25,
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`35, 52–56.) Each of these paragraphs appears, verbatim, in the ’203 publication.
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`Ex. 2019, p 16, ll. 11–22 (¶ [0041]); id., p. 6, l. 20–p. 7, l. 6 (¶ [0019]); id., p. 1,
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`ll. 9–11 (¶ [0002]); id., p. 6, ll. 8–14 (¶ [0017]); id., p. 4, ll. 21–p. 5, l. 7 (¶ [0014]);
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`id., p. 8, ll. 3–9 (¶ [0022]); id., p. 3, ll. 9–16 (¶ [0008]); id., p. 11, ll. 5–23
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`(¶ [0031]).
`
`C. The ’150 Patent (Ex. 1007) Was Considered by the Office
`Grounds 3 and 4 of the Petition rely on the ’150 patent (Ex. 1007). (Pet.
`
`at 6.) The ’150 patent is a U.S. patent to Brian Whittle et al. (Pet. at 4–5.) CFAD
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`alleges that it discloses discrete liquid droplets having a mean diameter of from
`
`about 30 to about 70 microns (as recited in claims 1, 4, and 5 of the ’460 patent).
`
`
`1 CFAD quotes from this paragraph but incorrectly cites to ¶ [0031]. (Pet. at 55.)
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`11
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`(See, e.g., Pet. at 41–43 (claim 1), 44–45 (claims 4 and 5). In addition, CFAD
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`Case IPR2015-01799
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`alleges that it discloses discrete liquid droplets having a diameter of at least about
`
`10 microns (as recited in claims 2 and 3 of the ’460 patent). (See, e.g., Pet. at 48–
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`49 (claim 2).) However, the Examiner already considered the ’150 patent.
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`Ex. 2028, p. 1. In fact, the ’150 patent served as the basis of rejection during
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`prosecution of the ’460 patent. See, e.g., Ex. 1020, pp. 4–5; see also Pet. at 11
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`(acknowledging that the Examiner asserted the ’150 patent during prosecution). At
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`least one of those rejections cited the combination of Ross_US2006 and the
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`’150 patent (id.), which is essentially what CFAD asserts in Ground 3 of the
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`Petition, albeit via Ross_GB rather than Ross_US2006. (Pet. at 40–45.) Ground 4
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`also asserts the combination of Ross_GB and the ’150 patent, adding the ’862
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`patent as a third reference. (Id. at 45–51.)
`
`D. CFAD’s Newly Presented References Are Deficient
`Though CFAD’s secondary reference (U.S. Patent 5,370,862 (“the ’862
`
`patent”; Ex. 1004) may not have been considered by the Examiner during
`
`prosecution of the ’460 patent, it is deficient for other reasons. For example, the
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`’862 patent does not concern non-propellant formulations of fentanyl, as claimed
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`in the ’460 patent. Rather, it concerns an aerosol (i.e., propellant-containing)
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`nitroglycerin spray for treating angina (see infra Section IV.B.3).
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`E. Conclusion
`In sum, three of the four references asserted in the Petition, or references
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`Case IPR2015-01799
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`disclosing the same or substantially the same information, were considered by the
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`Examiner during prosecution of the ’460 patent. While one secondary reference
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`was not expressly considered, it is deficient, at least because it pertains to non-
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`analogous art. Therefore, the Board should exercise its discretion under 35 U.S.C.
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`§ 325(d) and deny the Petition in its entirety.
`
`IV. CFAD Advances Flawed Obviousness Analyses
`A claim is unpatentable under 35 U.S.C. § 103(a) if the differences between
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`the subject matter sought to be patented and the prior art are such that the subject
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`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
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`Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). Obviousness is a question of
`
`law based on underlying factual findings, including: (1) the scope and content of
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`the prior art; (2) the differences between the claims and the prior art; (3) the level
`
`of ordinary skill in the art; and (4) objective indicia of nonobviousness. Graham v.
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`John Deere Co. of Kan. City, 383 U.S. 1, 17–18 (1966). All four Graham factors
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`must be considered in considering an assertion of obviousness. In re
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`Cyclobenza