U.S. Patent No. US 8,835,460
`
`
`
`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
`
`
`
`U.S. Patent 8,835,460
`
`
`
`__________________
`
`
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO.
`8,835,460 AND
`MANDATORY NOTICES UNDER 37 C.F.R. § 42.8
`
`Mailed August 24 2015
`
`
`
`
`
`
`i
`
`

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`U.S. Patent No. 8,835,460
`
`TABLE OF CONTENTS
`
`NOTICE OF EACH REAL-PARTY-IN-INTEREST .................................................................1
`
`NOTICE OF RELATED MATTERS .............................................................................................. 2
`
`NOTICE OF SERVICE INFORMATION ..................................................................................3
`
`GROUNDS FOR STANDING ......................................................................................................3
`
`STATEMENT OF PRECISE RELIEF REQUESTED ...............................................................3
`
`STATEMENT OF REASONS FOR RELIEF REQUESTED ....................................................6
`
`I.
`
`INTRODUCTION AND SUMMARY OF ARGUMENT ...................................................7
`
`II. THE ‘460 PATENT AND PROSECUTION HISTORY OF THE '460 PATENT ............8
`
`III. CLAIM CONSTRUCTION .................................................................................................13
`
`A. “DISCRETE LIQUID DROPLETS” .................................................................................14
`
`B. “PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER” ................................14
`
`C. “WHEREIN THE SUBLINGUAL FENTANYL FORMULATION CONSISTS
`ESSENTIALLY OF:” ..........................................................................................................16
`
`IV. LEVEL OF SKILL IN THE ART ..................................................................................... 17
`
`V. CLAIMS 1-5 ARE OBVIOUS .............................................................................................18
`
`A. GROUND 1 -- CLAIMS 1, 4AND 5 ARE UNPATENTABLE AS OBVIOUS
`OVER ROSS_GB, IN VIEW OF THE ’496 PUBLICATION .........................................18
`
`1.
`
`INDEPENDENT CLAIM 1 .................................................................................................19
`
`2. THE PRIOR ART AND ITS COMPARISON TO CLAIM 1 ..........................................19
`
`A. SUBLINGUAL FORMULATION COMPRISING DISCRETE LIQUID
`DROPLETS ...........................................................................................................................19
`
`B. OF AN EFFECTIVE AMOUNT OF FENTANYL OR A FENTANYL
`DERIVATIVE SELECTED FROM THE GROUP CONSISTING OF
`SUFENTANIL, CARFENTANIL, LOFENTANIL AND ALFATENIL, A FREE
`BASE OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, ......................20
`
`C. IN A PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER ................................20
`
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`ii
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`U.S. Patent No. 8,835,460
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`D. SAID DROPLETS HAVING A MEAN DIAMETER OF FROM ABOUT 30 TO
`ABOUT 70 MICRONS ..........................................................................................................21
`
`3.
`
`INDEPENDENT CLAIM 4 ..................................................................................................22
`
`4. THE PRIOR ART AND ITS COMPARISON TO CLAIM 4 ..........................................22
`
`A. A MULTI-DOSE DEVICE FOR SUBLINGUAL ADMINISTRATION OF A
`DRUG .....................................................................................................................................23
`
`B. A RESERVOIR CONTAINING THE LIQUID FORMULATION ....................................23
`
`C. COMPRISING FENTANYL, OR A FENTANYL DERIVATIVE SELECTED
`FROM THE GROUP CONSISTING OF SUFENTANIL, CARFENTANIL,
`LOFENTANIL AND ALFATENIL, A FREE BASE OR A
`PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, ...........................................23
`
`D. IN A PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER; ...............................24
`
`E. THE DEVICE HAVING AN ACTUATOR ..........................................................................24
`
`F. WHICH WHEN ACTUATED DELIVERS A THERAPEUTICALLY
`EFFECTIVE DOSE OF THE LIQUID FORMULATION ................................................24
`
`G. IN THE FORM OF LIQUID DROPLETS ..........................................................................24
`
`H. HAVING A MEAN DIAMETER OF FROM ABOUT 30 TO ABOUT 70
`MICRONS ..............................................................................................................................25
`
`5. DEPENDENT CLAIM 5 ......................................................................................................27
`
`6. THE PRIOR ART AND ITS COMPARISON TO CLAIM 5 ..........................................27
`
`A. A METHOD OF TREATING PAIN COMPRISING ..........................................................27
`
`B. SUBLINGUALLY ADMINISTERING AN EFFECTIVE AMOUNT OF THE
`SUBLINGUAL FORMULATION ACCORDING TO CLAIM 1 ........................................27
`
`C. TO A HUMAN PATIENT EXPERIENCING PAIN. ..........................................................28
`
`B. GROUND 2 -- CLAIMS 2 AND 3 ARE UNPATENTABLE AS OBVIOUS
`OVER ROSS_GB, IN VIEW OF THE ‘862 PATENT, AND THE ‘496
`PUBLICATION. ...................................................................................................................28
`
`1.
`
`INDEPENDENT CLAIM 2 .................................................................................................28
`
`2. THE PRIOR ART AND ITS COMPARISON TO CLAIM 2 ..........................................29
`
`A. A NON-PROPELLANT SUBLINGUAL FENTANYL FORMULATION .........................29
`
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`U.S. Patent No. 8,835,460
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`B. COMPRISING DISCRETE LIQUID DROPLETS ..............................................................30
`
`C. OF AN EFFECTIVE AMOUNT OF FENTANYL A FREE BASE OR A
`PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, ...........................................30
`
`D. A PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER .....................................31
`
`E. WHEREIN THE SUBLINGUAL FENTANYL FORMULATION COMPRISES:
`FROM ABOUT 0.001% TO ABOUT 15% BY WEIGHT OF FENTANYL FREE
`BASE ......................................................................................................................................31
`
`F. THE SUBLINGUAL FENTANYL FORMULATION COMPRISES … FROM
`ABOUT 50% TO ABOUT 60% BY WEIGHT OF ETHANOL ...........................................31
`
`G. THE SUBLINGUAL FENTANYL FORMULATION COMPRISES … FROM
`ABOUT 4% TO ABOUT 6% BY WEIGHT OF PROPYLENE GLYCOL ..........................32
`
`H. SAID DROPLETS HAVING A MEAN DIAMETER OF AT LEAST ABOUT 10
`MICRONS. .............................................................................................................................35
`
`3.
`
`INDEPENDENT CLAIM 3. .................................................................................................36
`
`4. THE PRIOR ART AND ITS COMPARISON TO CLAIM 3 ..........................................36
`
`A. A NON-PROPELLANT SUBLINGUAL FENTANYL FORMULATION .........................36
`
`B. COMPRISING DISCRETE LIQUID DROPLETS ..............................................................37
`
`C. OF AN EFFECTIVE AMOUNT OF FENTANYL A FREE BASE OR A
`PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, ...........................................37
`
`D. A PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER .....................................37
`
`E. WHEREIN THE SUBLINGUAL FENTANYL FORMULATION CONSISTS
`ESSENTIALLY OF: FROM ABOUT 0.001% TO ABOUT 15% BY WEIGHT OF
`FENTANYL FREE BASE ....................................................................................................37
`
`F. THE SUBLINGUAL FENTANYL FORMULATION CONSISTS ESSENTIALLY
`OF … FROM ABOUT 50% TO ABOUT 60% BY WEIGHT OF ETHANOL ...................37
`
`G. THE SUBLINGUAL FENTANYL FORMULATION CONSISTS ESSENTIALLY
`OF … FROM ABOUT 1% TO ABOUT 30% BY WEIGHT OF PROPYLENE
`GLYCOL ................................................................................................................................38
`
`H. SAID DROPLETS HAVING A MEAN DIAMETER OF AT LEAST ABOUT 10
`MICRONS. .............................................................................................................................40
`
`C. GROUND 3 -- CLAIMS 1, 4 AND 5 ARE UNPATENTABLE AS OBVIOUS
`OVER ROSS_GB, IN VIEW OF THE ’150 PATENT .....................................................40
`
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`U.S. Patent No. 8,835,460
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`1.
`
`INDEPENDENT CLAIM 1 .................................................................................................40
`
`2. THE PRIOR ART AND ITS COMPARISON TO CLAIM 1 ..........................................41
`
`A. SUBLINGUAL FORMULATION COMPRISING DISCRETE LIQUID
`DROPLETS ...........................................................................................................................41
`
`B. OF AN EFFECTIVE AMOUNT OF FENTANYL OR A FENTANYL
`DERIVATIVE SELECTED FROM THE GROUP CONSISTING OF
`SUFENTANIL, CARFENTANIL, LOFENTANIL AND ALFATENIL, A FREE
`BASE OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, ......................41
`
`C. IN A PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER ................................41
`
`D. SAID DROPLETS HAVING A MEAN DIAMETER OF FROM ABOUT 30 TO
`ABOUT 70 MICRONS ..........................................................................................................41
`
`3.
`
`INDEPENDENT CLAIM 4 ..................................................................................................43
`
`4. THE PRIOR ART AND ITS COMPARISON TO CLAIM 4 ..........................................43
`
`A. A MULTI-DOSE DEVICE FOR SUBLINGUAL ADMINISTRATION OF A
`DRUG .....................................................................................................................................43
`
`B. A RESERVOIR CONTAINING THE LIQUID FORMULATION ....................................44
`
`C. COMPRISING FENTANYL, OR A FENTANYL DERIVATIVE SELECTED
`FROM THE GROUP CONSISTING OF SUFENTANIL, CARFENTANIL,
`LOFENTANIL AND ALFATENIL, A FREE BASE OR A
`PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, ...........................................44
`
`D. IN A PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER; ...............................44
`
`E. THE DEVICE HAVING AN ACTUATOR ..........................................................................44
`
`F. WHICH WHEN ACTUATED DELIVERS A THERAPEUTICALLY
`EFFECTIVE DOSE OF THE LIQUID FORMULATION ................................................44
`
`G. IN THE FORM OF LIQUID DROPLETS ..........................................................................44
`
`H. HAVING A MEAN DIAMETER OF FROM ABOUT 30 TO ABOUT 70
`MICRONS ..............................................................................................................................44
`
`5. DEPENDENT CLAIM 5 ......................................................................................................44
`
`6. THE PRIOR ART AND ITS COMPARISON TO CLAIM 5 ..........................................45
`
`A A METHOD OF TREATING PAIN COMPRISING ..........................................................45
`
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`U.S. Patent No. 8,835,460
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`B SUBLINGUALLY ADMINISTERING AN EFFECTIVE AMOUNT OF THE
`SUBLINGUAL FORMULATION ACCORDING TO CLAIM 1 ........................................45
`
`C. TO A HUMAN PATIENT EXPERIENCING PAIN. ..........................................................45
`
`D. GROUND 4 -- CLAIMS 2 AND 3 ARE UNPATENTABLE AS OBVIOUS
`OVER ROSS_GB, IN VIEW OF THE ‘862 PATENT, AND THE ‘150
`PATENT. ...............................................................................................................................45
`
`1.
`
`INDEPENDENT CLAIM 2 .................................................................................................46
`
`2. THE PRIOR ART AND ITS COMPARISON TO CLAIM 2 ..........................................47
`
`A. A NON-PROPELLANT SUBLINGUAL FENTANYL FORMULATION .........................47
`
`B. COMPRISING DISCRETE LIQUID DROPLETS ..............................................................47
`
`C. OF AN EFFECTIVE AMOUNT OF FENTANYL A FREE BASE OR A
`PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, ...........................................47
`
`D. A PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER .....................................47
`
`E. WHEREIN THE SUBLINGUAL FENTANYL FORMULATION COMPRISES:
`FROM ABOUT 0.001% TO ABOUT 15% BY WEIGHT OF FENTANYL FREE
`BASE ......................................................................................................................................47
`
`F. THE SUBLINGUAL FENTANYL FORMULATION COMPRISES … FROM
`ABOUT 50% TO ABOUT 60% BY WEIGHT OF ETHANOL ...........................................48
`
`G. THE SUBLINGUAL FENTANYL FORMULATION COMPRISES … FROM
`ABOUT 4% TO ABOUT 6% BY WEIGHT OF PROPYLENE GLYCOL ..........................48
`
`H. SAID DROPLETS HAVING A MEAN DIAMETER OF AT LEAST ABOUT 10
`MICRONS. .............................................................................................................................48
`
`3.
`
`INDEPENDENT CLAIM 3 .................................................................................................49
`
`4. THE PRIOR ART AND ITS COMPARISON TO CLAIM 3 ..........................................50
`
`A. A NON-PROPELLANT SUBLINGUAL FENTANYL FORMULATION .........................50
`
`B. COMPRISING DISCRETE LIQUID DROPLETS ..............................................................50
`
`C. OF AN EFFECTIVE AMOUNT OF FENTANYL A FREE BASE OR A
`PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, ...........................................50
`
`D. A PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER .....................................50
`
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`U.S. Patent No. 8,835,460
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`E. WHEREIN THE SUBLINGUAL FENTANYL FORMULATION CONSISTS
`ESSENTIALLY OF: FROM ABOUT 0.001% TO ABOUT 15% BY WEIGHT OF
`FENTANYL FREE BASE ....................................................................................................50
`
`F. THE SUBLINGUAL FENTANYL FORMULATION CONSISTS ESSENTIALLY
`OF … FROM ABOUT 50% TO ABOUT 60% BY WEIGHT OF ETHANOL ...................50
`
`G. THE SUBLINGUAL FENTANYL FORMULATION CONSISTS ESSENTIALLY
`OF … FROM ABOUT 1% TO ABOUT 30% BY WEIGHT OF PROPYLENE
`GLYCOL ................................................................................................................................51
`
`H. SAID DROPLETS HAVING A MEAN DIAMETER OF AT LEAST ABOUT 10
`MICRONS. .............................................................................................................................51
`
`VI. CLAIMS 1, 4 AND 5 ARE ANTICIPATED ......................................................................51
`
`A. GROUND 5 -- CLAIMS 1, 4 AND 5 ARE UNPATENTABLE AS
`ANTICIPATED BY THE ’496 PUBLICATION. .............................................................51
`
`1.
`
`INDEPENDENT CLAIM 1 .................................................................................................51
`
`2. THE PRIOR ART AND ITS COMPARISON TO CLAIM 1 ..........................................52
`
`A. SUBLINGUAL FORMULATION COMPRISING DISCRETE LIQUID
`DROPLETS ...........................................................................................................................52
`
`B. OF AN EFFECTIVE AMOUNT OF FENTANYL OR A FENTANYL
`DERIVATIVE SELECTED FROM THE GROUP CONSISTING OF
`SUFENTANIL, CARFENTANIL, LOFENTANIL AND ALFATENIL, A FREE
`BASE OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, ......................53
`
`C. IN A PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER ................................53
`
`D. SAID DROPLETS HAVING A MEAN DIAMETER OF FROM ABOUT 30 TO
`ABOUT 70 MICRONS ..........................................................................................................54
`
`3.
`
`INDEPENDENT CLAIM 4 ..................................................................................................54
`
`4. THE PRIOR ART AND ITS COMPARISON TO CLAIM 4 ..........................................55
`
`A. A MULTI-DOSE DEVICE FOR SUBLINGUAL ADMINISTRATION OF A
`DRUG .....................................................................................................................................55
`
`B. A RESERVOIR CONTAINING THE LIQUID FORMULATION ....................................56
`
`C. COMPRISING FENTANYL, OR A FENTANYL DERIVATIVE SELECTED
`FROM THE GROUP CONSISTING OF SUFENTANIL, CARFENTANIL,
`LOFENTANIL AND ALFATENIL, A FREE BASE OR A
`PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, ...........................................56
`
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`U.S. Patent No. 8,835,460
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`D. IN A PHARMACEUTICALLY ACCEPTABLE LIQUID CARRIER; ...............................56
`
`E. THE DEVICE HAVING AN ACTUATOR ..........................................................................57
`
`F. WHICH WHEN ACTUATED DELIVERS A THERAPEUTICALLY
`EFFECTIVE DOSE OF THE LIQUID FORMULATION ................................................57
`
`G. IN THE FORM OF LIQUID DROPLETS ..........................................................................57
`
`H. HAVING A MEAN DIAMETER OF FROM ABOUT 30 TO ABOUT 70
`MICRONS ..............................................................................................................................58
`
`5. DEPENDENT CLAIM 5 ......................................................................................................58
`
`6. THE PRIOR ART AND ITS COMPARISON TO CLAIM 5 ........................................ 59
`
`A. A METHOD OF TREATING PAIN COMPRISING ........................................................ 59
`
`B SUBLINGUALLY ADMINISTERING AN EFFECTIVE AMOUNT OF THE
`SUBLINGUAL FORMULATION ACCORDING TO CLAIM 1 ...................................... 59
`
`C. TO A HUMAN PATIENT EXPERIENCING PAIN. ........................................................ 60
`
`VII. CONCLUSION .....................................................................................................................60
`
`TABLE OF AUTHORITIES
`
`
`
`
`
`CASES
`
`KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) .......................................... 18
`
`In re Cuozzo Speed Techs., LLC, No. 2014-1301, 2015 U.S. App. LEXIS 1699,
`Slip. Op. at 21 (Fed. Cir. Feb. 4, 2015). ................................................................. 13
`
`Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362, 1369 (Fed. Cir. 2012), cert
`denied, 133 S. Ct. 1736 (2013)). ............................................................................ 18
`
`In re Herz, 537 F.2d 549, 551-52, 190 USPQ 461, 463 (CCPA 1976) ..................... 16
`
`Verdegaal Bros. V. Union Oil Co. Of California 814 F.2d 628 (Fed. Cir. 1987) ..... 51
`
`Atofina V Great Lakes Chem. Corp., 441 F.3d 991 (Fed. Cir. 2006) ........................ 51
`
`Clearvalue, Inc. V. Pearl River Polymers, Inc., 668 F.3d 1340 (Fed. Cir. 2012) ..... 51
`
`
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`U.S. Patent No. 8,835,460
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`RULES
`
`37 C.F.R § 42.8(b)(1) ................................................................................................... 1
`
`37 C.F.R. § 42.100(b) ................................................................................................ 13
`
`
`
`OTHER
`
`M.P.E.P 2111.03 ………………………………………………………………….16
`
`
`
`
`
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`ix
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`U.S. Patent No. 8,835,460
`
`Coalition For Affordable Drugs XI LLC ("CFAD" or "Petitioner") requests
`
`inter partes review of claims 1 - 5 of U.S. Patent No. 8,835,460 ("the '460 Patent")
`
`(Exhibit 1001) assigned to Insys Pharm, Inc. (“Insys”).
`
`NOTICE OF LEAD AND BACKUP COUNSEL
`
`Lead Counsel:
`Dr. Gregory J. Gonsalves
`Reg. No. 43,639
`2216 Beacon Lane
`Falls Church, VA 22043
`(571) 419-7252
`gonsalves@gonsalveslawfirm.com
`
`Backup Counsel:
`Christopher Casieri
`McNeely, Hare & War LLP
`12 Roszel Road, Suite C104
`Princeton, NJ 08540
`Phone: 609 731 3668
`chris@miplaw.com
`
`
`
`
`NOTICE OF EACH REAL-PARTY-IN-INTEREST
`
`Pursuant to 37 C.F.R. § 42.8(b)(1), Petitioner certifies that Coalition For
`
`Affordable Drugs XI LLC (“CFAD”), Hayman Credes Master Fund, L.P.
`
`(“Credes”), Hayman Orange Fund SPC – Portfolio A (“HOF”), Hayman Capital
`
`Master Fund, L.P. (“HCMF”), Hayman Capital Management, L.P. (“HCM”),
`
`Hayman Offshore Management, Inc. (“HOM”), Hayman Investments, L.L.C.
`
`(“HI”), nXn Partners, LLC (“nXnP”), IP Navigation Group, LLC (“IPNav”), J Kyle
`
`Bass, and Erich Spangenberg are the real parties in interest (collectively, “RPI”).
`
`The RPI hereby certify the following information: CFAD is a wholly owned
`
`subsidiary of Credes. Credes is a limited partnership. HOF is a segregated portfolio
`
`
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`1
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`

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`U.S. Patent No. 8,835,460
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`company. HCMF is a limited partnership. HCM is the general partner and
`
`investment manager of Credes and HCMF. HCM is the investment manager of
`
`HOF. HOM is the administrative general partner of Credes and HCMF. HI is the
`
`general partner of HCM. J Kyle Bass is the sole member of HI and sole shareholder
`
`of HOM. CFAD, Credes, HOF and HCMF act, directly or indirectly, through HCM
`
`as the general partner and/or investment manager of Credes, HOF and HCMF. nXnP
`
`is a paid consultant to HCM. Erich Spangenberg is the Manager and majority
`
`member of nXnP. IPNav is a paid consultant to nXnP. Erich Spangenberg is the
`
`Manager and majority member of IPNav. Other than HCM and J Kyle Bass in his
`
`capacity as the Chief Investment Officer of HCM and nXnP and Erich Spangenberg
`
`in his capacity as the Manager/CEO of nXnP, no other person (including any
`
`investor, limited partner, or member or any other person in any of CFAD, Credes,
`
`HOF, HCMF, HCM, HOM, HI, nXnP or IPNav) has authority to direct or control (i)
`
`the timing of, filing of, content of, or any decisions or other activities relating to this
`
`Petition or (ii) any timing, future filings, content of, or any decisions or other
`
`activities relating to the future proceedings related to this Petition. All of the costs
`
`associated with this Petition will be borne by HCM, CFAD, Credes, HOF and/or
`
`HCMF.
`
`
`
`
`
`NOTICE OF RELATED MATTERS
`
`Petitioner is aware of a concurrently filed Petition for inter partes review
`
`2
`
`

`
`U.S. Patent No. 8,835,460
`
`(“IPR”) of U.S. Patent No. 8,486,972, upon which the ‘460 patent claims priority
`
`as a divisional patent application (Case No. Unassigned); and a concurrently
`
`filed Petition for IPR of U.S. Patent No. 8,835,459 (Case No. Unassigned). To
`
`the best of Petitioner’s knowledge, there are no pending litigations or other
`
`related matters related to the ’460 patent that would affect, or be affected by, a
`
`decision in this proceeding.
`
`NOTICE OF SERVICE INFORMATION
`
`Please address all correspondence to the lead and backup counsel at the
`
`address shown above. Petitioner also consents to electronic service by e-mail at:
`
`gonsalves@gonsalveslawfirm.com and chris@miplaw.com.
`
`
`
`GROUNDS FOR STANDING
`
`Petitioner certifies that the patent for which review is sought is available for
`
`inter partes review, and that Petitioner is not barred or estopped from requesting an
`
`inter partes review on the grounds identified in the petition.
`
`STATEMENT OF PRECISE RELIEF REQUESTED
`
`Petitioner relies on the following patents and printed publications to support
`
`its grounds of challenge to claims 1-5 of the ‘460 patent in this Petition:
`
`1. Great Britain patent publication GB2399286A by Calvin John Ross et al,
`
`entitled “Sub-lingual fentanyl formulation.” published September 15, 2004
`
`(“Ross_GB,” Exhibit 1003). Ross_GB is prior art to the ‘460 patent under
`
`
`
`3
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`

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`U.S. Patent No. 8,835,460
`
`at least 35 U.S.C. § 102(b) (pre-AIA) because it was published on
`
`September 15, 2004, more than one year prior to January 25, 2006, the
`
`earliest effective filing date for the claims of the ‘460 patent.
`
`2. United States Patent 5,370,862 by Karin Klokkers-Bethke et al., entitled
`
`“Pharmaceutical hydrophilic spray containing nitroglycerin for treating
`
`angina,” issued December 6, 1994 (“the ‘862 patent,” Exhibit 1004). The
`
`‘862 patent is prior art to the ‘460 patent under at least 35 U.S.C. § 102(b)
`
`(pre-AIA) because it issued on December 6, 1994, more than one year prior
`
`to January 25, 2006, the earliest effective filing date for the claims of the
`
`‘460 patent.
`
`3. United States Patent Publication 2002/0055496 by Randall McCoy et al.
`
`entitled “Formulation and System For Intra-oral Delivery Of Pharmaceutical
`
`Agents,” published May 9, 2002 (“the ‘496 publication,” Exhibit 1005). The
`
`‘496 publication is prior art to the ‘460 patent under at least 35 U.S.C. §
`
`102(b) (pre-AIA) because it was published on May 9, 2002, more than one
`
`year prior to January 25, 2006, the earliest effective filing date for the
`
`claims of the ‘460 patent.
`
`4. United States Patent 6,946,150 by Brian Whittle entitled “Pharmaceutical
`
`formulation” issued September 20, 2005 (“the ‘150 patent,” Exhibit 1007).
`
`The ‘150 patent is prior art to the ‘460 patent under at least 35 U.S.C. §
`
`
`
`4
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`

`
`U.S. Patent No. 8,835,460
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`102(a) (pre-AIA) because it was patented on September 20, 2005 in this
`
`country, before January 25, 2006, the earliest effective filing date for the
`
`claims of the ‘460 patent.
`
`Petitioner requests that claims 1-5 of the '460 patent be held unpatentable
`
`based on the following grounds:
`
`Ground 1. Claims 1, 4, and 5 are unpatentable as obvious over Ross_GB1,
`
`in view of the ’496 publication. The ‘496 publication was not cited by the
`
`Examiner as basis for rejection during the prosecution of the application that led
`
`to the ‘460 patent. See 35 U.S.C. § 103(a).2
`
`Ground 2. Claims 2 and 3 are unpatentable as obvious over Ross_GB, in
`
`view of the ‘496 publication and the ‘862 patent. The ‘496 publication was not
`
`cited by the Examiner as basis for rejection during the prosecution of the
`
`application that led to the ‘460 patent and the ‘862 patent was not before the
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`1 Ross_GB is a foreign priority document US2006/0062812, which was the cited
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`by the examiner during the prosecution of the application that led to the ‘460
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`patent.
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`2 The pre-AIA version of § 103 applies in this proceeding, because the ‘460 Patent
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`has an effective filing and issue date before March 16, 2013. The ‘460 patent
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`claims a priority date of January 25, 2006.
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`5
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`U.S. Patent No. 8,835,460
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`Examiner during the prosecution of the application that led to the ‘460 patent. See
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`35 U.S.C. § 103(a).
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`Ground 3. Claims 1, 4 and 5 are unpatentable as obvious over Ross_GB, in
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`view of the ‘150 patent. See 35 U.S.C. § 103(a).
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`Ground 4. Claims 2 and 3 are unpatentable as obvious over Ross_GB, in
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`view of the ‘862 patent and the ‘150 patent. See 35 U.S.C. § 103(a).
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`Ground 5. Claims 1, 4, and 5 are unpatentable as anticipated by the ’496
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`publication. See 35 U.S.C. § 102(b).
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`THRESHOLD REQUIREMENT FOR INT ER PA R T ES REVIEW
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`A petition for inter partes review must demonstrate "a reasonable
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`likelihood that the petitioner would prevail with respect to at least one of the
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`claims challenged in the petition." 35 U.S.C. § 314(a). This Petition meets that
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`threshold. All of the elements of claims 1-5 of the '460 Patent are taught or
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`suggested in the prior art, as explained below in the proposed grounds of
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`unpatentability. The reasons to combine the cited references, where applicable,
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`are established under 35 U.S.C. § 103(a). This Petition is supported by the
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`Declaration of Dr. Park (Exhibit 1002).
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`Therefore, in accordance with 37 C.F.R. § 42.22, Petitioner respectfully
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`requests cancellation of claims 1-5 of the ’460 patent.
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`STATEMENT OF REASONS FOR RELIEF REQUESTED
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`6
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`U.S. Patent No. 8,835,460
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`I.
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`INTRODUCTION AND SUMMARY OF ARGUMENT
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`The ‘460 patent is directed to a sublingual liquid fentanyl formulation, a
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`multi-dose device for administering a sublingual liquid fentanyl formulation, and a
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`method of treating pain using the sublingual liquid fentanyl formulation. The
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`recited elements were well known in the art at the time of the invention and each
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`element of the claims is clearly taught by prior art references, alone and in
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`combination. Further the combination of references would have been obvious to a
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`person of ordinary skill in the art. No evidence or arguments of unexpected results
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`or advantages were advanced during the prosecution of the ‘460 patent.
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`Accordingly, the claims of the ‘460 patent are anticipated by or obvious over the
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`prior art.
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`The public has a significant interest in ensuring monopoly privileges are not
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`granted by an invalid patent particularly where, as here, Subsys® (the drug
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`corresponding to the ‘460 patent) can cost up to $300 per day per patient. 3 The
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`3 See e.g., Exhibit 1013, Fallon community Health Plan, Prior Authorization
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`Approval Criteria, Subsys (fentanyl sublingual spray), 3/14/2012; Exhibit 1014,
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`Subsys Manufacturing/Pricing – Good RX, 2015; and Exhibit 1015, Subsys
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`Manufacture/Pricing – Epocrates Online, 2015.
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`U.S. Patent No. 8,835,460
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`patent owner can attempt to secure such high prices through FDA regulatory
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`exclusivity but should not be allowed to extend these privileges with an obvious
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`‘460 patent.
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`II. THE ‘460 PATENT AND PROSECUTION HISTORY OF THE '460
`PATENT
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`A. The '460 Patent
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`The ‘460 patent is directed to sublingual fentanyl formulations, a multi-dose
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`device for administering a sublingual fentanyl formulation, and a method of
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`treating pain using the sublingual fentanyl formulation. The common feature of
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`the four independent claims is that each recites a fentanyl formulation comprising
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`discrete liquid droplets (claims 1, 2 and 3) or a multi-dose device capable of
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`delivering a fentanyl formulation in the form of liquid droplets (claim 4). The
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`discrete liquid droplets have a mean diameter of from about 30 to about 70 microns
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`in independent claims 1 and 4 and at least about 10 microns in independent claims
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`2 and 3. In addition, independent claims 2 and 3 recite specific amounts by weight
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`of fentanyl, ethanol and propylene glycol.
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`U.S. Patent No. 8,835,460
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`The sublingual formulation of the independent claims (except for claim 1)
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`contains three recited components: fentanyl4; ethanol; and propylene glycol.
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`Fentanyl is a μ-opioid receptor agonist with analgesic potency approximately 80-
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`100 times that of morphine. See ‘460 patent 1:13-14. (Exh. 1001). Ethanol and
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`propylene glycol are both identified as organic solvents which are used to enhance
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`the solubility of fentanyl. Id. at 11: 22-29. (Exh. 1001).
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`In the prior art, fentanyl is administered by way of a number of different
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`routes including oral, parenteral, buccal, transdermal Id. at 1:30-34. (Exh. 1001).
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`and intranasal. See. U.S. Patent No. 8,889,176 (the ‘176 patent) 2:10-16. (Exh.
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`1006). Orally administered fentanyl is subject to first pass effect metabolism,
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`which leaves 50% or more of the fentanyl unabsorbed. See the ‘460 patent 1:30-
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`31. (Exh. 1001).The other forms of administration avoid or decrease the first pass
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`effect for fentanyl. Id. at 1:32-34. (Exh. 1001).
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`Transdermal administration of fentanyl is reportedly not suitable for severe
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`pain or breakthrough pain. See. ‘176 patent 1:58-64. (Exh. 1006). Buccal
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`administration of fentanyl via transmucosal lozenge is reported to have relatively
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`slow absorption times. Id. at 1:58-64. (Exh. 1006). However, sublingual spray
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`4 The claims of the ‘460 patent recite various forms of fentanyl and fentanyl
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`derivatives, which are referred to as “fentanyl” unless otherwise noted.
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`U.S. Patent No. 8,835,460
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`administration of fentanyl that is free of propellant is reported to provide rapid
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`onset of therapeutic effect. See Ross_GB p. 3, ll. 29-33. (Exh. 1003) In addition,
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`oral transmucosal administration of fentanyl is reported as providing rapid onset of
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`effect in as low as 5 minutes after dosing.5
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`B.
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`The Prosecution History Of The '460 Patent
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`The ‘460 patent was filed on May