UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
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`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
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`
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`
`
`WATSON LABORATORIES, INC.,
`Petitioner,
`
`v.
`
`UNITED THERAPEUTICS, INC.,
`Patent Owner.
`
`
`
`
`
`
`
`
`
`
`
`
`
`Case No. IPR2017-01621
`Patent No. 9,358,240
`
`
`
`
`
`
`
`
`
`
`
`
`
`PETITIONER’S REQUEST FOR REHEARING UNDER 37 C.F.R. § 42.71
`
`
`
`Mail Stop PATENT BOARD
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`PO Box 1450
`Alexandria, Virginia 22313-1450
`Submitted Electronically via the Patent Review Processing System
`
`

`

`INTRODUCTION ........................................................................................... 1
`I.
`LEGAL STANDARDS ................................................................................... 2
`II.
`III. ARGUMENT ................................................................................................... 2
`A.
`The Board Erroneously Rejected Dr. Donovan’s Use of 2-3
`Seconds Per Breath In Her Calculations. .............................................. 5
`1.
`The Board improperly resolved a genuine issue of
`material fact against Petitioner.................................................... 5
`Even if patients with lung disease have a shorter
`inhalation time, the method disclosed in the prior art
`would have produced a dose in the claimed range. .................. 10
`The Board Legally Erred By Failing to Recognize that
`Overlapping Ranges Render the Claimed Dosage Range Prima
`Facie Obvious. ..................................................................................... 11
`IV. CONCLUSION .............................................................................................. 13
`
`
`
`2.
`
`B.
`
`TABLE OF CONTENTS
`
`Page
`
`
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`
`
`
`
`i
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`

`

`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Aker Biomarine v. Neptune Techs. & Bioresources, Inc.,
`IPR2014-00003, Paper 45 (PTAB May 16, 2014) ............................................... 2
`
`In re Applied Materials, Inc.,
`692 F.3d 1289 (Fed. Cir. 2012) .......................................................................... 12
`
`Commissariat a l’Energie Atomique et aux Energies Alternatives v.
`Silicon Genesis Corp.,
`IPR2016-00831, Paper 14 (PTAB Sep. 28, 2016) ............................................ 1, 4
`
`In re Geisler,
`116 F.3d 1465 (Fed. Cir. 1997) .......................................................................... 11
`
`General Elec. Co. v. United Techs. Corp.,
`IPR2016-01289, Paper 7 (PTAB Dec. 27, 2016) ............................................. 1, 4
`
`In re Harris,
`409 F.3d 1339 (Fed. Cir. 2005) ............................................................................ 1
`
`Johns Manville Corp. v. Knauf Insulation, Inc.,
`IPR2015-01402, Paper 18 (PTAB Oct. 21, 2015) ................................................ 1
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .......................................................................... 11
`
`In re Wertheim,
`541 F.2d 257, 191 USPQ 90 (CCPA 1976) ........................................................ 12
`
`Other Authorities
`
`37 C.F.R. § 42.51(b)(1)(iii) ........................................................................................ 8
`
`37 C.F.R. § 42.71(c) ............................................................................................... 1, 2
`
`37 C.F.R. § 42.71(d) .................................................................................................. 1
`
`37 C.F.R. § 42.108(c) ........................................................................................passim
`
`
`
`ii
`
`

`

`81 Fed. Reg. 18755 .................................................................................................... 5
`
`81 Fed. Reg. 18756 ................................................................................................ 6, 7
`
`MPEP § 2144.05(I) .................................................................................................. 12
`
`
`
`
`
`
`
`
`
`iii
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`

`

`PETITIONER’S EXHIBIT LIST
`
`1003
`
`1004
`
`1005
`
`1006
`1007
`1008
`1009
`
`Exhibit Description
`1001
`U.S. Patent No. 9,358,240
`1002
`Declaration of Maureen D. Donovan in Support of the Petition for
`Inter Partes Review of U.S. Patent No. 9,358,240
`Robert Voswinckel, et al. “Inhaled treprostinil sodium for the
`treatment of pulmonary hypertension” Abstract #1414, Circulation,
`110, 17, Supplement (Oct. 2004): III-295 (“Voswinckel”)
`U.S. Patent Application Publication No. 2004/0265238 A1 to Chaudry
`(“Chaudry”)
`Hossein Ardeschi Ghofrani, Robert Voswinckel, et al., “Neue
`Therapieoptionen in der Behandlung der pulmonalarteriellen
`Hypertonie,” Hertz, 30,4 (June 2005): 296-302 (“Ghofrani”)
`Opti-Neb-ir® Operating Instructions, Model ON-100/2 (2005)
`RESERVED
`Venta-Neb-ir® A-I-C-I Operating Instructions, Model VN-100/4
`Annexes to Commission Decision C(2005)3436 of 05 September
`2005, http://ec.europa.eu/health/documents/community-
`register/2005/2005090510259/anx_10259_en.pdf (Annex III –
`Ventavis® Labelling and Package Leaflet)
`U.S. Patent No. 6,606,989 (“Brand ’989”)
`Amendment and Reply Accompanying RCE filed in 12/591,200 (Jul.
`2, 2013) (with accompanying Declaration of Lewis Rubin, M.D.)
`WO 93/00951 to Patton
`Declaration of Scott Bennett, Ph.D.
`Affidavit of Christopher Butler, June 15, 2017
`Affidavit of Christopher Butler, June 16, 2017
`RESERVED
`RESERVED
`U.S. Patent No. 6,521,212 (“Cloutier ’212”)
`U.S. Patent No. 4,306,075 (“Aristoff ’075”)
`U.S. Patent No. 5,190,972 (“Dumble ’972”)
`European Patent Specification 0347243 B1, published January 13,
`1993
`U.S. Patent No. 6,261,539 (“Adjei ’539”)
`European Patent Application Publication No. EP 0372777 A2
`(“Purewal EP ’777”)
`U.S. Patent No. 4,895,719 (“Radhakrishnan ’719”)
`
`1010
`1011
`
`1012
`1013
`1014
`1015
`1016
`1017
`1018
`1019
`1020
`1021
`
`1022
`1023
`
`1024
`
`iv
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`
`
`
`
`

`

`1025
`1026
`1027
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`1028
`
`1029
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`1030
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`1031
`1032
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`1033
`
`1034
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`
`
`U.S. Patent No. 5,153,222 (“Tadepalli ’222”)
`U.S. Patent No. 6,357,671 (“Cewers ’671”)
`Gessler, et al., Ultrasonic versus Jet Nebulization of Iloprost in Severe
`Pulmonary Hypertension, Eur. Respiratory J., 17:14-19 (2001)
`Olschewski H., et al., Aerosolized Prostacyclin and Iloprost in Severe
`Pulmonary Hypertension, 1996 Ann. Intern. Med. 124(9), 820-824
`(1996) (“Olschewski 199”)
`Olschewski, et al., Pharmacodynamics and Pharmacokinetics of
`Inhaled Iloprost, Aerosolized by Three Different Devices, in Severe
`Pulmonary Hypertension, Chest J., 124(4), 1294-1304 (Oct. 2003)
`Byron, Drug Delivery Devices: Issues in Drug Development, Proc.
`Am. Thorac. Soc., 1:321-328 (2004)
`U.S. Patent No. 5,544,646 (“Lloyd”)
`Edwards D.A. et al., Recent Advances in Pulmonary Drug Delivery
`Using Large Porous Inhaled Particles, Journal of Applied Physiology,
`85(2): 379-385 (1998) (“Edwards 1998”)
`Badesch, et al., Prostanoid Therapy for Pulmonary Arterial
`Hypertension, J. of the Am. C. of Cardiology, 43(12):Suppl. S (2004)
`U.S. Patent No. 6,054,486 (“Crow ’486”)
`U.S. Food and Drug Administration, Drug Approval Package:
`Remodulin® (approved on May 21, 2002),
`http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-
`272_Remodulin.cfm (“Remodulin® Approval Package”)
`Electronic Medicines Compendium, Ventavis®,
`http://www.medicines.org.uk/emc/medicine/13743
`European Agency Approves Ventavis for Primary Pulmonary
`Hypertension, P&T Community (Sep. 22, 2003),
`https://www.ptcommunity.com/news/2003-09-22-000000/european-
`agency-approves-ventavis-primary-pulmonary-hypertension
`EU Community Register of Medicinal Products, Homepage,
`http://ec.europa.eu/health/documents/community-
`register/html/index_en.htm
`EMEA Scientific Discussion, Ventavis® (2004),
`http://www.ema.europa.edu/docs/en_GB/document_library/
`EPAR_Scientific_Discussion/human/000474/WC500048688.pdf
`Muller et al., “Use of Inhaled Iloprost in a Case of Pulmonary
`Hypertension during Pediatric Congenital Heart Surgery,” 99
`Anesthesiology 743-747 (2003)
`
`v
`
`

`

`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1047
`
`1048
`
`1049
`
`1050
`
`1051
`
`
`
`Mueller et al., “Inhaled Iloprost in the Management of Pulmonary
`Hypertension in Infants Undergoing Congenital Heart Surgery,”
`21 Eur. J. Anaesthesiology (suppl. 33) 2-36 (2004)
`Commission Decision C(2005)3436 of 05 September 2005,
`http://ec.europa.eu/health/documents/community-
`register/2005/2005090510259/dec_10259_en.pdf
`EU Community Register of Medicinal Products for Human Use,
`Ventavis, http://ec.europa.eu/health/documents/community-
`register/html/h255.htm#
`Summary of Community Decisions, Official Journal of the European
`Union (Oct. 28, 2005) http://eur-lex.europa.eu/legal-
`content/EN/TXT/?uri=uriserv:OJ.C_.2005.268.01.0002.01.ENG&toc=
`OJ:C:2005:268:TOC (noting a modification of marketing approval for
`Ventavis®)
`Electronic Medicines Compendium, Ventavis®,
`http://www.medicines.org.uk/emc/history/13743#version1 (noting a
`change to section 4.2 – Posology and Method of Administration on
`September 22, 2005)
`Voswinckel, R., et al., “Inhaled treprostinil is a potent pulmonary
`vasodilator in severe pulmonary hypertension,” 25 European Heart
`Journal 22, at 218 (2004) (“Voswinckel II”)
`Sulica, R and Poon, M. “Medical Therapeutics for Pulmonary Arterial
`Hypertension From Basic Science and Clinical Trial Design to
`Evidence-Based Medicine.” 3(2) Expert Rev. Cardiovas. Ther. 347-
`360 (2005)
`American Heart Association’s Scientific Sessions 2004 – Largest
`Cardiovascular Meeting Plans to ‘Jazz It Up’ in New Orleans, PR
`Newswire (Oct. 13 2004), http://www.prnewswire.com/news-
`releases/american-heart-associations-scientific-sessions-2004---
`largest-cardiovascular-meeting-plans-to-jazz-it-up-in-new-orleans-
`74293197.html#
`EU Community Register of Medicinal Products, Frequently Asked
`Questions, http://ec.europa.eu/health/documents/community-
`register/register_faq_2015.pdf
`Regulation (EC) No 726/2004 of the European Parliament and of the
`Council of 31 March 2004, http://eur-lex.europa.eu/LexUriServ/
`LexUriServ.do?uri=OJ:L:2004:136:0001:0033:en:PDF
`Register of Commission Documents, European Union,
`https://ec.europa.eu/transparency/regdoc/index.cfm?fuseaction=home
`
`vi
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`

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`1052
`
`1053
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`1054
`1055
`1056
`1057
`1058
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`1059
`1060
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`1061
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`1062
`
`1063
`1064
`1065
`1066
`1067
`1068
`1069
`1070
`1071
`1072
`1073
`1074
`1075
`1076
`1077
`
`
`
`Regulation (EC) No. 1049/2001 of the European Parliament and of the
`Council of 30 May 2001,
`http://www.europarl.europa.eu/RegData/PDF/r1049_en.pdf
`Register of the Commission Documents, European Commission,
`https://ec.europa.eu/transparency/regdoc/index.cfm?fuseaction=
`list&n=10&adv=0&coteId=&year=2005&number=
`3436&version=ALL&dateFrom=&dateTo=
`&serviceId=&documentType=&title=&titleLanguage=&titleSearch=
`EXACT&sortBy=NUMBER&sortOrder=DESC (search result for
`document search of Commission reference number ‘3436’ for year
`‘2005’)
`U.S. Patent No. 5,234,953 (“Crow ’953”)
`Declaration of DeForest McDuff, Ph.D.
`U.S. Patent No. 9,339,507
`U.S. Patent No. 6,756,033
`Amendment and Reply filed in 12/591,200 (May 23, 2012) (with
`accompanying Declaration of Lewis Rubin, M.D.)
`Reply in 12/,591,200 (Apr. 28, 2014)
`William F. Ganong, Review of Medical Physiology 591-92 (17th ed.
`1995)
`Actelion Pharmaceuticals, “Actelion Announces Full Year 2003
`Financial Results” (March 2, 2004)
`Actelion Pharmaceuticals, “Actelion Announces Full Year 2005
`Financial Results” (Feb. 23, 2006)
`Actelion Pharmaceuticals, Annual Report, 2002
`Actelion Pharmaceuticals, Annual Report, 2006
`Actelion Pharmaceuticals, Annual Report, 2007
`Actelion Pharmaceuticals, Annual Report, 2008
`Actelion Pharmaceuticals, Annual Report, 2010
`Actelion Pharmaceuticals, Annual Report, 2011
`Actelion Pharmaceuticals, Annual Report, 2012
`Actelion Pharmaceuticals, Annual Report, 2013
`Actelion Pharmaceuticals, Annual Report, 2014
`Actelion Pharmaceuticals, Annual Report, 2015
`Actelion Pharmaceuticals, Annual Report, 2016
`Adcirca, FDA Label, 5/2017
`Adempas, FDA Label, 10/2016
`Bayer, Annual Report, 2014
`Bayer, Annual Report, 2015
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`vii
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`

`

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`1079
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`1080
`1081
`1082
`1083
`1084
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`1085
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`1086
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`1087
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`1088
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`1089
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`1090
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`1091
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`1092
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`1093
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`
`
`Bayer, Annual Report, 2016
`Highest paid female CEO: Race to save my daughter, CNBC (May 19,
`2015), http://www.cnbc.com/2015/05/19/
`highestpaidfemaleceoracetosavemydaughter.html
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`Returns to New Drug Development: A Review of the Evidence,” in
`Patricia Danzen and Sean Nicholson, ed., The Oxford Handbook of the
`Economics of the Biopharmaceuticals Industry, New York: Oxford
`University Press
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`Approved Drug Products with Therapeutic Equivalance Evaluations
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`FDA Drug Details Website, Adcirca,
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`cSearch.process (accessed 5/17/2017)
`FDA Drug Details Website, Adempas,
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`cSearch.process (accessed 5/17/2017)
`FDA Drug Details Website, Flolan,
`https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=Basi
`cSearch.process (accessed 5/17/2017)
`FDA Drug Details Website, Letairis,
`https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=Basi
`cSearch.process (accessed 5/17/2017)
`FDA Drug Details Website, Opsumit,
`https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=Basi
`cSearch.process (accessed 5/17/2017)
`FDA Drug Details Website, Orenitram,
`https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=Basi
`cSearch.process (accessed 5/17/2017)
`FDA Drug Details Website, Remodulin,
`https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=Basi
`cSearch.process (accessed 5/17/2017)
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`viii
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`1094
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`1095
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`1096
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`1097
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`1098
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`1099
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`1100
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`1101
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`1106
`1107
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`cSearch.process (accessed 5/17/2017)
`FDA Drug Details Website, Uptravi,
`https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=Basi
`cSearch.process (accessed 5/17/2017)
`FDA Drug Details Website, Veletri,
`https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=Basi
`cSearch.process (accessed 5/17/2017)
`FDA Drug Details Website, Ventavis,
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`Flolan, FDA Label, 4/2015
`
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`Federal Reserve Website, Data Download, USD to EUR, 1999‐2016,
`Federal Reserve Website, Data Download, USD to GBP, 1998‐2016,
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`Gilead, Form 10‐K, 2010
`Gilead, Form 10‐K, 2011
`Gilead, Form 10‐K, 2012
`Gilead, Form 10‐K, 2013
`Gilead, Form 10‐K, 2014
`Gilead, Form 10‐K, 2015
`Gilead, Form 10‐K, 2016
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`GlaxoWellcome, Annual Report, 1997
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`ix
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`

`1113
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`
`x
`
`

`

`UTC, Form 10‐K, 2000
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`UTC, Form 10‐K, 2014
`UTC, Form 10‐K, 2015
`UTC, Form 10‐K, 2016
`
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`Ventavis, FDA Label, 11/2013
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`Substantive Submission filed in 12/591,200 (Nov. 9, 2015) (with
`accompanying Declaration of Dr. Roham T. Zamanian)
`Amendment and Reply filed in 12/591,200 (Feb. 2, 2016) (with
`accompanying Second Declaration of Dr. Roham T. Zamanian)
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`1156
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`1158
`1159
`1160
`1161
`1162
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`1163
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`1164
`1165
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`1166
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`1167
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`1168
`1169
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`
`
`xi
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`

`

`I.
`
`INTRODUCTION
`
`
`
`Watson Laboratories, Inc. (“Petitioner”) seeks rehearing under 37 C.F.R. §
`
`42.71(c) and (d) of the Board’s decision not to institute trial on Petitioner’s Ground
`
`2: that the ’240 patent claims would have been obvious over Voswinckel, Patton and
`
`OptiNeb®. In denying institution on Ground 2, the Board questioned the reliability
`
`of one of the inputs to the Petitioner’s dose calculation—inhalation time—which
`
`was based on the teaching of the prior art. Inst. Dec., 37. In denying institution, the
`
`Board failed to view a disputed issue of material fact—i.e., inhalation time—“in the
`
`light most favorable to the Petitioner,” as it was required to do at the institution stage.
`
`See 37 C.F.R. § 42.108(c); General Elec. Co. v. United Techs. Corp., IPR2016-
`
`01289, Paper 7 at 11 (PTAB Dec. 27, 2016) (instituting trial where the parties’
`
`experts disagreed, creating a genuine issue of material fact); Commissariat a
`
`l'Energie Atomique et aux Energies Alternatives v. Silicon Genesis Corp., IPR2016-
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`00831, Paper 14 at 12 (PTAB Sep. 28, 2016) (same).
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`Further, the Board ignored the well-settled rule that overlap between a prior
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`art range and a claimed range renders the claimed range prima facie obvious. See,
`
`e.g., In re Harris, 409 F.3d 1339, 1341 (Fed. Cir. 2005). And a prima facie case is
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`more than enough to show a reasonable likelihood of prevailing to warrant
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`institution. Johns Manville Corp. v. Knauf Insulation, Inc., IPR2015-01402, Paper
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`18 at 9 (PTAB Oct. 21, 2015) (“[O]bviousness under § 103(a) . . . is reasonably
`
`
`
`1
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`

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`likely established based on (1) the evidence cited and relied upon by Petitioner and
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`(2) long-established obviousness ‘range’ precedent of our reviewing court.”).
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`II. LEGAL STANDARDS
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`When rehearing is requested, the Board’s decision is reviewed for abuse of
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`discretion. 37 C.F.R. § 42.71(c). “An abuse of discretion may be determined if a
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`decision is based on an erroneous interpretation of law, if a factual finding is not
`
`supported by substantial evidence, or if the decision represents an unreasonable
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`judgment in weighing relevant factors.” Aker Biomarine v. Neptune Techs. &
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`Bioresources, Inc., IPR2014-00003, Paper 45 at 2-3 (PTAB May 16, 2014).
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`Although the Board may take into account testimonial evidence provided by
`
`the Patent Owner in deciding whether to institute trial, “a genuine issue of material
`
`fact created by such testimonial evidence will be viewed in the light most favorable
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`to the petitioner solely for purposes of deciding whether to institute an inter partes
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`review.” 37 C.F.R. § 42.108(c).
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`III. ARGUMENT
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`In Ground 2, Petitioner demonstrated that the challenged claims of the ’240
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`patent would have been obvious over Voswinckel in view of Patton and OptiNeb®.
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`As the Board recognized in instituting Ground 1, Voswinckel in combination with
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`Patton taught all limitations of the claimed method except for the dosage range: 15-
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`90 µg of inhaled treprostinil. Inst. Dec., 27 (“Based upon our review of the current
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`2
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`record, we discern no deficiency in Petitioner’s characterization of the cited
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`references and the knowledge in the art, or in Petitioner’s assertions as to the
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`reasonable inferences an ordinary artisan would make from those references.”).
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`As recognized by the Board, Voswinckel discloses the administration of a 600
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`µg/ml treprostinil solution in 3 single breaths, using a “pulsed OptiNeb® ultrasound
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`nebulizer.” Inst. Dec., 25; Ex. 1003, III-295 (emphasis added). In its Petition,
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`Petitioner explained that based on this disclosure in Voswinckel, a POSA would
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`have looked to the OptiNeb® user manual to understand the dose of treprostinil that
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`was delivered in the 3 single breaths described by Voswinckel. Pet., 37. Arriving at
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`the dose would have been a matter of simple arithmetic for a POSA based on: (1)
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`the (disclosed) concentration of treprostinil; (2) the (disclosed) number of breaths;
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`(3) the length of the breaths (where average respiratory rates were known in the prior
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`art); and (4) the nebulization rate of the nebulizer (which was also disclosed in the
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`prior art). Id.
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`From this information, the POSA would have calculated the dose disclosed
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`by the administration of 3 breaths of a 600 µg/ml treprostinil solution with an
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`Optineb® nebulizer in Voswinckel. Id. As the Board correctly recognized, the
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`calculations are:
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`
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`3
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`

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`(600 μg/ml) * (0.6 ml/min)1 = 360 μg/min
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`(360 μg/min) / (60 seconds/min) = 6 μg/second.
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`(6 μg/second) * (2-3 seconds/breath)2 = 12-18 μg/breath
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`(12-18 μg/breath) * (3 breaths) = 36-54 μg
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`Inst. Dec., 35 (citing Pet., 37), Pet., 37. Accordingly, Petitioner asserted that a POSA
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`would have arrived at a dose that overlaps the claimed range based on the
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`information disclosed in Voswinckel, combined with an average human respiratory
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`rate and the nebulization capabilities of the OptiNeb® device. Pet., 38
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`The Board’s denial of institution despite these calculations suffers from two
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`oversights. First, the Board incorrectly made a credibility determination as to one
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`of the inputs: an “inhalation length of 2–3 seconds.” Inst. Dec., 35-36. In so doing,
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`the Board failed to view a dispute of material fact over how a POSA would have
`
`understood the length of the breaths disclosed in Voswinckel “in the light most
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`favorable to the Petitioner.” Gen. Elec., IPR2016-01289, Paper 7 at 11;
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`Commissariat a l'Energie Atomique, IPR2016-00831, Paper 14 at 12. Second, the
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`Board failed to recognize that Petitioner’s calculations, which showed that “the
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`
`1 As discussed below, this is the maximum nebulization rate of the OptiNeb®
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`device, which was disclosed in the prior art.
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`2 As discussed below, this is an average respiratory rate disclosed in the prior art.
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`
`
`4
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`

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`POSA would have known that a dose of 36-54 μg of treprostinil could be delivered
`
`using the solution and number of breaths from Voswinckel with the maximum
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`capabilities of the OptiNeb device” (Pet., 38), rendered the claimed dosage range of
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`15-90 µg (and thus, the claim as a whole) prima facie obvious under governing law.
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`A. The Board Erroneously Rejected Dr. Donovan’s Use of 2-3
`Seconds Per Breath In Her Calculations.
`
`1. The Board improperly resolved a genuine issue of material
`fact against Petitioner.
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`Where a Patent Owner’s expert’s declaration submitted during preliminary
`
`proceedings creates a “genuine issue of material fact,” the dispute must be viewed
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`“in the light most favorable to Petitioner” at the institution stage. 37 C.F.R. §
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`42.108(c). The PTO promulgated this rule because the Petitioner does not have the
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`ability to cross-examine a Patent Owner’s declarant before the institution decision.
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`81 Fed. Reg. 18755. As the PTO recognized, “deciding disputed factual issues in
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`favor of the patent owner when a petitioner has not had the opportunity to cross-
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`examine patent owner’s declarant is inappropriate and contrary to the statutory
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`framework for AIA review.” Id. at 18756. Although Petitioner filed a reply on other
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`issues, there was no reason to address the breathing rate issue, which (at best)
`
`presented a factual dispute plainly covered by Rule 42.108(c). Nevertheless, the
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`Board did not apply Rule 42.108(c) to this issue and failed to view a dispute between
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`5
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`the experts over inhalation times in the light most favorable to Petitioner—instead
`
`crediting Dr. Dalby’s testimony over Dr. Donovan’s. This was error.
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`In the calculation set forth in its Petition, Petitioner utilized 2-3 seconds as the
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`inhalation of each of the three breaths disclosed in Voswinckel. Pet., 37. Petitioner
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`arrived at this input based on the declaration of its expert, Dr. Donovan, which
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`asserted that a POSA would understand that an average breathing rate would be 12-
`
`15 breaths a minute, which would result in the average inhalation time of 2-3 seconds
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`per breath. Pet., 37 (citing Ex. 1002, ¶174); Ex. 1002, ¶174 n. 184 (citing Ex. 1060).
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`Dr. Donovan based this metric on a prior art treatise. Id. In response, Patent
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`Owner’s expert, Dr. Dalby, argued that a different breathing rate should have been
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`used. Ex. 2001, ¶¶ 33-34.
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`The Board incorrectly resolved this disagreement in Patent Owner’s favor at
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`the institution stage. The Board, citing Dr. Dalby, noted that there was “a broader
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`range of breathing rate in the literature,” and concluded that “patients with lung
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`disease, like pulmonary hypertension, may have a shorter inhalation than healthy
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`‘normal’ humans.” Inst. Dec., 36. Of course, Petitioner is aware that “not every
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`factual contradiction rises to the level of a genuine issue of material fact.” 81 Fed.
`
`Reg. 18756. But Dr. Donovan did not rest on her mere say-so; she relied on the
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`literature to determine that a POSA would know that “a normal human breathes at
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`a rate of 12–15 times per minute.” Ex. 1002, ¶ 174 (citing Ex. 1060). Indeed, the
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`
`
`6
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`

`

`Board did not question Dr. Donovan’s conclusion that a rate of 12-15 breaths per
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`minute corresponds to one full “inhalation cycle” (inhalation and exhalation) every
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`4-5 seconds. Id.; Inst. Dec., 35. Nor did the Board doubt that a “normal human”
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`would take approximately half of this time to inhale. Ex. 1002, ¶ 174 (“Thus, a
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`patient may inhale from somewhere between 2-3 seconds.”).
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`Although Dr. Dalby cited literature suggesting that “some patients” with
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`“some lung diseases” may have less time to inhale than healthy subjects (Ex. 2003
`
`at 4 (emphasis added)), the speculative nature of his testimony (at best) creates a
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`disputed issue of fact. Under the Board’s rules, such a dispute must—out of
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`deference to the AIA and fairness to petitioners, see 81 Fed. Reg. 18756—be
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`resolved in favor of the Petitioner at the institution stage. 37 C.F.R. § 42.108(c).
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`The Board was led astray when it concluded that there was “evidence of a
`
`broader range of breathing rate in the literature.” Inst. Dec., 36. This underscores
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`the rationale for the amendments to § 42.108(c) made when patent owners were
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`permitted to introduce new testimony before institution of trial. Patent Owner’s
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`presentation of alternative breathing rates could not have been anticipated given
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`Patent Owner’s contrary arguments to get this patent in the first place.
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`Petitioner came forward with evidence of normal respiratory rates known to a
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`POSA. Pet., 37 (citing Ex. 1002, ¶174); Ex. 1002, ¶174 n. 184 (citing Ex. 1060). Dr.
`
`Donovan cited a passage from the 17th edition of a well-respected treatise (“Ganong
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`
`
`7
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`

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`17th ed.”), which states: “At rest, a normal human breathes 12-15 times a minute.”
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`Ex. 1060 at 591. In response, Patent Owner and its expert, Dr. Dalby, accused Dr.
`
`Donovan of “cherry-pick[ing]” the breathing rate from Ganong 17th ed. and asserted
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`that a later edition of Ganong (“Ganong 23rd ed.”) (Ex. 2006 at 34) disclosed a “range
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`of 10-30 breaths per minute.” POPR at 35-36; Ex. 2001 at ¶ 33. Patent Owner
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`further criticized Dr. Donovan for not “distinguish[ing]” between the two editions
`
`of the Ganong reference. Id. In denying institution on Ground 2, the Board agreed
`
`with Patent Owner, crediting Patent Owner’s argument that Dr. Donovan “cherry
`
`picked” her breathing rate from Ganong 17th ed. and “ignor[ed]” Ganong 23rd ed.
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`Inst. Dec., 36.
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`Not only did the Board fail to weigh the evidence in the light most favorable
`
`to Petitioner, it reached its conclusion based on Patent Owner’s characterization of
`
`the Ganong references. Indeed, if anyone, it was Patent Owner that “cherry picked”
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`numbers out of the Ganong reference in an attempt to undermine Dr. Donovan. The
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`table in Ganong 23rd ed. relied on by Patent Owner did not purport to report an
`
`average or normal breathing rate but rather simply a rate of “rapid shallow
`
`breathing.” Ex. 2006 at 34. Remarkably, an earlier page from the same chapter of
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`Ganong 23rd ed., which Patent Owner failed to provide to the Board or Petitioner
`
`despite the Board’s rules requiring such disclosure, see 37 C.F.R. § 42.51(b)(1)(iii),
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`included the exact same passage relied on by Dr. Donovan from Ganong 17th ed.
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`
`
`8
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`

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`that: “At rest, a normal human breathes 12 to 15 times a minute.” Ex. 1169 at 5. In
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`short, Patent Owner’s attacks on Dr. Donovan’s reliance on Ganong 17th ed. were
`
`unfounded. At a minimum the Board improperly resolved them against Petitioner.
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`Patent Owner’s challenge to Dr. Donovan’s use of 12-15 breaths per minute
`
`is even more surprising considering that its own cited literature confirms that Dr.
`
`Donovan was correct: the “normal breathing rate in adults is around 15 breaths per
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`minute.” Ex. 2003 at 4. Even more inexplicable, during prosecution of the ’240
`
`patent, Patent Owner itself agreed: “a normal respiratory rate for an adult human at
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`rest is 10-14 breaths per minute.” Ex. 1168 at 9. Patent owner made this claim in
`
`order to distinguish prior art from an earlier set of claims, which required 10 or fewer
`
`breaths per dosing event. Id. Thus, Patent Owner used “normal respiratory rates”
`
`to distinguish over prior art during prosecution to try to obtain these claims, but now
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`has argued that Petitioner’s “reliance on the breathing rate of ‘normal humans’” is
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`somehow unreliable. Inst. Dec. at 35-36; POPR, 49-50. Patent Owner’s creation of
`
`a fact dispute is flatly contrary to its prior position before the Office and should be
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`resolved on a complete record after institution.
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`Indeed, the policy considerations behi