Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`LIQUIDIA TECHNOLOGIES, INC.,
`Petitioner
`
`v.
`
`UNITED THERAPEUTICS CORPORATION,
`Patent Owner
`
`
`
`
`IPR2021-00406
`U.S. Patent No. 10,716,793 B2
`
`
`
`REPLY DECLARATION OF NICHOLAS HILL, M.D.
`
`
`
`Liquidia's Exhibit 1106
`
`

`

`
`INTRODUCTION .......................................................................................... 1 
`I.
`II. QUALIFICATIONS ....................................................................................... 2 
`A. Qualifications and Experience ............................................................. 2 
`B. Materials Considered ............................................................................ 3 
`III. PERSON OF ORDINARY SKILL IN THE ART ......................................... 8 
`IV. STATEMENT OF LEGAL PRINCIPLES ..................................................... 8 
`V.
`THE ’793 PATENT ........................................................................................ 9 
`VI. APPLICATION OF THE PRIOR ART TO THE CLAIMS ........................ 11 
`A.
`Public Availability of Prior Art: A POSA in May 2006 Would
`Have Found and Relied upon Voswinckel JAHA and
`Voswinckel JESC ............................................................................... 12 
`
`Voswinckel JAHA ................................................................... 12 
`
`Voswinckel JESC ..................................................................... 19 
`B. Ground 1: Claims 1-8 Are Obvious Over the ’212 Patent in
`View of Voswinckel JAHA and Voswinckel JESC ........................... 26 
`
`Dr. Waxman’s Isolated Critique of the ’212 Patent Fails
`to Rebut My Obviousness Opinions ........................................ 39 
`Dr. Waxman’s Isolated Critique of Voswinckel JESC
`Fails to Rebut My Obviousness Opinions ............................... 51 
`Dr. Waxman’s Isolated Critique of Voswinckel JAHA
`Fails to Rebut My Obviousness Opinions ............................... 56 
`Dr. Waxman Never Considers the Combination of the
`Prior Art Disclosures ................................................................ 58 
`C. Ground 2: Claims 1-8 Are Obvious Over the ’212 Patent and
`Voswinckel JESC ............................................................................... 66 
`D. Grounds 3-6: Dr. Waxman Provides No Opinions Regarding
`Invalidity Based on Ghofrani and/or Voswinckel 2006 ..................... 68 
`Dr. McConville Like Dr. Waxman Fails to Rebut My
`Obviousness Opinions ........................................................................ 69 
`
`E.
`
`
`
`
`
`
`
`TABLE OF CONTENTS
`
`
`Page
`
`- i -
`
`Liquidia's Exhibit 1106
`Page i
`
`

`

`VII. SECONDARY CONSIDERATIONS DO NOT SUPPORT THE
`NON-OBVIOUSNESS OF CLAIMS 1-8 .................................................... 76 
`VIII. CONCLUSION ............................................................................................. 85 
`
`- ii -
`
`Liquidia's Exhibit 1106
`Page ii
`
`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`I, Nicholas Hill, M.D., declare as follows:
`
`I.
`
`INTRODUCTION
`
`I am over the age of eighteen and otherwise competent to make this
`
`declaration.
`
`
`
`Counsel for Liquidia Technologies, Inc. (“Liquidia” or “Petitioner”)
`
`retained me to offer technical opinions with respect to U.S. Patent No. 10,716,793
`
`(“the ’793 Patent”) and the prior art references cited in the inter partes review (IPR)
`
`proceedings for the ’793 Patent, Ex. 1001.
`
`
`
`I am being compensated for my time in connection with this IPR at my
`
`standard consulting rate of $550 per hour for review of materials and report
`
`preparation, and $650 per hour for any time I might spend testifying. For any weekend
`
`review and report preparation, I will be paid $600 per hour, and I will be paid $750
`
`per hour for any time spent testifying on a weekend. My compensation does not
`
`depend on the outcome of, or the content of my testimony in, the current IPR.1
`
`
`
`I incorporate by reference the opinions set forth in my First Declaration
`
`
`1 Any allegation by UTC that I am being “paid by Liquidia to say the opposite” of
`what I believe or to provide testimony is baseless. See Patent Owner Response at 35.
`As Dr. Waxman explained, I am “well regarded” within the field of pulmonary
`hypertension. Ex. 1108 at 141:3-5. Additionally, I am currently working on clinical
`trials sponsored by UTC. UTC’s arguments regarding the non-obviousness of the
`’793 Patent claims, however, lack merit, so UTC instead stoops to denigration.
`
` 1
`
`
`
`Liquidia's Exhibit 1106
`Page 1
`
`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`submitted as Ex. 1002 on January 7, 2021 (“Hill First Decl.”), as well as the exhibits
`
`cited therein.
`
`
`
`I have assessed the ’793 Patent. In doing so, I have considered the
`
`teachings of the scientific literature before May 15, 2006, in light of general
`
`knowledge in the art before that date.
`
`
`
`Counsel informs me that the Patent Trial and Appeal Board (“the Board”)
`
`has instituted inter partes review of the ’793 Patent based on the petition submitted
`
`by Liquidia. Since IPR institution, I understand that United Therapeutics Corporation
`
`(“UTC”) has filed a Patent Owner Response as well as declarations from Dr. Aaron
`
`Waxman, Dr. Jason McConville, and Ms. Pilar Wyman in support thereof.
`
`
`
`This declaration presents my additional expert opinions considering
`
`UTC’s Patent Owner Response and Supporting Declarations of Dr. Waxman, Dr.
`
`McConville, and Ms. Wyman, that Claims 1-8 of the ’793 Patent would have been
`
`obvious to a person of ordinary skill in the art (“POSA”) before May 15, 2006.
`
`II. QUALIFICATIONS
`A. Qualifications and Experience
`
`I summarized my background, qualifications, and experience relevant to
`
`the issues raised in the present IPR in Exhibit 1002, which I incorporate by reference.
`
`As part of my first declaration, I also provided a copy of my curriculum vitae, which
`
`includes a full description of my background and qualifications as Exhibit 1003. The
`
` 2
`
`
`
`Liquidia's Exhibit 1106
`Page 2
`
`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`CV I provided as Exhibit 1003 complied with Tufts guidelines and followed the Tufts
`
`template for CVs. See Ex. 2055 (Hill Depo. Tr.) at 17:14-18:7.
`
`B. Materials Considered
`
`The analysis that I provide in this Declaration is based on my education,
`
`research, and experience, as well as my investigation and study of relevant materials,
`
`including the ’793 Patent. I have reviewed Patent Owner Response, the supporting
`
`Declarations of Dr. Waxman in support of the POPR and POR (Exs. 2001, 2052), Dr.
`
`McConville (Ex. 2053), and Ms. Wyman (Ex. 2041), and the deposition testimony of
`
`Dr. Waxman (Ex. 1108), Dr. McConville (Ex. 1109), and Ms. Wyman (Ex. 1110). In
`
`addition to these materials, I have reviewed and considered additional documents that
`
`are cited in this declaration and listed in the table below. To the extent I am provided
`
`additional documents or information, I may offer further opinions.
`
`Exhibi
`Description of Document
`t No.
`1001 U.S. Patent No. 10,716,793 B2 to Olschewski, et al. (“’793 patent”)
`1002 Declaration of Dr. Nicholas Hill, M.D., dated January 7, 2021 (“First
`Declaration”)
`1003 Curriculum Vitae of Dr. Nicholas Hill
`1004 Declaration of Dr. Igor Gonda (“Gonda Decl.”)
`1006 U.S. Patent No. 6,521,212 B1 to Cloutier, et al. (“’212 patent”)
`1007 Voswinckel, R., et al., Abstract 218: “Inhaled treprostinil is a potent
`pulmonary vasodilator in severe pulmonary hypertension,” European
`Heart Journal 25:22 (2004) (“Voswinckel JESC”)
`
` 3
`
`
`
`Liquidia's Exhibit 1106
`Page 3
`
`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`
`1008 Robert Voswinckel, Beate Enke, Andre Kreckel, Frank Reichenberger,
`Stefanie Krick, Henning Gall, Tobias Gessier, Thomas Schmehl, Markus
`G. Kohstall, Friedrich Grimminger, Hossein A. Ghofrani, Werner Seeger,
`and Horst Olschewski, Abstract 1414: “Inhaled Treprostinil Sodium
`(TRE) For the Treatment of Pulmonary Hypertension,” Abstracts from the
`2004 Scientific Sessions of the American Heart Association, Circulation,
`110(17 Suppl.):III-295 (October 26, 2004) (“Voswinckel JAHA”)
`1009 Robert Voswinckel, Hossein A. Ghofrani, Friedrich Grimminger, and
`Werner Seeger, “Clinical Observations” on “Inhaled Treprostinil for
`Treatment of Chronic Pulmonary Arterial Hypertension,” “Letters”
`Section of the Annals of Internal Medicine, 144(2):149-50 (January 2006)
`(“Voswinckel 2006”)
`1010 Hossein Ardeschir Ghofrani, Robert Voswinckel, et al., Neue
`Therapieoptionen in der Behandlung der pulmonalarteriellen Hypertonie,
`30(4) HERZ, 30(4):296–302 (June 2005) (“Ghofrani”) (Foreign article
`and English translation attached)
`1018 Remodulin® 2004 Label
`1019 Stein, S.W., et al., “The History of Therapeutic Aerosols: A
`Chronological Review,” Journal of Aerosol Medicine and Pulmonary
`Drug Delivery, 30(1):20-41 (2017) (“Stein”)
`1020 Clark, A.R., “Medical Aerosol Inhalers: Past, Present, and Future,”
`Aerosol Science and Technology, 22:374-91 (1995) (“Clark”)
`1022 Walmrath, D., et al., “Direct Comparison of Inhaled Nitric Oxide and
`Aerosolized Prostacyclin in Acute Respiratory Distress Syndrome,”
`American Journal of Respiratory Critical Care Medicine, 153:991-96
`(1996) (“Walmrath 1996”)
`1023 Olschewski, H., et al., “Inhaled Prostacyclin and Iloprost in Severe
`Pulmonary Hypertension Secondary to Lung Fibrosis,” American Journal
`of Respiratory Critical Care Medicine, 160:600-07 (1999) (“Olschewski
`1999”)
`1025 De Wet, C.J., et al., “Inhaled prostacyclin is safe, effective, and affordable
`in patients with pulmonary hypertension, right heart dysfunction, and
`refractory hypoxemia after cardiothoracic surgery,” Journal of Thoracic
`and Cardiovascular Surgery, 127:1058-67 (2004) (“De Wet”)
`
` 4
`
`
`
`Liquidia's Exhibit 1106
`Page 4
`
`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`
`1028 U.S. Patent Application Publication No. US 2004/0265238 A1 to Chaudry
`(“Chaudry”)
`1029 Ventavis® Label 2004
`1030 Newman, S.P., “Aerosols”, Chapter from Encyclopedia of Respiratory
`Medicine pp. 58-64 (2006) (“Newman”)
`1031 Geller, D.E., “Comparing Clinical Features of the Nebulizer, Metered-
`Dose Inhaler, and Dry Powder Inhaler,” Respiratory Care, 50(10):1313-
`21 (2005) (“Geller 2005”)
`1032 Bender, B., et al., “Nonadherence in asthmatic patients: is there a solution
`to the problem?” Annals of Allergy, Asthma & Immunology, 79:177-86
`(1997) (“Bender 1997”)
`1034 Geller, D., et al., “Bolus Inhalation of rhDNase with the AERx System in
`Subjects with Cystic Fibrosis,” Journal of Aerosol Medicine, 16(2):175-
`82 (2003) (“Geller 2003”)
`1035 Chattaraj, S.C., “Treprostinil sodium Pharmacia,” Current Opinion in
`Investigational Drugs, 3(4):582-86 (Apr. 2002), available at
`https://pubmed.ncbi.nlm.nih.gov/12090728/ (“Chattaraj”)
`1037 English translation of OptiNeb® User Manual 2005
`1043 2009 Tyvaso® Label, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022387s015l
`bl.pdf
`1046 U.S. Patent No. 9,358,240 to Olschewski, et al. (“’240 Patent”)
`1047 Hoeper, M.M., et al., “Long-Term Treatment of Primary Pulmonary
`Hypertension with Aerosolized Iloprost, a Prostacyclin Analogue,” N
`Engl J Med, 342:1866-70 (2000) (“Hoeper”)
`1048 Walmrath, D., et al., “Aerosolised prostacyclin in adult respiratory
`distress syndrome,” Lancet, 342:961-62 (1993) (“Walmrath 1993”)
`1059 Nauser, T.D., “Pulmonary Hypertension: New Perspectives,” CHF,
`9:155-62 (2003) (“Nauser 2003”)
`1065 Olschewski, H., et al., “Inhaled Iloprost for Several Pulmonary
`Hypertension,” N Engl J Med, 347(5):322-29 (2002) (“Olschewski 2002”)
`
` 5
`
`
`
`Liquidia's Exhibit 1106
`Page 5
`
`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`
`1068 Vachiéry, J.-L., et al., “Transitioning From IV Epoprostenol to
`Subcutaneous Treprostinil in Pulmonary Arterial Hypertension,” CHEST,
`121:1561-65 (2002) (“Vachiéry 2002”)
`1077 Boyle, M.P., “So Many Drugs, So Little Time. The Future Challenge of
`Cystic Fibrosis Care,” CHEST, 123(1):3-5 (2003) (“Boyle 2003”)
`1078 Azmacort® Label 2003
`1079 Hill, N.S., et al., “Inhaled Therapies for Pulmonary Hypertension,”
`Respiratory Care, 60(6):794-805 (2015) (“Hill 2015”)
`1087 Butler Affidavit
`1088 Tyvaso® 2021 Label
`1089 Voswinckel JESC, UWash
`1090 Voswinckel JESC, UWisc
`1091 Voswinckel JESC, British Library
`1092 Voswinckel JESC, Additional Pages
`1093 Voswinckel JAHA, British Library
`1094 Voswinckel JAHA, Library of Congress
`1095 Voswinckel JAHA, Stanford
`1096 Voswinckel JAHA, UC Davis
`1104 Roxana Sulica and Michael Poon, “Medical Therapeutics for Pulmonary
`Arterial Hypertension: From Basic Science and Clinical Trial Design to
`Evidence Based Medicine, EXPERT REV. CARDIOVASCULAR
`THERAPY 3(2):347-360, at 359 (2005) (“Sulica 2005”)
`1105 European Society of Cardiology® Annual Report 2005
`1108 Transcript from the January 8, 2022 Deposition of Aaron Waxman, M.D.,
`Ph.D., Liquida Technologies, Inc. v. United Therapeutics Corp., IPR2021-
`00406 (“Waxman Depo. Tr.”)
`1109 Transcript from the January 11, 2022 Deposition of Jason McConville,
`Liquida Technologies, Inc. v. United Therapeutics Corp., IPR2021-00406
`(“McConville Depo. Tr.”)
`
` 6
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`Liquidia's Exhibit 1106
`Page 6
`
`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`
`1110 Transcript from the December 29, 2021 Deposition of Lyndsey Pilar
`Wyman, Liquida Technologies, Inc. v. United Therapeutics Corp., IPR2021-
`00406 (“Wyman Depo. Tr.”)
`1113 Voswinckel JAHA Supplemental Author Index
`1132 Transcript from the January 15, 2022 deposition of Aaron B. Waxman,
`M.D., Ph.D., United Therapeutics Corp. v. Liquidia Technologies, Inc., Case
`No. 1:20-cv-00755 (D. Del.) (“Waxman District Court Depo. Tr.”)
`2001 Declaration of Dr. Aaron Waxman dated May 17, 2021 (“Waxman POPR
`Decl.”)
`2029 Hess et al., 2007, A guide to aerosol delivery devices for respiratory
`therapists. American Association for Respiratory Care
`2030 Dennis JH, 2002, Standardization issues: in vitro assessment of nebulizer
`performance. Respir. Care. 47(12):1455-1458
`2031 Hess et al., 1996, Medication nebulizer performance. Effects of diluent
`volume, nebulizer flow, and nebulizer brand. Chest, 110(2):498-505
`2035 Bourge et al., Cardiovascular Therapeutics, 31:38-44 (2013)
`2036 McLaughlin et al., Efficacy and safety of treprostinil: an epoprostenol
`analog for primary pulmonary hypertension, J. Cardiovascular
`Pharmacology, 41:293-299 (2003)
`2041 Declaration of Ms. Pilar Wyman (“Wyman Decl.”)
`2052 Second Declaration of Dr. Aaron Waxman (“Waxman Decl.”)
`2053 Declaration of Dr. Jason McConville (“McConville Decl.”)
`2055 Deposition of Dr. Nicholas Hill (“Hill Depo. Tr.”)
`2060 Waxman et al., Inhaled Treprostinil in Pulmonary Hypertension Due to
`Interstitial Lung Disease, N. Eng. J. Med. 384:325-334 (2021)
`2085 Roscigno et al., Comparative bioavailability of inhaled
`treprostinil administered as LIQ861 and Tyvaso® in healthy
`subjects, Vascular Pharmacology 138:106840 (2021) (“Roscigno 2021”)
`
`
`
` 7
`
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`
`Liquidia's Exhibit 1106
`Page 7
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`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`III. PERSON OF ORDINARY SKILL IN THE ART
` My First Declaration detailed my definition of a person of ordinary skill
`
`in the art (“POSA”). I incorporate that definition as if fully set forth herein.
`
`
`
`I understand that Dr. Waxman states that, with respect to the ’793 Patent,
`
`a POSA “would have an M.D. or a graduate degree (Masters or Ph.D.) in a field
`
`relating to drug development and at least two years of practical experience in either
`
`(i) the investigation or treatment of pulmonary hypertension or (ii) the development
`
`of potential drug candidates, specifically in the delivery of drugs by inhalation.” Ex.
`
`2052 (Waxman Decl.) at ¶ 15; see also Ex. 2053 (McConville Decl.) at ¶ 30. I note
`
`that I would have qualified as a POSA by May 15, 2006 under the definition provided
`
`by Dr. Waxman. I further note that Dr. McConville states that “[t]he standards
`
`proposed by Drs. Hill and Gonda and Dr. Waxman are not radically different.” Ex.
`
`2053, ¶ 31. For purposes of this declaration, I continue to apply my definition of a
`
`POSA, but my opinions would not change if I were to apply the definition provided
`
`by Dr. Waxman.
`
`IV. STATEMENT OF LEGAL PRINCIPLES
`
`I am not an attorney and do not provide any opinions regarding the law.
`
`However, I have been informed of certain legal principles relating to the issues I
`
`discuss. I specifically incorporate by reference the legal principles, including for
`
`anticipation and obviousness, set forth in my First Declaration. Ex. 1002, §§ IV.B-C.
`
` 8
`
`
`
`Liquidia's Exhibit 1106
`Page 8
`
`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`
` Due to apparent errors in Dr. Waxman’s application of the obviousness
`
`legal standard (see ¶ 37 below; see also §§ VI.B.2-3 below), I reiterate my
`
`understanding that “a POSA can combine various prior art references based on the
`
`teachings of those references, the general knowledge present in the art, or common
`
`sense.” Ex. 1002 (Hill First Decl.) at ¶ 26. Further, “one may take into account the
`
`inferences and creative steps that a person of ordinary skill in the art would employ to
`
`combine the known elements in the prior art in the manner claimed by the patent at
`
`issue.” Id.
`
` My First Declaration further set forth the legal standard for secondary
`
`considerations of non-obviousness. Ex. 1002, ¶ 25. There, I noted my understanding
`
`that secondary considerations should be connected, or have a “nexus,” with the
`
`invention claimed in the patent at issue. Id. For example, I understand that a nexus
`
`must exist between the specific evidence of long-felt but unmet need and the invention
`
`as claimed. Likewise, evidence of unexpected results must establish that there is a
`
`difference between the claimed results and the closest prior art, and that the difference
`
`would not have been expected by a POSA at the time of the invention.
`
`V. THE ’793 PATENT
` My First Declaration submitted in this IPR proceeding summarizes the
`
`’793 Patent. See Ex. 1002, § IV. I incorporate that section of Exhibit 1002 as if fully
`
` 9
`
`
`
`set forth herein.
`
`Liquidia's Exhibit 1106
`Page 9
`
`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`
`
`
`It is still my opinion that the following claims of the ’793 Patent were
`
`either directly disclosed/anticipated in the prior art or would have been obvious to a
`
`skilled artisan by May 15, 2006:
`
`1[d]
`2
`
`Claim Limitation
`
`1[a] A method of treating pulmonary hypertension comprising
`administering by inhalation to a human suffering from pulmonary
`hypertension a therapeutically effective single event dose of a
`formulation comprising treprostinil or a pharmaceutically acceptable
`salt thereof
`1[b] with an inhalation device, 
`1[c] wherein the therapeutically effective single event dose comprises from
`15 micrograms to 90 micrograms of treprostinil or a pharmaceutically
`acceptable salt thereof 
`delivered in 1 to 3 breaths. 
`The method of claim 1, wherein the inhalation device is a soft mist
`inhaler.
`The method of claim 1, wherein the inhalation device is a pulsed
`ultrasonic nebulizer.
`The method of claim 1, wherein the inhalation device is a dry powder
`inhaler.
`The method of claim 1, wherein the inhalation device is a pressurized
`metered dose inhaler.
`The method of claim 4, wherein the formulation is a powder.
`The method of claim 6, wherein the powder comprises particles less
`than 5 micrometers in diameter.
`The method of claim 1, wherein the formulation contains no
`metacresol.
`
`3
`
`4
`
`5
`
`6
`7
`
`8
`
`
`10
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`Liquidia's Exhibit 1106
`Page 10
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`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`VI. APPLICATION OF THE PRIOR ART TO THE CLAIMS
`
`In my opinion, the limitations of claims are disclosed by the following
`
`combination of prior art references:
`
`Ground
`1
`
`2
`
`3
`4
`
`5
`6
`
`References
`Obvious over the combination of the ’212 Patent,
`Voswinckel JAHA, and Voswinckel JESC
`Obvious over the combination of the ’212 Patent
`and Voswinckel JESC
`Anticipated by Ghofrani
`Obvious over the combination of Voswinckel
`JAHA and Ghofrani
`Anticipated by Voswinckel 2006
`Obvious over the combination of Voswinckel
`2006 and the ’212 Patent
` My First Declaration provided detailed opinions, which I incorporate by
`
`Claim(s)
`1-8
`
`1-8
`
`1
`1, 3, 8
`
`1, 3
`2, 4-8
`
`reference, regarding the invalidity of Claims 1-8 of the ’793 Patent in light of the prior
`
`art. See Ex. 1002, § V.
`
` Here, I reply to the specific arguments set forth in the Declarations of Dr.
`
`Waxman, Dr. McConville, and Ms. Wyman. As explained below, their arguments
`
`fail to rebut my opinions demonstrating Claims 1-8 are obvious and/or anticipated by
`
`the prior art.
`
`
`11
`
`Liquidia's Exhibit 1106
`Page 11
`
`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`
`A.
`
`Public Availability of Prior Art: A POSA in May 2006 Would Have
`Found and Relied upon Voswinckel JAHA and Voswinckel JESC
`
`Voswinckel JAHA
` As an initial matter, I understand that Ms. Wyman opines and UTC
`
`argues that neither Voswinckel JAHA nor Voswinckel JESC were “disseminated in
`
`any predictable way such as to be accessible more than one year before the May 15,
`
`2006 priority date . . . .” Ex. 2041 (Wyman Decl.) at ¶¶ 9, 29; see also Ex. 2052
`
`(Waxman Decl.) at ¶ 75 n.9 (explaining “I understand that Patent Owner has asserted
`
`that Petitioner has not set forth sufficient evidence to show that Voswinckel JESC and
`
`Voswinckel JAHA were publicly accessible prior art”). For the reasons set forth
`
`below, I disagree.
`
` Voswinckel JAHA is an abstract published in 2004 in the Supplement to
`
`volume 110, issue 17 of the journal Circulation.2 Ex. 1008 (Voswinckel JAHA). As
`
`indicated by the Supplement in which Voswinckel JAHA appears and Ms. Wyman’s
`
`Declaration, “the title of the Supplement, Abstracts from Scientific Sessions 2004,
`
`suggests the Supplement was released in relation to the Scientific Sessions 2004
`
`Conference in November 2004.” Ex. 2041 (Wyman Decl.) at ¶ 11; Ex. 1008
`
`
`2 In my experience, a supplement is published in addition to the articles included in
`the main issue of a journal and may contain, for example, a copy of the meeting
`program or abstracts from a conference. The supplement to volume 110, issue 17 of
`Circulation (“JAHA Supplement”), for example, contains abstracts from the 2004
`conference Scientific Sessions, a conference of the American Heart Association.
`
`12
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`Liquidia's Exhibit 1106
`Page 12
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`

`

`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`(Voswinckel JAHA) at 1. Scientific Sessions is a regular conference of the American
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`Heart Association (AHA) attended by physicians and researchers working on and
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`studying the cardiovascular system, including pulmonary circulation.
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`In my experience, a POSA in 2004 would have attended the Scientific
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`Sessions 2004 Conference, as it is one of the principal conferences on the circulatory
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`system and diseases and conditions affecting circulation, including pulmonary
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`hypertension.3 As well, in my experience, abstracts from the meeting are published
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`in meeting programs or abstract books in advance of the meeting, and are at least
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`available on the first day of the meeting, if not before. A person attending the meeting
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`can thus use the meeting program to determine which researchers and clinicians are
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`presenting at the meeting as well as the subject matter on which the clinicians or
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`researchers are presenting. These meeting programs, or at least the abstracts from the
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`meeting programs, are also published as journal supplements. A POSA attending the
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`Scientific Sessions 2004 Conference would have been interested in presentations on
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`treatments for pulmonary hypertension, including pulmonary arterial hypertension,
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`and contrary to Ms. Wyman’s opinions, would have been able to identify the abstracts
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`3 Dr. Waxman agrees that attendance at the conference would have been large. See
`Ex. 1108 (Waxman Depo. Tr.) at 116:4-21 (explaining he expects attendance at the
`AHA Scientific Sessions conference would have been bigger than the ESC conference
`which had over 18,000 professionals in attendance).
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`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`disclosing such treatments, including Voswinckel JAHA. See Ex. 2041 (Wyman
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`Decl.) at ¶ 25 (stating without evidence that “a POSA conducting diligent research
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`would not sift through such voluminous results”). The meeting programs and
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`supplements are provided for just this purpose, and I myself use such meeting
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`programs and supplements to identify abstracts on subject matter of interest.
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` Dr. Waxman agrees with me. He, too, expects that the abstract books for
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`the Scientific Sessions 2004 Conference would have been provided to conference
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`registrants and people who subscribe to Circulation prior to the conference, and
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`further that a copy of the abstract book would have at least been made available at the
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`time of the meeting. See Ex. 1108 (Waxman Depo. Tr.) at 108:3-20 (answering “yes”
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`when asked if the Scientific Sessions 2004 abstract book would have been provided
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`to registrants and Circulation subscribers as well as provided at the meeting to late
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`registrants). Dr. Waxman further agrees with me that a conference attendee, which in
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`my opinion would include POSA physicians and researchers, would have been able
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`to find Voswinckel JAHA within the Circulation supplement. Id. at 111:11-19
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`(explaining “[h]ad they been in possession of the supplement, yes” a conference
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`attendee would have been able to identify Abstract 1414 within the supplement). His
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`testimony thus contradicts Ms. Wyman’s opinion “that a POSA exercising reasonable
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`diligence could [not] have located the Voswinckel JAHA abstract before May 15,
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`2006.” Ex. 2041 (Wyman Decl.) at ¶ 27.
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`Page 14
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`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`
` Ms. Wyman further opines that neither Voswinckel JAHA nor the
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`Supplement in which it appeared “was disseminated in any predictable way such as
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`to be accessible more than one year before the May 15, 2006 priority date . . . .” Ex.
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`2041 (Wyman Decl.) at ¶ 9. She further criticizes Ex. 1007 for lacking a “received”
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`or “accepted” stamp (Ex. 2041, ¶ 18) and opines Voswinckel JAHA could have been
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`published “years after” the Scientific Sessions 2004 Conference. Ex. 2041, ¶ 14.
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`Directly contradicting her opinions, I have been provided with stamped copies of
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`Voswinckel JAHA. See, e.g., Ex. 1093 (Voswinckel JAHA stamped on 11/19/2004
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`by the British Library).4 I have been informed that the stamps on these copies of
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`Voswinckel JAHA indicate that Voswinckel JAHA was disseminated and accessible
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`4 I was provided with date-stamped copies of Voswinckel JAHA from the British
`Library (stamped on 11/19/2004) (Ex. 1093), the Library of Congress (stamped on
`10/2004) (Ex. 1094), the Lane Medical Library at Stanford University (stamped on
`11/11/2004) (Ex. 1095), and the University of California Davis Medical Library
`(stamped on 11/26/2004) (Ex. 1096). I was also provided with date-stamped copies
`of Voswinckel JESC from the British Library (stamped on 9/27/2004) (Ex. 1091), the
`University of Washington Health Sciences Libraries (stamped on 11/16/2004) (Ex.
`1089), and the Ebling Library at the University of Wisconsin (stamped on 10/15/2004)
`(Ex. 1090). Except as otherwise noted, any reference to Voswinckel JAHA in this
`declaration refers to all the date-stamped copies as well as the copy I cited in my First
`Declaration (Ex. 1008). Similarly, any reference to Voswinckel JESC in this
`declaration refers to any of these date-stamped copies of Voswinckel JESC as well as
`the copy originally provided with my First Declaration (Ex. 1007). However, purely
`for simplicity, my subsequent citations to Voswinckel JESC will be to Ex. 1007 and
`Ex. 1091, and my citations to Voswinckel JAHA will be to Ex. 1008 and Ex. 1093,
`unless noted otherwise.
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`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`by the stamp date. One of the stamped copies of Voswinckel JAHA was even stamped
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`with a “10/2004” date (Ex. 1094), indicating it was available before the date of the
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`Scientific Sessions 2004 conference, which took place from November 7-10, 2004.
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`Ex. 1094 at 2-3. The stamp further indicates the abstract was available well before
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`May 15, 2006. Thus, Ms. Wyman’s opinions regarding the dissemination and
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`accessibility of Voswinckel JAHA is incorrect.
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`I further disagree with Ms. Wyman’s assertion that a POSA exercising
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`reasonable diligence could not have located Voswinckel JAHA. In fact, publications
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`available at the time of the ’793 Patent would have directed a POSA to the work of
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`the authors disclosed in the abstract. I am informed by counsel that these publications
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`can act as “research aids” which would have directed a POSA to Voswinckel JAHA.
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` As one example, a 2005 article by Sulica and Poon, cites to Voswinckel
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`JAHA. See Ex. 1104 (“Sulica 2005”) at 359. Sulica 2005 cites to Voswinckel JAHA
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`in explaining “[i]n a recent report from Germany, inhaled treprostinil demonstrated
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`substantial pulmonary vasodilatory efficacy in acute administration, as well as
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`symptomatic and functional benefits in chronic use in a small number of PAH
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`patients.” Id. at 351. A POSA would have been interested in understanding the report
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`described in Sulica 2005 and would have sought out Voswinckel JAHA, as disclosed
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`Reply Declaration of Nicholas Hill in Support of
`Petition for Inter Partes Review
`of U.S. Patent No. 10,716,793 B2
`
`by Sulica 2005, to learn more.5 Indeed, as Ms. Wyman agrees, the fact that Sulica
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`2005 cites Voswinckel JAHA only further establishes the public availability of this
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`reference and that a POSA would readily find it. See Ex. 1110 (Wyman Depo. Tr.) at
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`122:9-12 (explaining Sulica 2005 is “giving them the information so that they could -
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`- they would know to go to that issue of Circulation”); see also id. at 119:11-18 (“Q.
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`And considering the authors of [Sulica 2005] provided a citation to the abstract, they
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`were able to find Voswinckel JAHA, is that correct? . . . [A.] Right. It looks like they
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`knew about it.”). While Ms. Wyman further opined during her deposition that she
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`does not know how the authors of Sulica 2005 knew about Voswinckel JAHA and
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`that “references can often include personal . . . communication,” in my experience,
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`researchers indicate that a citation is a personal communication when they cite such a
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`communication. See id. at 121:7-17. I note that Sulica 2005 does not indicate
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`Voswinckel JAHA is a personal communication; rather it provides a citation to
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`Voswinckel JAHA as disclosed in the Supplement of Circulation. Ex. 1104 at 359.
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`For this additional reason, Ms. Wyman’s opinion regarding the dissemination and
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`accessibility of Voswinckel JAHA is incorrect.
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`5 For example, in my experience, a POSA in May 2006 could have contacted the
`authors of the abstract t