UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________
`
`
`ARADIGM CORPORATION
`Petitioner
`
`v.
`
`INSMED INCORPORATED
`Patent Owner
`
`____________
`
`
`Case PGR2017-_____
`U.S. Patent No. 9,402,845
`
`____________
`
`
`PETITION FOR POST GRANT REVIEW
`
`
`
`
`
`
`

`

`TABLE OF CONTENTS
`
`TABLE OF AUTHORITIES .................................................................................. v
`
`LIST OF EXHIBITS ............................................................................................ vii
`
`I.
`
`INTRODUCTION ........................................................................................ 1
`
`II. MANDATORY NOTICES ........................................................................... 7
`
`A.
`
`B.
`
`C.
`
`Real Party-in-Interest (37 C.F.R. §42.8(b)(1)) .................................... 7
`
`Related Matters (37 C.F.R. §42.8(b)(2)) ............................................. 7
`
`Lead and Backup Counsel and Service Info (37 C.F.R.
`§42.8(b)(3)-(4)) ................................................................................... 7
`
`III.
`
`PAYMENT OF FEES (37 C.F.R. §§42.15(b), 42.203) ................................. 8
`
`IV. GROUNDS FOR STANDING (37 C.F.R. §42.204(a)) ................................. 8
`
`V.
`
`IDENTIFICATION OF CHALLENGE (37 C.F.R. §42.204(b)) ................... 8
`
`VI. BACKGROUND ........................................................................................ 10
`
`A.
`
`State of the Art as of the ’845 Patent’s Earliest Possible Priority
`Date of December 8, 2005 ................................................................ 10
`
`1.
`
`2.
`
`General Background ...............................................................10
`
`Aerosolized Formulations .......................................................18
`
`State of the Art as of the ’845 Patent’s Actual Filing Date of
`January 4, 2016 ................................................................................. 20
`
`The ’845 Patent ................................................................................. 20
`
`Continuity Data of the ’845 Patent .................................................... 21
`
`Prosecution History of the ’845 Patent .............................................. 23
`
`Prior Art ............................................................................................ 27
`
`1.
`
`Finlay ......................................................................................27
`
`B.
`
`C.
`
`D.
`
`E.
`
`F.
`
`i
`
`

`

`2.
`
`3.
`
`4.
`
`5.
`
`Saiman ....................................................................................30
`
`Zhanel .....................................................................................31
`
`Ciofu .......................................................................................32
`
`Bakker ....................................................................................33
`
`6. WO’341 ..................................................................................37
`
`7.
`
`Gay .........................................................................................40
`
`VII. LEVEL OF ORDINARY SKILL IN THE ART ......................................... 41
`
`VIII. CLAIM CONSTRUCTION ........................................................................ 41
`
`A.
`
`“pharmaceutical formulation comprising a mixture of free
`quinolone antibiotic agent, a quinolone antibiotic agent
`encapsulated in a plurality of liposomes” .......................................... 42
`
`IX. DETAILED EXPLANATION OF GROUNDS FOR
`UNPATENTABILITY ............................................................................... 45
`
`A.
`
`The ’845 Patent Is a Post-AIA Patent Eligible for PGR .................... 45
`
`1.
`
`2.
`
`3.
`
`Legal Standard for Enablement and Written Description ........46
`
`The Effective Filing Date of Claims 1-26 Is the Actual
`Filing Date of the ’845 Patent, Because the ’845 Parent
`Apps. and the ’468 Provisional Do Not Enable the Full
`Scope of the Claims ................................................................47
`
`The Effective Filing Date of Claims 1-26 Is the Actual
`Filing Date of the ’845 Patent, Because the ’845 Parent
`Apps. and the ’468 Provisional Lack Written Description
`of the Broadly-Claimed Subject Matter ...................................53
`
`B.
`
`C.
`
`D.
`
`Claims 1-26 Are Invalid for Nonenablement..................................... 55
`
`Claims 1-26 Are Invalid for Lack of Written Description ................. 55
`
`Claims 1-6, 8, 11-12, 14-16, 19, and 23 Are Invalid as Obvious
`over Finlay in View of Saiman or Zhanel or Ciofu ........................... 55
`
`ii
`
`

`

`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`Claim 1 ...................................................................................56
`
`Claims 2-4 ..............................................................................68
`
`Claims 5-6, 8 ..........................................................................69
`
`Claims 11-12 ..........................................................................69
`
`Claims 14-15 ..........................................................................70
`
`Claim 16 .................................................................................71
`
`Claim 19 .................................................................................72
`
`Claim 23 .................................................................................72
`
`E.
`
`F.
`
`Claims 18 Is Invalid as Obvious over Finlay in view of Gay............. 73
`
`Claims 7, 9-10, 13, 17, 22, and 24-26 Are Invalid as Obvious
`over Finlay in view of Bakker and Saiman or Zhanel or Ciofu.......... 75
`
`1.
`
`2.
`
`3.
`
`Claims 7 and 9 ........................................................................77
`
`Claims 10, 13, and 24 .............................................................78
`
`Claims 17, 22, and 25-26 ........................................................78
`
`G.
`
`Claims 20 and 21 Are Invalid as Obvious over Finlay in view
`of Bakker and Gay ............................................................................ 80
`
`H.
`
`Claims 1-26 Are Invalid as Anticipated by WO’341 ......................... 81
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`Claim 1 ...................................................................................82
`
`Claims 2-4 ..............................................................................87
`
`Claims 5-9 ..............................................................................88
`
`Claims 10-13 and 24 ...............................................................89
`
`Claims 14-15 ..........................................................................90
`
`Claims 16 and 17 ....................................................................90
`
`Claims 18 and 20-21 ...............................................................91
`
`iii
`
`

`

`8.
`
`9.
`
`Claims 19, 22, and 26 .............................................................91
`
`Claims 23 and 25 ....................................................................92
`
`X.
`
`SECONDARY CONSIDERATIONS ......................................................... 92
`
`XI. CONCLUSION .......................................................................................... 93
`
`CLAIM LISTING APPENDIX ............................................................................. 94
`
`CERTIFICATE OF COMPLIANCE..................................................................... 99
`
`CERTIFICATE OF SERVICE ............................................................................ 100
`
`iv
`
`

`

`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`
`Amgen, Inc. v. Chugai Pharm. Co.,
`927 F.2d 1200 (Fed. Cir. 1991) ........................................................................ 46
`
`Ariad Pharm., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336 (Fed. Cir. 2010) (en banc) ........................................................ 46
`
`Arkema Inc. v. Honeywell Int’l Inc.,
`PGR2016-00011, Paper 13 (PTAB Sept. 2, 2016)........................................ 4, 45
`
`Cuozzo Speed Techs., LLC v. Lee,
`136 S. Ct. 2131 (2016) ..................................................................................... 41
`
`Fujikawa v. Wattanasin,
`93 F.3d 1559 (Fed. Cir. 1996) .................................................................... 46-47
`
`Inguran, LLC v. Premium Genetics (UK) Ltd.,
`PGR2015-00017, Paper 8 (PTAB Dec. 22, 2015) ........................................ 4, 45
`
`MagSil Corp. v. Hitachi Glob. Storage Techs., Inc.,
`687 F.3d 1377 (Fed. Cir. 2012) ........................................................................ 46
`
`Microsoft Corp. v. Proxyconn, Inc.,
`789 F.3d 1292 (Fed. Cir. 2015) ........................................................................ 42
`
`Purdue Pharma L.P. v. Faulding Inc.,
`230 F.3d 1320 (Fed. Cir. 2000) ........................................................................ 47
`
`US Endodontics, LLC v. Gold Standard Instruments, LLC,
`PGR2015-00019, Paper 17 (PTAB Jan. 29, 2016) ....................................... 4, 45
`
`In re Wands,
`858 F.2d 731 (Fed. Cir. 1988) .......................................................................... 46
`
`Statutes
`
`35 U.S.C. §100(i) .................................................................................................. 45
`
`35 U.S.C. §102 .......................................................................... 9, 27, 30-33, 38, 40
`
`v
`
`

`

`35 U.S.C. §103 ....................................................................................................... 9
`35 U.S.C. §103 ..................................................................................................... ..9
`
`35 U.S.C. §112(a) ................................................................................... 1, 8, 45, 46
`35 U.S.C. §112(a) ................................................................................. .. 1, 8, 45, 46
`
`35 U.S.C. §321(c) ................................................................................................. 45
`35 U.S.C. §321(c) ............................................................................................... ..45
`
`35 U.S.C. §325(a)(1) ............................................................................................. 45
`35 U.S.C. §325(a)(1) ........................................................................................... ..45
`
`Other Authorities
`Other Authorities
`
`37 C.F.R. §1.57(d) ................................................................................................ 50
`37 CPR. §1.57(d) .............................................................................................. ..50
`
`37 C.F.R. §42.8(b) .................................................................................................. 7
`37 CPR. §42.8(b) ................................................................................................ ..7
`
`37 C.F.R. §42.15(b) ................................................................................................ 8
`37 C.F.R. §42.15(b) .............................................................................................. ..8
`
`37 C.F.R. §42.100(b) ............................................................................................ 41
`37 CPR. §42.100(b) .......................................................................................... ..41
`
`37 C.F.R. §42.202 ................................................................................................... 8
`37 CPR. §42.202 ................................................................................................. ..8
`
`37 C.F.R. §42.203 ................................................................................................... 8
`37 CPR. §42.203 ................................................................................................. ..8
`
`37 C.F.R. §42.204(a) .............................................................................................. 8
`37 CPR. §42.204(a) ............................................................................................ ..8
`
`37 C.F.R. §42.204(b) .............................................................................................. 8
`37 CPR. §42.204(b) ............................................................................................ ..8
`
`
`
`
`
`
`
`
`
`vi
`Vi
`
`

`

`LIST OF EXHIBITS
`
`Document
`
`Exhibit
`No.
`1001 U.S. Patent No. 9,402,845
`1002 U.S. Provisional Application No. 60/748,468
`1003
`Prosecution history of U.S. Patent No. 9,402,845 (excerpted)
`1004
`[Reserved]
`1005
`[Reserved]
`1006
`[Reserved]
`1007 U.S. Patent No. 8,226,975 (U.S. Patent Application No. 11/634,343)
`1008 U.S. Patent No. 8,632,804 (U.S. Patent Application No. 13/527,213)
`1009 U.S. Patent No. 8,642,075 (U.S. Patent Application No. 13/666,420)
`U.S. Patent Publication No. 2014/0072620 (U.S. Patent Application
`No. 14/080,922)
`[Reserved]
`1011
`[Reserved]
`1012
`[Reserved]
`1013
`1014 U.S. Patent No. 8,673,349
`1015
`[Reserved]
`1016
`[Reserved]
`1017
`[Reserved]
`1018
`[Reserved]
`1019
`[Reserved]
`1020 Declaration of A. Bruce Montgomery, M.D.
`1021
`[Reserved]
`1022
`[Reserved]
`1023
`[Reserved]
`Finlay et al., “Regional lung deposition of nebulized liposome-
`encapsulated ciprofloxacin,” International Journal of Pharmaceutics,
`167:121-127 (1998)
`
`1010
`
`1024
`
`vii
`
`

`

`Exhibit
`No.
`
`Document
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`1033
`
`1034
`
`1035
`
`1036
`
`1037
`
`Saiman et al., “Antibiotic Susceptibility of Multiply Resistant
`Pseudomonas aeruginosa Isolated from Patients with Cystic Fibrosis,
`Including Candidates for Transplantation,” Clinical Infectious
`Diseases, 23:532-537 (September 1996)
`Zhanel et al., “A Critical Review of the Fluoroquinolones Focus on
`Respiratory Tract Infections,” Drugs, 62 (1), pp. 13-59 (2002)
`Ciofu et al., “Occurrence of Hypermutable Pseudomonas aeruginosa
`in Cystic Fibrosis Patients is Associated with the Oxidative Stress
`Caused by Chronic Lung Inflammation,” Antimicrobial Agents and
`Chemotherapy, Vol. 49, No. 6, pp. 2276-2282 (June 2005)
`Gay et al., “In Vitro Activities of Norfloxacin and Ciprofloxacin
`Against Mycobacterium tuberculosis, M. avium Complex, M. chelonei,
`M. fortuitum, and M. kansaii,” Antimicrobial Agents and
`Chemotherapy, Vol. 26, No. 1, pp. 94-96 (July 1984)
`Bakker-Woudenberg et al., “Ciprofloxacin in Polyethylene Glycol-
`Coated Liposomes: Efficacy in Rat Models of Acute or Chronic
`Pseudomonas aeruginosa Infection,” Antimicrobial Agents and
`Chemotherapy, Vol. 46, No. 8, pp. 2575-2581 (August 2002)
`International Patent Pub. No. WO2008/063341
`NebuPent® on Drugs@FDA
`(https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=Bas
`icSearch.process) (last visited April 24, 2017)
`Prescribing Information for TOBI® (October 2015)
`Prescribing Information for CAYSTON® (2014)
`Betageri et al., Liposome Drug Delivery Systems, (Technomic
`Publishing Co. ed., 1993) (excerpted)
`Cullis et al., “Liposomes as Pharmaceuticals,” Liposomes From
`Biophysics to Therapeutics, pp. 39-72 (M. Ostro ed., 1987)
`Fenske et al., “Encapsulation of weakly-basic drugs, antisense
`olidonucleotides, and plasmid DNA within large unilamellar vesicles
`for drug delivery applications,” Liposomes Second Edition A Practical
`Approach, pp. 167-191 (V. Torchilin et al. eds., 2003)
`Cullis et al., “Generating and loading of liposomal systems for drug-
`delivery applications,” Advanced Drug Delivery Reviews, 3, pp. 267-
`282 (1989)
`
`viii
`
`

`

`Exhibit
`No.
`
`Document
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`Amikacin – DrugBank (https://www.drugbank.ca/drugs/DB00479)
`(last visited April 14, 2017)
`Ciprofloxacin – DrugBank
`(https://www.drugbank.ca/drugs/DB00537) (last visited April 14,
`2017)
`Yu et al., “The Effect of Temperature and pH on the Solubility of
`Quinolone Compounds: Estimation of Heat of Fusion,”
`Pharmaceutical Research, Vol. 11, No. 4, pp. 522-527 (1994)
`Asthma Center website
`(http://www.theasthmacenter.org/index.php/disease_information/asthm
`a/using_special_devices/nebulizer_instructions/) (last visited April 14,
`2017)
`Cipolla et al., “Assessment of aerosol delivery systems for
`recombinant human deoxyribonuclease,” S.T.P. Pharma Sciences,
`4(1), pp. 50-62 (1994)
`Sangwan et al., “Aerosolized Protein Delivery in Asthma: Gamma
`Camera Analysis of Regional Deposition and Perfusion,” Journal of
`Aerosol Medicine, Vol. 14, No. 2, pp. 185-195 (2001)
`Niven et al., “Nebulization of Liposomes. I. Effects of Lipid
`Composition,” Pharmaceutical Research, Vol. 7, No. 11, pp. 1127-
`1133 (1990)
`1045 U.S. Patent Publication No. 2004/0009126 to Pilkiewicz
`Wichert et al., “Amikacin liposomes: characterization, aerosolization,
`and in vitro activity against Mycobacterium avium-intracellulare in
`alveolar macrophages,” International Journal of Pharmaceutics, 78,
`pp. 227-235 (1992)
`Wong et al., “Liposome delivery of ciprofloxacin against intracellular
`Francisella tularensis infection,” Journal of Controlled Release, 92,
`pp. 265-273 (2003)
`Conley et al., “Aerosol Delivery of Liposome-Encapsulated
`Ciprofloxacin: Aerosol Characterization and Efficacy against
`Francisella tularensis Infection in Mice,” Antimicrobial Agents and
`Chemotherapy, Vol. 41, No. 6, pp. 1288-1292 (June 1997)
`
`1046
`
`1047
`
`1048
`
`ix
`
`

`

`Exhibit
`No.
`
`Document
`
`Sunamoto et al., “Unexpected Tissue Distribution of Liposomes
`Coated With Amylopectin Derivatives And Successful Use In The
`Treatment Of Experimental Legionnaires’ Diseases,” Receptor-
`Mediated Targeting of Drugs, Vol. 82, pp. 359-371 (G. Gregoriadis et
`al. eds., 1984)
`Sunamoto et al., “Improved drug delivery directed to specific tissue
`using polysaccharide-coated liposomes,” Multiphase Biomedical
`Materials, pp. 167-190 (T. Tsuruta et al. eds., 1989)
`“Nonclinical Safety Evaluation of Reformulated Drug Products and
`Products Intended for Administration by an Alternate Route, Guidance
`for Industry and Review Staff, Good Review Practice,” October 2015
`Driscoll et al., “Intratracheal Instillation as an Exposure Technique for
`the Evaluation of Respiratory Tract Toxicity: Uses and Limitations,”
`Toxicological Sciences, 55, pp. 24-35 (2000)
`Hyde et al., “Anatomy, pathology, and physiology of the
`treacheobronchial tree: Emphasis on the distal airways,” J. Allergy
`Clin. Immunol., Vol. 124, No. 6, pp. S72-S77 (2009)
`Bruinenberg et al, “Inhaled Liposomal Ciprofloxacin: Once a Day
`Management of Respiratory Infections,” Respiratory Drug Delivery
`2010, pp. 73-82 (2010)
`Cipolla et al., “Development of Liposomal Ciprofloxacin to Treat
`Lung Infections,” pharmaceutics, 8(1), 6 (March 1, 2016)
`Oh et al., “Formulation and Efficacy of Liposome-Encapsulated
`Antibiotics for Therapy of Intracellular Mycobacterium avium
`Infection,” Antimicrobial Agents and Chemotherapy, Vol. 39, No. 9,
`pp. 2104-2111 (September 1995)
`
`1049
`
`1050
`
`1051
`
`1052
`
`1053
`
`1054
`
`1055
`
`1056
`
`
`
`x
`
`

`

`I.
`
`INTRODUCTION
`
`Aradigm Corporation (“Petitioner” or “Aradigm”) hereby requests post grant
`
`review (“PGR”) of claims 1-26 of U.S. Patent No. 9,402,845 (“the ’845 Patent”)
`
`(Ex. 1001), assigned to Insmed Incorporated (“Patent Owner” or “Insmed”). As
`
`detailed herein and in the accompanying Declaration of A. Bruce Montgomery,
`
`M.D. (a renowned physician-scientist who has focused for over three decades on
`
`the development of aerosolized pharmaceutical formulations for inhalation,
`
`including liposomal formulations to treat pulmonary infections) (Ex. 1020), the
`
`’845 Patent is eligible for PGR. The ’845 Patent’s filing date is January 4, 2016
`
`(after the PGR eligibility date of March 16, 2013) and at least one of its claims is
`
`not supported under post-AIA 35 U.S.C. §112(a) by any of its parent applications.
`
`In turn, claims 1-26 are unpatentable because they are: (1) not enabled; (2) lack
`
`written description; and (3) anticipated by or obvious over the prior art.
`
`The ’845 Patent is generally directed to methods for treating pulmonary/lung
`
`infections with aerosolized formulations of antiinfectives (such as antibiotics)
`
`administered to patients with an inhalation device. One such device, a nebulizer,
`
`releases aerosolized drug formulations as a mist that is, in turn, inhaled by a patient
`
`into his or her lungs. The ’845 Patent teaches the administration of two forms of
`
`antiinfectives in aerosolized form: (1) free or unencapsulated, which is associated
`
`with immediate drug treatment, and (2) encapsulated, which is associated with
`
`1
`
`

`

`sustained drug treatment. The encapsulated form is enclosed within liposomes,
`
`spherical vehicles that have been used for decades to transport drugs into the body.
`
`In this way, the ’845 Patent applies the well-known concepts of immediate and
`
`sustained drug treatment to aerosolized antiinfective formulations for treating
`
`pulmonary infections.
`
`Sole independent claim 1 applies the ’845 Patent’s general disclosure of
`
`methods for treating pulmonary infections with aerosolized formulations to a
`
`particular class of antibiotics, quinolones; the claimed pharmaceutical formulation
`
`comprises a mixture of two types of quinolone: free (for immediate bactericidal
`
`activity) and liposome-encapsulated (for sustained bactericidal activity). But claim
`
`1 – and claims 2-26 that depend from it – suffers from a critical defect: there is no
`
`written description support in the parent applications for the ’845 Patent (with the
`
`earliest possible priority date of December 8, 2005) for quinolone formulations.
`
`The specification only discloses quinolones in the context of “non-limiting”
`
`laundry lists of over 16 families of antiinfective agents, where “[e]ach family
`
`comprises many members.” Ex. 1001 at 9:19-26. There are no quinolone-specific
`
`embodiments disclosed in the specification. There are no examples of quinolone-
`
`containing formulations. The only two examples in the ’845 Patent, instead, are
`
`directed to amikacin, a member of the aminoglycoside family of antiinfectives.
`
`And yet, during prosecution, to overcome a double-patenting rejection in relation
`
`2
`
`

`

`to patents with claims directed to aminoglycosides, Patent Owner expressly argued
`
`that aminoglycosides and quinolones are two “distinct class[es]of antiinfectives”
`
`that are “unrelated” to each other. Ex. 1003 at 201, 2911. Those distinct classes
`
`have distinct properties such as fundamentally different chemical structures, water
`
`solubility, and hydrophilicity – which directly impact liposome selection for
`
`encapsulation of drug. And the Examiner granted the ’845 Patent based on that
`
`distinction drawn by Patent Owner, acknowledging that “[a]minoglycosides and
`
`fluoroquinolones are distinct classes of drugs and would not be considered an [sic]
`
`obvious variants/substitutes.” Id. at 212-213.
`
`The parent applications for the ’845 Patent also do not enable the full scope
`
`of sole independent claim 1. There is no disclosure of liposomes suitable for
`
`quinolones. In fact, the only two (amikacin/aminoglycoside) examples provide no
`
`guidance or description of the liposomes made by Patent Owner. But the
`
`determination of which liposome is appropriate for any given quinolone
`
`antiinfective requires anything-but-routine experimentation by a person of ordinary
`
`skill in the art (“POSITA”). There is no “one-size-fits-all” liposome; aerosolized
`
`
`1 Except for citations to the patents and patent publications (which refer to the
`
`originally-published column and line numbers in the following format __:__-__)
`
`and the Declaration (Ex. 1020), this Petition cites to the page numbers added at the
`
`bottom of each Exhibit (and designated “PTAB PAGE __/__”).
`
`3
`
`

`

`liposomal pharmaceutical formulation work is tailored for the unique
`
`characteristics of the drug at issue. A POSITA would have had to carry out undue
`
`experimentation to make the claimed mixtures of free and liposome-encapsulated
`
`quinolones that provide both immediate and sustained bactericidal activity. And
`
`the same holds true with respect to claims 2-26 that depend from claim 1 and
`
`merely recite additional formulation details (claims 2-17 and 24), specific
`
`pulmonary infections (claims 18-22 and 26), and specific inhalation devices
`
`(claims 23 and 25).
`
`The effective filing date of Claims 1-26 of the ’845 Patent is therefore the
`
`actual filing date, January 4, 2016 (after the PGR eligibility date of March 16,
`
`2013) and the ’845 Patent is a post-AIA patent that is available for PGR in the
`
`nine-month period following its issuance (August 2, 2016).2 Because the
`
`specifications of the ’845 Patent and its parent applications are substantively the
`
`same, claims 1-26 are invalid for lack of enablement and lack of written
`
`description. Notably, there is also no novelty to sole independent claim 1 and
`
`claims 2-26 that depend from it. With the effective filing date of January 4, 2016,
`
`
`2 See, e.g., Arkema Inc. v. Honeywell Int'l Inc., PGR2016-00011, Paper 13 at 27
`
`(PTAB Sept. 2, 2016); US Endodontics, LLC v. Gold Standard Instruments, LLC,
`
`PGR2015-00019, Paper 17 at 21 (PTAB Jan. 29, 2016); Inguran, LLC v. Premium
`
`Genetics (UK) Ltd., PGR2015-00017, Paper 8 at 17-18 (PTAB Dec. 22, 2015).
`
`4
`
`

`

`International Patent Pub. No. WO2008/063341 (“WO’341”) (dated 2006)
`
`anticipates claims 1-26. WO’341 (Ex. 1030) teaches aerosolized pharmaceutical
`
`compositions for inhalation to treat respiratory tract infections; those compositions
`
`feature the combination of free and liposome-encapsulated ciprofloxacin (a
`
`quinolone) to provide immediate and sustained drug release.
`
` Even if the Board determines that any claims of the ’845 Patent are entitled
`
`to an effective filing date of December 8, 2005, the prior art renders those claims
`
`obvious. Prior to December 8, 2005, aerosolized formulations for combined
`
`immediate and sustained drug release were known, including mixtures of free and
`
`liposome-encapsulated quinolones. Prior art combinations based on the primary
`
`prior art reference, Finlay (1998) (Ex. 1024), render the claims obvious;
`
`specifically, Finlay (1998) in view of Saiman (1996) (Ex. 1025) or Zhanel (2002)
`
`(Ex. 1026) or Ciofu (2005) (Ex. 1027) renders obvious claims 1-6, 8, 11-12, 14-16,
`
`19, and 23. Finlay teaches aerosolized formulations of free and liposome-
`
`encapsulated ciprofloxacin – at the claimed weight ratio of claim 1 of the ’845
`
`Patent – that can be administered to the lungs of a patient via a nebulizer inhalation
`
`device. While Finlay teaches how much free and liposome-encapsulated
`
`ciprofloxacin gets delivered to the lungs, Saiman, Zhanel and Ciofu each teach
`
`how much ciprofloxacin is sufficient to provide immediate and sustained
`
`bactericidal activity against pulmonary infection. In view of Saiman, Zhanel, or
`
`5
`
`

`

`Ciofu, Finlay teaches sufficient free ciprofloxacin to provide immediate
`
`bactericidal activity and sufficient liposome-encapsulated ciprofloxacin to provide
`
`sustained bactericidal activity.
`
`With respect to claim 18, which recites a specific mycobacterial pulmonary
`
`infection, the combination of Finlay and Gay (1984) (Ex. 1028) renders that claim
`
`obvious. While Finlay teaches how much free and liposome-encapsulated
`
`ciprofloxacin gets delivered to the lungs, Gay teaches how much ciprofloxacin is
`
`sufficient to provide immediate and sustained bactericidal activity against
`
`mycobacterial pulmonary infection.
`
`With respect to claims 7, 9-10, 13, 17, 22, and 24-26, Finlay in view of
`
`Bakker (2002) (Ex. 1029) and Saiman or Zhanel or Ciofu renders those claims
`
`obvious. Claims 7, 9-10, 13, 17, 22, and 24-26 all depend from claim 1 but further
`
`require liposomes with “electrically neutral lipids consist[ing] of hydrogenated soy
`
`phosphatidylcholine (HSPC) and a sterol [or cholesterol].” Both Finlay and
`
`Bakker teach pharmaceutical formulations administered as combinations of free
`
`and liposome-encapsulated ciprofloxacin; both Bakker and Finlay’s liposomes
`
`provide treatment against Pseudomonas aeruginosa. Given their overlapping
`
`disclosures of formulations comprising ciprofloxacin and liposomes comprising
`
`lipids made of phosphatidylcholine and cholesterol, it would have been obvious to
`
`a POSITA to replace the phosphatidylcholine in Finlay with HSPC, a specific
`
`6
`
`

`

`phosphatidylcholine disclosed in Bakker, to make a liposome with lipids consisting
`
`of HSPC and cholesterol, a sterol.3
`
`II. MANDATORY NOTICES
`
`A. Real Party-in-Interest (37 C.F.R. §42.8(b)(1))
`
`The real party-in-interest is: Petitioner Aradigm Corporation.
`
`B. Related Matters (37 C.F.R. §42.8(b)(2))
`
`Pending U.S. Patent Application No. 15/376,086 is a continuation of the
`
`’845 Patent. Petitioner is unaware of any other judicial or administrative matter
`
`that would affect, or be affected by, a decision in this proceeding.
`
`C. Lead and Backup Counsel and Service Info (37 C.F.R.
`§42.8(b)(3)-(4))
`
`Lead counsel is Arlene L. Chow (Reg. No. 47,489), Hogan Lovells US LLP,
`
`875 Third Avenue, New York, NY 10022, Phone: 212-918-3000, Fax: 212-918-
`
`3100, and Email: arlene.chow@hoganlovells.com. Back-up counsel is Peter H.
`
`Noh (pro hac vice to be requested), Hogan Lovells US LLP, 875 Third Avenue,
`
`New York, NY 10022, Phone: 212-918-3000, Fax: 212-918-3100, and Email:
`
`peter.noh@hoganlovells.com.
`
`Petitioner consents to electronic service.
`
`
`3 With respect to claims 20 and 21 (requiring specific pulmonary infections), based
`
`on a similar rationale as with claim 18, Finlay in view of Bakker and Gay render
`
`those claims obvious.
`
`7
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`

`

`III. PAYMENT OF FEES (37 C.F.R. §§42.15(b), 42.203)
`
`Petitioner submits the required fees with this Petition. Please charge any
`
`additional fees required during this proceeding to Deposit Account No. 50-1349.
`
`IV. GROUNDS FOR STANDING (37 C.F.R. §42.204(a))
`
`Petitioner certifies that the ’845 Patent is available for PGR; as discussed
`
`herein, at least one claim of the ’845 Patent has an effective filing date of January
`
`4, 2016, after the PGR eligibility date of March 16, 2013, making the ’845 Patent
`
`available for PGR. AIA §§3(n)(1), 6(f)(2)(A). This Petition is timely. The ’845
`
`Patent issued August 2, 2016, and the Petition is being filed less than nine months
`
`after the issuance of the patent. 37 C.F.R. §42.202. Finally, Petitioner certifies
`
`that it is not barred or estopped from requesting review on the grounds identified in
`
`this Petition.
`
`V.
`
`IDENTIFICATION OF CHALLENGE (37 C.F.R. §42.204(b))
`
`Petitioner challenges claims 1-26 of the ’845 Patent, and respectfully
`
`submits that the claims are unpatentable based on the following grounds:
`
`Ground 1. Claims 1-26 are unpatentable under post-AIA §112(a) for lack
`
`of enablement.
`
`Ground 2. Claims 1-26 are unpatentable under post-AIA §112(a) for lack
`
`of written description.
`
`8
`
`

`

`Ground 3. Claims 1-6, 8, 11-12, 14-16, 19, and 23 are unpatentable as
`
`obvious under post-AIA §103 over Finlay (Ex. 1024) in view of Saiman (Ex. 1025)
`
`or Zhanel (Ex. 1026) or Ciofu (Ex. 1027).
`
`Ground 4. Claim 18 is unpatentable as obvious under post-AIA §103 over
`
`Finlay (Ex. 1024) in view of Gay (Ex. 1028).
`
`Ground 5. Claims 7, 9-10, 13, 17, 22, and 24-26 are unpatentable as
`
`obvious under post-AIA §103 over Finlay (Ex. 1024) in view of Bakker (Ex. 1029)
`
`and Saiman (Ex. 1025) or Zhanel (Ex. 1026) or Ciofu (Ex. 1027).
`
`Ground 6. Claims 20-21 are unpatentable as obvious under post-AIA §103
`
`over Finlay (Ex. 1024) in view of Bakker (Ex. 1029) and Gay (Ex. 1028).
`
`Ground 7. Claims 1-26 are unpatentable as anticipated under post-AIA
`
`§102 over WO’341 (Ex. 1030).
`
`The above prior art references (including publication information) are
`
`summarized in Section VI.F. infra; claim construction is addressed in Section VIII
`
`infra; and a detailed explanation of the grounds for unpatentability is provided in
`
`Section IX infra.
`
`9
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`

`

`VI. BACKGROUND
`
`A.
`
`State of the Art as of the ’845 Patent’s Earliest Possible Priority
`Date of December 8, 2005
`
`1. General Background
`
`a.
`
`Liposomes
`
`Liposomes are vesicles that have been used for decades to transport drugs
`
`into the body. Ex. 1020, ¶25. Liposomes (depicted below) are spherical vesicles
`
`with at least one lipid bilayer that encloses an aqueous space. Id.
`
`
`
`
`
`The lipid bilayer is typically made of phospholipids, a class of lipids wi