IN THE UNITED STATES PATENT AND TRADEMARK OFFICE (USP100)
`Application Serial Number
`TBD
`Confirmation Number
`TBD
`Filing Date
`Herein
`Title of Application
`Methods of Treating Term and Near-Term
`Neonates Having Hypoxic Respiratory
`Failure Associated with Clinical or
`Echocardiographic Evidence of Pulmonary
`Hypertension
`James S. Baldassarre
`lkaria, Inc.
`TBD
`TBD
`1001-0002USC1
`
`First Named Inventor
`Assignee
`Group Art Unit
`Examiner
`Attorney Docket Number
`
`Pre-Examination Search Document
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
`
`This pre-examination search statement is provided in support of the Petition for
`
`Accelerated Examination filed herewith.
`
`A pre-examination search was conducted involving U.S. patents and patent application
`
`publications, foreign patent documents and non-patent literature as indicated below. The results
`
`of the search are provided on an Information Disclosure Statement filed concmTently herewith.
`
`The search primarily includes the following aspects:
`
`• The method of reducing adverse events in patients in need of treating with nitric
`
`oxide- excluding patients with pre-existing left ventricular dysfunction.
`
`• The patients have a pulmonary capillary wedge pressure greater than 20mm Hg.
`
`• Patients with left ventricular dysfunction have conditions like systolic or diastolic
`
`dysfunction, hypertensive, viral, iodopathic cardiomyopathy, autoimmune disease
`
`related cariomyopathy, structural heart disease, idiopathic pulmonary arterial
`
`hypertension, pulmonary hypertension cardiomyopathy.
`
`Atty Docket No: JOOJ-0002USCJ
`
`Page 1 of5
`
`Lee & Hayes PLLC
`
`Ex. 2007-0001
`
`

`
`• The patient's population are children and adults.
`
`• Adverse events are pulmonary edema, hypotension, cardiac arrest, ECG changes,
`
`hypoxemia, hypoxia and bradycardia.
`
`• The patient in need of nitric oxide inhalation has PCWP<= 15mg,
`
`PVRI>3micro.sq.meters.
`
`• Left ventricular afterload is minimized by administering a pharmaceutical dosage
`
`form comprising nitroglycerin and calcium channel blocker to the patient, using an
`
`inter-am1ic balloon pump.
`
`8 (A) Pre-examination Search
`
`Details of US Patent Classification Codes used
`
`http://www.uspto.gov/go/classification/
`
`128-Surgery
`
`128/200.14- Liquid Medicament Atomizer or Sprayer
`
`128/200-24 -Respiratory Method or Device
`
`128/203.15 -Particular treating agent carried by breathes gas
`
`128/203.12- Means for mixing treating agent with respiratory gas
`
`558- Organic Compounds
`
`558/486- Glyceryl trinitrate per se (i.e., trinitroglycerin)
`
`423 -Chemistry or Inorganic Compounds
`
`423/405- Nitric Oxide (NO)
`
`600- Surgery
`
`600/481 - Cardiovascular
`
`600/513 -Detecting heartbeat electric signal and diverse cardiovascular characteristic
`
`A fly Docket :\'o: IOOJ-0002USC 1
`
`Page 2 ofS
`
`Lee & Hm·es PLLC
`
`Ex. 2007-0002
`
`

`
`Details of IPC-8 Codes used
`
`http://www. wipo. int/classi fications/ipc/ipc8/?lang=en
`
`A61 K- Preparations for Medical, Dental, or Toilet Purposes
`
`A61K 33/00- Medicinal preparations containing inorganic active ingredients
`
`A61K 33/08- Oxides; Hydroxides
`
`A61 P- Specific Therapeutic Activity of Chemical Compounds or Medicinal Preparations
`
`A61 P 9/00- Drugs for disorders of the cardiovascular system
`
`A6 1 P 9/04- Inotropic agents, i.e. stimulants of cardiac contraction; drugs for hemi failure
`
`A61 P 9/08 -Vasodilators for multiple indications
`
`A61 P 43/00- Drugs for specific purposes
`
`COl B- Non-Metallic Elements; Compounds Thereof
`
`C01B 21/24- Nitric oxide (NO)
`
`Dates Conducted:
`
`May 10,2010 and May 17,2010
`
`Database Service: Legal Advantage
`
`Data Searched: All patents and Non-patent literature
`
`Database Searches
`
`Database Used: MicroPatent, USPTO, European Patent Office/Espacenet, WIPRO, JPO,
`
`Google, Springerlink, Wiley lnterscience, ScienceDirect, Scirus, Journal of Medicinal
`
`Chemistry, ACS Publications, and, Journal of American Academy of Pediatrics.
`
`Arzv Docker No: 1001-0002USCJ
`
`Page 3 of5
`
`Lee & Hares PLLC
`
`Ex. 2007-0003
`
`

`
`Search Concept
`No.
`1
`2
`,.,
`
`.)
`
`4
`
`5
`
`6
`
`7
`
`8
`
`Identify
`
`Left
`ventricular
`dysfunction
`Pulmonary
`Capillary
`wedge pressure
`Respiratory
`failure
`
`Nitric oxide, nitrogen monoxide, nitrogen oxide, iNO, NO
`Nitric oxide
`Inhale, breath, gasp
`Inhale
`Reduce, minimize, prevent, avoid, exclude, reject, except, omit
`Reduce
`Adverse event Adverse/undesirable/unfavorable/unfavorable
`event/effect/consequence/indication, side effect, toxicity, toxin
`Identify, select, choose, opt, pick, screen, find, segregate,
`separate, distinguish, take out
`Left ventricular dysfunction, LVD, diastolic/systolic
`dysfunction, cardiomyopathy, hemt disease
`
`Search Logic
`
`Keywords
`
`Pulmonary Capillary wedge pressure, PCWP
`
`Respiratory failure, Pulmonary edema, hypotension or cardiac
`arrest, heart failure, heart attack, electrocardiogram/ECG
`change, hypoxia, hypoxemia, bradycardia
`
`8(B) Search Directed to the Invention
`
`The pre-examination search was directed to the claimed invention, encompassing all the
`
`features of the claims and giving the claims their broadest reasonable interpretation.
`
`8(C) Search Directed to the Disclosure
`
`No disclosed features that are unclaimed at this time are currently seen as features that
`
`may be claimed later.
`
`8(D) Search Report from a Foreign Patent Office
`
`Search reports from Australia, Japan, and the EPO are attached herewith.
`
`8(E) Statement of Good Faith
`
`All statements above in suppmt ofthe petition to make special are based on a good faith
`
`belief that the search was conducted in compliance with the requirements ofthis rule.
`
`Arty Docket Xo.· !OOJ-0002L'SCJ
`
`Page4of5
`
`Lee & Hayes PLLC
`
`Ex. 2007-0004
`
`

`
`Respectfully Submitted,
`
`Christopher P. Rogers, Reg. No. 36,334
`
`{Efla~
`Zt-:YuvVl{ zo;o
`
`Date:
`
`Lee & Hayes, PLLC
`601 W. Riverside A venue, Suite 1400
`Spokane, W A 99201
`
`Ally Docket Xo: !001-0002USCJ
`
`Page 5 of5
`
`Lee & Hm·es PLLC
`
`Ex. 2007-0005
`
`

`
`Australian Government
`IP Australia
`
`Disco~-ery Ho~, Phillip ACf 26C6
`PO Box 200, Woden Aa 2606
`Austral!a
`Phone; BOO 651 010·
`lnt€fnational Callers: +61-2 6283 2999
`Facsimile: +61-2 6283 7999
`Ema~: assist@ipaustralia.gov.au
`Website: www.ipaustralia.gov.au
`
`15 March 2010
`
`RECE\VED 17 M~.R 10'\U
`
`PIZZEYS
`Level 14, ANZ Centre
`324 Queen Street
`Brisbane QLD 4000 ·
`Australia
`
`Your Ref: 28686IKA/ AMM:Is
`
`Examiner's first report on patent application no. 2009202685
`by Ikaria Holdings, Inc.
`
`Last proposed amendment no.
`
`Dear Madam/Sir,
`
`lam replying to the request for normal examination. I have examined the application and I believe
`that there are lawful grounds of objection to the application. These grounds of objection are:
`
`L The invention defined in claims 1-30 does not involve an inventive step when compared to the
`disclosure of each ofthe foHowing prior art documents*:
`
`D 1: LOH, E. et al. "Cardiovascular Effects of Inhaled Nitric Oxide in Patients with Left
`Ventricular Dysfunction". CIRCULATION, 1994, vol.90: 2780-2785.
`02: CUJEC, B. et al. «Inhaled Nitric Oxide Reduction in Systolic Pulmonary Artery Pressure is
`Less in Patients with Decreased Left Ventricular Ejection Fraction". CANADIAN
`JOURNAL OF CARDIOLOGY, 1997, vol.13(9): 816-824.
`D3: ROSALES, A et al. "Adverse Hemodynamic Effects Observed with Inhaled Nitric Oxide
`After Surgical Repair of Total Anomalous Pulmonary Venous Return". PEDIATRIC
`CARDIOLOGY, 1999, vol.20: 224-226.
`D4: BOCCHI, E. et al. "Inhaled Nitric Oxide Leading to Pulmonary Edema in Stable Severe
`Heart Failure". THE AMERICAN JOURNAL OF CARDIOLOGY, 1994, vol.74: 70-71.
`D5: ARGENZIANO, M. et al. "Inhaled Nitric Oxide is not a Myocardial Depressant in a
`Porcine Model of Heart Failure". THE JOURNAL OF THORACIC AND
`CARDIOVASCULAR SURGERY, 1998, vol.llS: 700-704.
`
`The problem addressed by the current application is reducing adverse events or serious adverse
`events associated with inhaled nitric oxide in patients who have pre-existing left ventricular
`dysfunction.
`
`The cited art is directed to a problem similar to the applicant's problem, and in searching the
`problem a person skilled in the a1t could reasonably be expected to have found, and to have
`ascertained, understood, and regarded, this prior art as relevant.
`
`D 1 investigated the use of inhalation of the pulmonary vasodilator, nitric oxide (NO), in
`patients with heart failure due to left ventricular dysfunction (L VD). The cause of heart failure
`in half the patients was ischemic cardiomyopathy and in the other half it was caused by
`idiopathic dilated cardiomyopathy (see abstract and Methods: Study Population). Following
`
`di?Australia • Patents. Trade Marks. Designs • Plant Breeder's Rights
`
`ABN 38 11 3 072 755
`
`Ex. 2007-0006
`
`

`
`administration ofNO via a face masks patients showed an increase in the mean pulmonary
`artery wedge pressure associated with decreases in cardiac index and stroke volume index (see
`Results). It is suggested that selective pulmonary vasodilation is not desirable in patients with
`left ventricular failure (see page 2784, last paragraph).
`
`D2 discloses that there have been reports that a decrease in pulmonary vascular resistance
`following iNO inhalation occurs in patients with LVD as a result of an increase in pulmonary
`capillary wedge pressure. D2 further investigated the effects of iNO in a group of patients with
`a broad range ofleft ventricular function in a randomized manner (see page 817, left col.).
`Some of the patients received oxygen in addition to NO (see page 818, Study protocol). Three
`patients with depressed left ventricular ejection fraction (L VEF) presented with pulmonary
`oedema after administration of nitric oxide (see page 821, left col. 1st paragraph and page 822,
`right col., lines 4-6). Other adverse events to occur in patiens with depressed L VEF were an
`increase in pulmonary wedge pressure and decreased pulmonary vascular resistance (the latter
`patients were also cardiomyopathy patients) (see page 821, right coL). There is a clear
`suggestion that the use of nitric oxide is limited in patients with pre-existing LVD (see
`CONCLUSIONS).
`
`D3 discloses a case report of a one month old patient who underwent corrective surgery with
`pulmonary vein confluence to left atrial anastomosis (see abstract). The patient was treated with
`NO therapy following development of sudden onset systemic-level pulmonary pressure with
`concomitant systemic hypotension. However, favourable changes were followed by "rebound"
`pulmonary hypertension that occurred with concomitant systemic hypotension and central
`venous pressure. Therapy with NO was discontinued based on the rationale that this episode of
`pulmonary hypertension may have been caused by left atrial hypertension secondary to a
`sudden increase in fulmona1y blood flow into a noncompliant left atrium and ventriGle (see
`page 225,4111 and 511 paragraphs). As a result, D3 states that NO therapy can be detrimental in
`patients with LVD and/or cardiomyopathy as these patients may develop pulmonary oedema
`(see abstract and page 226, left col., Jast paragraph).
`
`04 pertains to a study in which patients with refractory heart failure and severe pulmonary
`hypertension having impaired L VEF and severe and diffuse systolic dysfunction were
`administered NO via inhalation. Following NO therapy patients presented with an increase in
`pulmonary wedge pressure and developed pulmonary oedema (see whole document).
`
`DS discloses that there have been reports of increases in left ventricular end-diastolic pressure
`and episodes of pulmonary oedema during the clinical use of inhaled nitric oxide (iNO) in
`patients with pre-existing LVD (see abstract and the introduction).
`
`Each of D 1-DS differs from the instant specification in that they do not specifically disclose
`excluding patients with L VD from iNO treatment nor the steps of informing a medical provider
`that excluding patients with LVD from iNO treatment reduces adverse events. However, each of
`Dl-DS discloses that adverse events occur in patients with pre-existing LVD following
`administration of iNO and they clearly suggest that precautions should be taken when
`administering iNO.
`
`Therefore the person skiHed in the art would directly and without difficulty, by routine steps,
`arrive at a solution which is the same as the claimed solution, and therefore the claimed
`invention lacks an inventive step.
`
`*As found during a national phase search
`
`NOTE: There is a current postponement of acceptance in place. If you overcome all other objections
`before the expiration of that postponement, the Commissioner will only accept the application at that
`time if you have filed a 9lear and unambiguous statement requesting the withdrawal of that·
`postponement. Otherwise, a further adverse report will be issued.
`
`You have 21 months from the date ofthis report to overcome all my objection(s) otherwise
`your application will lapse.
`
`Ex. 2007-0007
`
`

`
`You wiH need to pay a monthly fee for any response you file after 12 months fi·om the date
`of the first report.
`
`You will also need to pay any annual continuation fees that apply. These win normally be
`first due five years from the· filing date. Please note however that earlier commencement
`dates apply for divisional applications. ·
`
`Information about fees may be obtained by phoning 1300 651 010.
`
`Yours faithfully,
`
`EDWINA VANDINE
`Patent Examination A
`A 1 - PBR Plants & Biotechnology
`Phone: (02) 6225 6113
`
`Ex. 2007-0008
`
`

`
`J A KEMP & CO
`
`(3)
`
`26.May. 2010 16:41
`~'~:. "~ Europ~isch~s
`
`!~1tentilmt
`
`~~;~~~Oft~'! -· ~
`Office eufop!,zn
`des brevet:s;
`
`1111111111111111111111111111111111111111111111111111111
`,.,
`Duckworth, Timothy John
`J.A. Kemp & Co.
`14 South square
`Gray's Inn
`London WG1 R 5JJ
`GRANDE BRETAGNE
`
`"':·-· · ~'-- & Co
`J. J\. K".~t\.1:"'"'
`
`.... .-u •. •'il
`
`P. 5
`No. 4473
`European Palen\ Office
`8029$ MUNICH
`LithMANY
`Tel. +49 (0)89 2399-0
`Fax +49 {0)89 2399 • 4465
`
`For any questions about
`this communication:
`Te1.:+31 (0)70 340 45 00
`
`R'::C'9 10 MAY 2010
`
`c:.~~ t~'L···:·····:..:.:-.....................
`I ~_phe3i:IO!l N<;>./Patent Nil,
`
`09251949.5- 2123
`
`I~.
`
`10.05.10
`
`I
`
`Heterence
`N.1 08660-T JD
`
`Applicant/ Propro;:f;Dr
`lkaria Holdings, Inc.
`
`Communication
`-~ ne·exterided l:.uropean search report is enclosed.
`
`The extended European search report includes, pursuant to Rule 62 EPC, the European search report
`(R 61 EPC) or the partial European seatch teportl declaration of no search (R 63 EPG) and the
`European search opinion.
`Copies ?f documents cited in the European search report are attached.
`
`1iJ
`
`1 additional set(s) of oopi~s of such documents is (are) enclosed as welL
`
`The following have been approved:
`liJ
`
`Ab$tract
`
`&r
`
`Title
`
`0
`
`The Abstract was modified and the definitive text is attached to this communication.
`
`The following figura(s) will be published together with the abstract:
`
`Refund of the search fea
`
`If applicable under Articje 9 Rules relating to fees, a separate comtt1Linication from th9 Receiving Section
`on the refund of the search fee will be sent later,
`
`EPO F;;>rm15071\j
`
`04.10
`
`Ex. 2007-0009
`
`

`
`26.May. 2010 16:41
`
`" A KEMP & CO
`
`(3)
`
`No.4473
`
`P. 6
`
`Europi:II:Stht;s
`P~t$~l~rr1t
`
`l;:,u-apt~"
`P•1t:tnt; ~If'«
`
`orn~e t:'\iropi!'efl
`dti bf"¥111~,
`
`EUROPEAN SEARCH REPORT
`
`EP 09 25 1949
`
`Category
`
`X
`
`X,D
`
`X,D
`
`X
`
`DOCUMENTS CONSIDERED TO BE RELEVANT
`Citation of document with indication, where appropdate,
`of relevant passanes
`LOH EVAN ET AL:
`"Cardiovascular Effects
`of Inhaled Nitric Oxide in patients W1th
`Left Ventricular Dysfunctionu
`CIRCULATION,
`val. 90, no. 6, 1994, pages 2780-2785,
`XP002577161
`.
`ISSN: 0009-7322
`* the whole document *
`SEMIGRAN MARC J ET AL:
`"Hemodynamic
`effects of inhaled nitric oxide in heart
`failure 11
`JOURNAL OF THE AMERICAN COLLEGE OF
`CARDIOLOGY,
`vol. 24, no. 4, 1994, pages 982-988,
`XP009131903
`ISSN: 0735-1097
`* the whole document *
`HAYWARP C S .FT AL:
`"I!'!hB.1ed ~it:ic ox11e 1-9
`in cardiac fa1lure: Vascular versus
`ventr1cu1ar effects"
`JOURNAL OF CARDIOVASCULAR PHARMACOLOGY,
`vol. 27, no. 1, 1996, pages 80-85,
`XP009131904
`ISSN: 0160-2446
`* the whole document *
`OVODOV ET AL:
`"Nitric ox1de: Clinical
`applications~~
`SEMINARS IN ANESTHESIA, SAUNDERS, CO, NEW
`YORK, NY, US LNKD(cid:173)
`DOI:l0.1053/SA.2000.6785,
`vol. 19, no. 2, 1 June 2000 (2000-06-01),
`pages 68-97, XP005426335
`ISSN: 0277~0326
`* page 90, column 1 *
`* page 93; column 2 ~ page 94 *
`
`Relevant
`to claim
`1-9
`
`1-9
`
`CLASSIF!GATION OF TI-lE
`APPLICATION (IPC)
`
`INV.
`A61K33/00
`I A61P9/08
`' A61P9/12
`
`TECHNICAL FIE;LOS
`SEAACHEO
`(IPC)
`A61K
`
`1-9
`
`-/--
`
`I
`
`l Albrec~a;t~erSilke
`
`rhe present search report has been drawn up for aH claims
`2r-----~~·--~--------~----~~--~~~~--L-~--~~~o---------~
`~
`;:~;~;~~h
`7;or;;~ti;no~~;~·~r
`&~--------~-------------~--------~·~·~------------~~------------~------~
`1il
`E:: earller pate-nt document, wt publiShed on, or
`CATEGORY OF CITED DOCUMENTS
`T: lheory or principle IJ1id0~ying the invenlion
`8
`after the filing elate
`~
`0: oocu~Tli'>nt cltN In 11'18 applicqlion
`l. docllmen! crted for olher reasons
`::s
`·•··'·· ·························r'"''fH' ''"''"''••••••••• .. ••'''''""'''''"'''''''''"' ......... .
`0:
`2
`& : member of the so11me pol.1MI1amily. corresponolng
`doqument
`P: irll&rmediate dooumefl1
`0
`0..
`w~--------------------------------------------~------------~~------------J
`
`X: particularly televan! if tiilken <t.lon~
`Y: particularly reiEwanl if oon1bln.;>d With another
`document of the same cal&gOI'y
`A : ledmologit:;al backgWU:'ld
`
`0 : nDn-wrUtf1!n disclosure
`
`page 1 of 3
`
`Ex. 2007-0010
`
`

`
`26.May. 2010 16:42
`
`" A KEMP & CO
`
`(3)
`
`No.4473
`
`P. 7
`
`~urcp.lj;.;;h~
`~-~•"•an~r
`
`Evr¢pf!'~il
`~llt-ent Offlc.e
`
`Clllcc:eul'c.pi~~:n
`.. ~, !;lf~y~-$
`
`EUROPEAN SEARCH REPORT
`
`Applleatl(ln Number·
`EP 09 25 1949
`
`CL.ASSIFICATION OF THE
`APPLICATION
`(IPC)
`
`Relevant
`to claim
`1-9
`
`1-9
`
`1-9
`
`TECHNICAL f'IELDS
`SEARCHED
`(IPC)
`
`Category
`
`X
`
`X
`
`X
`
`DOCUMENTS CONSIDERED TO BE RELEVANT
`CltaliOn or (locurnent with Indication, where appropriate,
`of relevant passages
`HENRICHSEN ET AL:
`"Inhaled nitric oxide
`can cause severe systemic hypotens1onu
`JOURNAL OF PEDIATRICS, MOSBY-YEAR BOOK,
`ST. LOUIS, MO, US LNKD(cid:173)
`DOI:l0.1016/S0022-3476(96)70230-5,
`vol. 129, no. 1, 1 July 1996 (1996-07-01),
`page 183, XP022199226
`ISSN: 0022-3476
`* the whole document *
`ADATIA ET AL:
`«Inhaled nitric oxide and
`hemodynamic evaluation of patients with
`pulmonary hypertension before
`transplantat1on"
`JOURNAL OF THE AMERICAN COLLEGE OF
`CARDIOLOGY, ELSEVIER, NEW YORK, NY, US
`LNKD- DOI:10.1016/0735-1097(95)00048-9,
`val. 25~ no. 7, 1 June 1995 (1995-06-01),
`pages 1656-1664, XP005857183
`ISSN: 0735-1097
`* page 1663, column 1 *
`CUJEC BIBIANA ET Al:
`nlnhaled nitric
`oxide reduction 1n systolic pulmonary
`artery pressure is less 1n patients with
`decreased left ventricular eject1on
`fraction"
`CANADIAN JOURNAL OF CARDIOLOGY,
`val. 13, no. 9, 1997, pages 816-824,
`XP002577162
`ISSN: 0828-282X
`* the whole document *
`
`-1--
`
`Pi«Qe c>t ~ar¢11
`
`~~ ol ccrnp!etlon o! 1Me seard-1
`
`.:x,..,;n~r
`
`The presem search fe_oort: has been drawn up for all claim::;
`2r-----~~:~---------.~--~~~~~--~-L-,----L-~~----~~~
`0
`Munich
`13 April 2010
`Albrecht, Silke
`~
`~r-----------,~~--------~----~------------------~----------------------~
`T: tno;;ory or principle underlyin>;~ the lnv·entlon
`"'
`CATEGORY OF CITED DOCUMENTS
`""
`·
`E : earlier palen! document, but published on. or
`~
`X : particular!): retevaru <!taKen alone
`attertne filing date
`:il
`Y , particularly relevant if combined w1th another
`0; aocul'll8nl cited in the application
`::;:
`oocumem or the same categozy
`L: document c~ed for otner reasons
`A : I~CMological background
`~
`:::::
`0: non-written CliSCI::>sure
`& : mernber of I he same patent lamlly, con"Gsponding
`P: lntennooiate document
`documen!
`~
`"'L---~----------~--------------~----------------~---------------------~~
`
`page 2 of 3
`
`Ex. 2007-0011
`
`

`
`26.May. 2010 16:42
`
`" A KEMP & CO
`
`(3)
`
`No.4473
`
`P. 8
`
`C:.~rc~..,iHhrr:.:
`P"~·~tilt .. rt't
`
`1;v:'9p~:;\n
`ll'lt'tl!'"4tOffice
`
`Of11t..:~'l.irill~"'n
`da.: (Jf~.,.f!~~
`
`EUROPEAN SEARCH REPORT
`
`A.ppllcatlot'l Number
`EP 09 25 1949
`
`,----~·------------------~~------------~----------------~
`
`Category
`
`X
`
`l
`X,D
`
`DOCUMENTS CONSIDERED TO BE RELEVANT
`Citatron of document with Indication, where appropriate,
`of relevant pass~ges
`FINDLAY G P:
`11 Paradoxical haemodynami c
`response to inhaled nitric ox1de"
`INTERNATIONAL JOURNAL OF INTENSIVE CARE
`1998 GB,
`vol. 5, no. 4, 1998j pages 134-139,
`XP001536771
`ISSN: 1350-2794
`* the whole document *
`-----
`BOCCHI E A ET AL:
`"Inhaled nitric oxide
`lead1ng to pulmonary edema in stable
`severe heart failure"
`AMERICAN JOURNAL OF CARDIOLOGY, CAHNERS
`PUBLISHING CO., NEWTON, MA 1 US LNKD-
`001:10.1016/0002-9149(94)90496-0r
`val. 74, no. 1, 1 July 1994 (1994-07-01},
`pages 70-72, XP02327B686
`ISSN: 0002-9149
`[retrieved on 1994-07-01]
`* the whole document *
`
`Relevant
`to claim
`
`Cl.A$$1FICATI0N OF THE
`Af'PI.!CATION (IPC)
`
`1-9
`
`1-9
`
`TECHNICA~ Fll:.f.DS
`SeARCHED
`(IPC)
`
`The present saarch report has been drawn up for all claims
`2~----~~~--------~----~~~~~--=--L-,----L-~=---------~
`I Albre~~~;l~erSilke
`~
`;~~;~~~~~h
`7;ot;;~~ti;~o~~~~~·~
`
`~r-------------------------~------------------------~~--------------~------~
`g
`"'
`CATEGORY OF CITI;:O DOCUMENTS
`T: theory or pr!roclp!e underlying the invenUon
`E : eatiler patent document but published on. or
`X: part1Cul~l1Y rel~vant if taken alone
`ar-ter lh8 filing O<ll<i>
`0; document ~Md in lha applica.tion
`~
`Y ; par11CUiarly relevanl if combined with another
`oooument of the samli! category
`L: de>curnent cited for other reasons
`::0. 5 .....
`A : lecttnologlo<ll McKground
`0: 1101'1-Wtillen disclosure
`& : member ot IM ,;;ame paient family. corresponding
`P: intermeoiate docvrnen\
`2
`document
`w~------------~------------------------~------------------------------------~
`
`••••••••••••••••••••••••••••••••••'H'HIO,,,._,,,,,,,,,,,,, •••••••••••••••<"\"'"""H'•h<'•••••••••••
`
`page 3 of 3
`
`Ex. 2007-0012
`
`

`
`16. Mar. 2 0 1 0 11 : 3 2
`
`KVOWA PATENT & LAW OFFICE
`
`iW. 6593
`
`P. 4
`
`(Translation of Official Action)
`NOTIFICATION OF REASON FOR REJECTION
`
`Mailed: February 23~ 2010
`
`Japanese Patent Application No. 2009-157623
`
`Applicant: IKARIA HOLDINGS, INC.
`
`If the
`The present application should be rejected for the following reason(s).
`applicant has any argument against the reason(s), an Argument must be filed within
`three months of the mailing date of this Official Action.
`
`REASON 1
`The present invention as claimed in the following claim(s) is unpatentable under Article
`29, paragraph 1, sub-paragraph 3 of the Japanese Patent Law as being anticipated by the
`following publication(s) distributed in Japan or elsewhere or as being identical with an
`invention made available to the public through electric telecommunications prior to the
`filing of the present application.
`
`REASON2
`The present invention as claimed in the following claim(s) is unpatentable under Article
`29, paragraph 2 of the Japanese Patent Law since the invention could have been easily
`made by those skilled in the art to which it pertains on the basis of the invention(s)
`described in the following publication(s) distributed in Japan or elsewhere or an
`invention/inventions made available to the public through electric telecommunications
`prior to the filing of the present application.
`
`NOTE:
`Citation 1: Inglessis~ I. et al., Journal of the American College of Cardiology~ 2004} Vol.
`44, No.4, pp. 793-798
`Citation 2: Loh, B. et al.~ Circulation; 1994~ 90, pp. 2780-2785
`Citation 3: Steinborn, R.H. et al .• Pulmonary Hypertensio~ Persistent-Newborn,
`emedicine, updated Apr. 19, 2007
`[http:/ /emedicine.medscape.com/article/89843 7 -overview]
`Citation 4: BOCCHI, E. A. et al., The American Journal of Cardiology, 1994) Vol. 74, pp.
`70-72
`
`Page 1/3
`NOTIFICATION OF REASON FOR REJECTION
`Japanese Patent Appln. No. 2009-157623
`
`Ex. 2007-0013
`
`

`
`16. Mar. 2 0 1 0 11 : 3 2
`
`KVOWA PATENT & LAW OFFICE
`
`iW. 6593
`
`P. 5
`
`A.
`Reasons 1 and 2/ Claims 1 to 14/ Citation 1
`Citation 1 discloses that inhaled nitric oxide is known as a selective pulmonary
`vasodilator (Abstract), and that inhaled nitric oxide~ when administered to patients with
`right ventricular myocardial infarction and cardiogenic shock, reduced the pulmonary
`arterial pressure (Abstract). Citation 1 also discloses that the inhalation of nitric oxide
`is known to decrease pulmonary vascular tone in adults and children with pulmonary
`hypertension (page 793, right column, lines 11 to 6 from the bottom), and that nitric
`oxide is delivered by means of a ventilator or is mixed with oxygen (page 795, left
`column,. "NO administration'~). Especially, Table 2 presents hemodynamic parameters
`of target patients at the time of study enrollment, indicating that most of the patients
`have a pulmonary capillary wedge pressure (PCWP) of less than 20 mmHg.
`In light of the present specification (paragraph [0013]); the patients of Citation
`1 having a PCWP of less than 20 mmHg are not deemed to have pre-existing left
`ventricular dysfunction (LVD).
`Thus, the present invention as claimed in claims 1 to 14 is indistinguishable
`from the invention disclosed in Citation 1.
`(The present invention and the invention disclosed in Citation 1 are identical in
`active ingredient and target patients, and thus are deemed to necessarily provide the
`same functions/effects.)
`
`B.
`Reasop 21 Claims 1 to 14/ Citations 1 to 4
`Inhaled nitric oxide is well known as a selective pulmonary vasodilator, as
`disclosed in Citation 1.
`On the other hand, Citation 2 (for example~ Abstract) discloses that inhaled
`nitric oxide, when administered to patients with left ventricular dysfunction~ may cause
`a decrease in pulmonary vascular resistance associated with an increase in left
`ventricular filling pressure, leading to the risk of the occurrence of adverse events.
`Citation 3 (for example, see Abstract and "Treatment with iNO") discloses that,
`although inhaled nitric oxide is used for the treatment of pulmonary hypertension of
`newborns) patients suffering from congenital cardiac disease characterized by left
`
`Page2/3
`NOTIFICATION OF REASON FOR REJECTION
`Japanese Patent Appln. No. 2009-1.57623
`
`Ex. 2007-0014
`
`

`
`16. Mar. 2 0 1 0 11 : 3 2
`
`KVOWA PATENT & LAW OFFICE
`
`iW. 6593
`
`P. 6
`
`ventricular outflow tract obstruction and severe left ventricular dysfunction have a
`contraindication to the treatment with inhaled nitric oxide.
`Citation 4 (page 71, left column, lines 13 to 15) discloses that inhaled nitric
`oxide, when administered to patients with severe heart disease~ may cause pulmonary
`edema.
`
`In view of the above, it would have been obvious to those skilled in the art to
`exclude patients with pre-existing left ventricular dysfunction from patients to be treated
`with a selective pulmonary vasodilator, in order to avoid the occurrence of adverse
`events) based on Citations 1 to 4.
`Further. the present invention as claimed in claims 1 to 14 is not deemed to
`provide particularly remarkable advantages, in view of Citations 1 to 4.
`
`REASON3
`The present application should be rejected on the grounds that the recitation of the
`claim(s) fails to meet the requirement of Article 36, paragraph 6, sub-paragraph 2 of the
`Japanese Patent Law in the following respect(s).
`
`NOTES:
`(1) The abbreviations ''PAPm, '' ~'PCWP" and ~'PVRI" are unclear in meaning.
`(2) The term ~~neat' renders the scope of the claimed invention unclear; and
`thus is inappropriate as an expression for use in the claims.
`
`Background Art Information*
`
`Field of Search:
`
`lPC
`
`A61K33/00
`
`*The information provided herein constitutes no reason for rejection.
`
`Page 3/3
`NOTIFICATION OF REASON FOR REJECTION
`Japanese Patent Appin. No. 2009-1576.23
`
`Ex. 2007-0015
`
`

`
`~~~~:17945901
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`
`3
`
`Ex. 2007-0017
`
`

`
`~~~~:17945901
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`
`1. Inglessis, I. et al., Journal of the American College of Cardiology,
`2 0 0 4~, Vol.44, No.4, p. 793-798.
`2. Loh, E. et al., Circulation, 1 9 9 4 ~. 90, p. 2780-2785
`3.Steinhorn, R.H. et al., Pulmonary Hypertension, Persistent-Newborn, e
`medicine, Updated Apr 19, 2007 [http://emedicine.medscape. com/article/89
`8437-overview]
`4. BOCCHI, E. A. et al. , The American Journal of Cardiology, 1