UNITED STAmS PAmNT AND TRADEMARK OrncE
`
`OF COMMERCE
`UNITED STATES DEPARTMENT
`United States Patent and Trademark Office
`Address COMMISSIONER FOR PATENTS
`P.O Box 1450
`Alexandria Virginia 223 13-1450
`www.uspto.gov
`
`APPLICATION NO
`
`14/454373
`
`FILING DATE
`
`08/07/2014
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO
`
`CONFIRMATION NO
`
`James
`
`Baldassarre
`
`26047-0003011
`
`3860
`
`94169
`
`7590
`Richardson PC
`Fish
`P.O.Box 1022
`minneapolis MN 55440
`
`12/01/2015
`
`EXAMINER
`
`ARNOLD ERNST
`
`ART UNIT
`
`1613
`
`MAIL DATE
`
`12/01/2015
`
`PAPER NUMBER
`
`DELIVERY MODE
`
`PAPER
`
`Please find below and/or attached an Office communication concerning this application or proceeding
`
`The time period for reply if any is set in the attached communication
`
`PTOL-90A Rev 04/07
`
`Ex. 2014-0001
`
`

`
`Application No
`
`Applicants
`
`Notice of Abandonment
`
`14/454373
`Examiner
`
`BALDASSARRE JAMES
`Art Unit
`
`ARNOLD
`ERNST
`1613
`-- The MAILING DATE of this communication appears on the cover sheet with the correspondence address--
`
`This application is abandoned in view of
`
`if this is utility or plant
`
`reply to the Office letter mailed on 29 April2015
`Applicants failure to timely file
`proper
`reply was received on ______ with
`which is after the expiration of the
`Certificate of Mailing or Transmission dated _____
`total extension of time of ______ months which expired on ______
`period for reply including
`proper reply under 37 CFR 1.113 to the final rejection
`it does not constitute
`proposed reply was received on _____but
`reply under 37 CFR 1.113 to
`timely filed amendment which places the
`final rejection consists only of
`proper
`timely filed Notice of Appeal with appeal fee or
`application in condition for allowance
`for Continued Examination ACE in compliance with 37 CFR 1.114 Note that ACEs are not
`
`application
`
`timely filed Request
`
`permitted in design applications
`reply was received on ______ but it does not constitute
`proper reply or
`final rejection See 37 CFR 1.85a and 1.111 See explanation in box
`No reply has been received
`
`bona fide attempt at
`below
`
`proper reply to the non-
`
`Applicants failure to timely pay the required issue fee and publication fee if applicable within the statutory period of three months
`from the mailing date of the Notice of Allowance PTOL-85
`The issue fee and publication fee if applicable was received on _____ with
`dated
`Certificate of Mailing or Transmission
`______ which is after the expiration of the statutory period for payment of the issue fee and publication fee set in the Notice of
`Allowance PTOL-85
`The submitted fee of $_____ is insufficient
`The issue fee required by 37 CFR 1.18 is
`The issue fee and publication fee if applicable
`
`balance of $______ is due
`The publication fee if required by 37 CFR 1.18d is $_____
`has not been received
`
`3.0 Applicants failure to timely file corrected drawings as required by and within the three-month period set in the Notice of
`Allowability PTO-37
`Proposed corrected drawings were received on _____ with
`after the expiration of the period for reply
`
`Certificate of Mailing or Transmission dated ______ which is
`
`No corrected drawings have been received
`
`The letter of express abandonment which is signed by the attorney or agent of record or other party authorized under 37 CFR
`1.33b See 37 CFR 1.138b
`
`The letter of express abandonment which is signed by an attorney or agent acting in
`1.34 upon the filing of
`continuing application
`
`representative capacity under 37 CFR
`
`The decision by the Board of Patent Appeals and Interference rendered on
`of the decision has expired and there are no allowed claims
`
`and because the period for seeking court review
`
`The reasons below
`
`The six month statutory period of reply expired on 10/29/15 with no reply from Applicant
`
`/ERNSTVARNOLD/
`Primary Examiner Art Unit 1613
`
`Petitions to revive under 37 CFR 1.137 or requests to withdraw the holding of abandonment
`term
`any negative effects on patent
`U.S Patent and Trademark Office
`PTOL-1 432 Rev 07-14
`
`Notice of Abandonment
`
`under 37 CFR 1.181 should be promptly filed to minimize
`
`Part of Paper No 20151130
`
`Ex. 2014-0002
`
`

`
`UNITED STAms PAmNT AND TRADEMARK OfficE
`
`OF COMMERCE
`UNITED STATES DEPARTMENT
`United States Patent and Trademark Office
`Address COMMISSIONER FOR PATENTS
`P.O Box 1450
`AIexmdria Virghü 22313-1450
`www.uspto.gov
`
`APPLICATION NO
`
`14/454373
`
`FILING DATE
`
`08/07/2014
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO
`
`CONFIRMATION NO
`
`James
`
`Baldassarre
`
`26047-0003011
`
`3860
`
`94169
`
`7590
`Richardson PC
`Fish
`P.O.Box 1022
`minneapolis MN 55440
`
`04/29/2015
`
`EXAMINER
`
`ARNOLD ERNST
`
`ART UNIT
`
`1613
`
`MAIL DATE
`
`04/29/2015
`
`PAPER NUMBER
`
`DELIVERY MODE
`
`PAPER
`
`Please find below and/or attached an Office communication concerning this application or proceeding
`
`The time period for reply if any is set in the attached communication
`
`PTOL-90A Rev 04/07
`
`Ex. 2014-0003
`
`

`
`Office Action Summary
`
`Application No
`14/454373
`
`Applicants
`BALDASSARRE
`
`JAMES
`
`Examiner
`ERNST
`
`ARNOLD
`
`Art Unit
`1613
`
`AlA First Inventor to File
`Status
`No
`-- The MAILING DATE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE MONTHS FROM THE MAILING DATE OF
`THIS COMMUNICATION
`of 37 CFR 1.136a In no event however may
`Extensions of time may be available under the provisions
`MONTHS from the mailing date of this communication
`after SIX
`MONTHS from the mailing date of this communication
`If NO period for reply is specified above the maximum statutory period will apply and will expire SIX
`Failure to reply within the set or extended period for reply will by statute cause the application to become ABANDONED 35 U.S.C
`133
`Any reply received by the Office later than three months after the mailing date of this communication even if timely filed may reduce any
`term adjustment See 37 CFR 1.704b
`earned patent
`
`reply be timely filed
`
`Status
`
`Responsive to communications filed on 2/6/15
`under 37 CFR 1.130b was/were filed on ______
`declarations/affidavits
`2b This action is non-final
`2aE This action is FINAL
`3E An election was made by the applicant
`restriction requirement set forth during the interview on
`in response to
`______ the restriction requirement and election have been incorporated into this action
`4E Since this application is in condition for allowance except
`for formal matters prosecution as to the merits is
`closed in accordance with the practice under Exparte Quayle 1935 C.D 11453 0G 213
`Disposition of Claims
`Claims 1-60 is/are pending in the application
`5a Of the above claims _____ is/are withdrawn from consideration
`6E Claims _____ is/are allowed
`Claims 31-60 is/are rejected
`8E Claims _____ is/are objected to
`9E Claims ______ are subject
`to restriction and/or election requirement
`If any claims have been determined allowable you may be eligible to benefit
`
`from the Patent Prosecution Highway program at
`
`For more information please see
`participating intellectual property office for the corresponding
`application
`events/h/ndex.sQ or send an inquiry to PFHfeedbackCäusQtoov
`
`httQ//wwwusptopovftatents/nft
`
`Application Papers
`OE The specification is objected to by the Examiner
`The drawings filed on _____ is/are aE accepted or bE objected to by the Examiner
`See 37 CFR .85a
`that any objection to the drawings be held in abeyance
`the drawings is objected to See 37 CFR 1.121d
`
`11
`
`Applicant may not
`
`request
`
`Replacement drawing sheets including the correction is required if
`
`claim for foreign priority under 35 U.S.C 119a-d or
`
`Priority under 35 U.S.C 119
`12E Acknowledgment
`is made of
`Certified copies
`aE All bE Some cE None of the
`Certified copies of the priority documents have been received
`2.E Certified copies of the priority documents have been received in Application No _____
`3.E Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau PCT Rule 7.2a
`See the attached detailed Office action for
`list of the certified copies not received
`
`Attachments
`Notice of References Cited PT0892
`
`Information Disclosure Statements PTO/SB/08a
`Paper Nos/Mail Date 2/6/15
`
`and/or PTO/SB/08b
`
`Interview Summary PTO-413
`
`Paper Nos/Mail Date
`
`er
`
`U.S Patent and Trademark Office
`PTOL-326 Rev 11-13
`
`Office Action Summary
`
`Part of Paper No/Mail Date 20150427
`
`Ex. 2014-0004
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page
`
`The present application is being examined under the pre-AIA first
`
`to invent
`
`provisions
`
`DETAILED ACTION
`
`Continued Examination Under 37 CFR 1.114
`
`request
`
`for continued examination under 37 CFR 1.114 including the fee set
`
`forth in 37 CFR 1.17e was filed in this application after allowance or after an Office
`
`action under Ex Parte Quayle 25 USPQ 74 453 0.0 213 Commr Pat 1935 Since
`
`this application is eligible for continued examination under 37 CFR 1.114 and the fee
`
`set forth in 37 CFR .17e has been timely paid prosecution in this application has
`
`been reopened pursuant
`
`to 37 CFR .114 Applicants submission filed on 2/6/15
`
`has
`
`been entered
`
`Claims 31-60 are pending and under examination
`
`In formation Disclosure Statement
`
`The information disclosure statement
`
`IDS submitted on 2/6/15 was filed after
`
`the mailing date of the NOA on 11/20/14
`
`The submission is in compliance with the
`
`provisions of 37 CFR .97 Accordingly the information disclosure statement
`
`is being
`
`considered by the examiner
`
`Claim Rejections -35 USC 112
`
`quotation of 35 U.S.C 112b
`The following is
`CONCLUSIONThe specification
`shall conclude with one or more claims particularly
`pointing out and distinctly claiming the subject matter which the inventor or
`inventor
`regards as the invention
`
`joint
`
`Ex. 2014-0005
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page
`
`quotation of 35 U.S.C 112 pre-AIA second paragraph
`The following is
`The specification shall conclude with one or more claims particularly pointing out and distinctly
`claiming the subject matter which the applicant
`regards as his invention
`
`Claims 54-60 are rejected under 35 U.S.C 112b or 35 U.S.C 112 pre-AIA
`
`second paragraph as being indefinite for failing to particularly point out and distinctly
`
`claim the subject matter which the inventor or
`
`joint
`
`inventor or for pre-AIA the
`
`applicant
`
`regards as the invention Claim 54 is directed to steps a-d where steps b-d
`
`are
`
`it
`
`thiit
`
`deterriu that
`
`1b piiei
`
`prex.iti kfl irkr
`iid tric 33xb
`of hnonap crra hcti a.ed with it
`th lt Wflh
`pp tid TIC R.k mc
`iinuin thc mhkd urk oxide tr
`he dermnat.on
`
`fljCtIj
`
`li..t.tig
`
`disc
`
`nt due
`
`It
`
`is unclear to the Examiner how step
`
`can be performed at all when
`
`requires
`
`cessation of
`
`iNO treatment due to determination of step
`
`which comes before step
`
`One knows
`
`before performing
`
`This is
`
`self-referential paradox of performing
`
`steps that contradict one another While the claim is directed to reducing the risk of
`
`inducing pulmonary edema and has the artisan determining that the patient has pre
`
`existing LVD and is at risk of pulmonary edema when treated with iNO the claim also
`
`then has the artisan treat the patient with iNO Then the artisan remembers that iNO
`
`can cause pulmonary edema in this situation and so discontinues the iNO treatment
`
`This makes no sense The claim preamble states that the method reduces the risk of
`
`inducing pulmonary edema and step
`
`states that patients with pre-existing LVD are at
`
`particular
`
`risk of pulmonary edema when treated with iNO The artisan would not
`
`then
`
`Ex. 2014-0006
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page
`
`treat the patient with iNO which would increase the risk of
`
`inducing pulmonary edema
`
`That is contradictory to the purpose of the method The discontinuation is due to
`
`determination of pre-existing LVD and therefore once pre-existing LVD is determined in
`
`step
`
`step
`
`would not be performed as that would increase the risk of inducing
`
`pulmonary edema Therefore the claimed subject matter is paradoxical and indefinite
`
`Dependent claims are rejected as indefinite because they are dependent upon
`
`an indefinite base claim These claims cannot be further examined as it would be
`
`speculation as to what method steps are intended to be claimed MPEP 2173.06 II
`
`.where there is
`
`great deal of confusion and uncertainty as to the proper
`
`interpretation of the limitations of
`
`claim it would not be proper to reject such
`
`claim
`
`on the basis of prior art As stated in In re Steele 305 F.2d 859 134 USPQ 292 CCPA
`
`1962
`
`rejection under 35 U.S.C 103 should not be based on considerable
`
`speculation about the meaning of terms employed in
`
`claim or assumptions that must
`
`be made as to the scope of the claims
`
`Claim Rejections
`
`35 USC 103
`
`The following is
`
`quotation of 35 U.S.C 103a which forms the basis for all
`
`obviousness rejections set forth in this Office action
`
`patent may not be obtained
`identically disclosed
`though the invention is not
`the subject matter as
`differences
`between the subject matter sought
`to be patented and the prior art are such that
`obvious at the time the invention was made to
`to which said subject matter pertains Patentability
`person having ordinary skill
`in which the invention was made
`by the manner
`shall not be negatived
`
`in the art
`
`or described
`
`as set forth in section 102 of this title if
`the
`whole would have been
`
`Ex. 2014-0007
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page
`
`The factual
`
`inquiries set forth in Graham
`
`John Deere Co 383 U.S
`
`148
`
`USPQ 459 1966 that are applied for establishing
`
`background for determining
`
`obviousness under 35 U.S.C 103a are summarized as follows
`
`Determining the scope and contents of
`the prior art
`Ascertaining the differences between the prior art and the claims at issue
`Resolving the level of ordinary skill
`in the pertinent art
`Considering objective evidence present
`in the application indicating
`obviousness or nonobviousness
`
`Claims 31-53 are rejected under 35 U.S.C 103a as being unpatentable over
`
`Zapol US 5570683 and Bland Acta Paediatr Scand 1983 Suppl 30592-99 and
`
`Jaypee Pediatric and Neonatal Mechanical Ventilation 2006 Jaypee Brothers
`
`Publishers Khilnani pages 155-1 56 and Greenough Neonatal Respiratory Disorders
`
`2003 2ed CRC Press pages 183-187 and 392 and Wyka et al Foundations of
`
`Respiratory Care Cengage Learning 2002pages 503-504 and Marter chapter in
`
`Cloherty et al Manual of Neonatal Care 2004 5th edition pages 377-382 IDS filed
`
`2/6/1
`
`This application currently names joint inventors In considering patentability of
`
`the claims under 35 U.S.C 103a the examiner presumes that the subject matter of
`
`the various claims was commonly owned at the time any inventions covered therein
`
`were made absent any evidence to the contrary Applicant
`
`is advised of the obligation
`
`under 37 CFR .56 to point out
`
`the inventor and invention dates of each claim that was
`
`not commonly owned at the time
`
`later invention was made in order for the examiner
`
`to
`
`consider the applicability of 35 U.S.C 103c and potential 35 U.S.C 102e
`
`or
`
`prior art under 35 U.S.C 103a
`
`Ex. 2014-0008
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Applicant claims for example
`
`Page
`
`cNe
`ethd of improvuig the stiy of
`monxy ee methd crirc
`by rthEcn the risk of SHdr
`KCJH lU
`Iiu ij
`he
`
`plu
`
`tt
`
`tch
`
`nca act pfsH ef
`
`fll
`
`1yCxt resmrmry FThire tt
`
`krti2I3IaE csfion
`
`thc
`
`1irt
`
`trz
`
`th Um patieL WErc UC
`tt tcrtnn
`43 oF2O pnn .htkd ui oxde far 11 diws ot
`
`ca
`nt-niiwnt C1tt cotnpnses
`xcin hMtt F.s chcd
`mnrn
`
`tLk
`
`ria pLd
`
`SO
`
`tft
`
`Ilk
`
`1ir
`
`den tpon tren
`
`.s1rL Lit
`hkc nit
`
`cn
`
`irnt
`
`tL nir
`dijmi 1\LntL1
`tei rzr do tct
`ripi ehe
`d3im3 mNnn of ded mtnc ctdc
`
`ifd
`to .he exmcL ttt tvhetetiE hcr twnd neauiELElI
`fl tfl IC Itx ki
`sdTh3alM
`Nt21tC tkrS jXXn tE1 rCSftcd 43d
`or ore oiht thepc.s
`seccd Iim vsx1Ii3tm ii temu flwds ticatbotiac mnnrt atd techatc
`
`tfliI
`
`co3nprE
`
`vend Latki
`
`Determination of the scope and content of the prior art
`
`MPEP 2141.01
`
`Zapol teaches methods of
`
`identifying patients for whom an improvement
`
`in gas
`
`exchange in the lung would be beneficial and providing NO gas to the hypoxic mammal
`
`for inhalation claims 26 and 27 Zapol teach treating patients such as humans that
`
`have or are at risk of developing clinical conditions such as persistent pulmonary
`
`hypertension of the newborn hence term or near-term neonates hypoxia and chronic
`
`hypoxia column
`
`lines 51-column
`
`line
`
`and claims
`
`and 15 by administration
`
`of
`
`inhaled NO gas at
`
`concentration of at
`
`least 0.01 ppm claims
`
`and 7-9 To know
`
`the patient population it
`
`is implicit
`
`that the patient was diagnosed with the condition
`
`Zapol warns that when the capillary wedge pressure increases pulmonary edema can
`
`Ex. 2014-0009
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page
`
`result that can be fatal column
`
`lines 7-30 Indeed Zapol suggests various direct and
`
`indirect monitoring methods such as ultrasound and Doppler techniques
`
`echocardiography to measure the pulmonary artery pressure column 12 lines 56-67
`
`Zapol also warns that higher levels of NO can produce NO2 which can produce
`
`pulmonary edema column
`
`lines 40-44 Zapol
`
`teaches that the invention produces
`
`pulmonary vasodilation and increased blood flow to the alveoli Examiner added
`
`emphasis
`
`.an important advantage of both the bronchodilating and the pulmonary
`
`vasodilating methods of the invention is that one can selectively prevent or treat
`
`bronchospasm and/or pulmonary hypertension without producing
`
`concomitant
`
`lowering of the systemic blood pressure to potentially dangerous levels The invention
`
`allows for effective reversal of pulmonary hypertension without
`
`the risk of
`
`underperfusion of vital organs venous pooling ischemia and heart failure that may
`
`accompany systemic vasodilation
`
`Such isolated pulmonary vasodilation is also
`
`important in treating PPHN in newborn infants as systemic vasodilation aggravates the
`
`undesired mixing of oxygenated and de-oxygenated blood through the ductus arteriosus
`
`or the foramen ovale of newborns Furthermore by concomitantly bronchodilating and
`
`increasing blood flow to ventilated alveoli.. column
`
`line 67-column 10 line 13
`
`It
`
`is important
`
`to note the increased blood flow to the alveoli
`
`Zapol suggest administration of 0.001 ppm to 40 ppm NO in air pure oxygen or
`
`other suitable gas column 12 lines 45-48 and teaches that 20 ppm increases blood
`
`oxygen levels in human patients column 13 lines 5-12
`
`Ex. 2014-0010
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page
`
`Bland teaches premature newborn infants are at
`
`increased risk of acquiring
`
`pulmonary edema page 98 Implications and that neonatal pulmonary edema often
`
`results from sustained hypoxia in left ventricular
`
`failure associated with congenital heart
`
`disease and in conditions that increase pulmonary blood flow Abstract Thus
`
`measures that may lessen the likelihood of edema formation or reduce its severity are
`
`to avoid conditions that increase blood flow to the lungs bottom right page 98 through
`
`top left page 99 Bland also teaches that edema often accompanies interstitial
`
`emphysema where water can accumulate in the lungs Abstract and page 97 lower left
`
`column Indeed pulmonary interstitial emphysema is
`
`condition that may interfere with
`
`lymphatic drainage in the newborn lung and thereby facilitate edema formation Table
`
`and result in death Figure
`
`Bland teaches that in cases of left ventricular outflow
`
`obstruction hence left ventricular dysfunction the heart fails and left atrial pressure
`
`increases causing elevated pressure in the microcirculature of the lungs often resulting
`
`in pulmonary edema page 93 Pulmonary microvascular hypertension Increased
`
`pulmonary blood flow may lead to edema page 93 right column
`
`Jaypee teaches pediatric and neonatal mechanical ventilation and that iNO can
`
`be used in hypoxic conditions of the newborn/neonate such as pulmonary hypertenstion
`
`page 156 summary Jaypee teaches that the adverse effects of
`
`iNO in patients with
`
`elevated pulmonary capillary wedge pressure with left ventricular dysfunction can lead
`
`to pulmonary edema pages 155-156
`
`Ex. 2014-0011
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page
`
`Wyka et al teach uses of
`
`iNO for the newborn including pulmonary hypertension
`
`and hypoxemic respiratory distress of the newborn Table 16-12 In Table 16-13 Wyka
`
`et al teach that pulmonary edema is an adverse effect of nitric oxide therapy
`
`Wyka et al teach that doses less than 20 ppm show minimum adverse effects page
`
`503 right column Wyka et al describe the practitioner of iNO therapy in the summary
`
`as being well versed in all aspects of therapy and has critical
`
`thinking skills which are
`
`vital
`
`hrtn
`
`hr ht
`
`stra
`
`hn
`
`St
`
`Puhn
`
`8S
`
`rse th
`
`re
`hr rap
`tkUk are
`fl RaJ UUnk.ffl
`nprrni tir.Unn rd Rtu
`
`it
`
`tapv Hm4
`fflzkd Ibtsr
`
`paith ut ih
`kSittd kS4
`tttfl ttk@ hd fl\fl
`tk tfl
`ifth rt frE
`
`H\tflfflt
`
`Uk
`
`thrt ktj
`fl\r.c tibu th
`tts x3
`
`Greenough is generally directed to neonatal respiratory disorders and discuss
`
`nitric oxide and inhaled nitric oxide therapy with 20 ppm NO producing improvement
`
`in
`
`oxygenation in term infants with PPHN as well as preterm infants for whom the
`
`treatment
`
`is an indication if they have hypoxic respiratory failure usually with an 01
`
`greater than 25 pages 183-1 84 and page 87 Discontinuing
`
`trial of
`
`iNO is taught
`
`page 184 as well as weaning infants from iNO page 184 With respect to
`
`contraindications Greenhough clearly set forth that severe left ventricular dysfunction is
`
`Ex. 2014-0012
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page 10
`
`absolutely contraindicated page 187 as highlighted by the Examiner below for
`
`Applicants benefit
`
`COTRMNOCTJONS
`ik
`
`hui
`
`ihk
`
`Jdt
`
`Thus the art makes it clear that if
`
`neonatal patient has severe left ventricle
`
`dysfunction then iNO is con traindicated
`
`Greenough also teaches that pulmonary edema can occur in the infant due to
`
`all
`
`forms of left ventricular dysfunction leading to left atrial hypertension page 392 left
`
`column and the plasma oncotic pressure is normally around 25 mmHg higher than the
`
`pulmonary capillary pressure of about 7-12 mmHg page 392 left column Greenough
`
`teach that causes of pulmonary edema can be diagnosed from an echocardiogram or
`
`electrocardiogram page 392 right column
`
`Marter discusses persistent pulmonary hypertension of the newborn page 377
`
`lower right which is epidemiologically associated with left ventricular dysfunction pages
`
`378-379 Marter discusses diagnosis bottom page 379 with ECO echocardiogram or
`
`other procedures page 380 D-G and expressly states that left ventricular dysfunction
`
`needs to be ruled out as
`
`competing condition page 380
`
`Marter discusses
`
`management with supplemental oxygen page 380 V.A-page 381 intubation and
`
`Ex. 2014-0013
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page 11
`
`mechanical ventilation ECMO sedation metabolic alkalosis hemodynamic support
`
`and inhaled NO page 381 -382 B-C Marter teaches administration of 20 ppm NO to
`
`improve oxygenation or decrease
`
`lability page 381 -382
`
`which can occur over 3-4
`
`days top of page 382 Marter teaches that not all
`
`infants respond to iNO and therefore
`
`treatment should be at centers with ECMO page 382 Thus it
`
`is implicit that one should
`
`discontinue iNO therapy in certain conditions Marter also teach that iNO can cause
`
`other adverse conditions such as methemoglobinemia which should be monitored page
`
`382
`
`Summary
`
`It
`
`is well known in the art to administer 20 ppm iNO to term/near-term neonates
`
`to treat hypoxic respiratory failure
`
`is well known in the art that if
`
`It
`
`the neonate has severe left ventricular
`
`dysfunction then iNO is contraindicated
`
`It
`
`is well known in the art to use diagnostic processes such as echocardiography
`
`to determine left ventricular dysfunction in neonates with hypoxic respiratory
`
`failure
`
`is well known in the art that iNO can cause pulmonary edema
`
`is well known in the art that left ventricular dysfunction can cause pulmonary
`
`It
`
`It
`
`edema
`
`It
`
`is well known in the art to treat neonates with hypoxic respiratory failure with
`
`other therapies than iNO
`
`Ascertainment of the difference between the prior art and the claims
`
`Ex. 2014-0014
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page 12
`
`MPEP 2141.02
`
`The difference between the instant application and Zapol
`
`is that Zapol do not expressly
`
`teach determining if
`
`the first patient does not have pre-existing left ventricular dysfunction and
`
`administering 20 ppm iNO for 14 days or until
`
`the first patients hypoxia is resolved and
`
`determining
`
`second patient has pre-existing left ventricular dysfunction so as at particular risk
`
`of pulmonary edema upon treatment with iNO and administering second treatment regimen
`
`that does not comprise iNO for 14 days or iNO until the hypoxia has resolved but does comprise
`
`one or more therapies selected from vasodilators iv fluids bicarbonate therapy and mechanical
`
`ventilation This deficiency in Zapol
`
`is cured by the teachings of Marter Bland Wyka Jaypee
`
`and Greenough
`
`The difference between the instant application and Zapol
`
`is that Zapol do not expressly
`
`teach determining the patients PCWP increased during the treatment This deficiency in Zapol
`
`is
`
`cured by the teachings of Bland Wyka Marter Jaypee and Greenough
`
`Level of Ordinary Skill
`
`in the Art
`
`MPEP 2141.03
`
`The hypothetical person having ordinary skill
`
`in the art to which the claimed
`
`subject matter pertains would of necessity have the capability of understanding the
`
`scientific and engineering principles applicable to the pertinent art Exparte Hiyamizu
`
`10 USPQ2d 1393 1394 Bd Pat App
`
`Inter 1988 The examiner must ascertain
`
`what would have been obvious to one of ordinary skill
`
`in the art at
`
`the time the invention
`
`Ex. 2014-0015
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page 13
`
`was made and not to the inventor
`
`judge
`
`layman those skilled in remote arts or to
`
`geniuses in the art at hand Environmental Designs Ltd
`
`Union Oil Co 713 F.2d 693
`
`218 USPQ 865 Fed Cir 1983 cert denied 464 U.S 1043 1984
`
`The level of ordinary skill will often predetermine whether an implicit suggestion
`
`exists to modify the prior art Persons of varying degrees of skill not only possess
`
`varying bases of knowledge they also possess varying levels of
`
`imagination and
`
`ingenuity in the relevant
`
`field particularly with respect to problem-solving abilities If
`
`the
`
`level of skill
`
`is low for example that of mere technician then it may be rational
`
`to
`
`assume that such an artisan would not think to combine references absent explicit
`
`direction in
`
`prior art reference If however
`
`the level of skill
`
`is that of medical
`
`research scientist as is the case here then one can assume comfortably that such an
`
`educated artisan will draw conventional
`
`ideas from medicine pharmacy physiology and
`
`chemistry without being told to do so
`
`Finding of prima facie obviousness
`
`Rational and Motivation MPEP 2142-2143
`
`It would have been obvious to one of ordinary skill
`
`in the art at the time the claimed
`
`invention was made to perform the method of Zappol by determining if
`
`the first patient does not
`
`have pre-existing left ventricular dysfunction and administering 20 ppm iNO for 14 days or until
`
`the first patients hypoxia is resolved and discontinuing iNO therapy to
`
`second patient whose
`
`PCWP has increased as suggested by Marter Bland Wyka Jaypee and Greenough and
`
`produce the instant invention
`
`Ex. 2014-0016
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page 14
`
`One of ordinary skill
`
`in the art would have been motivated to do this because iNO
`
`is contraindicated for infants with severe left ventricular dysfunction LVD as taught by
`
`Greenough and the artisan would diagnose for LVD to screen for patients with LVD and
`
`exclude them from iNO therapy because of the possible risk of pulmonary edema as
`
`taught by Jaypee or other risks of serious adverse events of
`
`iNO therapy such as
`
`methemoglobinemia and consequently apply another known therapy that does not
`
`include iNO such as those suggested by Marter including sodium bicarbonate ECMO
`
`and mechanical ventilation page 382 The artisan understands that by increasing the
`
`blood flow by performing the method of Zapol
`
`there is an increased risk of pulmonary
`
`edema as suggested by Bland Wyka and Jaypee The duration of treatment
`
`for 14 days
`
`or until
`
`the first patients hypoxia is resolved is
`
`normal endpoint of treatment
`
`determined by the physician Discontinuing treatment of
`
`iNO is
`
`decision of the
`
`physicians based upon the patients lack of response to iNO which would be known
`
`immediately by monitoring oxygenation in the patient hence the hypoxia is not resolved
`
`as taught by Greenough page 184 or increase in PCWP which will
`
`lead to pulmonary
`
`edema as taught by Greenough and Jaypee Thus increase in PCWP or pulmonary
`
`edema itself are indications to discontinue iNO therapy before 14 days or the hypoxia
`
`has been resolved for the patients benefit The Examiner notes that the ordinary artisan
`
`in the iNO art is skilled and has critical
`
`thinking skills as taught by Wyka Wyka et al
`
`describe the practitioner of
`
`iNO therapy in the summary as being well versed in all
`
`aspects of therapy and has critical
`
`thinking skills which are vital
`
`Ex. 2014-0017
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page 15
`
`\hdk at
`dtC
`er
`rrt
`sUL
`
`1k914
`
`it
`
`nflt
`
`t4k
`
`t%4k
`
`tci
`kUU
`nh
`
`cafl
`
`tt
`
`tbtt
`t4hi
`enrhs
`ike
`
`flV\
`
`fl
`UK
`
`tfl tfl
`hU
`id flnr Rrs
`nt Hk
`Ut
`
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`
`kUs
`sktkn n4 nu
`ptt dtsftqU il
`
`tn
`tn and
`
`kfl%h%jVft fld
`
`Thus the ordinary artisan can make the instantly claimed determinations based
`
`on the facts at hand and discontinue iNO treatment at any time period including before
`
`14 days or before the hypoxia has resolved for the patients benefit and reduce the risk
`
`of pulmonary edema if
`
`it has not already produced pulmonary edema which is
`
`known
`
`outcome of
`
`increased PCWP
`
`Consequently it
`
`is obvious for the ordinary artisan to screen term or near-term
`
`neonates who have hypoxic respiratory failure for pre-existing LVD with an
`
`echocardiogram to reduce the risk of inducing pulmonary edema or other serious
`
`adverse events from iNO and those patients who have pre-existing LVD perform some
`
`other known treatment
`
`regimen such as mechanical ventilation and for those patients
`
`without pre-existing LVD administer 20 ppm NO until
`
`the hypoxia is treated or 14 days
`
`It would have been obvious to one of ordinary skill
`
`in the art at the time the claimed
`
`invention was made to perform the method of Zappol by determining the patients PCWP
`
`Ex. 2014-0018
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page 16
`
`increased during the treatment as suggested by Bland Wyka Marter Jaypee and Greenough
`
`and produce the instant invention
`
`One of ordinary skill
`
`in the art would have been motivated to do this because
`
`Zapol warns that when the capillary wedge pressure increases pulmonary edema can
`
`result that can be fatal column
`
`lines 7-30 Indeed Zapol suggests various direct and
`
`indirect monitoring methods such as ultrasound and Doppler techniques
`
`echocardiography to measure the pulmonary artery pressure column 12 lines 56-67
`
`An increase in PCWP will
`
`lead to pulmonary edema as taught by Greenough and
`
`Jaypee Thus PCWP is an obvious metric to measure during treatment
`
`to avoid the risk
`
`of pulmonary edema As noted above the ordinary artisan in this art has critical
`
`thinking
`
`skills and can make decisions based upon the facts at hand Therefore it
`
`is
`
`conventional practice to monitor PWCP as means to avoid pulmonary edema by the
`
`ordinary artisan
`
`In light of the forgoing discussion the Examiner concludes that the subject matter
`
`defined by the instant claims would have been obvious within the meaning of 35 USC
`
`103a
`
`From the teachings of the references it
`
`is apparent
`
`that one of ordinary skill
`
`in
`
`the art would have had
`
`reasonable expectation of success in producing the claimed
`
`invention Therefore the invention as whole was prima facie obvious to one of
`
`ordinary skill
`
`in the art at the time the invention was made as evidenced by the
`
`references especially in the absence of evidence to the contrary
`
`Ex. 2014-0019
`
`

`
`Application/Control Number 14/454373
`
`Art Unit 1613
`
`Page 17
`
`Conclusion
`
`No claims are allowed
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Ernst
`
`Arnold whose telephone number is 571 -272-
`
`8509 The examiner can normally be reached on M-F 715 am-445 pm
`
`If attempts to reach the examiner by telephone are unsuccessful
`
`the examiners
`
`supervisor Brian Kwon can be reached on 571 -272-0581 The fax phone number for
`
`the organization where this application or proceeding is assigned is 571 -273-8300
`
`Information regarding the status of an application