In
`
`
`
`°
`
`
`
`
`
`
`Application No.
`“pplicant{s)
`
`
`VOGELSTEIN ET AL.
`09/613,826
`
`Advisory Action
`Art Unit
`Examiner
`
`
`
`
`Jefiray Slew
`1656
`
`
`
`~The MAILING DATE of this communication appears on the cover sheet with tha correspondance adress --
`THE REPLY FILED 06 December 2001 FAILS TO PLACE THIS APPLICATION IN CONDITION FOR ALLOWANCE.
`Therefore, further action by
`the applicant Is required to avoid abandonmentof this application. A proper reply toa
`
`
`finat rejection under 37 CFR 1.113 may only be either: (1) a timely filed amendment which placesthe application in
`
`
`condition for allowance: (2) a timely filed Notice of Appeal (with appealfee); or (3) a timely filed Requestfor Continued
`Examination (RCE) in compliance with 37 CFR 1.114.
`
`
`PERIOD FOR REPLY[checkeithera) orb)]
`
`
`
`
`a) BQ The pariod for reply expires 3monthe from the malling date of the final rejaction.
`b) oO) The periad for reply expires on: (1) the mailing date ofthis Advisory Action, or (2) the date satforth In the finalreflection, whicheveris tater.
`
`
`no event, however, will the statutory period for reply expire lalar than SIX MONTHSfrom the maiiing date of the final rejection.
`
`
`ONLY CHECK THIS BOX WHEN THE FIRST REPLY WAS FILED WITHIN TWO MONTHS OF THE FINAL REJECTION. See MPEP
`708.07(f).
`
`
`Extensionsoftime may be obtained under 37 CFR.1.136(a). The date on which thepetition under 37 CFR 1.136(a) and the appropriate extension
`fea have been filed Is the date for purposes of determining the period of extension and the correapanding amountof the fee. The appropriate extension
`
`
`fee under 37 CFR 1.17(a) is calculated from: (1) the explration date of the shortened statutory parlod for reply originally set In the final Office action; or
`(2) as setforth In (b) above, If checked. Anyreply received by the Offica later than three months after the malilng date ofthe final rejection, even if
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`timalyfiled, may reduce any eamed patent tarm adjustment. Sea 37 CFR 1.704{b).
`
`
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`41.2) ANotice of Appeal wasfiled on
`. Appellant's Brief must be filed within the period set forth in
`37 CFR 1,192(a), or any extension thereof (37 CFR 1.191(d)), to avold dismissal of the appeal.
`
`
`2.4] The proposed amendment(s) will nat be entered because:
`(a)KIthey ralse new issues that would require further consideration and/or search (see NOTEbelow),
`
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`(b) C1 they ralsethe Issue of new mattar (see Note below),
`
`
`(c) C1 they are not deemedto place the application In better form for appeal by materially reducing or simpiliying the
`
`
`issues for appeal; and/or
`(d) 0]
`they prasent additional clalms without canceling a corresponding numberof finallyrejected claims.
`
`
`NOTE: fhe Jimifath
`consist
`-
`ould require
`new
`search and considerati
`3.1 Applicant's reply has overcomethe following rejection(s): See Continuation Sheet.
`
`
`
`4.0] Newly proposed or amended clalm(s)
`would be allowable if submitted in a separate,timely filed amendment
`canceling the non-allowable claim(s).
`
`
`5.00 The a} affidavit, b)C] exhibit, or c)L] requestfor reconsideration has been considered but does NOTplacethe
`
`
`
`application in condition for allowance because:
`6.0] Theaffidavit or exhibit will NOT be considered because itis not directed SOLELYto issues which were newly
`
`
`raised by the Examinerin thefinal rejection.
`’
`7.[) For purposesof Appeal, thie proposed amendment(s) @)[_] will not be entered or b)L] will ba entered and an
`
`
`explanation of how the new or amended claims would be rejected is provided below or appended.
`.
`
`
`The status of the claim(s)is (or will be) as follows:
`
`
`
`
`
`
`
`
`
`
`
`
`.
`
`Clalm(s) allowed: 1-64.
`
`Claim(s) objected to:
`Claim(s) rejected: 65-69.
`Claim(s) withdrawn from consideration:
`is a)] approved or bj] disapproved by the Examiner.
`8.0] The proposed drawing correction filed on
`
`9.0) Notethe attached Information Disclosure Statement(s)( PTO-1449) Paper No(s).
`.
`10.0] Other:
`
`
`
`
`US. Patant end Tradamark Gifice
`Page 353GPORAB9. 04-01)
`mae Soe ee _— -
`
`AdvisoryAction
`
`PartofPaperNo. 14
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`Page 393 of 1237
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`

`

`Gontinusiien Sheet (PTG-303)
`
`Application No. 08/613,826
`
`the propoged amendment would over acmverthe 112first
`Continuation of 3. Applicant's raply has overcomethe following rejection(s):
`written description and second paragraphselections. Theoffice wouldlike to thank applicant to bringing attention the inadvertent oversight
`of 102(s) rejection over Tyagi US6,037,130. The 102(e) rejection appears overcome by the new amendment.
`
`duu
`Ssfo 2
`cop, Ohad (2s/o
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`Page 394 of 1237
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`Page 394 of 1237
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` i
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`Group Art Unit: 1656
`
`GF
`Bb @
`2B -
`B
`
`In Re Application of:
`Bert VOGELSTEIN etal.
`
`Serial No. 09/613,826
`
`Examiner: J. Siew
`
`Filed:—July 11, 2000 Box: AF
`
`For:
`
`DIGITAL AMPLIFICATION
`
`Attorney Docket No. 01107.00031
`
`INFORMATION DISCLOSURE STATEMENT
`
`Assistant Commissioner for Patents
`Washington, D.C. 20231
`
`Sir:
`
`Pursuant to 37 C.F.R. § 1.56 and in compliance with 37 C.F.R. § 1.97(d), Applicants
`
`herewith submit Form PTO 1449listing references for consideration in connection with the
`
`above-identified application. A copy ofeach referenceis provided herewith.
`
`Eachitem of information contained in the information disclosure statement was first
`
`cited in any communication from a foreign patentoffice in a counterpart foreign application
`
`not more than three months priorto the filing of the information disclosure statement.
`
`O1/26/2002 HADHAHAL QOO00149 190733
`OL Fesleé
`160.00 CH
`
`05612026
`
`Page 395 of 1237
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`Page 395 of 1237
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`Serial No. 09/613,826
`
`Applicants respectfully request that the Examiner consider and enter these documents
`
`into the file of the above-identified application. A fee of $180.00 as set forth in 37 C.F.R. §
`
`1.17(p) is enclosed herewith to ensure consideration and entry ofthe cited documents by the
`
`Examiner.
`
`If any additional fee is deemed necessary, the Commissioner is authorized to
`
`charge our Deposit Account No. 19-0733.
`
`Respectfully submitted,
`
`[i |
`
`Jn.
`
` Date: January 23, 2002
`
`By:
`
`Michelie L. Holmes-Son
`Registration No. 47,660
`
`BANNER & WITCOFF, LTD
`1001 G Street, N.W.
`Eleventh Floor
`Washington, D.C, 20001-4597
`(202) 508-9100
`
`-2-
`
`Page 396of 1237
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`Page 396 of 1237
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`

`PTO/SB/O8A (10-01)
`ase through 10/34/2002, OMB 0651-0034
`Approve.
`U.S. Patani and Trademark. «ice: U.S. DEPARTMENT OF COMMERC!
`
`
`
`toed respondtoa oolactionofinfornationuntogs (tcontains avad OMG control umber,
`
`
`Substitute for form 1449A/PTO
`ant
`\
`Complete IfKnown
`
`[fppiaioainner[613,620
`as]ee.
`Lenexa
`Filing Date
`3
`Bert Vogelstein stal.
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`"U.S, PATENT DOCUMENTS
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`"EXAMINER:Initial itreference conaiderad, whetheror no! citation Is fn conformance with MPEP 609, Draw Iine through cltation tf nat in conformahca
`and nol considered, include copyofthis formwith maxt communication to applicant.
`}
`* applicsnt’s unique ciation designation number(oplional) .?Sas Kinds Codes ofUSPTOPatent Documents atwwuuspto.cayof MPEP poipd,
`Enter Office that laeued the document, by the twoleiter coda (WIPO Standard ST.3}. * For Japanaee patent documents, the Indication ofthé yaar of
`the reignof the Emporot must precade the estat numberoftha patant document. " Kind ofdocumentby the appropriate symbolsag Indiéated on the
`documant under WIPO Standard ST. 16 Hf possiite. © Appficant Is to placa a check mark here If English tfanguage Tranalatlon'le etiachad.
`Burden Hour Ststement: This farm {s eetimated to take 2.0 hours to completa. Time will vary depending uponthe needsof the Individual casa. Any
`comments on tha amountof fime you ere required lo completa this form ehould be eentto tha Chief information Officar, U.S, Patent and Teadamark
`Office, Weshington, OC 20231. DO NOT SEND FEES OR COMPLETED FORMS TO THIS ADDRESS. SENDTO:Assistant Commisslonar for
`Patents, Washington, DC 20231.
`
`Page 397 of 1237
`
`2n
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`__
`Ex
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`a|
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`
`
` Faraign Patant Document
`Where Relavant
`
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`Applicant of Cited
`Examiner
`Passages or Relgvant
`Inliiate”
`
`County Code? Numbar’ «Kind Code" (known)|aaopeyyyy Bocument
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`
`
`Page 397 of 1237
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`

`

`Cc?Z
`
`
`
`
`
`
`Dale "
`(Examiner
`
`
`
`Considered
`Signature
`
`
`
`
`
`“EXAMINER:InitialIf reference considered, whather of not citation la in conformenca with MPEP603. Drawfina throughcitation ifnotIn canformance
`and not considered. Include copy of this form wilh naxt communication to applicant.
`* Unique citation designation number (optional). * Applicantls to place 8 check mark here ifEnglish lenguege Translation fs eliachad,
`Burdan HourStatemant: This form le eallmatadto take 2.0 hours to complete. Time will vary depending upon the neads of the Individuel cesa. Any
`comments on tha amountoftins you era cequirad to completa thia form Bhould be éentto the ChiefInformation Officer, U.S. Patant end Trademark
`oe Office, Washington, DC 20231, DO NOT SEND FEESORCOMPLETED FORMS TOTHISADDRESS. SENOTO: AgeistantCommissionerfor
`Patents, Weshington, DC 20231.
`
`PTO/SBMAB(10-01)
`Approvedfor use through 10/31/2002. OMB 0851-0031
`U.S.Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`
`
`Undertha PaperworkReduction Act of 1995, no persans aro required to respand ln acollectionofr¢ormration urtess ktcontains avadOMS coriiierumbe
`Complete if Known
`"Substitute for form 1449APTO
`
`
`|
`09/613,826
`_Appilcation Number
`_.
`
`
`
`TION DISCLOSURE
`
`
` Firet NamedInventor
`ENT BY APPLICANT
`
`Bert Vogelstein etal.
`4
`
`Group Ar Unit
`PiesenCf
`“a
`
`cAG
`
`
`Examiner Name
`
`01107.00031
`
`:
`Attorney Docket Number
`
`
`
`
`- NONPATENT LITERATURE DOCUMENTS
`Include name of the author(In CAPITAL LETTERS),title of thearticle (when appropriate),ttle of
`
`
`Examiner
`
`the Item (book, magazine, journal, serial, symposium, catalog, efc.), date, page{s), volume-issue
`
`als °
`number(s), publisher,
`clty
`and/or country where published.
`
`
`al, *Moletular Beacon Sequence Analyela for Detecting Drug Resistance in Mycobactertum
`Tuberculocls®,Nature Biotechnology, April 1698, pp. 256-383, Vol, 18, No. 4
`
`S. TYAG!et al., “Multicolor MatecularBeaconsfor allale diserimination*, Nature Blolechnology,pp. 303-308,
`January 1995, Vol. 16, No. 4
`
` J. A.M, VETetaf., "Muitllex Detection of Four Pathogenic Retroviruses Using Molecular Beacons”, Proceedings of
`
`(ha Natlonal Acadamy of Sciences of the United ‘Ststes”, May 25, 1999, pp. 6304-6399, Vol. 86, No, 11
`
`S. TYAGIet al., "Molecular Beacons: probas that Fuorescatijgen Hybridization’, Nature Blotachnolagy, 1986, pp.
`303-308,Vol. 14, No. 3
`
`W. P. HALFORD at al, "The Inherent Quantitatlve Capacity of the Reveren Transcription-Polymerasa Chain
`
`Reaction’, Analylical Biochemistry, January 15, 1890, pp, 161-184, Vol. 266, No. 2
`
`
` ®. VOGELSTEIN at al, "Digttal PCR®, Proceedings of tha Nationel Acade
`Auguat 3, 1888,pp. 8236-0241, Vol. 98, No.46
`
`Page 398 of 1237
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`Page 398 of 1237
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`

`
`
`Undertha PeperReduction Act of 1.
`
`HL UIDO LAUT}
`Approvedfor usa through 10/31/2002. OMB 0651-0032
`“ffice: U.S, DEPARTMENT OF COMMERCE
`U.S.Patent and Trade
`Jeréons are8 required |to0 Fospond to a collection of Informati.
`aitdisplays @ Valld OMB contra! number,
`(——-FEE TRANSMITTAL
`“Complete UsKnown
`Applicalion Number{08/613,826
`
`
`for FY 2002
`
`aeensfoes faeOe|Spoup/artunt|
`et NamadInvantor|Bert Vogelstein et al.
`Patent fogs ore subject to annualrevision.
`
`TOTALAMOUNTOFPAYMENT NeygiongeSM,
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`FEE CALCULATION continued
`METHOD OF PAYMENT (checkall that apply
`3. ADDITIONAL FEES
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`1,840"
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`2150083
`Extension for reply wihis frat month
`110
`115
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`320
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`280
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`103
`18
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`examined (37 CFR § 1.128(b))
`102
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`178
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`emount of time you ens required to complate this form should be sentta the Chiaf information Officer. US. Patent and Tratemark Offica, Washington, DC 20231,
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`Page 399 of 1237
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`Page 399 of 1237
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`(656.
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`PTO/SB/21 (06-90) ©
`
`Ploase ypeaplus gign (+) inside this box —> Appraved for use through 10/31/2002, OMB 0851-6034
`\
`U.S, Patent and Tradamark Office: U.S. DEPARTMENT OF COMMERCE
`Under the Papenvork Reduction Act of 1895, no peréonsere reared to respond lo a collectionof Information unless B displays a valid OND control number.
`[ApplicationNumber| 09/613,826
`
`mo
`
`AC)
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`Y[ExaminerName [Siow bs
`
`Cte eS
`:
`\ Total Number of Pages In This Submissions| Attorney Docket Number|07107.00031
`ENCLOSURES(check all that apply)
`_
`~
`"
`oO Assignment Papers
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`C1 prawing(s)
`
`Fea Transmittal Form
`FeeAttached
`
`O
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`{J Appeal Communication to Board of
`Appeals and Interferences
`(1 Appeal Communication to Group
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`(2) Proprietary Information
`
`
`
`(1) Licensing-related Papers
`C1 Petition
`C1 Patition to Convert toa
`CStatus Letter
`Provistonal Application
`Bg]
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`[1 exenson of rine Requat Chengoo! Conespontonce naioss|EXOferEnos)
`(1 Terminal Diaclaimer
`PTO-1449 (wireferences)
`(FD Requestfor Refund
`(1 cb, Number of CD(s)
`Remaiks
`
`(Amendment/ Response
`(J After Final
`
`LD atfidavits/dectaration(s)
`
`(1 Express Abandonment Request
`
`[XJ information Disclosure Statement
`(C1 certited Copy of Priority
`Dacument(s)
`C1 Responseto Missing Parte!
`Incomplete Application
`(1 Response to Missing
`Parts under 37 CFR
`1.52 of 1.53
`
`Fim
`or
`Individual neme
`
`SIGNATURE OF APPLICANT, ATTORNEY, OR AGENT __
`,
`
`Michelle L, Halmee-Sen, Registration No. 47,660
`
`
`Burden Hour Statamant: This form {s estimated to take 0.2 hours fo complete. Time wii vary depending upon the neads oftha individual case. Any
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`PTO/SBV22{10-00}
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`Approved for
`‘ough 10/91/2002. OMB 0657-0031
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`PETITION FOR EXTENSION OF TIME UNDER 37 GFR 1.138(a)|poitornous)
` 091107.00031
`6. PE “OL
`inre Application ofBertVOGELSTEIN, eta. Se
`Sy
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`Application Number 09/613,826
`Filed July 11,2000
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`For Digital Amplification
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`Jeffrey Siew _
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`Yr4 TANS
`This ts a request underthe provisionsof 37 CFR 1.138(a) ta extend the period forfiling a
`S
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`responsein the above Identified application.
`&
`The requested extension and approprate non-small-entity fea are as follows
`(check time period desired):
`(2 One month (37 GFR 1.17(a)(1))
`Two months (37 CFR 1.17(a)(2))
`( Three months (37 CFR 1.17(a)(3))
`
`SU
`$400.00
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`0 Four months (37 CFR 1.17(a)(4))
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`Five months (37 GFR 1,17(a)(5))
`Applicant claims small entity status. Sae 37 CFR 1.27. Tharefore, the fee amount shown
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`Paymentbycredit-card. Form PTO-2036Is attached.
`The Commissioner has already been authorized to charge fees in this
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`X]|The Commissioneris hereby authorized to charge any fees which may be required,
`or credit any overpayment, to Deposit Account Numbar 19-0733 .
`| have enclosed a duplicate copyof this sheet.
`1am the () applicant/inventor.
`[1 assignee of record of the entire Interest. See 37. CFR 3.71
`Statement under 37 CFR 3.73(b) le enclosed. (Form PTO/SB/96).
`attorney or agentof racord.
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`WARNING:Infermation on this form may become publle, Credit card Information should not
`be Inctuded on this form. Provide credit card Information and authorization on PTO-203B.
`February20, 2002
`vi/ ul4 Lyfdr
`
`|
`|
`
`So US/2O50 APOUDHTL 02600084 190733
`YE
`1200.00 CH
`
`Date
`G9GLINEL
`
`Signature
`Michella L, Holmes-Son,
`Reg. No. 47,660
`Typedorprinted name
`
`
`
`Burden Hour Statement: Thia form {a eatimated to lake 0 1 hours to compiato. Time will vary depending Upon {ha needa of the individual casa. Any
`commanta on the amaunt af tine you are required fo complete this form shoutd be eant to tha Chief Information Oficer, LLS. Patent and Trademark
`Offee, Washington, OC 20234, DO NOT BEND FEES OR COMPLETED FORMS TO THIS ADDRESS. GEND TO:Assigtant Commisalonarfor
`Petenta, Washington, DC 20231.
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`i{
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`Page40Tofa Ni 7
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`Underthe Paperwork Reduction Aci of 186
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`Complete IfKnown
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`r|r
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`= TRANSMITTAL
`
`
`Application Number|09/813,826
`
`ingootefitz O
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`[—__ METHOD OF PAYMENT (check all thateppiy) |
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`3, ADDITIONAL FEES
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`Large
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`Cotte=(8) Cade (8) Fee Description
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`408
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`Requestingpublicaion OfSIR after
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`Charge any additonal foa(s) during the pendencyef this eppication
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`Extension fer reply within fret month,
`115 0 2156
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`C1 Chaitfee{s) indicated betow, except far the filing for
`to the above-Idantified da: pos
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`BASIC FILING FEE
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`128 960=Extension for raply within fiflh month1,660 228
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`421
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`140
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`105,
`20 0 165
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`135
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`140
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`142
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`BUBTOTAL (1)
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`143
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`Filing a. aubmiselon afier final mfection
`
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`(7 CER § 1.1280)
`
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`ycode 149©740-248=I} -70_—“For each adKlonaliwention to bo
`
`
`
`103
`18 203
`8
`Claims In enitéea of 20
`exeminad (37 GFR § 1.12e{b))
`
`Oz
`a4
`° a2
`42
`Indapentent cleima {n exeegs of 3
`|
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`104 «6370«=Request for Conlinusd Examination (RCL)200 204 440 Muipte dependant cle’m, nol pald 178 140 276
`
`
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`405 BOO=Requestforexpedited examinaliona4 208 a2 * Refseue Indspendeni claima over 189 200 169
`
`
`
`
`
`
`
`
`
`ofa dang application Retasus Claims In axcere of 20 and
`original patent,
`
`
`110
`18-210 Ber erigmal patent
` || Otharfes (epacty)____
`
`con
`*Reduced by Bale Fiing Fea Paid
`SUBTOTAL {3}
`
`
`
`seeabove
`
`
`
`
`
`
`or number previously paid,greater,For Refssuas,
`
`Rugensor a Aone
`
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`
`casna
`
`
`
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`WARRING! Information on this form may become public, Credit card Information should not ba
`included on this farm, Previde credit card informaiton and authorization on PTO-2036,
`Burden Houy Steternant: This form ts @atmated bo take 0.2 houre to completo, Tima wid wary dapending upon the needs afthe kvdividuel caze, Any commenta on the
`gmmount of ima you ere raquirad to complste ihla form should be sen to bre Chlef Information Officer, U.S. Patent and Traemark Office, Washington, DC 20234,
`00 NOT SEND FEES OR COMPLETED FORMS TO THIS ADDRESS. SEND To;Asslatant Commisalonarfor Patenta, Weshington, DC 20231
`
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`3
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`
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`Page 402 of 1237
`
`Page 402 of 1237
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`

`

`Michelle L. Hofmes-Son, Reg. No. 47,860 Approved for use through 10/91/2002. OMB 065
`
`J taformation Disclosure Statement
`LD Centified Copyef Priarity
`Document(s)
`0 Response to Missing Parta/
`incomptate Applicatlen
`CO Reepones fo Missing
`Paris under 37 CFR
`_1.520F 1.83
`
`Fea Transmittal Form
`
`(7 Fee Attached
`
`Amendment / Raaponse
`Afer Final
`
`LO Affidavits/dactaration(s)
`
`Extension of Time Request
`
`| Express Abandonment Request
`
`C] Drawing{s)
`
`[7] Ucensing-ralatad Papers
`C1 Petition
`0D Petiilon to Convert toa
`Provisional Apptication
`
`Ol Power of Attorney, Revocation
`Change of Corraapondence Address
`
`(1) Terminal Disciaimer
`C1 Requestfor Refund
`CJ eb, Numberof GDis)
`
`oO Aftar Allowance Communication to
`Group
`C Appeal Communication to Board of
`Appeats and Interferences
`oO Appeal Gammunication to Group
`(Appeal Notice, Brat, Reply Brief
`(1 Proprietary information
`
`CO Statue Letter
`
`Other Enclosure(s)
`{plonse identify bolow):
`Sequence Liating
`Computer Readable Disk
`
`_ SIGNATURE OF APPLICANT, ATTORNEY, OR AGENT
`
`_
`
`| Fimor
`Individual name
`
`rw
`
`Typed or printed nams
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`Burden Hour Statement. This formfo
`ot
`comments on the ameunt of tima you are required to compte!
`Offica, Waehington, DC 20231, UO NOT SEND FEES OR COMPLETED FORMS TO THE
`Petenia, Washington, DC 20231.
`
`Page 403 of 1237
`
`e type a plus sign (+) inskie this box ——>
`ar the Paperwork Reducilon Act of 1805, no persans are required to
`
`pes
`
`U.S. Patent and Trademark Office; U.S, DEPARTMENT OF COMMI
`respond to a collection of infarmation unlass Hl displays a vadid OMB control
`00/613,826
`TRANSMITTAL
`[rungbee|
`Bert VOGELSTEIN,et al,
`FORM
`1866
`(io be usad for elfcorrespondence afterinitialfiling)
`
`|I |[
`
`|iL
`
`:t
`
`.QSAiS03
`
`Jeffrey Siew
`001107.00031__
`
`(ariaoPapeTnSon|[AtomsDekeNanbor_|
`ENCLOSURES(chackall thatapp)
`oO Assignment Papers
`{for an Application)
`
`Page 403 of 1237
`
`

`

`
`
`SATEREI)
`NT ER ET
`MARE
`
`
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Group Art Unit: 1656
`
`))
`
`) )
`
`Examiner: J Siew
`5
`} Box AF
`} Docket No. 01107.00031
`
`In re Application of
`
`Bert Vogelstein,et, al.
`
`Serial No. 09/613,826
`
`Filing Date: July 11, 2000
`
`For: DIGITAL AMPLIFICATION
`
`AMENDMENT AFTER FINAL REJECTION
`
`Assistant Commissioner for Patents
`Washington, D.C. 20231
`
`Sir:
`
`In responseto the Final Office Action mailed September 20, 2001, applicants
`
`requestentry of the following amendments. Claims 1-64 are pending in the application
`and are allowed. A petition for a two-month extension oftime is enclosed herewith. No
`
`other fees are believed due to makethis response filed timely, If any additionalfee is due
`
`il?
`
`please change our Deposit Account No. 19-0733.
`
`THE CL.
`
`Please cancel
`
`claims 65-69.
`
`
`
`Page-404of4237--- - - saeee
`
`
`
`Page 404 of 1237
`
`

`

`(SEQUENCE LISTING
`Please replace the sequence listing in the application with the accompanying substitute
`
`sequencelisting. A computer readable form and paper copy ofthe substitute sequence
`
`listing are enclosed, They are believed to be identical in content. The substitute
`
`|
`|
`
`sequencelisting introduces no new matter.
`
`IN
`
`SPECIFICATION
`
`‘Theparagraphbeginningpage4,line 19.
`
`Fig. 2. Discrimination between WT and mutant PCR products by Molecular Beacons.
`Ten separate PCR products, each generated from ~25 genome equivalents ofgenomic
`
`DNAofcells containing the indicated mutations of c-Ki-Ras, wete analyzed with the
`, \ Molecular Beacon probesdescribed in the text, Representative examples of the PCR
`
`products used for Molecular Beacon analysis were purified and directly sequenced.
`
`In
`
`the cases with Gly 12Cys (SEQ ID NO:11) and Gly12Arg (SEQ ID NO:10) mutations,
`
`contaminating non-neoplastic cells within the tumor presumably accounted for the
`
`i
`
`i
`
`relatively low ratios. In the cases with Glyl2Ser (SEQ ID NO:8) and Glyi2Asp (SEQ
`
`ID NO: 12), there were apparently two or morealleles of mutant c-Ki-Ras for every WT
`
`allele (SEQ ID NO:7); both these tumors were aneuploid. Analysis of the GlyI3Asp
`
`mutation is also shown (SEQ ID NO;9).
`
`
`} Theparagraphbeginningpage5,line 10.
`
`j—
`
`Page 405 of 1237
`
`#
`
`.
`
`Page 405 of 1237
`
`

`

`||
`
`
`
`
`
`t
`
`' |
`
`
`
`Fig. 4. Discriminating WT from mutant PCR products obtained in Dig-PCR.
`
`RED/GREEN ratios were determined from the
`
`fluorescence of MB-RED and
`
`MB-GREENas described in Materials and Methods, The wells shown are the same as
`
`C ad
`
`those illustrated in Fig, 3, The sequences of PCR products from the indicated wells were
`
`determined as described in Materials and Methods, The wells with RED/GREEN ratios
`
`>3.0 each contained mutant sequences while those with RED/GREENratios of ~1.0
`
`contained WT sequences, WT c-Ki-Ras (SEQ ID NO: 7), Gly12Asp (SEQ ID NO:13),
`
`and Gly13Asp (SEQ ID NO:9) were analyzed.
`
`» _
`
`__-Theparagraph beginning page 5, line 17.
`
`Fig. 5. Dig-PCR of DNA from a stool sample. The 384 wells used in the experiment are
`
`-
`
`displayed. Those colored blue contained 25 genome equivalents of DNA from normal
`
`cells. Each of these registered positive with MB-RED and the RED/GREENratios were
`
`1.0 +/- 0.1 (mean +/- 1 standard deviation). The wells colored yellow contained no
`
`template DNA and each wasnegative with MB-RED (ie., fluorescence <3500
`
`fluorescence units.). The other wells contained diluted DNA from the stool sample.
`
`Those registering as positive with MB-RED were colored either red or green, depending
`on their RED/GREENratios. Those registering negative with MB-RED werecolored
`
`white. PCR products from the indicated wells were used for automated sequence
`
`analysis. The sequence of WT ¢-Ki-Ras in well K1 (SEQ ID NO: 7), and mutant c-Ki-
`
`Ras in wells C10, £11, M10, and L12 (SEQ ID NO:14), and well F21 (SEQ ID NO: 15)
`
`were analyzed.
`iS
`3
`
`Page 406 of 1237
`
`Page 406 of 1237
`
`

`

`REMARKS
`
`The Amendments
`
`The specification has been amendedto enter a substitute sequence listing. The
`
`substitute sequence listing includes sequences that were notpresentin the prior sequence
`
`listing. The additional sequences are disclosed in Figures 2, 4, and 5 of the drawings.
`The paragraph beginningat page 4, line 19. has been amended to disclose the
`
`sequence identifier of each of the wildtype or mutant ras sequences shown in Figure 2.
`
`The paragraph beginning at page 5, line 10 and the paragraph beginningat page 5,
`
`line 17 have each been amended to disclose the sequence identifier for each of the
`
`wildtype or mutant ras sequences shownin Figures 4 and 5,respectively.
`
`These amendments were not madeearlier as applicants only first became aware of
`
`this oversight after the final rejection was mailed, Rejected claims 65-69 have been
`
`canceled without prejudice to their future prosecution in continuation applications. A
`
`notice of allowanceis respectfully requested.
`
`Page 407 of 1237
`
`Page 407 of 1237
`
`

`

`Respectfully submitted,
`
`oxAVlep00fluff
`
`Date: February 20, 2002
`
`Michelie Holmes-Son
`Registration No. 47,660
`
`Banner & Witcoff, Ltd.
`1001 G Street, NW
`Washington, DC 20001
`202-508-9100
`
`ort
`
`Page 408 of 1237
`
`Page 408 of 1237
`
`

`

`
`
`MARKED UP VERSION TO SHOW CHANGES MADE
`
`The paragraph beginning page 4, line 19.
`
`Fig. 2. Discrimination between WT and mutant PCR products by Molecular Beacons,
`
`Ten separate PCR products, each generated from ~25 genome equivalents of genomic
`
`DNAofcells containing the indicated mutations of c-Xi-Ras, were analyzed with the
`
`Molecular Beacon probes described in the text, Representative examples of the PCR
`
`products used for Molecular Beaconanalysis were purified and directly sequenced.
`
`In
`
`the cases with Gly12Cys (SEQ ID NO: 11) and Gly12Arg (SEQ ID NO: 10) mutations,
`
`contaminating non-neoplastic cells within the tumor presumably accounted for the
`
`