RAW SEQUENCE
`
`
`
`LISTING
`
`
`
`Loaded by SCORE,no errors detected.
`
`Application Serial Number: —_13071105
`Source:
`,
`OPAP
`Date Processed by SCORE:
`04/08/11
`
`
`
`
`
`
`
`
`
`
`
`
`
`(NTERED
`
`
`
`
`
`
`
`Page 712 of 1365
`
`
`
`
`
`Page 712 of 1365
`
`

`

`26
`
`24
`
`20
`
`27
`
`
`
`SEQUENCE LISTING
`
`<110>
`
`Vogelstein, Bert
`Kingler, Kenneth W.
`
`<120>
`
`DIGITAL AMPLIFICATION
`
`<130>
`
`01107 .00195
`
`<140>
`<141>
`
`13071105
`2011-03-24
`
`<150>
`<151>
`
`09981356
`2001-10-12
`
`<150>
`<151>
`
`<150>
`<151>
`
`US 60/146,792
`1999-08-02
`
`US 09/613, 826
`2000-07-11
`
`<160>
`
`“15
`
`<170>
`
`PatentIn version 3.1
`
`1 2
`
`6
`DNA
`homo sapiens
`
`<210>
`<211>
`<212>
`€<213>
`
`<400>
`
`1
`
`catgttctaa tatagtcaca ttttca
`
`22
`
`4
`.
`DNA
`homo sapiens
`
`<210>
`<211>
`<212>
`<213>
`
`<400>
`
`2
`
`tctgaattag ctgtatcgtc aagg
`
`3 2
`
`0
`DNA
`homo sapiens
`
`<210>
`<211>
`<212>
`
`<213>
`
`<400>
`
`3
`
`tagctgtatc gtcaaggcac
`
`42
`
`7
`DNA
`homo sapiens
`
`<210>
`<211>
`<212>
`<213>
`
`4
`
`<400>
`cacgggcctg ctgaaaatga ctgcgtg
`
`Page 713 of 1365
`
`Page 713 of 1365
`
`

`

`<210>
`<211>
`<212>
`<213>
`
`5
`24
`DNA
`homo sapiens
`
`<400>
`5
`cacgggagct ggtggcegtag cgtg
`
`<210>
`<211l>
`<212>
`<213>
`
`6
`24
`DNA
`homo sapiens
`
`<400>
`
`6
`
`cattattttt attataagge ctge
`
`<210>
`<211l>
`<212>
`<213>
`
`7
`12
`DNA
`homo sapiens
`
`7
`<400>
`gctggtqgcg ta
`
`<210> .8
`<211>
`12
`<212>
`DNA
`<213>
`homo sapiens
`
`8
`.<400>
`gctagtggceg ta
`
`<210> 9
`<211>
`12
`<212>
`DNA
`<213>
`homo sapiens
`
`<400>
`9
`gctggtgacg ta
`
`<210> 10
`<21ll>
`12
`<212>
`DNA
`<213>
`homo sapiens
`
`10
`<400>
`gctcgtggcg ta
`
`11
`<210>
`<2li> 13
`<212>
`DNA
`<213>
`homo sapiens
`
`<400>
`
`11
`
`Page 714 of 1365
`
`24
`
`24
`
`12:
`
`12
`
`12
`
`12
`
`
`
`
`
`Page 714 of 1365
`
`

`

`gcttgtggcc gta
`
`<210>
`<211>
`<212>
`/<213>
`
`12
`
`130”
`DNA
`homo sapiens
`
`<400>
`
`12
`
`gctgatggge gta
`
`<210>
`<211l>
`<212>
`<213>
`
`13
`12
`DNA
`homo sapiens
`
`<400>
`
`13
`
`gctgatggcg ta
`
`<210>
`<211>
`<212>
`<213>
`
`14
`12
`DNA
`homo sapiens
`
`14
`<400>
`gctgctggcg ta
`
`<210>
`
`' <211>
`<212>
`_$213> 0
`<400>
`
`15
`12.
`DNA
`homo sapiens
`
`15
`
`gctggtggtg ta
`
`Page 715 of 1365
`
`13
`
`13
`
`12
`
`12
`
`12
`
`
`
`
`
`
`
`Page 715 of 1365
`
`

`

`PTO/SB/05 (08-08)
`Approved for use through 09/30/2010. OMB 0651-0032
`U.S. Patent and Trademark Office. US. DEPARTMENT OF COMMERCE
`__Under the Paperwork Reduction Act of 1995, no persons are requiredtorespond to a collection of information unlessit displays a validOMB control number.
`
`
`
`UTILITY
`PATENT APPLICATION
`[riefbtomtaLaMPuiricarion|
`TRANSMITTAL
`(Onlyfornewnonprovisionalapplications under37 CFR 1.53(b))|expressMaitabeiNo.|ss
`APPLICATION ELEMENTS
`ADDRESSTO:
` poBeotusoents
`
`See MPEP chapter 600 concerning utility patent application contents.
`Alexandria VA 22313-1450
`
`ACCOMPANYING APPLICATION PARTS
`9. C Assignment Papers (cover sheet & document(s))
`meat
`co That
`Name of Assignee_The Johns Hapkins Universit
`
`
`1. C] Fee Transmittal Form (e.g., PTO/SB/17)
`20] ApplicaMeaimssmal entity status.
`30
`[Total Pages___
`Specification
`Both the claims and abstract muststart on a new page
`(For information on the preferred arrangement, see MPEP 608.01(a))
`4. [7] Drawing(s) (35 U.S.C. 113)
`[Total Sheets
`7
`[]Powerof
`10. [__| 37 CFR 3.73(b) Statement
`5. Oath or Declaration
`[Total Sheets___2
`Attorney
`(whenthere is an assignee)
`a.
`|__| Newly executed (original or copy)
`b. A copyfromaprior application (37 CFR 1.63(d))
`
`for continuation/divisional with Box 18 completed)
`11. L] English Translation Document(if applicable)
`DELETION OF INVENTOR(S)
`Signed statementattached deletinginventor(s)
`12.
`Inforengtion Disclosure Staternent (PTO/SB/08 or PTO-1449)
`namein the prior application, see 37 CFR
`‘ati
`4,63(d)(2)and 4.33(b).
`Copiesofcitations attached
`
`3.
`
`i.
`
`
`
`
`6,
`: 7. CI
`
`13, L-] pretiminary Amendment
`14. oO Return Receipt Postcard (MPEP 503)
`(Shouldbe specifically itemized)
`15. [_] Certified Copyof Priority Document(s)
`(if foreign priority is claimed)
`
`Application Data Sheet. See 37 CFR 1.76
`CD-ROMor CD-Rin duplicate, large table or
`aaRlle
`8. Nucleotide and/or Amino Acid Sequence Submission
`(if applicable, items a. -c. are required)
`a.
`Computer Readable Form (CRF)
`16. [_] Nonpublication Requestunder 35 U.S.C. 122(b)(2)(B)()).
`b.
`Specification SequenceListing an:
`Applicant must attach form PTO/SB/35 or equivalent.
`/
`i. [J CD-ROM or CD-R(2 copies); or
`17. [4] other: Piease use the CRF from parent 09/981,356
`i.
`Paper
`2
`coples)
`filed on Nov. 14, 2003. Contents are identical.
`Statements verifying identity of above copies
`C.
`18. Ifa CONTINUING APPLICATION, check appropriate box, and supply the requisite information below andin the first sentence ofthe
`Specification following the title, or in an Application Data Sheet under 37 CFR 1.76:
`of prior application No.:12/647,368..0.ee
`Continuation
`CI Divisional
`CI Continuation-in-part (CIP)
`
`Art Unit: 1637
`Prior application information:
`Examiner Samuel C. WOOLWINE
`
`
`19. CORRESPONDENCE ADDRESS
`
`The address associated with Customer Number:
`
`22908
`
`OR [| Correspondence address below
`
`a (
`
` Name
`Signature ISarah A. Kagan’
`March 24, 2011
`;
`Registration No. lata
`(Print/Type
`Sarah A. Kagan
`‘Attorney/Agent)
`{22141
`
`This collection of information Is required by 37 CFR 1.53(b). The information is required to obtain or retain a benefit by the public which is to file (and by the
`USPTO to process) an application. Confidentiality is governed by 35 U.S.C. 122 and 37 CFR 1.11 and 1.14. This collection is estimated to take 12 minutes to
`complete, including gathering, preparing, and submitting the completed application form to the USPTO. Time will vary depending upon theindividual case. Any
`comments on the amount oftime you require to complete this form and/or suggestions for reducing this burden, should be sent to the Chief Information Officer,
`U.S. Patent and Trademark Office, U.S. Department of Commerce, P.O. Box 1450, Alexandria, VA 22313-1450. DO NOT SEND FEES OR COMPLETED
`FORMS TO THIS ADDRESS. SEND TO: Commissionerfor Patents, P.O. Box 1450, Alexandria, VA 22313-1450.
`{f you need assistance in completing the form, call 1-800-PTO-9199 and select option 2.
`
`Page 716 of 1365
`
`Page 716 of 1365
`
`

`

`Privacy Act Statement
`
`The Privacy Act of 1874 (P.L. 93-579) requires that you be given certain information in connection
`with your submission of the attached form related to a patent application or patent. Accordingly,
`pursuantto the requirements of the Act, please be advised that: (1) the general authority for the
`collection of this information is 35 U.S.C. 2(b)(2); (2) furnishing of the information solicited is voluntary;
`and (3) the principal purpose for which the information is used by the U.S. Patent and Trademark
`Office is to process and/or examine your submission related to a patent application or patent. If you do
`notfurnish the requested information, the U.S. Patent and Trademark Office may not be able to
`process and/or examine your submission, which mayresult In termination of proceedings or
`abandonmentof the application or expiration of the patent.
`
`The information provided by youin thls form will be subject to the following routine uses:
`
`1. The information on this form will be treated confidentially to the extent allowed underthe
`Freedom ofInformation Act (5 U.S.C. 552) and the Privacy Act (5 U.S.C 552a). Records from
`this system of records may be disclosed to the Departmentof Justice to determine whether
`disclosure of these records Is required by the Freedom of Information Act.
`A record from this system of records may be disclosed, as a routine use, in the course of
`presenting evidence to a court, magistrate, or administrative tribunal, including disclosures to
`opposing counselin the course of settlement negotiations.
`A record in this system of records may be disclosed, as a routine use, to a Memberof
`Congress submitting a request involving an Individual, to whom the record pertains, when the
`individual has requested assistance from the Memberwith respect to the subject matterof the
`record,
`Arecord in this system of records may be disclosed, as a routine use, to a contractorof the
`Agency having needfor the information in order to perform a contract. Recipients of
`information shall be required to comply with the requirements of the Privacy Act of 1974,as
`amended, pursuant to 5 U.S,C. 652a(m).
`A record related to an International Application filed under the Patent Cooperation Treaty In
`this system of records maybe disclosed, as a routine use, to the International Bureau of the
`World Intellectual Property Organization, pursuant to the Patent Cooperation Treaty.
`A record in this system of records may be disclosed, as a routine use, to another federal
`agencyfor purposes of National Security review (35 U.S.C. 181) and for review pursuantto
`the Atomic Energy Act (42 U.S.C. 218(c)).
`A record from this system of records maybe disclosed, as a routine use, to the Administrator,
`General Services, or his/her designee, during an inspection of records conducted by GSA as
`part of that agency's respons)bility to recommend improvements in records management
`practices and programs, underauthority of 44 U.S.C. 2904 and 2906. Such disclosure shall
`be madein accordancewith the GSA regulations governing inspection of records forthis
`purpose, and any otherrelevant(/.e., GSA or Commerce)directive. Such disclosure shall not
`be used fo make determinations aboutindividuals.
`Arecord from this system of records may be disclosed, as a routine use, to the public after
`either publication of the application pursuant to 35 U.S.C. 122(b) or issuance of a patent
`pursuantto 35 U.S.C. 151. Further, a record may be disclosed, subject to the limitations of 37
`CFR 1.14, as a routine use, to the public if the record wasfiled in an application which
`became abandonedorin which the proceedings were terminated and which application is
`referenced by elther a published application, an application open to public inspection or an
`issued patent.
`A tecord from this system of records may be disclosed, as a routine use, to a Federal, State,
`orlocal law enforcement agency,if the USPTO becomesawareof a violation or potential
`violation of law or regulation.
`
`Page 717 of 1365
`
`
`
`
`
`Page 717 of 1365
`
`

`

`PTO/SB/14 (11-08)
`Approved for use through 09/30/2010. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF GOMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unless it contains a valid OMB contro! number.
`
`
`
`
`Attorney Docket Number
`
`Application Data Sheet 37 CFR 1.76
`—
`
`Application Number
`
`
`
`vd Title of Invention|Digital Amplification
`
`The application data sheetis part of the provisional or nonprovisional application for which it is being submitted. The following form contains the
`bibliographic data arranged in a format specified by the United States Patent and Trademark Office as outlined in 37 CFR 1.76.
`
`This document may be completed electronically and submitted to the Office in electronic format using the Electronic Filing System (EFS) or the
`
`
`document may be printed and included in a paperfiled application.
`
`
`
`001107.00866
`
`secrecy Order 37 CFR 5.2
`
`
`
`Remove
`
`| [] Portionsorall ofthe application associatedwiththisApplication Data Sheet mayfall undera Secrecy Orderpursuant|
`37 CFR 5.2 (Paperfilers only. Applications that fall under Secrecy Order may not be filed electronically.)
`Applicant Information:
`
`
`
`
`Applicant 1
`Applicant Authority @)Inventor|C)Legal Representative under 35 U.S.C. 117 Carty ofInterest under 35 U.S.C. 118
`
`Suffix
`Given Name
`Middle Name
`Family Name
`ert
`VOGELSTEIN
`(@) US Residency
`esidenceInformation (Select One)
`(©) NonUS Residency
`() Active US Military Service
`
`Gity|Baltimore Country of Residencei|US
`Citizenship under 37 GFR 1.41(b)i|US
`Mailing Address of Applicant:
`Address 1
`3700 Breton Way
`
`Address 2
`
`Postal Code
`
`21208
`
`US
`
`Applicant2
`Applicant Authority @)Inventor|C)Legal Representative under 35 U.S.C. 117 Carty of Interest under 35 U.S.C. 118
`
`Given Name
`Middle Name
`Family Name
`Suffix
`enneth
`W.
`KINZLER
`
`
`
`
`
`
`
`
`Z||
`
`
`
`
`
`() Active US Military Service
`©) NonUS Residency
`Residence Information (Select One) @) USResidency
`
`Gity|Baltimore State/Province Country of Residencei
`
`
`
`
`
`
`ciy _[Baimoe—SSSSSSCS~*drrovince
`
`
`
`Inventor Information blocks may be
`Inventors Must Be Listed - Additional
`All
`generated within this form by selecting the Add button.
`
`Add
`
`
`
`
`Correspondence Information:
`Enter either Customer Number or complete the Correspondence Information section below.
`For further information see 37 GFR 1.33{a).
`
`
`
`[|] An Addressis being provided for the correspondence Intormation of this application.
`
`Page 718 of 1365
`EFS Web2.2.
`
`
`
`Page 718 of 1365
`
`

`

`PTO/SB/14 (11-08)
`Approved for use through 09/30/2010. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Underthe Paperwork Reduction Act of 1995, no persons are required to respondto a collection of information unlessit contains a valid OMBcontro! number.
`
`Title of Invention|Digital Amplification
`
`
`
`oa. Attorney Docket Number|001107.00866
`
`
`
`Application Data Sheet 37 CFR 1.76
`—
`
`
`Gustomer Number Email Address
`
`Add Email
`
`Remove Email
`
`Application Information:
`
`
`
`Title of the Invention
`Digital Amplification
`
`
`
`
`
`
`
`
`
`Suggested Technology Center(if any) PO
`Total Number of Drawing Sheets (if any)
`Suggested Figure for Publication (if any)
`
`
`
`
`
`
`
`
`
`
`
`Publication Information:
`
`
`[-] Request Early Publication (Fee required at time of Request 37 CFR 1.219)
`Request Not to Publish. | hereby requestthat the attached application not be published under 35 U.S.
`
`
`[-] ©. 122(b) and certify that the invention disclosedin the attached application has not and will not be the subject of
`
`
`an applicationfiled in another country, or under a multilateral international agreement, that requires publication at
`
`
`eighteen monthsafterfiling.
`
`
`Representative Information:
`
` Representative information should be provided for all practitioners having a power of attorney in the application. Providing
`
`
`
`
`
`Please Select One: © US Patent Practitioner|(Limited Recognition (37 CFR 11.9)(e) Customer Number
`
`
`
`
`
`Customer Number
`22907
`
`this informationin the Application Data Sheet does not constitute a powerof attorney in the application {see 37 CFR 1.32).
`Enter
`either Customer Number
`or
`complete
`the Representative Name
`section
`below.
`If
`both
`are completed the Customer Numberwill be used for the Representative Information during processing.
`
`sections
`
`Domestic Benefit/National Stage Information:
`
`
`This section allowsfor the applicant to either claim benefit under 35 U.S.C. 119(e), 120, 121, or 365(c) or indicate National Stage
`entry from a PCTapplication. Providing this information in the application data sheet constitutes the specific reference required by
`35 U.S.C. 119(e) or 120, and 37 CFR 1.78(a)(2) or CFR 1.78(a)(4), and need not otherwise be made part of the specification.
`
`
`
`
`
`
`
`
`2009-11-12
`Po Continuation of
`Prior Application Status . [Remove]
`
`
`
`
`
`
`Page 719 of 1365
`EFS Web 2.2.2
`
`Page 719 of 1365
`
`

`

`PTO/SB/14 (11-08)
`Approved for use through 09/0/2010. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`
`Underthe Paperwork Reduction Act of 1995, no persons are required to respondto a collection of information untessit contains a valid OMB control number.
`
`Attorney Docket Number|001107.00866
`
`Application Number
`
`Application Data Sheet 37 CFR 1.76
`
`Title of Invention|Digital Amplification
`
`Application
`Number
`12617368
`
`Issue Date
`Filing Date
`a
`(YYYY-MM-DD)
`Patent Number
`(YYYY-MM-DD)
`Continuity Type
`
`
`
`11709742 2007-02-23 7824889Continuation of 2010-11-02
`
`Prior Application
`
`
`
`
`Prior Application Status|Abandoned
`
`Application Number Prior Application Number|—Filing Date (YYYY-MM-DD)Continuity Type
`
`
`11709742
`Continuation of
`10828295
`2004-04-21
`
`
`Prior Application Status|Patented Remove
`
`
`Application
`Prior Application
`Filing Date
`Issue Date
`Number (YYYY-MM-DD)|PatentNumber|(yyyy-m_-DD)Continuity Type Number
`
`
`
`
`40828295
`09981356
`Division of
`2001-10-12
`6753147
`2004-06-22
`
`Prior Application Status|Patented
`Application
`a
`Prior Application
`Filing Date
`Issue Date
`Number (YYYY-MM-DD)|PatentNumber|(yyyy-vim-DD)Continuity Type Number
`
`
`
`09981356
`2000-07-11
`2002-08-27
`
`by selecting the Add button.
`
`Prior Application Status
`
`Application Number
`09613826
`
`60146792
`
`Filing Date (YYYY-MM-DD)
`1999-08-02
`
`Additional Domestic Benefit/National Stage Data may be generated within this form
`
`
`
`
`
`Foreign Priority Information:
`This section allows for the applicant to claim benefit of foreign priority and to identify any prior foreign application for whichpriority is
`not claimed. Providing this information in the application data sheet constitutes the claim for priority as required by 35 U.S.C. 119(b)
`and 37 CFR 1.55(a).
`
`Add button.
`
`
`Priority Claimed
`Parent Filing Date (YYYY-MM-DD)
`Country |
` Application Number
`PO0No
`Additional Foreign Priority Data may be generated within this form by selecting the
`
`
`Assignee Information:
`Providing this information in the application data sheet does not substitute for compliance with any requirement of part 3 of Title 37
`of the CFRto have an assignment recordedin the Office.
`
`Assignee 1
`If the Assignee is an Organization check here.
`
`Organization Name|The Johns Hopkins University
`
`
`
`Page 720 of 1365
`EFS Web 2.2.2
`
`Page 720 of 1365
`
`

`

`Title of Invention|Digital Amplification
`
`PTO/SB/14 (11-08)
`Approved for use through 09/30/2010. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Underthe Paperwork Reduction Act of 1895, no persons are required to respondto a collection ofinformation unlessit contains a valid OMBcontrol number.
`
`
`
`oo. Attorney Docket Number|001107.00866
`Application Data Sheet 37 CFR 1.76
`—
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Additional Assignee Data may be generated within this form by selecting the Add
`button.
`
`-
`
`
`
`
`
`Signature:
`
`A signature ofthe applicant or representative is required in accordance with 37 CFR 1.33 and 10.18. Please see 37
`CFR 1.4(d) for the form of the signature.
`
`Signature
`
`|/Sarah A. Kagan/
`
`Date (YYYY-MM-DD)|
`
`2011-03-24
`
`This collection of information is required by 37 CFR 1.76. The information is required to obtain or retain a benefit by the public which
`is to file (and by the USPTO to process) an application. Confidentiality is govemed by 35 U.S.C. 122 and 37 CFR 1.14. This
`collection is estimated to take 23 minutes to complete, including gathering, preparing, and submitting the completed application data
`sheet form to the USPTO. Timewill vary depending upon theindividual case. Any comments on the amountoftime you require to
`complete this form and/or suggestions for reducing this burden, should be sent to the Chief Information Officer, U.S. Patent and
`Trademark Office, U.S. Department of Commerce, P.O. Box 1450, Alexandria, VA 22313-1450. DO NOT SEND FEES OR
`COMPLETED FORMS TO THIS ADDRESS. SEND TO: Gommissionerfor Patents, P.O. Box 1450, Alexandria, VA 22313-1450.
`
`
`
`Page 721 of 1365
`EFS Web 2.2.2
`
`Page 721 of 1365
`
`

`

`Privacy Act Statement
`
`
`
`The Privacy Act of 1974 (P.L. 93-579) requires that you be given certain information In connection with your submission of the attached form related to
`a patent application or patent. Accordingly, pursuant to the requirements of the Act, please be advised that: (1) the general authority for the collection
`ofthis information is 35 U.S.C. 2(b)(2); (2) furnishing of the Information solicited is voluntary; and (3) the principal purpose for which theinformation is
`used by the U.S. Patent and Trademark Office Is to process and/or examine your submission related to a patent application or patent.
`If you do not
`furnish the requested information, the U.S. Patent and Trademark Office may not be able to process and/or examine your submission, which may
`result in termination of proceedings or abandonmentof the application or expiration of the patent.
`
`Theinformation provided by you in this form will be subject to the following routine uses:
`
`1.
`
`The information on this form will be treated confidentially to the extent allowed under the Freedom of information Act (6 U.S.C. 552)
`and the Privacy Act (5 U.S.C, 552a). Records from this system of records may be disclosed to the Departmentof Justice to determine
`whether the Freedom of Information Act requires disclosure of these records.
`
`A record from this system of records may be disclosed, as a routine use, in the course of presenting evidence to a court, magistrate, or
`administrative tribunal, including disclosures to opposing counsel in the course of settlement negotiations.
`
`A record in this system of records may be disclosed, as a routine use, to a Member of Congress submitting a requestinvolving an
`individual, to whom the record pertains, whentheindividual has requested assistance from the Memberwith respect to the subject matter of
`the record.
`
`A record in this system of records may be disclosed, as a routine use, to a contractor of the Agency having needfor the information in
`order to perform a contract. Recipients of information shall be required to comply with the requirementsof the Privacy Act of 1974,as
`amended, pursuant to 5 U.S.C. 552a(m).
`
`A record related to an International Application filed under the Patent Cooperation Treaty in this system of records may be disclosed,
`as a routine use, to the International Bureau of the World Intellectual Property Organization, pursuant to the Patent Cooperation Treaty.
`
`A recordin this system of records may be disclosed, as a routine use, to another federal agency for purposes of National Security
`review (35 U.S.C. 181) and for review pursuant to the Atomic Energy Act (42 U.S.C. 218(c)).
`
`A record from this system of records may be disclosed, as a routine use, to the Administrator, General Services, or his/her designee,
`during an inspection of records conducted by GSAaspart of that agency’s responsibility to recommend improvementsin records
`management practices and programs, under authority of 44 U.S.C. 2904 and 2906. Such disclosure shall be madein accordance with the
`GSAregulations governing inspection of records for this purpose, and anyotherrelevant (i.e., GSA or Commerce)directive. Such
`disclosure shall not be used to make determinations aboutindividuals.
`
`A record from this system of records may be disclosed, as a routine use, to the public after either publication of the application pursuan
`to 35 U.S.C. 122(b) or issuance of a patent pursuant to 35 U.S.C. 151. Further, a record may be disclosed, subjectto the limitations of 37
`CFR 1.14, as a routine use, to the public if the record wasfiled in an application which became abandonedorin which the proceedings were!
`terminated and which application is referenced by either a published application, an application open to public inspections or an issued
`patent.
`
`A record from this system of records may be disclosed, as a routine use, to a Federal, State, or local law enforcement agency,if the
`USPTO becomesawareof a violation or potential violation of law or regulation.
`
`EFS Web 2.2.2
`
`
`
`
`Page 722 of 1365
`
`

`

`2 &
`
`at
`—
`iy
`;
`4
`JOINT DELARATION FOR PATENT APPL. ATION
`
`As the below named inventor, we hereby declare that:
`
`Ourresidence, post office address and citizenship are as stated below next to our names;
`
`Webelieve weare the original, first and joint inventors of the subject matter which is claimed and for which a
`
`patent is sought on the invention entitledDIGITALAMPLIFICATION,the specification of which
`0
`is attached hereto.
`
`id wasfiled onJuly11,2000as Application Serial Number 09/613,826 and was amended on (if
`applicable).
`wasfiled under the Patent Cooperation Treaty (PCT)and accorded International Application
`No.filedand amendedon if any).
`
`O
`
`Weherebystate that we have reviewed and understand the contents of the above identified specification,
`including the claims, as amended by any amendmentreferred to above,
`
`Wehereby acknowledgethe duty to disclose information which is material to patentability in accordance with —
`Title 37, Code of Federal Regulations, §1.56(a).
`.
`
`Prior Foreign Application(s)
`Weherebyclaim foreign priority benefits underTitle 35, United States Code, §119 ofany foreign application(s)
`for patent or inventor's certificate listed below and havealso identified below any foreign application(s) for patent or
`inventor's certificate having a filing date before that of the application on which priority is claimed:
`
`
`Date ofFiling
`(day month year)
`
`
`'
`+e
`ApplicationNo,
`
`Date of Issue
`(day month year)
`
`Priority Claimed
`Under 35 U.S.C. §119
`
`
`
`
`
`:
`.
`U.S. Provisional Application No.
`caae TR
`
`:
`
`
`
`
`
`
`.
`Prior United States Application(s)
`Weherebyclaiin thie benefit underTitle 35, United States Code, §120 ofany United States application(s) listed -
`below and,insofar as the subject matter ofeach ofthe claimsofthis application is not disclosed in the prior United States
`application in the mannerprovided bythefirst paragraph ofTitle 35, United States Code, §112, we acknowledgethe duty
`to disclose material information as defined in Title 37, Code of Federal Regulations, §1.56(a) which occurred between
`the filing date of the prior application and the national or PCT internationalfiling date of this application:
`
`Prior United States Provisional Application(s)
`Wehereby claim priority benefits under Title 35, United States Code, §119(e)(1) of any U.S. provisional
`application listed below:
`
`
`
`DateofFiling
`(day month year)
`
`02 Avge199
`
`Priority Claimed
`Under 35 U.S.C. §119(e)(1)
`
`
`
`
`
`
`
`
`
`:
`as
`+
`Application Seriat No.
`
`
`
`DateofFiling
`(Day, Montb, Year)
`
`,
`
`Status — Patented
`Pending, Abandoned
`
`
`
`
`
`
`Banner & Wrcorr, Lip.
`
`Attomey Docket No. 0! 107.00034
`
`‘age
`
`Page 723 of 1365
`
`
`
`Page 723 of 1365
`
`

`

`And weherebyappoint, both jointly atid severally,as our attonieys with fullpower ofSubstitutionatid revocation; toprosecute’
`this application and to transact all business in the Patent and Trademark Office connected herewith the following attomeys andagents, their
`registration numbers beinglisted afler their names:
`
`Powerof Attorney
`
`31,810
`ALTHERR,Robert F.
`47,037
`BANNER, Donald W.
`29,888
`BANNER,Mark FT.
`33,644
`BANNER,Pamela I.
`18,262
`BECKETT,William W.
`42,338
`BODNER,Jordan
`42,373
`BUROW,Scott A.
`20,095
`CALLAHAN,James V.
`42,402
`CHANG,Steve S
`40,959
`COHAN,Gregory J.
`34,143
`COOPERMAN,Marc S.
`34,571
`CURTIN,Joseph P.
`39,504.
`DAWSON,John R.
`39,654
`DEMOOR,Laura J.
`35,805
`EVANS,ThomasL.
`35,509
`FEDOROCHKO,Gary D.
`32,133
`FISHER,William J.
`GLEMBOCKI, Christopher R.38,800
`HANLON,BrianE.
`40,449
`HEMMENDINGER,Lisa M.42,653
`HONG,Patricia E.
`34,373,
`
`19,090
`HOSCHEIT,Dale H.
`34,628
`IWANICK],John P.
`29,808
`JACKSON,ThomasH.
`32,141
`KAGAN,Sarah A.
`36,402
`KATZ,Robert S.
`43,719
`KLEIN, William J,
`32,578
`KRAUSE,Joseph P.
`29,822
`LINEK,Emest V.
`"32,155
`MALONE,Dale A.
`45,301
`MANNAVA,Ashok K.
`29,411
`McDERMOTT, PeterD.
`32,384
`McKEE,Christopher L.
`17,335
`McKIE, Edward F.
`29,673
`MEDLOCK,Nina L.
`38,553
`MEECE,Timothy C.
`35,282
`MEEKER,Frederic M.
`43,805
`MILLER,Charles L.
`43,808
`MITRIUS,Janice V.
`MORENO,Christopher P. 38,566
`NELSON,Jon OQ.
`24,566
`NIEGOWSKI, James A.
`28,331
`
`PATEL,BinalJ.
`PATRAK,AjayS.
`PAYNE,Stephen S.
`PETERSON, ThomasL.
`* POTENZA,Joseph M.
`PRATT,ThomasK.
`RENK,ChristopherJ.
`RESIS, Robert H.
`RIVARD,Paul M.
`SCHAD,Steve P.
`SHANAHAN,Michael H.
`SHIFLEY,Charles W.
`SKERPON,Joseph M.
`STOCKLEY,D.3.
`VANES,J. Picter
`WITCOFF,Sheldon W.
`WOLFFE,Franklin D.
`WOLFFE,Susan A.
`WRIGHT,Bradley C,
`
`42,065
`38,266
`35,316
`30,969
`28,175
`37,210
`33,763
`32,168
`43,446
`32,550
`24,438
`28,042
`29,864
`34,257
`37,746
`17,399
`19,724
`33,568
`38,061
`
`All correspondence and telephone communications should be addressed to:
`Banner & Witcoff, Ltd.
`Customer Number: 22907
`1001 G Sweet, N.W., 11th Floor
`Tel: (202) 508-9100
`Washington, D.C. 20001-4597
`Fax: (202) 508-9299
`
`We hereby declare that afl statements made herein of our own knowledgeare true and thalall statements made on information
`and beliefare believed to be true; and furtherthat these statements were made with the knowledge that willful false statements and the
`like so madeare punishable by fine or imprisonment, or both, under Section 1001 of Tile 18 of the United States Code andthat such
`willful false stglements may jeopardize (fe validity of the application or any patent issuing thercon.
`
`
`
`.
`
`A gl
`Date.
`&
`(( 2
`Signature.
`Bert
`in
`Full NameofFiést Inventor, Wa og
`
`LC/ Family Name First GivenName econd GivenName
`
`Residence___
`Baltimore, Maryland
`Citizenship United States
`Post Office Address,
`
`wv,
`
`
`
`
`
`wae 112¢H00
`"Signature_
`
`Full Nameof SecondInventor,
`.
`Second Given Name
`Family Name
`First Given Name
`‘Residence.
`Citizenship_ United States
`
`
`
`
`Post Office Address___1403 HalkirkWay,BelAir,Maryland21015
`
`
`
`Banner & Wircorr, 11D.
`
`Page 724 of 1365
`
`Attomey Docket No. 01 107.0003 Lage
`
`Page 724 of 1365
`
`

`

`
`
`PATENT
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Prior Group Art Unit: 1637
`
`Prior Examiner: Samuel Woolwine
`
`Confirmation No. TBD
`
`Atty. Dkt. No. 001107.00866
`
`)
`)
`)
`)
`)
`
`))
`
`) )
`
`)
`
`In re Application of
`
`Bert VOGELSTEIN etal
`
`Continuation Application of
`Serial No. 12/617,368
`
`Filed: Herewith
`
`For:
`
`DIGITAL AMPLIFICATION
`
`
`RECOGNITION OF PRACTITIONERS OF RECORD UNDER 37 C.E.R, § 1.32(c)(3)
`
`U.S. Patent and Trademark Office
`Customer Service Window
`Randolph Building
`401 Dulany Street
`Alexandria, VA 22314
`
`Sir:
`
`Pursuant to 37 C.F.R. § 1.32(c)(3), please recognize the following patent practitioners, originally
`
`named in the Power of Attorney from an earlier-filed application, as being of record in the above-
`
`identified application:
`
`
`
`Sarah A. Kagan
`Dale H. Hoscheit
`Joseph M.Skerpon
`Lisa M. Hemmendinger —
`William J. Fisher
`
`32,141
`19,090
`29,864
`42,653
`32,133
`
`A copy of the Power of Attorney from the earlier-filed application is submitted herewith.
`
`Respectfully submitted,
`BANNER & WITCOFF, LTD.
`
`
`
`Dated: March 24, 2011 By:|/SARAHA, KAGAN/
`Sarah A. Kagan
`Registration No. 32,141
`
`Customer No. 22907
`
`Page 725 of 1365
`
`Page 725 of 1365
`
`

`

`DIGITAL AMPLIFICATION
`
`The U.S. governmentretains certain rights in this invention by virtue of
`
`its support of the underlying research, supported by grants CA 43460, CA
`
`57345, and CA 62924 from the National Institutes of Health.
`
`The disclosureofall claimed priority applications is expressly
`
`incorporated herein.
`
`TECHNICAL FIELD OF THE INVENTION
`
`This inventionis related to diagnostic genetic analyses, In particularit
`
`relates to detection of genetic changes and gene expression.
`
`BACKGROUND OF THE INVENTION
`
`In classical genetics, only mutations of the germ-line were considered
`
`important for understanding disease. With the realization that somatic
`
`new genetic principles have arisen. These discoveries have provided a wealth
`
`of new opportunities for patient managementas well as for basic research into
`the pathogenesis of neoplasia. However, many of these opportunities hinge
`
`upon detection of a small number ofmutant-containing cells among a large
`
`excess ofnormalcells. Examples include the detection of neoplastic cells in
`
`urine, stool, and sputum of patients with cancers of the bladder, colorectum,
`
`and lung, respectively. Such detection has been shown in somecases to be
`
`possible at a stage when the primary tumorsare still curable and the patients
`asymptomatic. Mutant sequences from the DNA ofneoplastic cells have also
`
`been found in the blood of cancerpatients. The detection of residual disease in
`
`lymph nodesor surgical margins may be useful in predicting which patients
`
`Page 726 of 1365
`
`mutationsare the primary cause of cancer, and mayalsoplayarole in aging,
`
`
`
`
`Page 726 of 1365
`
`

`

`might benefit most from further therapy. From a basic research standpoint,
`analysis of the early effects of carcinogensis often dependent on the ability to
`
`detect small populations of mutantcells.
`
`Becauseof the importance of this issue in so many settings, many
`
`useful techniques have been developed for the detection of mutations. DNA
`sequencing is the gold standardfor the detection of germ line mutations, but is
`
`useful only when the fraction of mutatedalleles is greater than ~20%.
`
`Mutant-specific oligonucleotides can sometimes be used to detect mutations
`present in a minor proportionofthe cells analyzed, but the signal to noise ratio
`
`distinguishing mutant and wild-type (WT) templates is variable. The use of
`mutant-specific primers or the digestion ofpolymerase chain reaction (PCR)
`
`products with specific restriction endonucleases are extremely sensitive
`
`methods for detecting such mutations,butit is difficult to quantitate the
`
`fraction of mutant moleculesin the starting population with these techniques.
`
`Other innovative approachesfor the detection of somatic mutations