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`WIPO
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`DOCUMENT MADE AVAILABLE UNDER THE
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`PATENT COOPERATION TREATY (PCT)
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`International application number:
`
`PCT/US2013/058061
`
`International filing date:
`
`04 September 2013 (04.09.2013)
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`Document type:
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`Document details:
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`Certified copy of priority document
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`Country/Office:
`Number:
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`US
`61/845,987
`13 July 2013 (13.07.2013)
`
`Date of receipt at the International Bureau:
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`13 September 2013 (13.09.2013)
`
`Remark: Priority document submitted or transmitted to the International Bureau in compliance with Rule
`17.1(a),(b) or (b-bis)
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`“ES 1) E‘ PARTM EN!“ 0!“ C()I=\’iii\~‘ll€9R(TE
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`United States Patent and? ‘Tradenuu‘k ()ffiet
`
`
`September 12, 2013
`
`
`
`
`
` THIS IS TO CERTIFY THAT ANNEXED HERETO IS A TRUE COPY FROM
`
`
`THE RECORDS OF THE UNITED STATES PATENT AND TRADEMARK
`OFFICE OF THOSE PAPERS OF THE BELOW IDENTIFIED PATENT
`
`
`
`
`
`
`APPLICATION THAT MET THE REQUIREMENTS TO BE GRANTED A
`FILING DATE.
`
`APPLICATION NUMBER: 61/845,987
`FILING DATE: July 13, 2013
`RELATED PCT APPLICATION NUMBER: PCT/USl3/58061
`
` THE COUNTRY CODE AND NUMBER OF YOUR PRIORITY
`APPLICATION, TO BE USED FOR FILING ABROAD UNDER THE PARIS
`CONVENTION, IS US61/845,987
`
`
`
`Certified by
`
`
` 111,443,914”;«vow/aux:
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`Pamm and ‘I’radmxmrk 0me
`
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`Doc Code: TR.PROV
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`Document Description: Provisional Cover Sheet (8816)
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`PTOISBJ16 (11-08)
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`Provisional Application for Patent Cover Sheet
`This is a request for filing a PROVISIONAL APPLICATION FOR PATENT under 37 CFR 1.53(c)
`
`lnventor(s)
`
`Inventor 1
`Remove
`
`
`Given Name
`Middle Name
`Family Name
`City
`State
`Country i
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`
`AmirAli
`Talasaz
`Menlo Park
`CA
`US
`
`
`Inventor 2
`Remove
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`Given Name
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`Middle Name
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`Family Name
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`City
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`State
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`Country i
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`All Inventors Must Be Listed— Additional Inventor Information blocks may be
`generated within this form by selecting the Add button.
`
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`Title Of Invention
`
`Systems and Methods to Detect Rare Mutations and Copy Number Variation
`
`Attorney Docket Number (if applicable)
`
`42534-704_104
`
`
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`Correspondence Address
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`Direct all correspondence to (select one):
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`Q) The address corresponding to Customer Number 0 Firm or Individual Name
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`Customer Number
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`1 15823
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`The invention was made by an agency of the United States Government or under a contract with an agency of the United
`States Government.
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`6) No.
`
`0 Yes, the invention was made by an agency of the United States Government. The US. Government agency name is:
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`0 Yes, the invention was under a contract with an agency of the United States Government. The name of the US.
`Government agency and Government contract number are:
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`Doc Code: TR.PROV
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`Document Description: Provisional Cover Sheet (8816)
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`PTOISBJ16 (11-08)
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`Entity Status
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`Warning
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`Signature
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`Signature
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`First Name
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`Please see 37 CFR 1.4(d) for the form of the signature.
`
`[John R. Storella/
`
`Date (YYYY-MM-DD)
`
`2013-07-13
`
`John R.
`
`Last Name
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`Storella
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`32944
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`PTOIAIA/t 4 (03-13)
`Approved for use through 0181/2014. OMB 0651—0032
`U.S. Patent and Trademark Office; US. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of1995, no persons are required to respond to a collection of information unless it contains a valid OMB control number.
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`Application Data Sheet 37 CFR 1.76
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`_
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`_
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`document may be printed and included in a paper filed application.
`
`Title Of Invention
`
`SYSTEMS AND METHODS TO DETECT RARE MUTATIONS AND COPY NUMBER VARIATION
`
`The application data sheet is 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.
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`Secrecy Order 37 CFR 5.2
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`I:I Portions or all of the application associated with this Application Data Sheet may fall under a Secrecy Order pursuant to
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`Inventor Information:
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`Inventor
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`1
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`Legal Name
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`Prefix Given Name
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`Middle Name
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`Family Name
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`Residence Information (Select One) @ US Residency 0 Non US Residency 0 Active US Military Service
`
`Menlo Park I US StatelProvince Country of Residence I
`
`
`
`Mailing Address of Inventor:
`
`Address 1
`
`2181 Camino a Los Cerros
`
`Address 2
`
`
`City
`
`Menlo Park
`
`StatelProvince
`
`
`Inventor
`2
`
`Legal Name
`
`mM—m
`-———-
`Residence Information (Select One) @ US Residency 0 Non US Residency 0 Active US Military Service
`StatelProvince Country of Residence I
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`Mailing Address of Inventor:
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`Address 1
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`2 Barry Lane
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`AddressZ
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`
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`City
`I Atherton
`I StatelProvince
`I CA
`Postal Code
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`Under the Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unless it contains a valid OMB control number.
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`_
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`Application Data Sheet 37 CFR 1.76
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`Attorney Docket Number
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`_
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`42534-704104
`
`Title of Invention
`
`
`SYSTEMS AND METHODS TO DETECT RARE MUTATIONS AND COPY NUMBER VARIATION
`
`|:| An Address is being provided for the correspondence Information of this application.
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`Customer Number
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`115823
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`Email Address
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`mskubatch@wsgr.com
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`Application Information:
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`
`
`Title of the Invention SYSTEMS AND METHODS TO DETECT RARE MUTATIONS AND COPY NUMBER VARIATION
`
`
`Attorney Docket Number 42534-704104
`Small Entity Status Claimed
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`Provisional
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`Subject Matter
`Utility
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`Suggested Figure for Publication (if any) -
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`|:| Request Early Publication (Fee required at time of Request 37 CFR 1.219)
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`El
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`Request Not to Publish. I hereby request that the attached application not be published under
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`publication at eighteen months after filing.
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`Representative Information:
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`0 Limited Recognition (37 CFR 11.9)
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`Customer Number 115823
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`Domestic Benefit/National Stage Information:
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`This section allows for the applicant to either claim benefit under 35 U.S.C. 119(e), 120, 121, or 365(c) or indicate
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`specific reference required by 35 U.S.C. 119(e) or 120, and 37 CFR 1.78.
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`PTOIAIA/t 4 (03-13)
`Approved for use through 0181/2014. OMB 0651—0032
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`Under the Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unless it contains a valid OMB control number.
`
`_
`_
`Application Data Sheet 37 CFR 1.76
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`Attorney Docket Number
`_
`_
`
`42534-704104
`
` Title of Invention
`
`SYSTEMS AND METHODS TO DETECT RARE MUTATIONS AND COPY NUMBER VARIATION
`
`Foreign Priority Information:
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`This section allows for the applicant to claim priority to a foreign application. Providing this information in the application data sheet
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`property office, or a certified copy of the foreign priority application is filed, within the time period specified in 37 CFR 1.55(g)(1).
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`This application (1) claims priority to or the benefit of an application filed before March 16, 2013 and (2) also
`contains, or contained at any time, a claim to a claimed invention that has an effective filing date on or after March
`|:| 16, 2013.
`NOTE: By providing this statement under 37 CFR 1.55 or 1.78, this application, with a filing date on or after March
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`Under the Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unless it contains a valid OMB control number.
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`_
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`Application Data Sheet 37 CFR 1.76
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`Attorney Docket Number
`_
`_
`
`42534-704104
`
`Title of Invention
`
`
`SYSTEMS AND METHODS TO DETECT RARE MUTATIONS AND COPY NUMBER VARIATION
`
`If checked the undersigned hereby grants the USPTO authority to provide the European Patent Office (EPO)
`the Japan Patent Office (JPO) the Korean Intellectual Property Office (KIPO), the World Intellectual Property Office (WIPO)
`and any other intellectual property offices in which a foreign application claiming priority to the instant patent application
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`does not wish the EPO, JPO, KIPO, WIPO, or other intellectual propeIty office In which a foreign application claiming priority
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`In accordance with 37 CFR 1.14(h)(3), access will be provided to a copy of the instant patent application with respect
`to: 1) the instant patent application-as—filed; 2) any foreign application to which the instant patent application
`claims priority under 35 U.S.C. 119(a)—(d) if a copy of the foreign application that satisfies the certified copy requirement of
`37 CFR 1.55 has been filed in the instant patent application; and 3) any US. application-as-filed from which benefit is
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`Applicant Information:
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`Providing assignment information in this section does not substitute for compliance with any requirement of part 3 of Title 37 of CFR
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`If the applicant is the inventor (or the remaining joint inventor or inventors under 37 CFR 1.45), this section should not be completed.
`The information to be provided in this section is the name and address of the legal representative who is the applicant under 37 CFR
`1.43; or the name and address of the assignee, person to whom the inventor is under an obligation to assign the invention, or person
`who otherwise shows sufficient proprietary interest in the matter who is the applicant under 37 CFR 1.46. If the applicant is an
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`Guardant Health, Inc.
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`Address 1
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`2686 Mlddlefield Rd, Suite D
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`Add ress 2
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`City StatelProvince Redwood City
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`PTOIAIA/t 4 (03-13)
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`Under the Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unless it contains a valid OMB control number.
`
`.
`
`.
`
`Application Data Sheet 37 CFR 1.76
`
`Application Number
`
`
`
`Title of Invention
`
`SYSTEMS AND METHODS TO DETECT RARE MUTATIONS AND COPY NUMBER VARIATION
`
`Email Address
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`Additional Applicant Data may be generated within this form by selecting the Add button.
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`Add
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`Non-Applicant Assignee Information:
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`Providing assignment information in this section does not subsitute for compliance with any requirement of part 3 of Title 37 of CFR to
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`Assignee 1
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`Complete this section only if non-applicant assignee information is desired to be included on the patent application publication in
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`If the Assignee is an Organization check here.
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`|:|
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`Mailing Address Information:
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`Address 1
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`Address 2
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`Country i
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`Phone Number
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`Postal Code
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`Fax Number
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`Additional ASSIQnee Data may be generated Within this form by selecting the Add button.
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`Signature:
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`NOTE: This form must be signed in accordance with 37 CFR 1.33. See 37 CFR 1.4 for signature requirements and
`certifications
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`Additional Signature may be generated within this form by selecting the Add button.
`
`
`
`
`
`lJohn R. StorellalSignature 2013—07-13 Date (YYYY-MM-DD)
`
`First Name
`
`John R.
`
`Last Name
`
`Registration Number
`
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`Application Data Sheet 37 CFR 1.76
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`Application Number
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`SYSTEMS AND METHODS TO DETECT RARE MUTATIONS AND COPY NUMBER VARIATION
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`PROVISIONAL PATENT APPLICATION
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`SYSTEMS AND METHODS TO DETECT RARE MUTATIONS AND COPY
`NUMBER VARIATION
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`Docket No. 42534-704104
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`Invcntor(s): AmirAli Talasaz,
`a citizen of the United States,
`2181 Camino a Los Cerros
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`Menlo Park, CA 94025
`
`Helmy Eltoukhy
`a citizen of the United States,
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`2 Barry Lane
`Atherton, CA 94027
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`Assignee:
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`Guardant Health, Inc.
`2686 Middlefield Rd, Suite D
`Redwood City, CA 94063 USA.
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`Entity:
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`Large
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`Filed Electronically on: July 13, 2013
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`SYSTEMS AND METHODS TO DETECT RARE MUTATIONS AND COPY NUMBER
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`VARIATION
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`BACKGROUND OF THE INVENTION
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`[0001] The detection and quantification of polynucleotides is important for molecular biology and
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`medical applications such as diagnostics. Genetic testing is particularly useful for a number of
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`diagnostic methods. For example, disorders that are caused by rare genetic alterations (e.g.,
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`sequence variants) or changes in epigenetie markers, such as cancer and partial or complete
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`aneuploidy, may be detected or more accurately characterized with DNA sequence information.
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`[0002] Early detection and monitoring of genetic diseases, such as cancer is often useful and needed
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`in the successful treatment or management of the disease. One approach may include the monitoring
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`of a sample derived from cell free nucleic acids, a population of polynucleotides that can be found in
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`different types of bodily fluids. In some cases, disease may be characterized or detected based on
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`detection of genetic aberrations, such as a change in copy number variation and/or sequence variation
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`of one or more nucleic acid sequences, or the development of other certain rare genetic alterations.
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`Cell free DNA has been known in the art for decades, and may contain genetic aberrations associated
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`with a particular disease. With improvements in sequencing and techniques to manipulate nucleic
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`acids, there is a need in the art for improved methods and systems for using cell free DNA to detect
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`and monitor disease.
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`SUMMARY OF THE INVENTION
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`[0003] The disclosure provides for a method for detecting copy number variation comprising: a)
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`sequencing extracellular polynucleotides from a bodily sample from a subject, wherein each of the
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`extracellular polynucleotide are optionally attached to unique barcodes; b) filtering out reads that fail
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`to meet a set threshold; c) mapping sequence reads obtained from step (a) to a reference sequence; d)
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`quantifying/counting mapped reads in two or more predefined regions of the reference sequence; e)
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`determining a copy number variation in one or more of the predefined regions by (i) normalizing the
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`number of reads in the predefined regions to each other and/or the number of unique barcodes in the
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`predefined regions to each other; and (ii) comparing the normalized numbers obtained in step (i) to
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`normalized numbers obtained from a control sample.
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`[0004] The disclosure also provides for a method for detecting a rare mutation in a cell-free or
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`substantially cell free sample obtained from a subject comprising: a) sequencing extracellular
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`polynucleotides from a bodily sample from a subject, wherein each of the extracellular
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`-2-
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`polynucleotide generate a plurality of sequencing reads; sequencing extracellular polynucleotides
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`from a bodily sample from a subject, wherein each of the extracellular polynucleotide generate a
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`plurality of sequencing reads; b) sequencing extracellular polynucleotides from a bodily sample from
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`a subject, wherein each of the extracellular polynucleotide generate a plurality of sequencing reads;
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`sequencing extracellul