`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Addl'fiss. COMMISSIONER FOR PATENTS
`PO Box 1450
`Alexandria, ViJgLnia 22313-1450
`wwwuspto.gov
`
`APPLICATION
`NUMBER
`
`FILING or
`371(c) DATE
`
`GRP ART
`UNIT
`
`
`
`
`
`F
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`62/169,112
`
`06/01/2015
`
`FEE REC'D
`
`130
`
`72960
`
`33%”‘391‘11‘331’13, SUITE 310
`
`MIDDLETON, WI 53562
`
`ATTY.DOCKET.NO
`
`TOT CLAHVIS IND CLAIMS
`
`UCHI-34458/US-1fl3RO
`
`CONFIRMATION NO. 3728
`
`FILING RECEIPT
`
`IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII
`
`Date Mailed: 06/11/2015
`
`It will not be examined for patentability and will
`Receipt is acknowledged of this provisional patent application.
`become abandoned not later than twelve months after its filing date. Any correspondence concerning the application
`must include the following identification information: the U.S. APPLICATION NUMBER, FILING DATE, NAME OF
`APPLICANT, and TITLE OF INVENTION. Fees transmitted by check or draft are subject to collection. Please verify
`the accuracy of the data presented on this receipt. If an error is noted on this Filing Receipt, please submit
`a written request for a Filing Receipt Correction. Please provide a copy of this Filing Receipt with the
`changes noted thereon. If you received a "Notice to File Missing Parts" for this application, please submit
`any corrections to this Filing Receipt with your reply to the Notice. When the USPTO processes the reply
`to the Notice, the USPTO will generate another Filing Receipt incorporating the requested corrections
`
`lnventor(s)
`
`Applicant(s)
`
`Thomas F. Gajewski, Chicago, IL;
`Ayelet Sivan, Chicago, IL;
`Leticia Corrales, Chicago, IL;
`
`The University of Chicago, Chicago, IL
`
`Power of Attorney:
`David Staple-65903
`
`Permission to Access - A proper Authorization to Permit Access to Application by Participating Offices
`(PTO/SB/39 or its equivalent) has been received by the USPTO.
`
`If Required, Foreign Filing License Granted: 06/10/2015
`
`The country code and number of your priority application, to be used for filing abroad under the Paris Convention,
`is US 62/169,112
`
`Projected Publication Date: None, application is not eligible for pre-grant publication
`
`Non-Publication Request: No
`
`Early Publication Request: No
`** SMALL ENTITY **
`Title
`
`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`
`Statement under 37 CFR 1.55 or 1.78 for AIA (First Inventor to File) Transition Applications: No
`page 1 of 3
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`PROTECTING YOUR INVENTION OUTSIDE THE UNITED STATES
`
`Since the rights granted by a US. patent extend only throughout the territory of the United States and have no
`effect in a foreign country, an inventor who wishes patent protection in another country must apply for a patent
`in a specific country or in regional patent offices. Applicants may wish to consider the filing of an international
`application under the Patent Cooperation Treaty (PCT). An international (PCT) application generally has the same
`effect as a regular national patent application in each PCT-member country. The PCT process simplifies the filing
`of patent applications on the same invention in member countries, but does not result in a grant of "an international
`patent" and does not eliminate the need of applicants to file additional documents and fees in countries where patent
`protection is desired.
`
`Almost every country has its own patent law, and a person desiring a patent in a particular country must make an
`application for patent in that country in accordance with its particular laws. Since the laws of many countries differ
`in various respects from the patent law of the United States, applicants are advised to seek guidance from specific
`foreign countries to ensure that patent rights are not lost prematurely.
`
`Applicants also are advised that in the case of inventions made in the United States, the Director of the USPTO must
`issue a license before applicants can apply for a patent in a foreign country. The filing of a US. patent application
`serves as a request for a foreign filing license. The application's filing receipt contains further information and
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`Applicants may wish to consult the USPTO booklet, "General Information Concerning Patents" (specifically, the
`section entitled "Treaties and Foreign Patents") for more information on timeframes and deadlines for filing foreign
`patent applications. The guide is available either by contacting the USPTO Contact Center at 800-786-9199, or it
`can be viewed on the USPTO website at http://www.uspto.gov/web/offices/pac/doc/general/index.html.
`
`For information on preventing theft of your intellectual property (patents, trademarks and copyrights), you may wish
`to consult the US. Government website, http://www.stopfakes.gov. Part of a Department of Commerce initiative,
`this website includes self-help "toolkits" giving innovators guidance on how to protect intellectual property in specific
`countries such as China, Korea and Mexico. For questions regarding patent enforcement issues, applicants may
`call the US. Government hotline at 1-866-999-HALT (1-866-999-4258).
`
`LICENSE FOR FOREIGN FILING UNDER
`
`Title 35, United States Code, Section 184
`
`Title 37, Code of Federal Regulations, 5.11 & 5.15
`
`GRANTED
`
`if the phrase "IF REQUIRED, FOREIGN FILING
`The applicant has been granted a license under 35 U.S.C. 184,
`LICENSE GRANTED" followed by a date appears on this form. Such licenses are issued in all applications where
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`set forth in 37 CFR 5.15. The scope and limitations of this license are set forth in 37 CFR 5.15(a) unless an earlier
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`date indicated is the effective date of the license, unless an earlier license of similar scope has been granted under
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`
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`This license is to be retained by the licensee and may be used at any time on or after the effective date thereof unless
`it is revoked. This license is automatically transferred to any related applications(s) filed under 37 CFR 1.53(d). This
`license is not retroactive.
`
`The grant of a license does not in any way lessen the responsibility of a licensee for the security of the subject matter
`as imposed by any Government contract or the provisions of existing laws relating to espionage and the national
`security or the export of technical data. Licensees should apprise themselves of current regulations especially with
`respect to certain countries, of other agencies, particularly the Office of Defense Trade Controls, Department of
`State (with respect to Arms, Munitions and Implements of War (22 CFR 121-128)); the Bureau of Industry and
`Security, Department of Commerce (15 CFR parts 730-774); the Office of Foreign AssetsControl, Department of
`Treasury (31 CFR Parts 500+) and the Department of Energy.
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`NOT GRANTED
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`No license under 35 U.S.C. 184 has been granted at this time, if the phrase "IF REQUIRED, FOREIGN FILING
`LICENSE GRANTED" DOES NOT appear on this form. Applicant may still petition for a license under 37 CFR 5.12,
`if a license is desired before the expiration of 6 months from the filing date of the application. If 6 months has lapsed
`from the filing date of this application and the licensee has not received any indication of a secrecy order under 35
`U.S.C. 181, the licensee may foreign file the application pursuant to 37 CFR 5.15(b).
`
`
`SelectUSA
`
`The United States represents the largest, most dynamic marketplace in the world and is an unparalleled location for
`business investment, innovation, and commercialization of new technologies. The US. offers tremendous resources
`and advantages for those who invest and manufacture goods here. Through SelectUSA, our nation works to
`promote and facilitate business investment. SelectUSA provides information assistance to the international investor
`community; serves as an ombudsman for existing and potential investors; advocates on behalf of US. cities, states,
`and regions competing for global investment; and counsels US. economic development organizations on investment
`attraction best practices. To learn more about why the United States is the best country in the world to develop
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`PTO/AIN14 (07-14)
`Approved for use through 0480/2017. OMB 0651-0032
`US. Patent and Trademark Office; US. DEPARTMENT OF COMMERCE
`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.
`
`
`
`
`
`Title of Invention
`
`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`
`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.
`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 paper filed application.
`
`Secrecy Order 37 CFR 5.2
`
`CI Portions or all of the application associated with this Application Data Sheet may fall under a Secrecy Order pursuant to
`37 CFR 5.2 (Paper filers only. Applications that fall under Secrecy Order may not be filed electronically.)
`
`
`Inventor Information:
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`Inventor
`
`1
`
`Legal Name
`
`
`Prefix Given Name
`Middle Name
`Family Name
`———
`Residence Information (Select One)
`(9 US Residency 0 Non US Residency 0 Active US Military Service
`
`Suffix
`
`Mailing Address of Inventor:
`
`Address 1
`
`Address 2
`
`5801 S. Ellis Avenue
`
`Postal Code
`
`60637
`
`us
`
`
`Inventor
`2
`
`Legal Name
`
`Prefix Given Name
`
`Middle Name
`
`
`Sivan
`Ayelet
`
`Suffix
`
`
`
`
`
`
`
`Residence Information (Select One) @ US Residency 0 Non US Residency 0 Active US Military Service
`
`City
`
`Chicago
`
`StatelProvince
`
`IL
`
`Country of Residence i
`
`US
`
`
`Mailing Address of Inventor:
`
`
`
`Address 2
`
`Address 1
`
` 5801 S. Ellis Avenue
`
`
`Postal Code
`
`60637
`
`Inventor
`
`3
`
`Legal Name
`
`Prefix Given Name
`Leticia
`
`Middle Name
`
`Family Name
`Corrales
`
`Suffix
`
`
`Residence Information (Select One) @ US Residency 0 Non US Residency 0 Active USd/lgitag Serge 101 2
`
`EFS Web 2.2.12
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`Page 4 Of 68
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` _
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`_
`Application Data Sheet 37 CFR 1.76
`
`
`Attorney Docket Number
`UCHI-34458lUS-1/PRO
`
`
`
`Application Number
`
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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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` Attorney Docket Number
`UCHI-34458/US-1/PRO
`
`Application Data Sheet 37 CFR 1.76
`
`Application Number
`
`Title of Invention
`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`
`
`
`
`
`
`
`
`
`
`
`
`ChicagoCity US ‘ StatelProvince | IL | Country of Residencei
`
`
`
`
`
`
`
`
`
`Mailing Address of Inventor:
`Address 1
`5801 8. Ellis Avenue
`
`Address 2
`
`Postal Code
`
`60637
`
`
`
`Inventor Information blocks may be
`Inventors Must Be Listed - Additional
`All
`Add
`generated within this form by selecting the Add button.
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`Correspondence Information:
`
`Enter either Customer Number or complete the Correspondence Information section below.
`For further information see 37 CFR 1.33(a).
`
`|:| An Address is being provided for the correspondence Information of this application.
`
`Customer Number
`
`72960
`
`
`
`
`
`
`
`Email Address Add Email docketing@casimirjones.com |
`
`Application Information:
`
`Title of the Invention
`
`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`
`Attorney Docket Number UCHI-34458/US-IIPRO
`
`Small Entity Status Claimed
`
`Application Type
`
`Provisional
`
`Subject Matter
`
`Utility
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`
`
`7Total Number of Drawing Sheets (if any) Suggested Figure for Publication (if any)
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`Filing By Reference:
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`Only complete this section when filing an application by reference under 35 U.S.C. 1 11(c) and 37 CFR 1.57(a). Do not complete this section if
`application papers including a specification and any drawings are being filed. Any domestic benefit or foreign priority information must be
`provided in the appropriate sectionfs) below (i.e., "Domestic Benefit/National Stage Information" and "Foreign Priority Information").
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`For the purposes of a filing date under 37 CFR1.53(b), the description and any drawings of the present application are replaced by this
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`Application number of the previously
`filed application
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`Publication Information:
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`Filing date (YYYY-MM-DD)
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`Intellectual Property Authority or Country i
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`|:| Request Early Publication (Fee required at time of Request 37 CFR 1.219)
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`El
`
`Request Not to Publish. I hereby request that the attached application not be published under
`35 U.S.C. 122(b) and certify that the invention disclosed in the attached application has not and will not be the
`subject of an application filed in another country, or under a multilateral international agreemgtt, that re
`ires
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`_
`_
`Application Data Sheet 37 CFR 1.76
`
`Attorney Docket Number
`_
`
`UCHI-34458/US-1/PRO
`
`_ Title of Invention
`
`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`
`Representative Information:
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`Representative information should be provided for all practitioners having a power of attorney in the application. Providing
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`72960
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`0 us Patent Practitioner 0 Limited Recognition (37 CFR11.9)
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`Domestic Benefit/National Stage Information:
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`Appllcatlon Data Sheet 37 CFR 1.76
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`Attorney Docket Number
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`UCHI-34458/US-1/PRO
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`_ Title of Invention
`
`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
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`Statement under 37 CFR 1.55 or 1.78 for AIA (First Inventor to File) Transition
`Applications
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`
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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
`16, 2013, will be examined under the first inventor to file provisions of the AIA.
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`Authorization to Permit Access:
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`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
`is filed access to the instant patent application. See 37 CFR 1.14(c) and (h). This box should not be checked if the applicant
`does not wish the EPO, JPO, KIPO, WIPO, or other intellectual property 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
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`Application Data Sheet 37 CFR 1.76
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`Clear
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`6) Person to whom the inventor is obligated to assign.
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`Name of the Deceased or Legally lncapacitated Inventor::|
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`Organization Name
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`The University of Chicago
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` Application Data Sheet 37 CFR 1.76
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`Attorney Docket Number
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`Application Number
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`UCHI-34458/US-1/PRO
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`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`Title of Invention
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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
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`
`David W. Staple/
`
`Date (YYYY-MM-DD)
`
`Signature First Name
`
`Staple
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`Registration Number
`
`2015-06-01
`
`65903
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`result in termination of proceedings or abandonment of the application or expiration of the patent.
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`The information 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 (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 Department of 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.
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`A record in this system of records may be disclosed, as a routine use, to a Member of Congress submitting a request involving an
`individual, to whom the record pertains, when the individual has requested assistance from the Member with respect to the subject matter of
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`A record in this system of records may be disclosed, as a routine use, to a contractor of the Agency having need for 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
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`as a routine use, to the International Bureau of the World Intellectual Property Organization, pursuant to the Patent C o o p eration Treaty.
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`A record in 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)).
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`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 GSA as part of that agency's responsibility to recommend improvements in records
`management practices and programs, under authority of 44 U.S.C. 2904 and 2906. Such disclosure shall be made in accordance with the
`GSA regulations governing inspection of records for this purpose, and any other relevant (i.e., GSA or Commerce) directive. Such
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` The Privacy Act of 1974 (PL. 93-579) requires that you be given certain information in connection with your submission of the attached form related to
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`A record 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 ofa patent pursuant to 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 was filed in an application which became abandoned or in which the proceedings were
`terminated and which application is referenced by either a published application, an application open to public inspections or an issued
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`
`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 becomes aware of a violation or potential violation of law or regulation.
`
`Genome Ex. 1012
`
`
`EFS Web 2.2.12
`
`Page 1—0 Of 68
`
`Genome Ex. 1012
`Page 10 of 68
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`
`
`FIG. 1
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`1/7
`
`Genome Ex. 1012
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`Page 11 of 68
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`Genome Ex. 1012
`Page 11 of 68
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`
`
`FIG. 2
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`man
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`ck.
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`2/7
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`Genome Ex. 1012
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`Page 12 of 68
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`Genome Ex. 1012
`Page 12 of 68
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`Genome Ex. 1012
`
`Page 13 of 68
`
`Genome Ex. 1012
`Page 13 of 68
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`FIG. 4
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`4/7
`
`Genome Ex. 1012
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`Page 14 of 68
`
`Genome Ex. 1012
`Page 14 of 68
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`
`
`FIG. 5
`
`‘JAX
`
`B‘lBSlY
`
`
`
`
`
`
`
` Day .7
`[by 2‘:
`$qu ELF-SPOT
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`WTumor Growth mum-v3
`
`C
`
`
`
`%SlY‘LofCDS+Tcells
`
`*TAC feces
`‘A‘JAX feces
`
`
`
`
`
`TumorVolume(mmC‘)
`
` 18
`
`14
`‘ll
`Day Post Injection
`
`21
`
`7
`
`-
`2:)
`
`NS
`l-----1
`
`D
`
`.40
`
`30
`
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`%SlY+ofCD8‘Tcells
`mE)
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`b
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`5/7
`
`Genome Ex. 1012
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`Page 15 of 68
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`Genome Ex. 1012
`Page 15 of 68
`
`
`
`,.1
`E 1500
`
`2000 .Untreated
`<>Bii=
`JAX feces
`43* Heat kilted BIF
`
`/
`
` Ii\_ NS
`
`
`
`Day post injection
`
`5000 .‘. Untreated
`
`***$
`
`
`
`«\\,33\qq;i,q:e
`Day post injection
`
`FIG. 6
`
`B
`
`80
`
`:3
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`o
`
`60
`
`40
`
`20
`
`o
`
`
`
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`
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`10""1
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`
`0.02
`
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`
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`
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`
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`
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`
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`%SW”ofCD8+Tceiis
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`TumorVolume(mmS)
`
`6/7
`
`Genome Ex. 1012
`
`Page 16 of 68
`
`Genome Ex. 1012
`Page 16 of 68
`
`
`
`FIG. 7
`
`
` {.uza.~1.__.1.‘.<
`
`O
`Adoptive transfer of
`1x1OGCFSE~labeled
`CDB‘CD451CD452‘
`2C T ce|ls into CD452
`Be mice
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`1x10”B16.SIY
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`7
`Stimulation of whole
`spleen and TdLN cells
`ex viva with SIY
`peptide; measurement
`of IFN-ys
`
`mo
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`
`0
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`
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`
`7/7
`
`Genome Ex. 1012
`
`Page 17 of 68
`
`Genome Ex. 1012
`Page 17 of 68
`
`
`
`Attorney Docket No. UCHI-3445 8/US- l/PRO
`
`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`
`FIELD
`
`Provided herein are methods of treatment and/or prevention of cancer by manipulation of
`
`commensal microflora. In particular, the amount, identity, presence, and/or ratio of microflora
`
`(e. g., gut microflora) in a subject is manipulated to facilitate one or more co-treatments.
`
`BACKGROUND
`
`Harnessing the host immune system constitutes a promising approach for the treatment of
`
`cancer because of its potential to specifically target tumor cells while limiting harm to normal
`
`tissue, with durability of benefit associated with immunologic memory. Enthusiasm has been
`
`fueled by recent clinical success, particularly with antibodies that block immune inhibitory
`
`pathways, specifically CTLA-4 and the PD-l/PD-Ll axis (Hodi et al. The New England journal
`
`of medicine 363, 711-723 (2010).; Hamid et al. The New England journal of medicine 369, 134-
`
`144 (2013).; herein incorporated by reference in their entireties). Early data have indicated that
`
`clinical responses to these immunotherapies are more frequent in patients who show evidence of
`
`an endogenous T cell response ongoing in the tumor microenvironment at baseline (Tumeh et al.
`
`Nature 515, 568-571 (2014).; Spranger et al. Science translational medicine 5, 200ra116 (2013).;
`
`Ji et al. Cancer immunology, immunotherapy : C11 61, 1019-1031 (2012).; Gajewski et al.
`
`Cancer journal 16, 399-403 (2010).; herein incorporated by reference in their entireties). Despite
`
`the filnctional and clinical importance of this T cell-inflamed tumor microenvironment, the
`
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