`
`UNITED STATES PATENT AND TRADEMARK OFFIGE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`!
`OX.
`Address: COMMISSIONER FOR PATENTS
`Alexandria, Virginia 22313-1450
`www.uspto.gov
`
`APPLICATION
`NUMBER
`
`FILING or
`371(c) DATE
`
`GRP ART
`UNIT
`
`
`
`
`
`FIL
`
`62/248,741
`
`10/30/2015
`
`FEE REC'D
`
`130
`
`72960
`
`9978DEMINGWAY, SUITE 310
`
`MIDDLETON, WI 53562
`
`ATTY.DOCKET.NO
`
`ITOT CLAIMSJIND CLAIMS
`
`UCHI-34458/US-2/PRO
`
`CONFIRMATION NO. 1096
`FILING RECEIPT
`
`NDA.010
`
`Date Mailed: 11/17/2015
`
`It will not be examined for patentability and will
`Receipt is acknowledged of this provisional patent application.
`become abandonednotlater than twelve monthsafter its filing date. Any correspondence concerning the application
`mustinclude the following identification information: the U.S. APPLICATION NUMBER, FILING DATE, NAME OF
`APPLICANT, and TITLE OF INVENTION. Feestransmitted by checkor 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 processesthe reply
`to the Notice, the USPTO will generate another Filing Receipt incorporating the requested corrections
`
`Inventor(s)
`
`Applicant(s)
`
`Thomas F. Gajewski, Chicago, IL;
`Ayelet Sivan, Chicago, IL;
`Leticia Corrales, Chicago, IL;
`
`The University of Chicago, Chicago, IL
`Powerof 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: 11/16/2015
`
`The country code and number of your priority application, to be usedfor filing abroad under the Paris Convention,
`is US 62/248,741
`
`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
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`PROTECTING YOUR INVENTION OUTSIDE THE UNITED STATES
`
`Since the rights granted by a U.S. 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 thefiling 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 notresult in a grantof "an international
`patent" and doesnoteliminate the needof applicantsto 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 accordancewith 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 madein the United States, the Director of the USPTO must
`issue a license before applicants can apply for a patent in a foreign country. Thefiling of a U.S. patent application
`serves as a request for a foreign filing license. The application's filing receipt contains further information and
`guidance asto the status of applicant's license for foreign filing.
`
`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 deadlinesfor 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 U.S. Government website, http:/Avww.stopfakes.gov. Part of a Department of Commerceinitiative,
`this website includes self-help "toolkits" giving innovators guidance on how to protectintellectual property in specific
`countries such as China, Korea and Mexico. For questions regarding patent enforcementissues, applicants may
`call the U.S. Governmenthotline 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
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`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 issuedin all applications where
`the conditions for issuance of a license have been met, regardless of whether or not a license may be required as
`set forth in 37 CFR 5.15. The scope andlimitations of this license are set forth in 37 CFR 5.15(a) unless an earlier
`license has been issued under 37 CFR 5.15(b). The license is subject to revocation upon written notification. The
`date indicatedis the effective date of the license, unless an earlier license of similar scope has been granted under
`37 CFR 5.13 or 5.14.
`
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`This licenseis to be retained by the licensee and maybe usedat any time onor 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.
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`The grantof a license doesnot in any way lessen the responsibility of a licensee for the security of the subject matter
`as imposed by any Governmentcontract or the provisions of existing laws relating to espionage and the national
`security or the export of technical data. Licensees should apprise themselvesof 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
`
`No license under 35 U.S.C. 184 has been granted at this time, if the phrase "IF REQUIRED, FOREIGN FILING
`LICENSE GRANTED" DOESNOTappear on this form. Applicant maystill petition for a license under 37 CFR 5.12,
`if a license is desired before the expiration of 6 months from thefiling date of the application. If 6 months has lapsed
`from thefiling date of this application and the licensee has not received any indication of a secrecy order under 35
`U.S.C. 181, the licensee mayforeign 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
`businessinvestment, innovation, and commercialization of new technologies. The U.S. offers tremendous resources
`and advantages for those who invest and manufacture goods here. Through SelectUSA, our nation works to
`promote andfacilitate business investment. SelectUSAprovides information assistance to the international investor
`community; serves as an ombudsmanfor existing and potential investors; advocates on behalf of U.S. cities, states,
`and regions competing for global investment; and counsels U.S. economic developmentorganizations on investment
`attraction best practices. To learn more about why the United States is the best country in the world to develop
`technology, manufacture products, deliver services, and grow your business, visit http:/Awww.SelectUSA.govor call
`+1-202-482-6800.
`
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`PTO/AIA/14 (07-14)
`Approved for use through 04/30/2017. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respond to a collection ofinformation unless it contains a valid OMB control number.
`
` .
`
`. Attorney Docket Number|UCHI-34458/US-2/PRG
`
`
`Application Data Sheet 37 CFR 1.76
`
`Application Number
`
`
`
`
`
`
`
`Title of Invention|TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`
`The application data sheetis part of the provisional or nonprovisional application for whichit 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
`Oo Portions or all of the application associated with this Application Data Sheet may fall under a Secrecy Order pursuantto
`37 CFR 5.2 (Paperfilers only. Applications that fall under Secrecy Order may notbe filed electronically.}
`
`Inventor Information:
`
`
`Inventor
`Legal Name
`
`Prefix) Given Name
`Middle Name
`Family Name
`Suffix
`
`1
`
`
`Residence Information (Select One)
`(e) US Residency
`©) NonUS Residency
`() Active US Military Service
`
`Mailing Addressof Inventor:
`
`Address 1
`
`Address 2
`
`5801 S. Ellis Avenue
`
`Postal Code
`
`60637
`
`US
`
`2
`Inventor
`
`Legal Name
`
`
`
` Ayelet Sivan
`Residence Information (Select One)
`(@} US Residency
`©) NonUS Residency
`() Active US Military Service
`
`
`City|Chicago State/Province|IL Country of Residence i|US
`
`
`
`Mailing Address of Inventor:
`
`
`
` 5801 S. Ellis Avenue
`Address 1
`
`Address 2
`
`
`Postal Code
`
`60637
`
`Inventor
`Legal Name
`
`3
`
`Middle Name Family NamePrefix) Given Name Suffix
`
`
`Leticia
`Corrales
`Residence Information (Select One)
`©) NonUSResidency
`EFS Web 2.2.12
`
`
`
`(@) US Residency
`
`() Active USMilitary Service 1013
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` Application Data Sheet 37 CFR 1.76
`
`Application Number
`
`Mailing Address of Inventor:
`
`Address 1
`5801 S. Ellis Avenue
`
`
`
`Address 2
`
`Postal Code
`
`60637
`
`Add
`Inventor Information blocks may be
`Inventors Must Be Listed - Additional
`All
`generatedwithin this form by selecting the Add button.
`
`CorrespondenceInformation:
`
`Enter either Customer Number or complete the CorrespondenceInformation section below.
`For further information see 37 CFR 1.33(a}.
`
`[|]An Addressis being provided for the correspondence Information of this application.
`
`Customer Number
`
`72960
`
`Email Address
`
`docketing@casimirjones.com
`
`|
`
`Add Email
`
`
`
`Title of the Invention
`
`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`
`Application Information:
`
`
`
`
`
`PTO/AIA/14 (07-14)
`Approved for use through 04/30/2017. 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 respond to a collection of information unless it contains a valid OMB control number.
`
`Attorney Docket Number|UCHI-34458/US-2/PRG
`
`
`
`
`
`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`Title of Invention
`
`
`
`
`
`Chicago | State/Province | ILCity | Country of Residencei|US
`
`
`
`
`
`Attorney Docket Number
`
`Application Type
`
`UCHI-34458/US-2/PRO
`Provisional
`
`Small Entity Status Claimed
`
`
`
`
`
`Utility
`Subject Matter
`
`Total Numberof Drawing Sheets (if any)
`15
`Suggested Figure for Publication {if any)
`
`Filing By Reference:
`
`Only complete this section whenfiling an application by reference under 35 U.S.C. 111{c) and 37 CFR 1.57{a). Do not complete this section if
`application papers including a specification and any drawings are beingfiled. Any domestic benefit or foreign priority information must be
`provided in the appropriate section(s) below (i.e., "Domestic Benefit/National Stage Information” and “Foreign Priority Information’).
`
`For the purposesof a filing date under 37 CFR 1.53(b), the description and any drawings of the present application are replaced by this
`reference to the previously filed application, subject to conditions and requirements of 37 CFR 1.57(a}.
`Application numberof the previously
`Filing date (YYYY-MM-DD)
`Intellectual Property Authority or Country i
`filed application
`
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`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
`35U.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 agreement, that requires
`publication at eighteen monthsafterfiling.
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`PTO/AIA/14 (07-14)
`Approved for use through 04/30/2017. 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 respond to a collection of information unless it contains a valid OMB control number.
`
`oo Attorney Docket Number|UCHI-34458/US-2/PRG
`
`Application Data Sheet 37 CFR 1.76
`
`— Title of Invention|TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`
`Representative Information:
`
`
`Representative information should be provided for all practitioners having a power of attorney in the application. Providing
`this information in the Application Data Sheet does not constitute a power of attorney in the application (see 37 CFR 1.32).
`Either enter Customer Number or complete the Representative Name section below.
`If both sections are completed the customer
`Numberwill be used for the Representative Information during processing.
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`72960
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`(©) US PatentPractitioner
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`©) Limited Recognition (37 CFR 11.9)
`
`Please Select One:
`Customer Number
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`(e) Customer Number
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`Domestic Benefit/National Stage Information:
`This section allows for the applicantto either claim benefit under 35 U.S.C. 119{e), 120, 121, 365(c), or 386(c) or indicate National
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`required by 35 U.S.C. 119(e) or 120, and 37 CFR 1.78.
`Whenreferring to the current application, please leave the application numberblank.
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`Application Number
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`Continuity Type
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`Prior Application Number
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`Filing Date (YYYY-MM-DD}
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`Additional Domestic Benefit/National Stage Data may be generated within this form
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`Add
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`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
`constitutes the claim for priority as required by 35 U.S.C. 119{b) and 37 CFR 1.55. Whenpriority is claimed to a foreign application
`thatis eligible for retrieval uncer the priority cocument exchange program (PDX) he information will be used by the Office to
`automatically attempt retrieval pursuant to 37 CFR 1.55{i)(1) and (2). Under the PDX program, applicant bears the ultimate
`
`responsibility for ensuring that a copy of the foreign application is received by the Office from the participating foreign intellectual
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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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`PTO/AIA/14 (07-14)
`Approved for use through 04/30/2017. 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 respond to a collection of information unless it contains a valid OMB control number.
`
`oo Attorney Docket Number|UCHI-34458/US-2/PRG
`
`Application Data Sheet 37 CFR 1.76
`
`— Title of Invention|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
`
`
`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: Byproviding 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 underthefirst inventorto file provisions of the AIA.
`
`Authorization to Permit Access:
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`Authorization to Permit Access to the Instant Application by the Participating Offices
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`If checked, the undersigned hereby grants the USPTO authority to provide the European Patent Office (EPO),
`the Japan Patent Office (JP©), the Korean Intellectual Property Office {(KIPO), the World Intellectual Property Office (WIPO),
`and any otherintellectual 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 checkedif the applicant
`does not wish the EPO, JPO, KIPO, WIPO, or otherintellectual property office in which a foreign application claiming priority
`to the instant patent application is filed to have accessto the instant patent application.
`
`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)-{c) if a copy of the foreign application that satisfies the certified copy requirement of
`37 CFR 1.55 has beenfiled in the instant patent application; and 3) any U.S. application-as-filed from which benefit is
`soughtin the instant patent application.
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`In accordance with 37 CFR 1.14(c}, access may be provided to information concerning the dateoffiling this Authorization.
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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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`PTO/AIA/14 (07-14)
`Approved for use through 04/30/2017. 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 respond to a collection of information unless it contains a valid OMB control number.
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`Attorney Docket Number|UCHI-34458/US-2/PRG
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`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`Title of Invention
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` Application Data Sheet 37 CFR 1.76
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`Application Number
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`1
`Applicant
`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 addressof the legal representative who is the applicant under 37 CFR
`1.43; or the name and addressof the assignee, person to whom theinventor is under an obligation to assign the invention, or person
`who otherwise showssufficient proprietary interest in the matter who is the applicant under 37 CFR 1.46. If the applicantis an
`applicant under 37 CFR 1.46 {assignee, person to whomthe inventoris obligated to assign, or person who otherwise showssufficient
`proprietary interest) together with one or morejoint inventors, then the joint inventor or inventors who are also the applicant should be
`identified in this section.
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`©)_Joint Inventor OQ Assignee
`QO Legal Representative under 35 U.S.C. 117
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` (e) Person to whom theinventoris obligated to assign. © Person who shows sufficient proprietary interest
`lf applicant is the legal representative, indicate the authority to file the patent application, the inventor is:
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`Nameof the Deceased or Legally Incapacitated Inventorfo
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`If the Applicant is an Organization check here.
`Organization Name
`The University of Chicago
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`Mailing Address Information For Applicant:
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`Address 1
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`Address 2
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`5801 S. Ellis Avenue
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`Complete this section if assignee information, including non-applicant assignee information, is desired to be included on the patent
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`PTO/AIA/14 (07-14)
`Approved for use through 04/30/2017. 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 respond to a collection of information unless it contains a valid OMB control number.
`
`Attorney Docket Number
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`UCHI-34458/US-2/PRO
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`Application Number
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`
`
`
`Application Data Sheet 37 CFR 1.76
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`
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`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`Title of Invention
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`Mailing Address Information For Assignee including Non-Applicant Assignee:
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`Attorney Docket No. UCHI-34458/US-2/PRO
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`TREATMENT OF CANCER BY MANIPULATION OF COMMENSAL MICROFLORA
`
`FIELD
`
`Provided herein are methodsof treatment and/or prevention of cancer by manipulation of
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`commensal microflora. In particular, the amount, identity, presence, and/or ratio of microflora
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`(e.g., gut microflora) in a subject is manipulated to facilitate one or more co-treatments.
`
`BACKGROUND
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`Harnessing the host immunesystem constitutes a promising approach for the treatment of
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`10
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`cancer becauseofits potential to specifically target tumor cells while limiting harm to normal
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`tissue, with durability of benefit associated with immunologic memory. Enthusiasm has been
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`fueled by recent clinical success, particularly with antibodies that block immuneinhibitory
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`pathways, specifically CTLA-4 and the PD-1/PD-L1 axis (Hodi et al. The New England journal
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`of medicine 363, 711-723 (2010).; Hamid et al. The New England journal of medicine 369, 134-
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`15
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`144 (2013).; herein incorporated by referencein their entireties). Early data have indicated that
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`clinical responses to these immunotherapies are more frequent in patients who show evidence of
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`an endogenous T cell response ongoing in the tumor microenvironmentat baseline (Tumehetal.
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`Nature 515, 568-571 (2014).; Spranger et al. Science translational medicine 5, 200ral116 (2013).;
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`Ji et al. Cancer immunology, immunotherapy : CI 61, 1019-1031 (2012).; Gajewskietal.
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`20
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`Cancer journal 16, 399-403 (2010).; herein incorporated by referencein their entireties). Despite
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`the functional and clinical importance ofthis T cell-inflamed tumor microenvironment, the
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`mechanismsthat govern the presence or absenceof this phenotype have not been well
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`understood. Theoretical sources of inter-patient heterogeneity include germline genetic
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`differencesat the level of the host, variability in patterns of somatic alterations in tumorcells,
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`and environmental differences with the potential to impact on systemic immunity.
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`SUMMARY
`
`Provided herein are methodsof treatment and/or prevention of cancer by manipulation of
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`commensal microflora. In particular, the amount, identity, presence, and/or ratio of microflora
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`30
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`(e.g., gut microflora) in a subject is manipulated to facilitate one or more co-treatments.
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`Attorney Docket No. UCHI-34458/US-2/PRO
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`In some embodiments, provided herein are methodsoftreating or preventing cancer in a
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`subject, comprising modulating levels of one or more commensal microbeswithin the subjectto:
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`(A) enhance an immuneresponse by the subject, (B) inhibit the growth or spread of the cancer,
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`(C) inhibit immuneevasion by the cancer, and/or (D) enhancethe efficacy of a therapeutic. In
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`some embodiments, the levels of one or more commensal microbes are modulated within the gut
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`of the subject. In some embodiments, modulating the levels of one or more commensal microbes
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`comprises increasing and/or decreasing levels of one or more bacterial selected from the genera
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`Bacteroides, Clostridium, Fusobacterium, Eubacterium, Ruminococcus, Peptococcus,
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`Peptostreptococcus, Bifidobacterium, Rikenella, Alistipes, Marinilabilia, Anaerostipes,
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`10
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`Escherichia, and/or Lactobacillus.
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`In some embodiments, modulating the levels of one or more commensal microbes
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`comprises administering a beneficial microbes to the subject. In some embodiments, the
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`beneficial microbes are bacteria. In some embodiments, the bacteria are selected from the genera
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`Bacteroides, Clostridium, Fusobacterium, Eubacterium, Ruminococcus, Peptococcus,
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`15
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`Peptostreptococcus, Bifidobacterium, Rikenella, Alistipes, Marinilabilia, Anaerostipes,
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`Escherichia, and/or Lactobacillus.
`
`In some embodiments,
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`the bacteria are Bifidobacterium. In some embodiments, the Bifidobacterium include bacteria
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`selected from the group consisting of Bifidobacterium lactis, Bifidobacterium bifidium,
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`Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium
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`20
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`infantis, Bifidobacterium catenulatum, Bifidobacterium pseudocatenulatum, Bifidobacterium
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`adolescentis, and Bifidobacterium angulatum. In some embodiments, the beneficial microbes are
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`administered as a probiotic composition or via microflora transplant from a donor.
`
`In some embodiments, modulating the levels of one or more commensal microbes
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`comprises administering one or more antimicrobials. In some embodiments, the antimicrobial
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`25
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`kills detrimental microbes. In some embodiments, the antimicrobial is an antibiotic. In some
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`embodiments, methods further comprise administration of beneficial microbes to the subj