/
`,0-1,
`
`a"°rR,,, UNITED STATES PATENT AND TRADEMARK OFFICE
`
`r
`
`/yam
`2
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`www.uspto.gov
`
`APPLICATION NO.
`
`FILING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONFIRMATION NO.
`
`15/718,735
`
`09/28/2017
`
`Thomas F. Gajewski
`
`UCHI-34458/US-4/CON
`
`5538
`
`7590
`72960
`Casimir Jones, S.C.
`2275 Deming Way Ste 310
`Middleton, WI 53562
`
`08/24/2018
`
`EXAMINER
`
`HINES, JANA A
`
`ART UNIT
`
`PAPER NUMBER
`
`1645
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`08/24/2018
`
`ELECTRONIC
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
`following e-mail address(es):
`
`docketing @casimirjones.com
`pto.correspondence@casimirjones.com
`
`PTOL-90A (Rev. 04/07)
`
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`

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`Office Action Summary
`
`Application No.
`15/718,735
`
`Examiner
`JA-NA A HINES
`
`Applicant(s)
`Gajewski et al.
`
`Art Unit
`1645
`
`AIA Status
`Yes
`
`— The MAILING DATE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTHS FROM THE MAILING
`DATE OF THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed
`after SIX (6) MONTHS from the mailing date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`
`Status
`1)® Responsive to communication(s) filed on 7/24/2018.
`0 A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
`2b) 111 This action is non-final.
`2a)0 This action is FINAL.
`3)0 An election was made by the applicant in response to a restriction requirement set forth during the interview on
`; the restriction requirement and election have been incorporated into this action.
`4)0 Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Ex paite Quay/e, 1935 C.D. 11, 453 O.G. 213.
`
`Disposition of Claims*
`20-49 is/are pending in the application.
`5) J Claim(s)
`5a) Of the above claim(s)
`is/are withdrawn from consideration.
`6) 0 Claim(s)
` is/are allowed.
`7) 0 Claim(s) 20-49 is/are rejected.
`8) 0 Claim(s)
`is/are objected to.
`9) 0 Claim(s)
`are subject to restriction and/or election requirement
`* If any claims have been determined allowable, you may be eligible to benefit from the Patent Prosecution Highway program at a
`participating intellectual property office for the corresponding application. For more information, please see
`http://www.uspto.gov/patents/init_events/pph/index.jsp or send an inquiry to PPHfeedback@uspto.gov.
`
`Application Papers
`10)0 The specification is objected to by the Examiner.
`1 )0 The drawing(s) filed on
`is/are: a)0 accepted or b)0 objected to by the Examiner.
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121(d).
`
`Priority under 35 U.S.C. § 119
`12)0 Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
`c)0 None of the:
`b)0 Some**
`a)0 All
`1.0 Certified copies of the priority documents have been received.
`.
`2.0 Certified copies of the priority documents have been received in Application No.
`3.0 Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau (PCT Rule 17.2(a)).
`** See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`1)
`Notice of References Cited (PTO-892)
`
`2) El Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`Paper No(s)/Mail Date
`.
`U.S. Patent and Trademark Office
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`3) 11 Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`.
`4) 11 Other:
`.
`
`Part of Paper No./Mail Date 20180821
`
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`Application/Control Number: 15/718,735
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`DETAILED CORRESPONDENCE
`
`Notice of Pre-AIA or AIA Status
`
`1.
`
`The present application is being examined under the pre-AIA first to invent
`
`provisions.
`
`Continued Examination Under 37 CFR 1.114
`
`2.
`
`A request for continued examination under 37 CFR 1.114, including the fee set
`
`forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this
`
`application is eligible for continued examination under 37 CFR 1.114, and the fee set
`
`forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action
`
`has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 24,
`
`2018 has been entered.
`
`Claim Amendments
`
`3.
`
`The amendment filed July 24, 2018 has been entered. Claims 1-19 were
`
`canceled. Claims 20-24, 27, and 40-42 have been amended. Claims 20-49 are under
`
`consideration in this Office Action.
`
`Withdrawal of Rejections
`
`4.
`
`The following rejections have been withdrawn in view of applicants' amendments:
`
`a) The rejection of claims 20-39 under pre-AIA 35 U.S.C. 103(a) as being
`
`unpatentable over Korman et al., in view of Mohania et al., and Prakash et al; and
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`b) The rejection of claims 40-49 under 35 U.S.C. 103 as being unpatentable over
`
`Korman et al., Mohania et al., and Prakash et al., as applied to claims 20-39 above, and
`
`further in view of Duncan et al.
`
`Response to Arguments
`
`5.
`
`Applicant's arguments, filed July 24, 2018, with respect to the rejection(s) of
`
`claims 20-49 under Korman et al., in view of Mohania et al., and Prakash et al., have
`
`been fully considered and are persuasive. Therefore, the rejection has been withdrawn.
`
`However, upon further consideration, a new ground of rejection is made in view of
`
`Stritzker et al., (US Patent Pub. 2008/0193373 published August 2008).
`
`New Grounds of Rejection Necessitated By Applicants Amendment
`
`Claim Rejections - 35 USC § 103
`
`In the event the determination of the status of the application as subject to AIA 35
`
`U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any
`
`correction of the statutory basis for the rejection will not be considered a new ground of
`
`rejection if the prior art relied upon, and the rationale supporting the rejection, would be
`
`the same under either status.
`
`The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis
`
`for all obviousness rejections set forth in this Office action:
`
`(a) A patent may not be obtained though the invention is not identically disclosed or described
`as set forth in section 102, if the differences between the subject matter sought to be patented
`and the prior art are such that the subject matter as a whole would have been obvious at the
`
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`time the invention was made to a person having ordinary skill in the art to which said subject
`matter pertains. Patentability shall not be negatived by the manner in which the invention was
`made.
`
`The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148
`
`USPQ 459 (1966), that are applied for establishing a background for determining
`
`obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
`
`1. Determining the scope and contents of the prior art.
`
`2. Ascertaining the differences between the prior art and the claims at issue.
`
`3. Resolving the level of ordinary skill in the pertinent art.
`
`4. Considering objective evidence present in the application indicating
`
`obviousness or nonobviousness.
`
`6.
`
`Claims 20-49 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable
`
`over Stritzker et al., (US Patent Pub. 2008/0193373 published August 2008) in view of
`
`Korman et al., (US Patent Publication 2009/0217401 published Aug. 2009).
`
`The claims are drawn to a method of treating cancer in a human subject
`
`comprising co-administering to the subject an immune checkpoint inhibitor and a
`
`bacterial formulation comprising bacteria of the genus Adlercreutzia, Oscillopira,
`
`Mollicutes, Butyrivibrio, Bacteroides, Clostridium, Fusobacterium, Eubacterium,
`
`Ruminococcus, Peptococcus, Peptostreptococcus, Rikenella, Alistipes, Marinilabilia, or
`
`Escherichia.
`
`Stritzker et al., teach methods which use microorganisms or cells for treating a
`
`disease, disorder or condition. Such sites, diseases and disorders include sites of cell
`
`proliferation, proliferative conditions, neoplasms, tumors and neoplastic diseases
`
`[abstract]. Further described are microorganisms and cells for use in the methods and
`
`compositions, combinations and kits, including diagnostic and pharmaceutical
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`compositions, containing a microorganism or cell [abstract]. Stritzker et al., uses of
`
`microorganisms or cells (e.g. Nissle) in the methods provided herein for detecting
`
`and/or treating a site of proliferation or a proliferative condition, such as a tumor, tumor
`
`tissue, cancer or metastasis [para. 0016]. Bacteria employed in the methods provided
`
`herein include, but are not limited to, mutual or commensal strains of Escherichia coli,
`
`Bacteroides, Eubacterium, and Fusobacterium [para. 0020]. And/or one that is a
`
`probiotic strain of Escherichia coli, Lactococcus, Lactobacillus reuteri, Lactobacillus
`
`amylovorus, Lactobacillus crispatus, Lactobacillus gallinarum, Lactobacillus gasseri,
`
`Lactobacillus johnsonii, Lactobacillus bifidum, Lactobacillus helveticus, [para. 0021].
`
`Bacteria can also be used in the methods provided herein. Any of a variety of bacteria
`
`possessing the desired characteristics can be used. Exemplary bacteria provided herein
`
`include Oscillopira, Butyrivibrio, Bacteroides, Clostridium, Fusobacterium, Eubacterium,
`
`Ruminococcus, Peptococcus, Peptostreptococcus, Rikenella, Alistipes, Marinilabilia, or
`
`Escherichia [para 489]. The microbes used in the methods provided herein are typically
`
`attenuated [para. 478].
`
`The dosage regimen can be any of a variety of methods and amounts, and can
`
`be determined by one skilled in the art according to known clinical factors [para 616].
`
`Exemplary routes of administration, such as topical, local, or systemic administration
`
`can differ in the dosage given. For example, dosages for injections intravenously,
`
`intraperitoneally, or intratumorally can differ. Thus, dosages delivered directly into a
`
`tumor (i.e. intratumoral injection) can be administered at lower effective dosages [para.
`
`616]. Exemplary levels for administering a bacterium to a 65 kg human can include
`
`1x106 or about 1x106 cfu, 1x107 or about 1x107 cfu, 5x107 or about 5x107 cfu [para.
`
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`616]. The methods provided herein can include multiple administrations of a
`
`microorganism or cell to a subject [para. 618]. Separate administrations can include any
`
`number of two or more administrations, including two, three, four, five or six
`
`administrations [para. 620]. The time period can be a function of the time period for a
`
`subject to mount an immune response; for example, the time period can be more than
`
`the time period for a subject to mount an immune response, such as more than about
`
`one week [para 621]. Modes of administration for a co-administered substance can be
`
`the same mode of administration as the microorganism or cell or can be via a different
`
`mode of administration. Modes of administration can include, but are not limited to,
`
`intravenous, intraperitoneal, subcutaneous, intramuscular, topical, intratumor,
`
`multipuncture, inhalation, intranasal, oral, intracavity (e.g., administering to the bladder
`
`via a catheter, administering to the gut by suppository or enema), aural, ocular,
`
`transdermal, subcutaneous, intra-arterial (e.g. hepatic artery infusion), intravesicular
`
`perfusion, or intrapleural administration [para 624].
`
`Therapeutic agents for the compositions, methods and uses provided herein can
`
`be, for example, an anti-cancer agent. Anti-cancer agents provided herein include, but
`
`are not limited to, anti-cancer antibiotics, anti-cancer antibodies [para. 0040]. Stritzker
`
`et al., teach a combination, comprising a Nissle bacterium; and an anti-tumor or anti-
`
`cancer agent [claim 131]. An anti-cancer agent or compound (used interchangeably with
`
`"anti-tumor or anti-neoplastic agent") refers to any agents, or compounds, used in anti-
`
`cancer treatment. These include any agents, when used alone or in combination with
`
`other compounds, that can alleviate, reduce, ameliorate, prevent, or place or maintain in
`
`a state of remission of clinical symptoms or diagnostic markers associated with
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`neoplastic disease, tumors and cancer, and can be used in methods, combinations
`
`[para. 0072].
`
`Therefore Stritzker et al., teach a method of treating cancer in a human subject
`
`comprising co-administering to the subject an immune checkpoint inhibitor and a
`
`bacterial formulation comprising bacteria of the genus Oscillopira,
`
`Butyrivibrio, Bacteroides, Clostridium, Fusobacterium, Eubacterium, Ruminococcus,
`
`Peptococcus, Peptostreptococcus, Rikenella, Alistipes, Marinilabilia, Anacrostipcs, or
`
`Escherichia, wherein the immune checkpoint inhibitor is an anti-cancer antibody.
`
`Korman et al., teach methods for treating cancer, using anti-PD-1 antibodies. The
`
`methods provide for using a combination immunotherapy, such as the combination of
`
`anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as
`
`cancer [abstract]. Korman et al., teach the use of anti-PD-1 antibodies and the use of
`
`combination immunotherapy, including the combination of anti-CTLA-4 and anti-PD-1
`
`antibodies, to treat cancer [para. 0001]. The method of inhibiting growth of tumor cells in
`
`a subject, comprising administering to a subject a therapeutically effective amount of an
`
`anti-PD-1 antibody, or antigen-binding portion thereof [para. 0133]. The "subject"
`
`includes any human or nonhuman animal [page 232]. Korman et al., commercially
`
`available anti-PD-1 antibodies. Compositions comprising an antibody, or antigen-
`
`binding portion thereof, or immunoconjugate or bispecific molecule of the invention, and
`
`a pharmaceutically acceptable carrier, are also provided [para. 0130]. The antibodies of
`
`the invention exhibit one or more desirable functional properties, such as high affinity
`
`binding to PD-1, lack of cross-reactivity to other CD28 family members, the ability to
`
`stimulate T cell proliferation, IFN-y and/or IL-2 secretion in mixed lymphocyte reactions,
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`the ability to inhibit binding of one or more PD-1 ligands (e.g., PD-L1 and/or PD-L2), the
`
`ability to cross-react with monkey PD-1, the ability to stimulate antigen-specific memory
`
`responses, the ability to stimulate antibody responses and/or the ability to inhibit growth
`
`of tumor cells in vivo [para. 202]. Dosage regimens are adjusted to provide the optimum
`
`desired response (e.g., a therapeutic response). For example, a single bolus may be
`
`administered, several divided doses may be administered over time or the dose may be
`
`proportionally reduced or increased as indicated by the exigencies of the therapeutic
`
`situation [para. 450]. An exemplary treatment regime entails administration once per
`
`week, once every two weeks, once every three weeks, once every four weeks, once a
`
`month, once every 3 months or once every three to 6 months [para 451]. Preferred
`
`routes of administration for antibodies of the invention include intravenous,
`
`intramuscular, intradermal, intraperitoneal, subcutaneous, spinal or other parenteral
`
`routes of administration, for example by injection [para. 458].
`
`Therefore, it would have been prima facie obvious at the time of applicants'
`
`invention to incorporate Korman et al., anti-cancer (anti-PD-1 antibodies) to treat cancer
`
`within Stritzker et al., method of treating cancer in a human subject comprising co-
`
`administering to the subject an immune checkpoint inhibitor and a bacterial formulation
`
`when Stritzker et al., already it was known to treat cancer in a human subject
`
`comprising administering to the subject bacterial formulations in combination with other
`
`anti-cancer antibody therapies to treat cancer. One of ordinary skill in the art would have
`
`a reasonable expectation of success by combining both components because the prior
`
`art teach combination therapy was well known to produce beneficial cancer treating
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`results by interfering with PD-1 and reducing PD-1 expression and using bacteria to
`
`treat the site of cancer proliferation or a proliferative cancer condition.
`
`Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007),
`
`discloses combining prior art elements according to known methods to yield predictable
`
`results, thus the combination is obvious unless its application is beyond that person's
`
`skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses
`
`that "The combination of familiar element according to known methods is likely to be
`
`obvious when it does no more than yield predictable results". It is well known to take a
`
`method of treating cancer when each ingredient is well-known to treat cancer, and
`
`where there is no change in the respective function of immune check point inhibitor or
`
`the bacteria thus the combination would have yielded a reasonable expectation or
`
`success along with predictable results to one of ordinary skill in the art at the time of the
`
`invention. Therefore, it would have been obvious to a person of ordinary skill in the art
`
`to combine prior art elements according to known methods that is ready for
`
`improvement to yield predictable results. The claimed invention is prima facie obvious in
`
`view of the teachings of the prior art, absent any convincing evidence to the contrary.
`
`Claim Rejections - 35 USC § 103
`
`7.
`
`Claims 20-22, 25-29 and 32-39 are rejected under 35 U.S.C. 103 as being
`
`unpatentable over Langermann (US Patent Pub. 201 3/001 71 99 published Jan. 2013) in
`
`view of Stritzker et al., (US Patent Pub 2008/0193373 published August 2008).
`
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`The claims are drawn to a method of treating cancer in a human subject
`
`comprising co-administering to the subject an immune checkpoint inhibitor and a
`
`bacterial formulation comprising bacteria of the genus Adlercreutzia, Oscillopira,
`
`Mollicutes, Butyrivibrio, Bacteroides, Clostridium, Fusobacterium, Eubacterium,
`
`Ruminococcus, Peptococcus, Peptostreptococcus, Rikenella, Alistipes, Marinilabilia, or
`
`Escherichia.
`
`Langermann teach methods and compositions for treating cancer that results
`
`from (1) failure to elicit rapid T cell mediated responses, (2) induction of T cell
`
`exhaustion, T cell anergy or both, or (3) failure to activate monocytes, macrophages,
`
`dendritic cells and/or other APCs, for example, as required to kill intracellular
`
`pathogens. The method and compositions solve the problem of undesired T cell
`
`inhibition by simultaneously inhibiting the PD-1 ligands, PD-L1 and PD-L2. The immune
`
`response can be modulated by providing antagonists which bind with different affinity,
`
`by varying the dosage of agent which is administered, by intermittent dosing over a
`
`regime, and combinations thereof, that provides for dissociation of agent from the
`
`molecule to which it is bound prior to being administered again [abstract]. The
`
`immunomodulatory compositions and methods for treating diseases such as cancer or
`
`infections, in particular to diseases inducing T cell exhaustion, T cell anergy, or both, or
`
`diseases [para. 0001]. A preferred embodiment, the compositions simultaneously block
`
`both PD-L1 and PD-L2 mediated signal transduction in T cells, which have differential
`
`effects on T cell activity. Blocking PD-L1 mediated signal transduction induces robust
`
`effector cell responses, such as increasing the number of infiltrating IFNy producing T
`
`cells and M1 macrophages. Blocking PD-L2 mediated signal transduction decreases the
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`number of infiltrating Tregs. This decrease in Tregs can increase the number of Th17
`
`cells and the level of IL-17 production, and also reduce the number of PD-1 positive
`
`cells. Therefore, simultaneous blocking of two independent PD-1 ligands can enhance
`
`two different beneficial T cell activities. Preferred compositions include
`
`immunomodulatory agents that bind directly to PD-1, PD-L1, PD-L2, or a combination
`
`thereof and increase or activate T cell responses, such as T cell proliferation or
`
`activation [para. 0016]. Preferred immunomodulatory agents interfere with or inhibit the
`
`interaction between the endogenous ligands of PD-1 and PD-1. For example, the
`
`immunomodulatory agent interferes with, inhibits, or blocks PD-L1 (also known as B7-
`
`H1), PD-L2 (also known as B7-DC), or both ligands from interacting with PD-1 [para
`
`0061]. Additional embodiments include antibodies that bind to PD-L2, PD-L1, PD-1 or
`
`B7-1 polypeptides, and variants and/or fragments thereof [para 0065]. The
`
`immunomodulatory agents are administered intermittently over a period of days, weeks
`
`or months to elicit periodic enhanced immune response which are allowed to diminish
`
`prior to the next administration, which may serve to initiate an immune response,
`
`stimulate an immune response, or enhance an immune response. In some aspects, the
`
`immunomodulating agent is AMP-224. AMP-224 can be administered as a bolus dose
`
`at a specific dosage. In another aspect, AMP-224 is administered over the period of
`
`about a week [para. 0482].
`
`The compositions can be administered in combination or alternation with a
`
`vaccine containing one or more antigens such as bacterial antigens [para 0024].
`
`Vaccines require strong T cell response to eliminate infected cells. Immunomodulatory
`
`agents described herein can be administered as a component of a vaccine to promote,
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`augment, or enhance the primary immune response and effector cell activity and
`
`numbers. Vaccines include antigens, the immunomodulatory agent (or a source thereof)
`
`and optionally other adjuvants and targeting molecules. Sources of immunomodulatory
`
`agent include any of the disclosed PD-L1, PD-L2 or PD-1 polypeptides, fusion proteins,
`
`or variants thereof, nucleic acids encoding any of these polypeptides, or host cells
`
`containing vectors that express any of these polypeptides [para. 418]. The antigen can
`
`be derived from a bacterium, and can be a whole cell [para. 420]. The antigens are
`
`whole inactivated or attenuated organisms. These organisms may be infectious
`
`organisms such as bacteria [para. 421]. Bacterial antigens can originate from any
`
`bacteria including, but not limited to, Bacteroides, Clostridium, Escherichia, and
`
`Oscillatoria [page 427].
`
`Pharmaceutical compositions containing peptides or polypeptides may be for
`
`administration by parenteral (intramuscular, intraperitoneal, intravenous (IV) or
`
`subcutaneous injection), transdermal (either passively or using iontophoresis or
`
`electroporation), or transmucosal (nasal, vaginal, rectal, or sublingual) routes of
`
`administration [para 403]. Therapeutic uses for the disclosed compositions include the
`
`treatment of one or more symptoms of cancer and/or induction of tumor immunity.
`
`Exemplary tumor cells that can be treated, include but not limited to, sarcoma,
`
`melanoma, lymphoma, leukemia, neuroblastoma, or carcinoma cells [para. 0022]. The
`
`dose of immunomodulatory agent enhances an immune response to an antigen in a
`
`human [para 468]. Therefore, Langermann teaches a method of treating cancer in a
`
`human subject comprising co-administering to the subject an immune checkpoint
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`inhibitor wherein the immune checkpoint protein is PD-1 or PD-L1 and the inhibitor is
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`Genome Ex. 1015
`Page 13 of 278
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`

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`Application/Control Number: 15/718,735
`Art Unit: 1645
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`Page 13
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`AMP-224 and a whole cell bacterial formulation comprising Bacteroides, Clostridium,
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`Escherichia or Oscillatoria
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`Stritzker et al., has been discussed above as teaching a method of treating
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`cancer in a human subject comprising co-administering to the subject an immune
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`checkpoint inhibitor which is an anti-cancer antibody and a bacterial
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`formulation comprising bacteria of the genus Oscillopira, Butyrivibrio, Bacteroides,
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`Clostridium, Fusobacterium, Eubacterium, Ruminococcus,
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`Peptococcus, Peptostreptococcus, Rikenella, Alistipes, Marinilabilia, Anacrostipcs, or
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`Escherichia.
`
`Therefore, it would have been prima facie obvious at the time of applicants'
`
`invention to incorporate Stritzker et al's whole cell bacterial formulation to treat cancer
`
`within the method of treating cancer as taught by Langermann in order to treat cancer
`
`using combination therapy. One of ordinary skill in the art would have a reasonable
`
`expectation of success by combining the components because the prior art teach
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`combination therapy was well known to produce beneficial by promoting, augmenting,
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`or enhancing the primary immune response and effector cell activity and numbers while
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`also decreasing PD-1 expression and blocking PD-1.
`
`Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007),
`
`discloses combining prior art elements according to known methods to yield predictable
`
`results, thus the combination is obvious unless its application is beyond that person's
`
`skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses
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`that "The combination of familiar element according to known methods is likely to be
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`obvious when it does no more than yield predictable results". It is well known to take a
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`Genome Ex. 1015
`Page 14 of 278
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`Application/Control Number: 15/718,735
`Art Unit: 1645
`
`Page 14
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`method of treating cancer when each ingredient is well-known to treat cancer, and
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`where there is no change in the respective function of immune check point inhibitor, or
`
`the bacterial formulation; thus the combination would have yielded a reasonable
`
`expectation or success along with predictable results to one of ordinary skill in the art at
`
`the time of the invention. Therefore, it would have been obvious to a person of ordinary
`
`skill in the art to combine prior art elements according to known methods that is ready
`
`for improvement to yield predictable results. The claimed invention is prima facie
`
`obvious in view of the teachings of the prior art, absent any convincing evidence to the
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`contrary.
`
`Pertinent Art
`
`8.
`
`The prior art made of record and not relied upon is considered pertinent to
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`applicant's disclosure. Cojocaru et al., (US Pat. Pub 2014/0294765) teach antibodies
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`and antigen binding fragments and conjugates containing same, and/or alternative
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`scaffolds, specific for LSR molecules, which are suitable drugs for immunotherapy and
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`treatment of specific cancer. Lee et al., (US Patent Pub. 2014/0271557) teach methods
`
`of treating cancer comprising administering a therapeutically effective dose of a
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`probiotic organism in combination with anti PD-1 antibodies. The bacterium
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`Bacteroidetes fragilis is a probiotic organism that exerts a protective effect by
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`modulating inflammatory immune responses and E. coli is a well-known probiotic.
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`Genome Ex. 1015
`Page 15 of 278
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`

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`Application/Control Number: 15/718,735
`Art Unit: 1645
`
`Page 15
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`9.
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`No claims allowed.
`
`Conclusion
`
`10.
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to JA-NA A HINES whose telephone number is (571)272-
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`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
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`the organization where this application or proceeding is assigned is 571-273-8300.
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`Information regarding the status of an application may be obtained from the
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`Patent Application Information Retrieval (PAIR) system. Status information for
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`/JANA A HINES/
`Primary Examiner, Art Unit 1645
`
`Genome Ex. 1015
`Page 16 of 278
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`

`

`Notice of References Cited
`
`Application/Control No.
`15/718,735
`
`Examiner
`JA-NA A HINES
`
`Applicant(s)/Patent Under
`Reexamination
`
`aj ewski et al. Art
`A Unit
`1645
`
`Page 1 of 1
`
`U.S. PATENT DOCUMENTS
`
`Date
`MM-YYYY
`
`Name
`
`CPC Classification
`
`US Classification
`
`Document Number
`Country Code-Number-Kind Code
`A US-20130017199-A1
`
`B US-20080193373-A1
`
`08-2008
`
`Stritzker; Jochen Harald
`
`C US-20090217401-A1
`
`08-2009
`
`Korman; Alan J.
`
`01-2013
`
`Langernnann; Solomon
`
`A61K38/17
`
`A61K33/24
`
`A61K47/6849
`
`424/134.1
`
`424/1.17
`
`800/18
`
`*
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`*
`
`*
`
`*
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`*
`
`*
`
`D
`
`E
`
`F
`
`G
`
`H
`
`I
`
`J
`
`K
`
`L
`
`M
`
`N
`
`0
`
`P
`
`Q
`
`R
`
`S
`
`T
`
`U
`
`V
`
`W
`
`X
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`Document Number
`Country Code-Number-Kind Code
`
`Date
`MM-YYYY
`
`Country
`
`Name
`
`CPC Classification
`
`FOREIGN PATENT DOCUMENTS
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`NON-PATENT DOCUMENTS
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`Include as applicable: Author, Title Date, Publisher, Edition or Volume, Pertinent Pages)
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`*A copy of this reference is not being furnished with this Office action. (See MPEP § 707.05(a).)
`Dates in MM-YYYY format are publication dates. Classifications may be US or foreign.
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`U.S. Patent and Trademark Office
`PTO-892 (Rev. 01-2001)
`
`Notice of References Cited
`
`Part of Paper No. 20180821
`
`Genome Ex. 1015
`Page 17 of 278
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`

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`15/718,735
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`/JANA A HINES/
`Primary Examiner, A