UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 2231371450
`www.uspto.gov
`
`16/068, 830
`
`07/09/2018
`
`Robert COFFIN
`
`KEMP.P0086US
`
`4383
`
`NORTON ROSE FULBRIGHT US LLP
`
`98 SAN JACINTO BOULEVARD
`SUITE 1100
`
`AUSTIN, TX 78701-4255
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`LL 3A0 Q
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`1648
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`PAPER NUMBER
`
`NOTIFICATION DATE
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`DELIVERY MODE
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`08/22/2019
`
`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
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`following e—mail address(es):
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`aoipdocket @ nortonrosefulbright.com
`
`PTOL-90A (Rev. 04/07)
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`

`

`0/7709 A0170” Summary
`
`Application No.
`16/068,830
`Examiner
`BAO Q Li
`
`Applicant(s)
`COFFIN, Robert
`Art Unit
`AIA (FITF) Status
`1648
`Yes
`
`- The MAILING DA TE of this communication appears on the cover sheet wit/7 the correspondence address -
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE g 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.
`|f 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 12 July 2019.
`[:1 A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
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`2a)D This action is FINAL.
`
`2b)
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`This action is non-final.
`
`3)[:] 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.
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`4)[:] 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 Expat/7e Quay/e, 1935 CD. 11, 453 O.G. 213.
`
`Disposition of Claims*
`5)
`Claim(s)
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`1—18,27 and 38—46 is/are pending in the application.
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`5a) Of the above claim(s)
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`is/are withdrawn from consideration.
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`E] Claim(s)
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`is/are allowed.
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`Claim(s) 1—18,27 and 38—46 is/are rejected.
`
`[:1 Claim(s)
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`is/are objected to.
`
`) ) ) )
`
`6 7
`
`8
`
`
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`are subject to restriction and/or election requirement
`[j Claim(s)
`9
`* If any claims have been determined aflowable. you may be eligible to benefit from the Patent Prosecution Highway program at a
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`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 PPeredback@uspto.gov.
`
`Application Papers
`10)[:] The specification is objected to by the Examiner.
`
`11)[:] The drawing(s) filed on
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`is/are: a)D accepted or b)l:] 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):] Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
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`a)D All
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`b)I:J Some”
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`c)C] None of the:
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`1.[:] Certified copies of the priority documents have been received.
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`2.[:] Certified copies of the priority documents have been received in Application No.
`
`3.[:] 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) C] Notice of References Cited (PTO-892)
`
`2) .Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`Paper N0(s)/Mai| Date 10/16/2018, 6/17/2019, 7/11/2019, 7/30/2019, 7/30
`/2019_
`U.S. Patent and Trademark Office
`
`3) C] Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`4) CI Other-
`
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20190819
`
`

`

`Application/Control Number: 16/068,830
`Art Unit: 1648
`
`Page 2
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`DETAILED ACTION
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`Notice of Pre-AIA or AIA Status
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`1.
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`The present application, filed on or after March 16, 2013, is being examined
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`under the first inventor to file provisions of the AIA.
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`Election/Restrictions
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`2.
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`Applicant’s election of Group 1, claims 1-18, 27, 38, 39, 40-46 with species of
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`CD40, G protein of GALV, herpes virus and CMV promoter in the reply filed on
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`7/12/2019 is acknowledged. Because applicant did not distinctly and specifically point
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`out the supposed errors in the restriction requirement, the election has been treated as
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`an election without traverse (MPEP § 818.01 (a)).
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`3.
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`Claims 1-18, 27, 38, 39, 40-46 with species of CD40, G protein of GALV, herpes
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`virus and CMV promoter are considered.
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`Claim Rejections - 35 USC § 1 12
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`4.
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`The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
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`(a) IN GENERAL—The specification shall contain a written description of
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`the invention, and of the manner and process of making and using it, in
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`such full, clear, concise, and exact terms as to enable any person skilled
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`in the art to which it pertains, or with which it is most nearly connected, to
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`make and use the same, and shall set forth the best mode contemplated
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`by the inventor orjoint inventor of carrying out the invention.
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`5.
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`The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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`The specification shall contain a written description of the invention, and of
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`the manner and process of making and using it, in such full, clear,
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`concise, and exact terms as to enable any person skilled in the art to
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`which it pertains, or with which it is most nearly connected, to make and
`
`use the same, and shall set forth the best mode contemplated by the
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`inventor of carrying out his invention.
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`

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`Application/Control Number: 16/068,830
`Art Unit: 1648
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`Page 3
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`6.
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`Claim 12 is rejected under 35 U.S.C. 112, first paragraph, as containing subject
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`matter which was not described in the specification in such a way as to enable one
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`skilled in the art to which it pertains, or with which it is most nearly connected, to make
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`and/or use the invention.
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`7.
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`The specification is objected to under 35 U.S.C. § 112, first paragraph, as failing
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`to provide an adequate written description of the invention and failing to provide an
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`enabling disclosure without complete evidence either that the claimed biological
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`materials are known and readily available to the public or complete evidence of the
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`deposit of the biological materials.
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`8.
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`In the instant case, the invention is directed to a specially constructed virus with
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`special strains cited in claim 12, wherein the said viruses according to the disclosure are
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`deposited with variety Accession Nos cited in pages 16-17. While the specification
`
`provides the deposit numbers, it is insufficient. An assurance that the required deposit
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`has been made and all the conditions of 37 CFR 1.801 -1 .809 should be met.
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`9.
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`If the deposit is made under the provisions of the Budapest Treaty, filing of an
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`affidavit or declaration by applicant or assignees or a statement by an attorney of record
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`who has authority and control over the conditions of deposit over his or her signature
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`and registration number stating that the deposit has been accepted by an International
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`Depository Authority under the provisions of the Budapest Treaty and that all restrictions
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`upon public access to the deposited material will be irrevocably removed upon the grant
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`of a patent on this application. This requirement is necessary when deposits are made
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`under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to
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`the discretion of each State.
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`If the deposit is not made under the provisions of the
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`

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`Application/Control Number: 16/068,830
`Art Unit: 1648
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`Page 4
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`Budapest Treaty, then in order to certify that the deposits comply with the criteria set
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`forth in 37 CFR 1.801 -1 .809 regarding availability and permanency of deposits,
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`assurance of compliance is also required. Such assurance may be in the form of an
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`affidavit or declaration by applicants or assignees or in the form of a statement by an
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`attorney of record who has the authority and control over the conditions of deposit over
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`his or her signature and registration number averring:
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`10.
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`(a) during the pendency of this application, access to the deposits will be
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`afforded to the Commissioner upon request; (b) all restrictions upon the availability to
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`the public of the deposited biological material will be irrevocably removed upon the
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`granting of a patent on this application; (c) the deposits will be maintained in a public
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`depository for a period of at least thirty years from the date of deposit or for the
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`enforceable life of the patent of or for a period of five years after the date of the most
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`recent request for the furnishing of a sample of the deposited biological material,
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`whichever is longest; and (d) the deposits will be replaced if they should become
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`nonviable or non-replicable.
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`11.
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`If a deposit is made after the effective filing date of the application for patent in
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`the United States, a verified statement is required from a person in a position to
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`corroborate that the biological material described in the specification as filed is the same
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`as that deposited in the depository, stating that the deposited material is identical to the
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`biological material described in the specification and was in the applicant's possession
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`at the time the application was filed.
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`

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`Application/Control Number: 16/068,830
`Art Unit: 1648
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`Page 5
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`12.
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`Applicant's attention is directed to In re Lundak, 773 F.2d. 1216, 227 USPQ 90
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`(CAFC 1985) and 37 CFR 1.801 -1 .809 for further information concerning deposit
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`practice.
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`13.
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`This rejection affects any dependent claims if any too.
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`Claim Rejections - 35 USC § 102
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`14.
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`In the event the determination of the status of the application as subject to AIA 35
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`U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any
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`correction of the statutory basis for the rejection will not be considered a new ground of
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`rejection if the prior art relied upon, and the rationale supporting the rejection, would be
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`the same under either status.
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`15.
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`The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that
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`form the basis for the rejections under this section made in this Office action:
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`A person shall be entitled to a patent unless —
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`(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale
`or otherwise available to the public before the effective filing date of the claimed invention.
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`16.
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`Claims 1, 2, 3, 4, 13-18, 27, 39-46 are re rejected under 35 U.S.C. 102 (a) (1) as
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`being anticipated by WO 2014/036412A2 by Vanderwalde Ari et al.
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`17.
`
`Vanderwalde Ari et al. describe a method for the treatment of melanoma
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`comprising administering to a patient with stages lllb to IV melanoma an effective
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`amount of an immune checkpoint inhibitor and a herpes simplex virus, wherein the
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`herpes simplex virus lacks functional ICP34.5 genes, lacks a functional ICP47 gene and
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`comprises a gene encoding human GM-CSF (Claim 1), where the immune checkpoint
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`inhibitor is considered as an immune co-stimulatory pathway activating molecule gene,
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`which is CTLA-4 inhibitor, or more preferably is CTLLA-4 antibody or fragment thereof.
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`

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`Application/Control Number: 16/068,830
`Art Unit: 1648
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`Page 6
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`A method according to claim 3, wherein the treatment comprises administering to a
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`patient with stages lllb to IV melanoma a herpes simplex virus administered by
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`intratumoral injection into injectable cutaneous, subcutaneous, and nodal tumors at a
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`dose of up to 4.0 ml of 106 PFU/mL at day 1 of week 1 followed by a dose of up to 4.0
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`ml of 108 PFU/mL at day 1 of week 4, and every 2 weeks thereafter until complete
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`response, and an anti-CTLA-4 antibody administered intravenously at a dose of 3 mg/kg
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`every 3 weeks for 4 infusions beginning after the third dose of the herpes simplex virus
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`(Claims 1-23).
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`18.
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`Regarding a detail administering the composition comprising the recombinant
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`virus encoding GM-CSF and other immune stimulatory agent, such as antibody to
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`CTLA-4 etc. the cited reference describe in more detail in the specification of the W0
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`documentation (See pages 5-20). In brief, the W0 document provided is a method of
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`promoting a combination treatment comprising a herpes simplex virus lacking functional
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`ICP34.5 genes, lacking a functional ICP47 gene and comprising a gene encoding
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`human GM-CSF, and an immune checkpoint inhibitor for the treatment of a patient with
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`stages lllb to IV melanoma. In one embodiment the immune checkpoint inhibitor is an
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`anti-CTLA-4 antibody. In one embodiment the treatment comprises administering to a
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`patient with lllb to IV melanoma a herpes simplex virus administered by intratumoral
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`injection into injectable cutaneous, subcutaneous, and nodal tumors at a dose of up to
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`4.0 ml of 106 PFU/mL at day 1 of week 1 followed by a dose of up to 4.0 ml of 10S
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`PFU/mL at day 1 of week 4, and every 2 weeks thereafter until complete response, and
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`an anti-CTLA-4 antibody administered intravenously at a dose of 3 mg/kg every 3
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`weeks for 4 infusions beginning after the third dose of the herpes simplex virus.
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`

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`Application/Control Number: 16/068,830
`Art Unit: 1648
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`Page 7
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`Promotion may be by package insert that provides instructions to receive cancer
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`treatment with a herpes simplex virus lacking functional ICP34.5 genes, lacking a
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`functional ICP47 gene and comprises a gene encoding human GM-CSF in combination
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`with an immune checkpoint inhibitor. In one embodiment the immune checkpoint
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`inhibitor is an anti-CTLA-4 antibody. In another embodiment the anti-CTLA-4 antibody is
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`ipilimumab. In another embodiment the herpes simplex virus is talimogene
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`Iaherparepvec. Promotion may be by written or oral communication with a physician or
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`health care provider. In one embodiment the package insert is accompanied by a
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`commercial formulation of the herpes simplex virus lacking functional ICP34.5 genes,
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`lacking a functional ICP47 gene and comprises a gene encoding human GM-CSF
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`and/or an immune checkpoint inhibitor. In another embodiment, promotion is followed
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`by the treatment of the patient with the herpes simplex virus lacking functional ICP34.5
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`genes, lacking a functional ICP47 gene and comprises a gene encoding human GM-
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`CSF in combination with an immune checkpoint inhibitor. In another embodiment the
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`patient has previously untreated, unresectable, stages Illb to IV melanoma.
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`19.
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`The invention also provides a method of promoting a combination treatment
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`comprising talimogene Iaherparepvec and an immune checkpoint inhibitor, for the
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`treatment of a patient with stages Illb to IV melanoma. The invention provides a method
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`of promoting a combination treatment comprising talimogene Iaherparepvec and an
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`anti-CTLA-4 antibody, for the treatment of a patient with stages Illb to IV melanoma. The
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`invention provides a method of promoting a combination treatment comprising
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`talimogene Iaherparepvec and PD1 blocker, for the treatment of a patient with stages
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`Illb to IV melanoma. The invention provides a method of promoting a combination
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`

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`Application/Control Number: 16/068,830
`Art Unit: 1648
`
`Page 8
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`treatment comprising talimogene Iaherparepvec and a PD-Li blocker, for the treatment
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`of a patient with stages Illb to IV melanoma. The invention provides a method of
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`promoting a combination treatment comprising talimogene Iaherparepvec and an anti-
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`PD-LI antibody, for the treatment of a patient with stages Illb to IV melanoma. The
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`invention provides a method of promoting a combination treatment comprising
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`talimogene Iaherparepvec and an anti-PDI antibody, for the treatment of a patient with
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`stages Illb to IV melanoma. The invention provides a method of promoting a
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`combination treatment comprising talimogene Iaherparepvec and TIM3 inhibitor, for the
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`treatment of a patient with stages Illb to IV melanoma. The invention provides a method
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`of promoting a combination treatment comprising talimogene Iaherparepvec and LAG-3
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`inhibitor, for the treatment of a patient with stages Illb to IV melanoma. The invention
`
`provides a method of promoting a combination treatment comprising talimogene
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`Iaherparepvec and B7-H3 inhibitor, for the treatment of a patient with stages Illb to IV
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`melanoma. The invention provides a method of promoting a combination treatment
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`comprising talimogene Iaherparepvec and B7-H4 inhibitor, for the treatment of a patient
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`with stages Illb to IV melanoma. The invention provides a method of promoting a
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`combination treatment comprising talimogene Iaherparepvec and the immune
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`checkpoint inhibitor ipilimumab, for the treatment of a patient with stages Illb to IV
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`melanoma. The invention provides a method of promoting a combination treatment
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`comprising talimogene Iaherparepvec and the immune checkpoint inhibitor nivolumab,
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`for the treatment of a patient with stages Illb to IV melanoma. The invention provides a
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`method of promoting a combination treatment comprising talimogene Iaherparepvec
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`and the immune checkpoint inhibitor Iambrolizumab, for the treatment of a patient with
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`

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`Application/Control Number: 16/068,830
`Art Unit: 1648
`
`Page 9
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`stages Illb to IV melanoma. The invention provides a method of promoting a
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`combination treatment comprising talimogene Iaherparepvec and the immune
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`checkpoint inhibitor CT-011, for the treatment of a patient with stages Illb to IV
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`melanoma. The invention provides a method of promoting a combination treatment
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`comprising talimogene Iaherparepvec and the immune checkpoint inhibitor
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`tremelimumab, for the treatment of a patient with stages Illb to IV melanoma. The
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`invention provides a method of promoting a combination treatment comprising
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`talimogene Iaherparepvec and the immune checkpoint inhibitor AMP-224, for the
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`treatment of a patient with stages Illb to IV melanoma. The invention provides a method
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`of promoting a combination treatment comprising talimogene Iaherparepvec and the
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`immune checkpoint inhibitor EMS-936559, for the treatment of a patient with stages Illb
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`to IV melanoma. The invention provides a method of promoting a combination treatment
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`comprising talimogene Iaherparepvec and the immune checkpoint inhibitor MDX-1105,
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`for the treatment of a patient with stages Illb to IV melanoma. The invention provides a
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`method of promoting a combination treatment comprising talimogene Iaherparepvec
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`and the immune checkpoint inhibitor IMP321, for the treatment of a patient with stages
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`Illb to IV melanoma.
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`20.
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`Therefore, the cited reference anticipates claims 1, 2, 3, 4, 13-18, 27, 39-46.
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`21.
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`Claims 1, 10, 13, 14, 15, 17, 18. are rejected under 35 U.S.C. 102 (a) (1) as
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`being anticipated by Journal of Clinical Oncology 2009, Vol. 27, No. 34, pp. 5763-5771.
`
`To Senzer et al.
`
`22.
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`Senzer et al. teach an oncolytic virus named OncoVEXGM'CSF. OncoVEXGM'CSF
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`has been described previously. Briefly, the virus is based on HSV-1 strain JS—1 in which
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`

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`Application/Control Number: 16/068,830
`Art Unit: 1648
`
`Page 10
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`the genes encoding ICP34.5 and ICP47 have been completely deleted. Deletion of
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`ICP47 also results in the U811 gene being under the control of the ICP47 immediate
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`early promoter, rather than the U811 late promoter that results in enhanced tumor-
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`selective replication. The lCP34.5-encoding sequences have been replaced with a
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`cassette consisting of the cytomegalovirus promoter, the gene encoding human GM-
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`CSF, and the bovine growth hormone pA sequence (1St paragraph of Materials and
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`Methods. In detial, the methods comprises the steps of the first, single dose, part of the
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`study evaluated three escalating dose levels of OncoVEXG'V"CSF at 106, 107, and 108
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`plaque-forming units (pfu)/mL. At each dose level, four evaluable patients were to be
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`recruited irrespective of their HSV serology status. However, only HSV-seropositive
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`patients were dosed at 108 pfu/mL (see Results). Patients in the second part of the
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`study were given three injections testing three dosing regimens of the virus dependent
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`on their HSV serology status. For HSV-seronegative patients, the regimens tested were
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`106, 107, 107 pfu/mL and 106, 108, 108 pfu/mL and for HSV-seropositive patients 106,
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`108, 108 pfu/mL and 108, 108, 108 pfu/mL. The volume of virus injected depended on
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`tumor size (see below),
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`23.
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`Patients were assessed clinically, an electrocardiogram and a computed
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`tomography scan were also done, as well as routine hematology and biochemistry and
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`the other tests described below.: OncoVEXGM'CSF handling and injection. Virus was
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`stored at 1 x 108 pfu/mL at -70°C, diluted before use when necessary. The volume of
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`injectate was based on the diameter of the target lesion (51.5 cm, up to 1 mL; >15 to
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`52.5 cm, up to 2 mL; >2.5 cm, up to 4 mL).
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`24.
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`Therefore, the cited reference anticipates claims 1, 10, 13, 14, 15, 17, 18.
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`

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`Application/Control Number: 16/068,830
`Art Unit: 1648
`
`Page 11
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`25.
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`Claims1,10,13,14,15,17,18 are rejected under 35 U.S.C. 102 (a) (1) as being
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`anticipated by Coffin R et al. (Gene Therepy 2003, Vol. 10, pp. 292-303.
`
`26.
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`Coffin et al teach a method related using a Herpes simplex virus type-1 (HSV1)
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`in which the neurovirulence factor ICP34.5 is inactivated has been shown to direct
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`tumour-specific cell lysis in several tumour models. Such viruses have also been shown
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`to be safe in Phase I clinical trials by intra-tumoral injection in glioma and melanoma
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`patients. Previous work has used serially passaged laboratory isolates of HSV1 which
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`we hypothesized may be attenuated in their lytic capability in human tumour cells as
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`compared to more recent clinical isolates. To produce ICP34.5 deleted HSV with
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`enhanced oncolytic potential, we tested two clinical isolates. Both showed improved cell
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`killing in all human tumour cell lines tested compared to a laboratory strain (strain 17+).
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`ICP34.5 was then deleted from one of the clinical isolate strains (strain J81). Enhanced
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`tumour cell killing with ICP34.5 deleted HSV has also been reported by the deletion of
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`ICP47 by the up-regulation of U811 which occurs following this mutation. Thus to
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`further improve oncolytic properties, ICP47 was removed from JS1/lCP34.5-. As ICP47
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`also functions to block antigen processing in HSV infected cells, this mutation was also
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`anticipated to improve the immune stimulating properties of the virus. Finally, to provide
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`viruses with maximum oncolytic and immune stimulating properties, the gene for human
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`or mouse GM-CSF was inserted into the JS1/34.5-/47- vector backbone. GM-CSF is a
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`potent immune stimulator promoting the differentiation of progenitor cells into dendritic
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`cells and has shown promise in clinical trials when delivered by a number of means.
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`Combination of GM-CSF with oncolytic therapy may be particularly effective as the
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`necrotic cell death accompanying virus replication should serve to effectively release
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`

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`Application/Control Number: 16/068,830
`Art Unit: 1648
`
`Page 12
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`tumour antigens to then induce a GM-CSF-enhanced immune response. This would, in
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`effect, provide an in situ, patient-specific, anti-tumour vaccine. The viruses constructed
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`were tested in vitro in human tumour cell lines and in vivo in mice demonstrating
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`significant anti-tumour effects. These were greatly improved compared to viruses not
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`containing each of the modifications described. In vivo, both injected and non-injected
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`tumours showed significant shrinkage or clearance and mice were protected against re-
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`challenge with tumour cells. The data presented indicate that JS1/ICP34.5-/ICP47-/GM-
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`CSF acts as a powerful oncolytic agent which may be appropriate for the treatment of a
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`number of solid tumour types in man. Therefore, the cited reference anticipates claims
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`1,10,13,14,15,17,18.
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`Conclusion
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`27.
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`No claims are allowed.
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`28.
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`Any inquiry concerning this communication or earlier communications from the
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`examiner should be directed to BAO Q LI whose telephone number is (571)272-0904.
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`Application/Control Number: 16/068,830
`Art Unit: 1648
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`Page 13
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`you have questions on access to the Private PAIR system, contact the Electronic
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`BAO Q. Li
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`Examiner
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`Art Unit 1648
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`/BAO Q Ll/
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`Primary Examiner, Art Unit 1648
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