PATENT COOPERATION TREATY
`
`PCT
`
`INTERNATIONAL SEARCH REPORT
`
`(PCT Article 18 and Rules 43 and 44)
`
`Applicants or agents file reference
`N406716WO
`
`FOR FURTHER
`ACTION
`
`see Form PCT/ISA/220
`as well as, where applicable, item 5 below.
`
`International application No.
`
`International filing date (day/monfh/year)
`
`(Earliest) Priority Date (day/monfhyear)
`
`PCT/GBZO17/050038
`
`Applicant
`
`REPLIMUNE LIMITED
`
`9 January 2017 (09-01-2017)
`
`8 January 2016 (08-01-2016)
`
`This international search report has been prepared by this International Searching Authority and is transmitted to the applicant
`according to Article 18. A copy is being transmitted to the International Bureau.
`
`This international search report consists of a total of
`8
`sheets.
`El
`It is also accompanied by a copy of each prior art document cited in this report.
`
`1. Basis of the report
`a. With regard to the language, the international search was carried out on the basis of:
`the international application in the language in which it was filed
`, which is the language
`atranslation of the international application into
`of a translation furnished for the purposes of international search (Rules 12.3(a) and 23.1 (b))
`
`b. El
`
`This international search report has been established taking into account the rectification of an obvious mistake
`authorized by or notified to this Authority under Rule 91 (Rule 43.6bis(a)).
`
`With regard to any nucleotide and/or amino acid sequence disclosed in the international application, see Box No.
`
`I.
`
`Certain claims were found unsearchable (See Box No. II)
`
`Unity of invention is lacking (see Box No III)
`
`4. With regard to the title,
`
`the text is approved as submitted by the applicant
`
`the text has been established by this Authority to read as follows:
`
`
`
`5. With regard to the abstract,
`
`the text is approved as submitted by the applicant
`
`D the text has been established, according to Rule 38.2, by this Authority as it appears in Box No. IV. The applicant
`may, within one month from the date of mailing of this international search report, submit comments to this Authority
`
`6. With regard to the drawings,
`
`a.
`
`the figure of the drawings to be published with the abstract is Figure No.
`
`as suggested by the applicant
`El
`as selected by this Authority, because the applicant failed to suggest a figure
`El
`as selected by this Authority, because this figure better characterizes the invention
`El
`none of the figures is to be published with the abstract
`
`b.
`
`Form PCT/ISA/210 (first sheet) (January 2015)
`
`

`

`INTERNATIONAL SEARCH REPORT
`
`Intern ation al application No.
`
`PCT/GB2017/050038
`
`Box No. I
`
`Nucleotide and/or amino acid sequence(s) (Continuation of item 1 .c of the first sheet)
`
`With regard to any nucleotide and/or amino acid sequence disclosed in the international application, the international search was
`carried out on the basis of a sequence listing:
`
`a.
`
`b.
`
`forming part of the international application as filed:
`
`in the form of an Annex C/ST.25 text file.
`
`D on paper or in the form of an image file.
`furnished together with the international application under PCT Rule 13ter.1 (a) for the purposes of international search
`only in the form of an Annex C/ST.25 text file.
`
`Additional com ments:
`
`0. D furnished subsequent to the international filing date for the purposes of international search only:
`CI in the form of an Annex C/ST.25 text file (Rule 13ter.1(a)).
`D on paper or in the form of an image file (Rule 132er.1 (b) and Administrative Instructions, Section 713).
`
`D In addition, in the case that more than one version or copy of a sequence listing has been filed or furnished, the required
`statements that the information in the subsequent or additional copies is identical to that forming part of the application as
`filed or does not go beyond the application as filed, as appropriate, were furnished.
`
`Form PCT/ISA/21O (continuation of first sheet (1)) (January 2015)
`
`

`

`INTERNATIONAL SEARCH REPORT
`
`International application No.
`PCT/ (53201" 050038
`
`Box No. II
`
`Observations where certain claims were found unsearchable (Continuation of item 2 of first sheet)
`
`This international search report has not been established in respect of certain claims under Article 17(2)(a) for the following reasons:
`
`1. El Claims Nos.:
`because they relate to subject matter not required to be searched by this Authority, namely:
`
`Claims Nos.:
`because they relate to parts of the international application that do not comply with the prescribed requirements to such
`an extent that no meaningful international search can be carried out, specifically:
`
`
`
`Claims Nos.:
`because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6.4(a).
`
`Box No. Ill Observations where unity of invention is lacking (Continuation of item 3 of first sheet)
`
`This International Searching Authority found multiple inventions in this international application, as follows:
`
`see additional sheet
`
`As all required additional search fees were timely paid by the applicant, this international search report covers all searchable
`claims.
`
`As all searchable claims could be searched without effortjustifying an additional fees, this Authority did not invite payment of
`additional fees.
`
`As only some of the required additional search fees were timely paid by the applicant, this international search report covers
`only those claims for which fees were paid, specifically claims Nos.:
`
`No required additional search fees were timely paid by the applicant. Consequently, this international search report is
`restricted to the invention first mentioned in the claims; it is covered by claims Nos.:
`
`1-18(completely); 20-22, 24-48(partially)
`
`Remark on Protest
`
`The additional search fees were accompanied by the applicant‘s protest and, where applicable, the
`payment of a protest fee.
`
`The additional search fees were accompanied by the applicant‘s protest but the applicable protest
`fee was not paid within the time limit specified in the invitation.
`
`D No protest accompanied the payment of additional search fees.
`
`Form PCT/lSA/21O (continuation of first sheet (2)) (April 2005)
`
`

`

`INTERNAnONALSEARCHREPORT
`International application No
`
`
`A. CLASSIFICATION OF SUBJECT MATTER
`
`INV.
`ADD.
`
`C12N7/00
`
`PCT/GB2017/050038
`
`According to International Patent Classification (IPC) or to both national classification and IPC
`B. FIELDS SEARCHED
`Minimum documentation searched (classification system followed by classification symbols)
`C12N
`
`Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched
`
`Electronic data base consulted during the international search (name of data base and, where practicable, search terms used)
`
`EPO-Internal, BIOSIS, WPI Data
`
`C. DOCUMENTS CONSIDERED TO BE RELEVANT
`
`Category*
`
`Citation of document, with indication, where appropriate, of the relevant passages
`
`Relevant to claim No.
`
`
`
`X
`
`LIU B L ET AL:
`
`"ICP34.5 deleted herpes
`simplex virus with enhanced oncolytic,
`immune stimulating, and anti-tumour
`properties",
`GENE THERAPY, NATURE PUBLISHING GROUP, GB,
`vol. 10, no. 4,
`1 February 2003 (2003-02-01), pages
`292-303, XP002313120,
`ISSN: 0969-7128, DOI:
`10.1038/SJ.GT.3301885
`page 299,
`left-hand column
`page 295
`figure 2
`
`Further documents are listed in the continuation of Box 0.
`
`* Special categories of cited documents :
`
`"A" document defining the general state of the art which is not considered
`to be of particular relevance
`"E" earlier application or patent but published on or after the international
`filing date
`"L" documentwhich may throw doubts on priority claim(s) or which is
`cited to establish the publication date of another citation or other
`special reason (as specified)
`"0" document referring to an oral disclosure, use, exhibition or other
`means
`"P" document published prior to the international filing date but later than
`the priority date claimed
`
`Date of the actual completion of the international search
`
`23 February 2017
`Name and mailing address of the ISA/
`European Patent Office, PB. 5818 Patentlaan 2
`NL - 2280 HV Rijswijk
`Tel. (+31-70) 340-2040,
`Fax: (+31-70) 340-3016
`
`Form PCT/ISA/Zio (second sheet) (April 2005)
`
`later document published after the international filing date or priority
`date and not in conflict with the application but cited to understand
`the principle or theory underlying the invention
`
`"X" document of particular relevance; the claimed invention cannot be
`considered novel or cannot be considered to Involve an Inventive
`step when the document is taken alone
`"Y" document of particular relevance; the claimed invention cannot be
`considered to involve an inventive step when the document is
`combined with one or more other such documents, such combination
`being obvious to a person skilled in the art
`
`document member of the same patent family
`
`Date of mailing of the international search report
`
`24/04/2017
`Authorized officer
`
`Herrmann, Klaus
`
`page 1 of 3
`
`

`

`INTERNAWONALSEARCHREPORT
`
`
`
`International application No
`
`
`
`
`C(Continuation). DOCUMENTS CONSIDERED TO BE RELEVANT
`
`Category*
`
`Citation of document, with indication, where appropriate, of the relevant passages
`
`
`
`PCT/GB2017/050038
`
`Relevant to claim No.
`
`N. N. SENZER ET AL:
`
`"Phase II Clinical
`
`
`
`
`Trial of a Granulocyte- Macrophage
`Colony—Stimulating Factor-Encoding,
`Second—Generation Oncolytic Herpesvirus in
`Patients With Unresectable Metastatic
`Melanoma",
`JOURNAL OF CLINICAL ONCOLOGY,
`vol. 27, no. 34,
`2 November 2009 (2009-11-02), pages
`5763-5771, XP055207592,
`ISSN: 0732-183X, DOI:
`10.1200/JCO.2009.24.3675
`page 5763, right-hand column
`
`"Combination of a
`
`Fusogenic Glycoprotein, Prodrug
`Activation, and Oncolytic Herpes Simplex
`Virus for Enhanced Local Tumor Control",
`CANCER RESEARCH,
`1 May 2006 (2006-05-01),
`vol. 66, no. 9,
`pages 4835-4842, XPO55113042,
`ISSN: 0008-5472, DOI:
`10.1158/0008-5472.CAN-05-4352
`abstract
`
`page 4835, right-hand column,
`paragraph
`
`last
`
`"Talilmogene
`Piasecki et al.:
`laherparepvec increases the anti-tumor
`efficacy of the anti—PD—l
`immune
`checkpoint blockade.",
`
`19 April 2015 (2015—04-19), XP055348530,
`Retrieved from the Internet:
`
`URL:http://www.abstractsonline.com/Plan/Vi
`ewAbstract.aspx?mID=3682&sKey=ebc7290a—af2
`2-4fa6-9436-c27601lfbl81&cKey=b6lcll50-55l
`7-456b-acd3-2f8048807587&mKey=l9573a54-ae8
`f-4e00-9c23-bd6d62268424
`
`[retrieved on 2017-02-22]
`the whole document
`
` G. R. SIMPSON:
`
`"Oncolytic
`NICOLAS SOKOLOWSKI ET AL:
`virotherapy using herpes simplex virus:
`how far have we come?",
`ONCOLYTIC VIROTHERAPY,
`1 November 2015 (2015-11-01), page 207,
`XP055347641,
`DOI: 10.2147/0V.S66086
`tables 1-3
`
`(UNIV NEW YORK [05])
`we 2006/002394 A2
`5 January 2006 (2006-01-05)
`
`claims 1-3, 7, 8, ll, 12, 14-19
`
`Form PCT/ISA/ZIO (continuation of second sheet) (April 2005)
`
`_/__
`
`page 2 of 3
`
`

`

`INTERNAWONALSEARCHREPORT
`
`C(Continuation). DOCUMENTS CONSIDERED TO BE RELEVANT
`
`
` International application No
`
`
`PCT/GB2017/050038
`
`Citation of document, with indication, where appropriate, of the relevant passages
`
`Relevant to claim No.
`
`
`
`
`
`A
`
`
`
`"Developing novel
`YAN WEN ET AL:
`oncolytic adenoviruses through
`bioselection",
`JOURNAL OF VIROLOGY, THE AMERICAN SOCIETY
`FOR MICROBIOLOGY, US,
`vol. 77, no. 4,
`1 February 2003 (2003-02—01), pages
`2640-2650, XP002394479,
`ISSN: 0022-538X, DOI:
`10.1128/JVI.77.4.2640-2650.2003
`abstract
`
`page 2642, right-hand column, paragraph 2
`full
`
`"Preliminary
`Geoffrey Thomas Gibney:
`results from a phase 1/2 study of
`INCB024360 combined with ipilimumab (ipi)
`in patients (pts) with melanoma.
`: 2014
`ASCO Annual Meeting : Abstracts : Meeting
`Library",
`
`1 May 2004 (2004-05-01), XP055348796,
`Retrieved from the Internet:
`
`URL:http://meetinglibrary.asco.org/content
`/127143-144
`[retrieved on 2017-02-22]
`the whole document
`
`
`
`Form PCT/ISA/Zio (continuation of second sheet) (April 2005)
`
`page 3 of 3
`
`

`

`INTERNAWONALSEARCHREPORT
`Information on patent family members
`
`
`
`
`International application No
`
`PCT/GB2017/050038
`
`Patent document
`cited in search report
`
`Publication
`date
`
`Patent family
`member(s)
`
`Publication
`date
`
`
`
`
`
`W0 2006002394
`
`A2
`
`05—01—2006
`
`
`
`2006039894 A1
`2011236415 A1
`2013034586 A1
`2006002394 A2
`
`23—02—2006
`29—09—2011
`07—02—2013
`05—01—2006
`
`
`
`Form PCT/ISA/Zlo (patent family annex) (April 2005)
`
`

`

`1. claims:
`
`l—l8(completely); 20-22, 24-48(partially)
`
`(i) a GM-CSF-encoding gene;
`An oncolytic virus comprising:
`and (ii) an immune co-stimulatory pathway activating
`molecule or an immune co-stimulatory pathway activating
`molecule-encoding gene, and subject-matter relating thereto.
`
`2. claims: 19, 23(completely); 20-22, 24-48(partially)
`
`FURTHER INFORMATION CONTINUED FROM PCT/ISA/
`
`2 10
`
`International Application No. PCT/ 632017/ 050038
`
`This International Searching Authority found multiple (groups of)
`inventions in this international application, as follows:
`
`A virus which expresses three heterologous genes.
`
`

`

`PATENT COOPERATION TREATY
`
`From the
`INTERNATIONAL SEARCHING AUTHORITY
`
`see form PCT/ISA/220
`
`
`
`PCT
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`(PCT Rule 43bis.1)
`
`
`Date of mailing
`(day/month4/ear)
`
`see form PCT/ISA/210 (second sheet)
`
`
`
`Applicant's or agent‘s file reference
`see form PCT/ISA/220
`
`FOR FURTHER ACTION
`See paragraph 2 below
`
`International application No.
`PCT/GB2017/050038
`
`International filing date (day/fnonth/year)
`09.01.2017
`
`Priority date (day/month4/ear)
`08.01.2016
`
`
`
`
`
`International Patent Classification (IPC) or both national classification and IPC
`INV. C12N7/00
`
`
`Applicant
`REPLIMUNE LIMITED
`
`1.
`
`This opinion contains indications relating to the following items:
`
`Box No. I
`
`Basis of the opinion
`
`Box No. II
`
`Priority
`
`EEHXEIE Box No. V
`KEN] Box No. VIII Certain observations on the international application
`
`Box No. III
`
`Non-establishment of opinion with regard to novelty, inventive step and industrial applicability
`
`Box No. IV
`
`Box No. VI
`
`Lack of unity of invention
`Reasoned statement under Rule 43bis.1(a)(i) with regard to novelty, inventive step and industrial
`applicability; citations and explanations supporting such statement
`Certain documents cited
`
`Box No. VII
`
`Certain defects in the international application
`
`2.
`
`FURTHER ACTION
`
`If a demand for international preliminary examination is made, this opinion will usually be considered to be a
`written opinion of the International Preliminary Examining Authority ("IPEA") except that this does not apply where
`the applicant chooses an Authority other than this one to be the IPEA and the chosen IPEA has notifed the
`International Bureau under Rule 66.1bis(b) that written opinions of this International Searching Authority
`will not be so considered.
`
`If this opinion is, as provided above, considered to be a written opinion of the IPEA, the applicant is invited to
`submit to the IPEA a written reply together, where appropriate, with amendments, before the expiration of 3 months
`from the date of mailing of Form PCT/ISA/220 or before the expiration of 22 months from the priority date,
`whichever expires later.
`
`For further options, see Form PCT/ISA/220.
`
` Name and mailing address of the ISA:
`
`
`
`
`Date of completion of
`this opinion
`see form
`PCT/ISA/210
`
`Authorized Officer
`
`Herrmann, Klaus
`Telephone No. +49 89 2399-0
`
`F
`we“ “BMW-ts
`f3 o 6%:
`>
`3
`94’
`3.
`ewommw
`'
`
`
`
`—
`a) European Patent Office
`. J
`— D-80298 Munich
`Tel- +49 89 2399 ' 0
`Fax: +49 89 2399 - 4465
`
`Form PCT/ISA/237 (Cover Sheet) (January 2015)
`
`

`

`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/GBZO17/050038
`
`Box No. I Basis of the opinion
`
`1. With regard to the language, this opinion has been established on the basis of:
`
`the international application in the language in which it was filed.
`
`a translation of the international application into , which is the language of a translation furnished for the
`purposes of international search (Rules 12.3(a) and 23.1 (b)).
`
`This opinion has been established taking into account the rectification of an obvious mistake authorized
`by or notified to this Authority under Rule 91 (Rule 43bis.1(a))
`
`With regard to any nucleotide and/or amino acid sequence disclosed in the international application, this
`opinion has been established on the basis of a sequence listing:
`
`E E
`
`l
`
`a. E forming part of the international application as filed:
`
`E in the form of an Annex C/ST.25 text file.
`
`[I on paper or in the form of an image file.
`
`b. El furnished together with the international application under PCT Rule 13ter.1(a) for the purposes of
`international search only in the form of an Annex C/ST.25 text file.
`
`c. E furnished subsequent to the international filing date for the purposes of international search only:
`
`CI
`
`in the form of an Annex C/ST.25 text file (Rule 13ter.1(a)).
`
`El on paper or in the form of an image file (Rule 13ter.1(b) and Administrative Instructions, Section
`713).
`
`4.I:I
`
`In addition, in the case that more than one version or copy of a sequence listing has been filed or furnished,
`the required statements that the information in the subsequent or additional copies is identical to that
`forming part of the application as filed or does not go beyond the application as filed, as appropriate, were
`furnished.
`
`5. Additional comments:
`
`see separate sheet
`
`Form PCT/ISA/237 (January 2015)
`
`

`

`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/GBZO17/050038
`
`Box No. Ill Non-establishment of opinion with regard to novelty, inventive step and industrial
`applicability
`
`The questions whether the claimed invention appears to be novel, to involve an inventive step (to be non
`obvious), or to be industrially applicable have not been examined in respect of
`
`El
`
`the entire international application
`
`E claims Nos. 19, 23(completely); 20-22, 24-48(partially)
`
`because:
`
`El
`
`El
`
`El
`
`the said international application, or the said claims Nos.
`not require an international search (specify):
`
`relate to the following subject matter which does
`
`the description, claims or drawings (indicate particular elements below) or said claims Nos.
`that no meaningful opinion could be formed (specify):
`
`are so unclear
`
`the claims, or said claims Nos. are so inadequately supported by the description that no meaningful opinion
`could be formed (specify):
`
`E no international search report has been established for the whole application or for said claims Nos. E,
`
`23(completely): 20—22, 24—48(partially)
`
`El
`
`a meaningful opinion could not be formed without the sequence listing; the applicant did not, within the
`prescribed time limit:
`
`El furnish a sequence listing in the form of an Annex C/ST.25 text file, and such listing was not available
`to the International Searching Authority in the form and manner acceptable to it; or the sequence listing
`furnished did not comply with the standard provided for in Annex C of the Administrative Instructions.
`
`El furnish a sequence listing on paper or in the form of an image file complying with the standard provided
`for in Annex C of the Administrative Instructions, and such listing was not available to the International
`Searching Authority in the form and manner acceptable to it; or the sequence listing furnished did not
`comply with the standard provided for in Annex C of the Administrative Instructions.
`
`El pay the required late furnishing fee for the furnishing of a sequence listing in response to an
`invitation under Rule 13ter.1(a) or (b).
`
`E See Supplemental Box for further details
`
`Form PCT/ISA/237 (January 2015)
`
`

`

`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/GBZO17/050038
`
`Box No. IV Lack of unity of invention
`
`1. E In response to the invitation (Form PCT/ISA/206) to pay additional fees, the applicant has, within the
`applicable time limit:
`
`III
`
`El
`
`El
`
`paid additional fees
`
`paid additional fees under protest and, where applicable, the protest fee
`
`paid additional fees under protest but the applicable protest fee was not paid
`
`E not paid additional fees
`
`2. El
`
`This Authority found that the requirement of unity of invention is not complied with and chose not to invite
`the applicant to pay additional fees.
`
`3. This Authority considers that the requirement of unity of invention in accordance with Rule 13.1, 13.2 and 13.3 is
`
`III complied with
`
`E not complied with for the following reasons:
`
`see separate sheet
`
`4. Consequently, this report has been established in respect of the following parts of the international application:
`
`III all parts.
`
`E the parts relating to claims Nos. 1-18(completely); 20-22, 24-48(partially)
`
`Box No. V Reasoned statement under Rule 43bis.1(a)(i) with regard to novelty, inventive step or
`industrial applicability; citations and explanations supporting such statement
`
`Yes: Claims
`No:
`Claims
`
`Yes: Claims
`No:
`Claims
`
`Yes: Claims
`No:
`Claims
`
`1-18(completely); 20-22I 24-48(partially)
`
`1-18(completely); 20-22, 24-48(partially)
`
`1-18(completely); 20-22, 24-48(partially)
`
`1. Statement
`
`Novelty (N)
`
`Inventive step (IS)
`
`Industrial applicability (IA)
`
`2. Citations and explanations
`
`see separate sheet
`
`Form PCT/ISA/237 (January 2015)
`
`

`

`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/GBZO17/050038
`
`Box No. VIII Certain observations on the international application
`
`The following observations on the clarity of the claims, description, and drawings or on the question whether the
`claims are fully supported by the description, are made:
`
`see separate sheet
`
`Form PCT/ISA/237 (January 2015)
`
`

`

`WRITTEN OPINION OF THE
`
`INTERNATIONAL SEARCHING
`
`International application No.
`
`AUTHORITY (SEPARATE SHEET)
`
`PCT/GBZOI 7/050038
`
`Citations
`
`The documents mentioned in this Written Opinion are numbered as in the
`
`International Search Report (ISR), i.e. D1 and D8 correspond to the first and the last
`
`document of the search report, respectively.
`
`Re ITEM I
`
`The application as filed contains a sequence listing consisting of 45 sequences.
`
`Re ITEM III
`
`
`No search report was established for the subject-matter of claims 19 23 and partially
`
`claims 20-22 24-48 (see ITEM IV). Consequently, preliminary examination has been
`
`restricted to the subject-matter of invention 1 (Rule 66.1 (e) PCT).
`
`Re ITEM IV
`
`1
`
`In response to an invitation, the Applicant did not pay additional search fees.
`
`Consequently, international search and examination have been restricted to the
`
`subject-matter of claims 1-18 and partially claims 20-22 24-48 (invention 1). The
`
`present application lacks unity as required by Art. 3(4)(iii) and Rule 13 PCT because it
`
`contains 2 separate inventions:
`
`
`Invention 1: claims 1—1 8 and partially claims 20—22 24—48
`
`An oncolytic virus comprising: (i) a GM-CSF-encoding gene; and (ii) an immune co-
`
`stimulatory pathway activating molecule or an immune co-stimulatory pathway
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`activating molecule-encoding gene, and subject-matter relating thereto.
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`Invention 2: claims 19, 23 and partially claims 20-22, 24-48
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`A virus which expresses three heterologous genes.
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`2 According to Art. 3(4)(iii) and Rule 13 PCT an application shall relate to one
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`invention only or to a group of inventions so linked as to form a single general
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`inventive concept. Where a group of inventions is claimed, the requirement of unity of
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`invention referred to in Rule 13.1 PCT shall be fulfilled only when there is a technical
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`relationship among those inventions involving one or more of the same or
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`corresponding special technical features.
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`Form PCT/ISA/237 (Separate Sheet) (Sheet 1) (EPO-April 2005)
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`

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`WRITTEN OPINION OF THE
`
`INTERNATIONAL SEARCHING
`
`International application No.
`
`AUTHORITY (SEPARATE SHEET)
`
`PCT/GBZO17/050038
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`The technical feature which distinguishes invention 1 from invention 2 is presence of
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`(i) a GM-CSF-encoding gene and (ii) an immune co-stimulatory pathway activating
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`molecule or an immune co-stimulatory pathway activating molecule-encoding gene in
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`an oncolytic.
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`Invention 2 is not directed to oncolytic viruses, let alone oncolytic viruses comprising a
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`GM—CSF—encoding gene.
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`3 Since invention 2 does not share said technical feature of invention 1, each of the
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`above mentioned groups of claims represents an independent invention.
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`4
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`In view of the above the "single general concept" (Rule 13.1 PCT) linking the
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`above mentioned inventions cannot even be formulated as oncolytic viruses
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`comprising a GM-CSF-encoding gene, let alone oncolytic viruses comprising a GM-
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`CSF-encoding gene for use in the treatment of cancer.
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`Even if one formulated the single general concept in such a way then such concept
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`could not be regarded as novel with regard to the prior art:
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`For instance, D1 (Liu et al.), D2 (Senzer et al.), D3 (Simpson et al., 2006) and D4
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`(Piasecki et al.) disclose an oncolytic herpes simplex virus type 1 (HSV1) for use in
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`the treatment of cancer. Such viruses comprise inter alia an agonist of an immune co-
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`stimulatory pathway (GM-CSF). Said documents also disclose combination therapies.
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`D4 (Piasecki et al.), for instance, discloses the use of a combination of the vector
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`disclosed in D3 with an immune checkpoint inhibiting antibody for the treatment of
`cancer.
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`5
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`Said prior art documents also address and solve the problem underlying parts of
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`present application, namely the provision of means for an improved oncolytic therapy
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`or oncolytic immunotherapy, respectively (p. 3, l. 3-5).
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`6 Because said single general concept is evidently not novel it cannot be inventive
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`as required by Rule 13.1 PCT.
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`7
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`Furthermore, this authority is of the opinion that the effort necessary for searching
`
`the individual inventions justifies an additional search fee for each invention
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`mentioned above because, as explained above, the separate inventions are directed
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`to different subject-matter for which a separate search has to be performed in the
`available databases.
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`N.B.: The use of the term "invention" here in no way implies recognition of an
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`inventive step for the subject—matter of any group of claims.
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`Re ITEM V
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`Form PCT/ISA/237 (Separate Sheet) (Sheet 2) (EPO-April 2005)
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`

`

`WRITTEN OPINION OF THE
`
`INTERNATIONAL SEARCHING
`
`International application No.
`
`AUTHORITY (SEPARATE SHEET)
`
`PCT/G82017/050038
`
`1
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`Novelty and inventive step (Art. 33(2) and (3) PCT)
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`1.1
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`
`The subject-matter of claims 1-18 20-22 and 24-48 does not meet the
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`requirements of Art. 33(2) and 33(3) PCT.
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`1.2 The definitions "oncolytic virus comprising an immune co-stimulatory pathway
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`activating molecule" and "oncolytic virus comprising an immune co-stimulatory
`
`
`pathway activating molecule-encoding gene" render the scope of independent claim 1
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`so broad that practically any prior art virus falls under such definition. Practically any
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`prior art virus comprises molecules or genes having such property.
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`Prior art oncolytic viruses further comprising a GM-CSF-encoding gene are well
`1.3
`known in the art.
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`D1 (Liu et al.), for instance, discloses a "second generation" oncolytic herpes simplex
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`virus type 1 (HSV1) ("OncoVEXGM'CSF"), wherein the virus:
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`(a) does not express functional |CP34.5;
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`(b) does not express functional |CP47; and/or
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`(c) expresses the US11 gene as an immed iate early gene; and
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`(d) one or more immune stimulatory molecules or one or more immune stimulatory
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`molecule encoding genes, wherein the immune stimulatory molecule is GM-CSF (cf.
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`p. 299, left col. of D1).
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`1.4
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`Similar results are disclosed in D2 (Senzer et al.) (p. 5763, right col.).
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`1.5
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`Furthermore, a "third generation" oncolytic HSV1 ("OncoVEXGALV/CD" = T-VEC)
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`based on the "second generation" is disclosed in D3 (Simpson et al., 2006). Said
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`"third generation oncolytic HSV1 further comprises:
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`(e) a highly potent pro—drug activating gene (yeast cytosine deaminase (CD)/uraci|
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`phospho-ribosyltransferase (UPRP) fusion (Fcy::Fur)) and
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`(f) the fusogenic glycoprotein from gibbon ape leukemia virus (GALV) (e.g. D3, p.
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`4835, right co|., bottom). A method of treating cancer by applying such vector in
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`combination with 5—fluorocytosine (5—FC) is also disclosed in D3 (abstract, p. 4835,
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`right co|., bottom).
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`1.6 A method of treating cancer with the vector of D3 in combination with an
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`immune checkpoint inhibiting antibody is also known in the art (see e.g. D4 (Piasecki
`
`et al.): T-VEC + anti CTLA-4 mab ipilimumab or T-VEC + anti-PD1 mab
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`pembrolizumab).
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`1.7 The subject-matter of independent claim 1 can thus not be regarded as novel.
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`Form PCT/|SA/237 (Separate Sheet) (Sheet 3) (EPO-April 2005)
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`

`

`WRITTEN OPINION OF THE
`
`INTERNATIONAL SEARCHING
`
`International application No.
`
`AUTHORITY (SEPARATE SHEET)
`
`PCT/GBZO17/050038
`
`1.8 A positive international preliminary report on patentability can only be
`
`established if claims 2-18 20-22 and 24-48 refer to a claim which can be regarded as
`novel and inventive.
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`NB: No unified criteria exists among the PCT member states for the examination of
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`claims directed to methods for treatment of the human or animal body surgery or
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`therapy (claims 39—46).
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`2
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`Industrial application (Art. 33(4) PCT)
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`
`Claims 1-18 20-22 and 24-48 meet the criteria as set forth by Art. 33(4) PCT.
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`ITEM VIII
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`Clarity (Art. 6 PCT)
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`1 What is a "modified version" of e.g. GM—CSF (e.g. claims 2 and 3)?
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`2 No "SEQ ID" No is defined in claim 19.
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`Form PCT/ISA/237 (Separate Sheet) (Sheet 4) (EPO-April 2005)
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`