PCT/US2018/056783 20.12.2018
`
`PATENT COOPERATION TREATY
`
`PCT
`
`INTERNATIONAL SEARCH REPORT
`
`(PCT Article 18 and Rules 43 and 44)
`
`Applicant’s or agent’sfile reference
`44854-744601
`
`FOR FURTHER
`ACTION
`
`see Form PCT/ISA/220
`as well as, where applicable, item 5 below.
`
`International application No.
`PCT/US18/56783
`
`Internationalfiling date (day/month/year)
`19 October 2018 (19.10.2018)
`
`(Earliest) Priority Date (day/month/year)
`20 October 2017 (20.10.2017)
`
`Applicant
`TWIST BIOSCIENCE CORPORATION
`
`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.
`
`sheets.
`This international search report consists of a total of
`LJ It is also accompanied by a copy of each prior art documentcited in this report.
`
`Basis of the report
`a. With regard to the language,the international search wascarried out on the basis of:
`x] the international application in the language in whichit wasfiled.
`which is the language of
`| a translation of the international application into
`a translation furnished for the purposes of international search (Rules 12.3(a) and 23.1(b)).
`This international search report has been established taking into account the rectification of an obvious mistake
`authorized by ornotified 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).
`
`. With regardto the title,
`the text is approved as submitted by the applicant.
`[| the text has been established by this Authority to read as follows:
`
`b. | noneofthe figures is to be published with the abstract.
`
`With regard to the abstract,
`
`the text is approved as submitted by the applicant.
`C] the text has been established, according to Rule 38.2, by this Authority as it appears in Box No. 1V. The applicant may,
`within one month from the date of mailing of this international search report, submit commentsto this Authority.
`
`With regard to the drawings,
`a.
`the figure of the drawings to be published with the abstract is Figure No.
`ix] as suggested by the applicant.
`L] as selected by this Authority, because the applicantfailed to suggest a figure.
`[] as selected by this Authority, because this figure better characterizes the invention.
`
`4A
`
`Form PCT/ISA/210 (first sheet) (January 2015)
`
`

`

`1. 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 sequencelisting:
`
`forming part of the international application as filed:
`~ in the form of an Annex C/ST.25textfile.
`[] on paperorin the form ofan imagefile.
`
`a.
`
`furnished together with the international application under PCT Rule 13¢er. 1(a) for the purposes ofinternational search
`only in the form of an Annex C/ST.25 textfile.
`
`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 copiesis identical to that forming part of the application as
`filed or does not go beyondthe application as filed, as appropriate, were furnished.
`
`PCT/US2018/056783 20.12.2018
`
`INTERNATIONAL SEARCH REPORT
`
`International application No.
`PCT/US18/56783
`
`Box No.I
`
`Nucleotide and/or amino acid sequence(s) (Continuation of item 1.c of the first sheet)
`
`c. [] furnished subsequentto the international filing date for the purposesof international search only:
`[| in the form ofan Annex C/ST.25textfile (Rule 13¢er. 1(a)).
`[| onpaperorin the form ofan imagefile (Rule 13¢er.1(b) and Administrative Instructions, Section 713).
`
`3. Additional comments:
`
`Form PCT/ISA/210 (continuation offirst sheet (1)) (January 2015)
`
`

`

`PCT/US2018/056783 20.12.2018
`
`INTERNATIONAL SEARCH REPORT
`
`International application No.
`PCT/US18/56783
`
`Box No.II
`
`Observations where certain claims were found unsearchable (Continuation of item 2 offirst sheet)
`
`
`
`2. [| 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:
`
`This international search report has not been established in respect of certain claims under Article 17(2)(a) for the following reasons:
`1. [| Claims Nos.:
`becausethey relate to subject matter not required to be searched by this Authority, namely:
`
`
`
`
`
`
`
`
`3.
`
`
`Claims Nos.: 17, 29-31, 36-41, 46-55
`
`because they are dependent claims andare not drafted in accordance with the second and third sentences of Rule 6.4(a).
`
`
`
`Box No. II] Observations where unity of invention is lacking (Continuation ofitem 3 offirst sheet)
`
`This International Searching Authority found multiple inventions in this international application, as follows:
`
`
`
`
`
`it is covered by claims Nos.:
`
`Asall required additional search fees were timely paid by the applicant, this international search report covers all searchable
`claims.
`
`Asall searchable claims could be searched withouteffort justifying additional fees, this Authority did not invite payment of
`additional fees.
`
`As only someof 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;
`
`
`
`The additional search fees were accompanied by the applicant’s protest and, where applicable, the
`Remark on Protest
`paymentof a protestfee.
`
`
`U 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.
`
`
`
`No protest accompanied the paymentof additional search fees.
`Form PCT/ISA/210 (continuation offirst sheet (2)) (January 2015}
`
`

`

`PCT/US2018/056783 20.12.2018
`
`INTERNATIONAL SEARCH REPORT
`
`International application No.
`PCT/US18/56783
`
`CLASSIFICATION OF SUBJECT MATTER
`A.
`IPC - BO1J 19/00; C12N 15/10; C12P 19/34 (2018.01)
`CPC -
`
`C12N 15/10, 15/64, 15/66, 15/1031; C12P 19/34
`
`According to International Patent Classification (IPC) or to both national classification and IPC
`.
`FIELDS SEARCHED
`
`Minimum documentation searched (classification system followed by classification symbols)
`See Search History document
`
`Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched
`
`See Search History document
`
`°
`
`Category*
`
`Citation of document, with indication, where appropriate, of the relevant passages
`
`Relevant to claim No.
`
`Electronic data base consulted during the international search (name of data base and, where practicable, search terms used)
`See Search History document
`C. DOCUMENTS CONSIDERED TO BE RELEVANT
`
`
`
`Xx
`
`US 2017/0095785 A1 (TWIST BIOSCIENCE CORP.) 06 April 2017; abstract; paragraphs
`[0006], [0014], [0047], (0200), (0284), [0293], [0333], [0356], [0412], [0413], [0418], [0419},
`[0551]; claim 1
`
`US 2015/0099870 A1 (TRUSTEES OF TUFTS UNIVERSITY)09 April 2015; abstract;
`paragraphs [0061], [0140]
`
`US 2016/0017394 A1 (LIFE TECHNOLOGIES CORPORATION) 21 January 2016;entire
`document
`
`1-3, 4/1-3, 5/1-3, 6/1-3,
`7/1-3, 8/1-3, 9/1-3,
`10/1-3, 11/1-3, 12/1-3,
`13/1-3, 14/1-3, 15/1-3,
`16/1-3, 18, 19/1-2, 25-27,
`28/1-3, 32-34, 35/32-34,
`42-44, 45/42-44
`
`20, 21/1-2, 22, 23/1-2, 24
`
`20, 21/1-2, 22, 23/1-2, 24
`1-3, 4/1-3, 5/1-3, 6/1-3,
`7/1-3, 8/1-3, 9/1-3,
`10/1-3, 11/1-3, 12/1-3,
`13/1-3, 14/1-3, 15/1-3,
`16/1-3, 18, 19/1-2, 20,
`21/1-2, 22, 23/1-2, 24-27,
`28/1-3, 32-34, 35/32-34,
`42-44, 45/42-44
`
`[} Further documentsare listed in the continuation of Box C.[] See patent family annex.
`Special categories of cited documents:
`op
`later documentpublished after the internationalfiling date or priority
`documentdefining the general state ofthe art which is not considered
`date and not in conflict with the application but cited to understand
`to be of particular relevance
`the principle or theory underlying the invention
`earlier application or patent but published on orafter the international
`document of particular relevance; the claimed invention cannot be
`filing date
`considered novel or cannot be considered to involve an inventive
`document which may throw doubts onpriority claim(s) or which is
`step when the documentis taken alone
`:
`:
`:
`cited to establish the publication date of another citation or other
`.
`.
`special reason (as specified)
`documentofparticular relevance;the claimed invention cannot be
`:
`:
`ae:
`considered to involve an inventive step when the documentis
`documentreferring to an oral disclosure, use, exhibition or other
`combined with one or more other such documents, such combination
`means
`being obvious to a person skilled in the art
`documentpublishedprior to the internationalfiling date but later than
`the priority date claimed
`document memberof the samepatent family
`‘&”
`Date of the actual completion of the international search
`Date of mailing of the international search report
`
`05 December 2018 (05.12.2018)
`
`2 0 D E ¢ 2018
`
`Nameand mailing address of the ISA/
`Mail Stop PCT,Attn: ISA/US, Commissioner for Patents
`P.O. Box 1450, Alexandria, Virginia 22313-1450
`Facsimile No. 571-273-8300
`Form PCT/ISA/2 10 (second sheet) (January 2015)
`
`Authorized officer
`
`PCTHelpdesk: 571-272-4300
`PCT OSP: 871-272-7774
`
`Shane Thomas
`
`

`

`PCT/US2018/056783 20.12.2018
`
`PATENT COOPERATION TREATY
`
`From the
`INTERNATIONAL SEARCHING AUTHORITY
`
`To: David S. Harburger
`
`Wilson Sonsini Goodrich & Rosati
`650 Page Mill Road
`Palo Alto, California 94304-1050
`United States of America
`
`PCT
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`(PCT Rule 43bis. 1)
`
` Date ofmailing
`
`(day/month/year)
`
`20 D E C 2018
`
`Applicant’s or agent’s file reference
`44854-744601
`
`FOR FURTHER ACTION
`
`See paragraph 2 below
`
`International application No.
`PCT/US18/56783
`
`Internationalfiling date (day/month/year)
`19 October 2018 (19.10.2018)
`
`Priority date (day/month/year)
`20 October 2017 (20.10.2017)
`
`International Patent Classification (IPC) or both national classification and IPC
`IPC - BO1J 19/00; C12N 15/10; C12P 19/34 (2018.01)
`CPC -
`
`C12N 15/10, 15/64, 15/66, 15/1031; C12P 19/34
`
`Applicant twist BIOSCIENCE CORPORATION
`
`
`
`
`
`1. This opinion contains indications relating to the following items:
`XX
`[|
`
`Box No.
`
`I
`
`Basis of the opinion
`
`Box No. If
`
`Priority
`
`Box No. III
`
`Non-establishment of opinion with regard to novelty, inventive step and industrial applicability
`
`Box No. IV
`
`Lack of unity of invention
`
`Box No. V___
`
`Reasonedstatement under Rule 43 dis. 1(a)(i) with regard to novelty, inventive step and industrial applicability,
`citations and explanations supporting such statement
`
`Rox No. VI Certain documents cited
`
`Box No. VII Certain defects in the international application
`
`Box No. VIII Certain observations on the international application
`
`LI
`
`CL]
`
`L]
`
`2. FURTHER ACTION
`If a demandfor international preliminary examination is made, this opinion will be considered to be a written opinion ofthe
`International Preliminary Examining Authority (“IPEA”) exceptthat this does not apply where the applicant chooses an Authority
`other than this one to be the IPEA and the chosen IPEA has notified the Intemational Bureau under Rule 66.1/s(b) that written
`opinionsof this International Searching Authority will not be so considered.
`Ifthis opinion is, as provided above, consideredto be a written opinion ofthe IPEA,the applicantis 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 ofForm
`PCT/ISA/220 or before the expiration of 22 monthsfrom the priority date, whicheverexpireslater.
`For further options, see Form PCT/ISA/220.
`
`
`Nameand mailing address of the ISA/US|Date of completion ofthis opinion Authorized officer
`Mail Stop PCT, Attn: ISA/US
`Commissioner for Patents
`05 December 2018 (05.12.2018)
`Shane Thomas
`P.O. Box 1450, Alexandria, Virginia 22313-1450
`PCT Helpdesk: 571-272-4300
`Facsimile No. 571-273-8300
`PCT OSP:571-272-7774
`
`
`
`Form PCT/ISA/237 (cover sheet) (January 2015)
`
`

`

`PCT/US2018/056783 20.12.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/US 18/56783
`
`Box No. I
`
`Basis of this opinion
`
`2. [] This opinion has been established taking into accountthe rectification of an obvious mistake authorized by or notified to
`this Authority under Rule 91 (Rule 43 dis. 1(a)).
`
`3. xl 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 sequencelisting:
`
`which is the languageofa translation
`
`1. With regard to the language, this opinion has been established on the basis of:
`[xX]
`the international application in the language in whichit wasfiled.
`a translation of the international application into
`furnished for the purposes ofinternational search (Rules 12.3(a) and 23.1(b)).
`
`
`
`
`
`
`
`
`
`
`
`a.
`
`formingpart of the international application asfiled:
`kK]
`in the form of an Annex C/ST.25 textfile.
`[_] on paperor in the form ofan imagefile.
`b.[] furnished together with the international application under PCT Rule 13¢er.1(a) for the purposesof international
`
`
`search only in the form of an Annex C/ST.25 textfile.
`
`
`c. [J furnished subsequentto the internationalfiling date for the purposes of international search only:
`CL]
`in the form of an Annex C/ST.25text file (Rule 13¢er.1(a)).
`[J on paperor in the form of an imagefile (Rule 13ter.1(b) and Administrative Instructions, Section 713).
` 4. _ In addition, in the case that more than one version or copy of a sequencelisting has been filed or furnished, the required
`
`
`
`statements that the information in the subsequentor 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:
`
`Form PCT/ISA/237 (Box No. I) (January 2015)
`
`

`

`PCT/US2018/056783 20.12.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/US18/56783
`
`Box No. III
`
`Non-establishment of opinion with regard to novelty, inventive step and industrial applicability
`
`The questions whetherthe claimed invention appears to be novel, to involve an inventive step (to be non obvious), or to be industrially
`applicable have not been examinedin respect of:
`[] the entire international application.
`SX]_slaims Nos. 17, 29-31, 36-41, 46-55
`
`because:
`
`the said international application, or the said claims Nos.
`subject matter which does not require an international search (specify):
`
`relate to the following
`
`[] See Supplemental Box for further details.
`
`[] a meaningfulopinion could not be formed without the sequence listing; the applicant did not, within the prescribed time limit:
`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 manneracceptable to it, or the sequencelisting furnished did not
`comply with the standard provided for in Annex C of the Administrative Instructions.
`furnish a sequencelisting on paperor in the form of an image file complying with the standard provided for in Annex
`C ofthe Administrative Instructions, and suchlisting was not available to the International Searching Authority in the
`form and manneracceptableto it; or the sequence listing furnished did not comply with the standard providedfor in
`Annex C of the Administrative [nstructions.
`
`DX]
`
`the description, claims or drawings (indicate particular elements below) or said claims Nos. 17, 29-31, 36-41, 46-55
`are so unclear that no meaningful opinion could be formed (specify):
`
`Claims Nos: 17, 29-31, 36-41, 46-55 are dependentclaims and are not drafted in accordance with the second andthird sentences of
`Rule 6.4(a).
`
`[] the claims, or said claims Nos. are so inadequately supported
`
`
`by the description that no meaningful opinion could be formed (specify):
`
`SX]
`
`nointernational search report has been established for said claims Nos. 17, 29-31, 36-41, 46-55
`
`pay the required late furnishing fee for the furnishing of a sequence listing in response to an invitation under
`Rule 13¢er.1(a) or (b).
`
`Form PCT/ISA/237 (Box No.III) (January 2015)
`
`

`

`PCT/US2018/056783 20.12.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/US 18/56783
`
`Box No. V
`
`Reasonedstatement under Rule 43dis.1(a)(i) with regard to novelty, inventive step and industrial applicability;
`citations and explanations supporting such statement
`
`Statement
`
`Novelty (N)
`
`Inventive step (IS)
`
`Claims
`Claims
`
`Claims
`Claims
`
`
`-***-Please See Below-***-
`32-34, 35/32-34, 42-44, 45/42-44
`
`NONE
`-***-Please See Below-***-
`
`Industrial applicability (1A)
`
`Claims
`Claims
`
`-***-Please See Below-***-
`NONE
`
`Citations and explanations:
`
`-Continued from Box No. V: 1. Statement:
`
`Novelty (N): YES: Claims 1-3, 4/1-3, 5/1-3, 6/1-3, 7/1-3, 8/1-3, 9/1-3, 10/1-3, 11/1-3, 12/1-3, 13/1-3, 14/1-3, 15/1-3, 16/1-3, 18, 19/1-2, 20,
`21/1-2, 22, 23/1-2, 24-27, 28/1-3
`
`inventive step (IS): NO: Claims 1-3, 4/1-3, 5/1-3, 6/1-3, 7/1-3, 8/1-3, 9/1-3, 10/1-3, 11/1-3, 12/1-3, 13/1-3, 14/1-3, 15/1-3, 16/1-3, 18,
`19/1-2, 20, 21/1-2, 22, 23/1-2, 24-27, 28/1-3, 32-34, 35/32-34, 42-44, 45/42-44
`
`Industrial Applicability (IA): YES: Claims 1-3, 4/1-3, 5/1-3, 6/1-3, 7/1-3, 8/1-3, 9/1-3, 10/1-3, 11/1-3, 12/1-3, 13/1-3, 14/1-3, 15/1-3, 16/1-3,
`18, 19/1-2, 20, 21/1-2, 22, 23/1-2, 24-27, 28/1-3, 32-34, 35/32-34, 42-44, 45/42-44
`
`-Continued from Box No. V. 2: Citations and Explanations:
`
`Claims 32-34, 35/32-34, 42-44, and 45/42-44 lack novelty under PCT Article 33(2) as being anticipated by US 2017/0095785 A1 (Twist
`Bioscience Corp.) (hereinafter ‘Twist’).
`
`-***-Continued Within the Next Supplemental Box-***-
`
`As per claim 32, Twist discloses a method for polynucleotide synthesis (a method for de novo synthesis of oligonucleotides and
`polynucleotides; abstract; paragraphs [0047], [0200]; claim 1), the method comprising: a. providing predetermined sequencesfora library
`of polynucleotides (providing preselected (predetermined) sequencesfor a genelibrary (a library of polynucleotides), paragraph [0006));
`b. providing a substrate comprising a surface (providing a solid support comprising a surface; abstract; paragraphs [0047], [0200]; claim
`1); c. synthesizingthe library of polynucleotides extending from the surface, wherein a solventin the solid phase prevents deblocking of
`at least one polynucleotide extending from the at least one regionof the surface (synthesizing the library of polynucleotides extending
`from the surface, wherein a solventin the solid phase prevents deblocking of at least one polynucleotide extending from the at least one
`region of the surface; abstract; paragraphs [0006], [0047], [0200], [0413]), wherein the solvent has a melting temperature of no more than
`about 18 degrees C (wherein the solvent is acetonitrile, which has a melting point of about -45 C (wherein the solvent has a melting
`temperature of no more than about 18 degrees C); paragraphs [0333], [0413], [0418], [0419)).
`As perclaim 33, Twist discloses the methodof claim 32, and Twist further discloses wherein synthesizing the library of polynucleotides
`extending from the surface comprises contacting the surface with a first nucleotide phosphoramidite (contacting the surface with a first
`nucleotide phosphoramidite; paragraph [0047], (0412]).
`
`As perclaim 34, Twist discloses the methodof claim 33, and Twist further discloses wherein synthesizingthe library of polynucleotides
`extending from the surface further comprises contacting the surface with a second nucleotide phosphoramidite (elongation of a growing
`oligodeoxynucleotide may be achieved through subsequent additions of phosphoramidite building blocks (contacting the surface with a
`second nucleotide phosphoramidite); paragraph [0413]), wherein the solvent is not removed betweencontactwith thefirst nucleotide
`phosphoramidite and the second nucleotide phosphoramidite (wherein the acetonitrile solvent is not removed betweencontactwith the
`first nucleotide phosphoramidite and the second nucleotide phosphoramidite; paragraphs [0412], [04 13)).
`
`As per claims 35/32-34, Twist discloses the method ofclaims 32-34, and Twist further discloses wherein synthesizing thelibrary of
`polynucleotides extending from the surface further comprises melting the solvent present at the at least one region of the surface, and
`deblocking at least one extended polynucleotide extending from the surface in the at least one region (continuous liquid conditions are
`used until the deblocking solution is substantially removed from the oligonucleotide synthesis loci on a substrate (melting the solvent
`presentatthe atleast one regionof the surface, and deblockingat least one extended polynucleotide extending from the surfacein the at
`least one region); paragraph [0419]).
`
`Form PCT/ISA/237 (Box No. V) (January 2015)
`
`

`

`PCT/US2018/056783 20.12.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/US18/56783
`
`Claims 1-3 are objected to under PCT Rule 66.2(a)(iii) as containing the following defect(s) in the form or contents thereof: Claims 1-3
`
`contain the typographicalerror, “the the”.
`
`Box No. VI¥ Certain defects in the international application
`
`The following defects in the form or contents of the international application have been noted:
`
`Form PCT/ISA/237 (Box No. VII) (January 2015)
`
`

`

`PCT/US2018/056783 20.12.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/US 18/56783
`
`Supplemental Box
`
`
`
`
`
`
`In case the spacein any of the preceding boxesis not sufficient.
`Continuation of:
`
` -***-Continued from Box V: Citations and Explanations-***-
`
`
`
`Asperclaim 42, Twist discloses a method for polynucleotide synthesis (a method for de novo synthesisof oligonucleotides and
`polynucleotides; abstract; paragraphs [0047], [0200]; claim 1), the method comprising: d. providing predetermined sequencesfor a
`library of polynucleotides (providing preselected (predetermined) sequencesfor a genelibrary (a library of polynucleotides); paragraph
`
`
`[0006)): e. providing a substrate comprising a surface (providing a solid support comprising a surface; abstract; paragraphs[0047],
`[0200]; claim 1); f. synthesizing thelibrary of polynucleotides extending from the surface, wherein a solventin the gas phase prevents
`deblockingof at least one polynucleotide extending from the at least one region of the surface (synthesizing the library of
`
`
`polynucleotides extending from the surface, wherein a solventin the solid phase prevents deblocking ofat least one polynucleotide
`
`
`extendingfrom the at least one regionof the surface; abstract; paragraphs [0006], [0047], [0200], [0413]), wherein the solvent has a
`
`
`boiling temperature no more than about 82 degrees C (wherein the acetonitrile solvent has a boiling temperature of about 82 degrees C;
`paragraphs [0333], [0413)).
`
`
`As perclaim 43, Twist discloses the method ofclaim 42, and Twist further discloses wherein synthesizing thelibrary of polynucleotides
`extending from the surface comprises contacting the surface with a first nucleotide phosphoramidite (contacting the surface withafirst
`nucleotide phosphoramidite; paragraph [0047], [0412)).
`
`Asperclaim 44, Twist discloses the method ofclaim 43, and Twist further discloses wherein synthesizingthelibrary of polynucleotides
`
`extending from the surface further comprises contacting the surface with a second nucleotide phosphoramidite (elongation of a growing
`
`oligodeoxynucleotide may be achieved through subsequentadditions of phosphoramidite building blocks (contacting the surface with a
`second nucleotide phosphoramidite); paragraph [0413]), wherein the solvent is not removed betweencontactwith thefirst nucleotide
`phosphoramidite and the second nucleotide phosphoramidite (wherein the acetonitrile solvent is not removed between contactwith the
`first nucleotide phosphoramidile and the second nucleotide phosphoramidite; paragraphs [0412], [0413)).
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`Claims 1-3, 4/1-3, 5/1-3, 6/1-3, 7/1-3, 8/1-3, 9/1-3, 10/1-3, 11/1-3, 12/1-3, 13/1-3, 14/1-3, 15/1-3, 16/1-3, 18, 19/1-2, 25-27, and 28/1-3
`lack an inventive step under PCT Article 33(3) as being obvious over Twist.
`
`
`
`As perclaim 1, Twist discloses a device for polynucleotide synthesis (devices for de novo synthesisof oligonucleotides and
`polynucleotides; abstract; paragraph [0200]; claim 1) comprising: a. a solid support comprising a surface (a solid support comprising a
`surface;claim 1); b. a plurality of structures for polynucleotide extension located onthe surface(a plurality of structures for
`
`
`polynucleotide extension located on the surface; Figure 1A; claim 1), wherein eachstructure has a width of about 10 nm to about 1000
`nm (wherein the microchannels have a width of 1-100 um, from a longlist; paragraph [0293]), wherein each structureis in contact with a
`
`
`heating unit, and wherein the heating unit comprisesat least one electrode (wherein eachstructureis in contact with a heating unit, and
`
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`wherein the heating unit comprises at least one electrode; paragraph [0356], [0551]); and c. a solventdistributed across the surface,
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`whereinthe solvent is a polar solvent(a solventdistributed across the surface, wherein the solventis acetonitrile (a polar solvent);
`
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`paragraph [0333]). Twist does not provide a motivation for selecting a width of about 10 nm to about 1000 nm.
`It would have been
`
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`obviousto one ofordinary skill in the art at the time the invention was madeto disclose about 10 nm to about 1000 nm, since the
`
`
`previous disclosure by Twist includes wherein the microchannels have a width of 1-100 um, fromalong list (paragraph [0293]), and
`
`discovering the optimum value of a result effective variable involves only routine skill in the art, and the result would have been a
`superior configuration for the device.
`
`
`As perclaim 2, Twist discloses a device for polynucleotide synthesis (devices for de novo synthesis of oligonucleotides and
`polynucleotides; abstract; paragraph [0200]; claim 1) comprising: a. a solid support comprising a surface (a solid support comprising a
`
`
`surface; claim 1); b. a plurality of structures for polynucleotide extension located on the surface(a plurality of structures for
`polynucleotide extension located on the surface; Figure 1A; claim 1), wherein each structure has a width of about 10 nm to about 1000
`
`
`nm (wherein the microchannels have a width of 1-100 um,from a longlist; paragraph [0293]), wherein each structure is in contact with a
`
`
`heating unit, and wherein the heating unit comprises at least one electrode (wherein each structure is in contact with a heating unit, and
`
`
`wherein the heating unit comprises at least one electrode; paragraph [0356], [0551]); and c. a solventdistributed across the surface,
`
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`wherein the solvent has a melting temperature of no more than about 18 degrees C (a solvent distributed across the surface, wherein
`
`
`the solventis acetonitrile, which has a melting point of about -45 C (whereinthe solvent has a melting temperature of no more than
`
`
`It
`about 18 degrees C); paragraph [0333]). Twist does not provide a motivation for selecting a width of about 10 nm to about 1000 nm.
`
`
`would have been obviousto oneof ordinary skill in the art at the time the invention was madeto disclose about 10 nm to about 1000 nm,
`
`
`since the previous disclosure by Twistincludes wherein the microchannels have a width of 1-100 um, from a longlist (paragraph [0293)),
`
`
`and discovering the optimum value of a result effective variable involves only routine skill in the art, and the result would have beena
`
`
`superior configuration for the device.
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`As per claims 45/42-44, Twist discloses the method of claims 42-44, and Twistfurther discloses wherein synthesizing thelibrary of
`polynucleotides extending from the surface further comprises melting the solvent presentat the at least one region of the surface, and
`deblockingat least one extended polynucleotide extending from the surfacein the at least one region (continuousliquid conditions are
`used that minimize evaporation of the solvent until the deblocking solution is substantially removed from the oligonucleotide synthesis
`loci on a substrate (melting the solvent presentat the at least one region of the surface, and deblockingat least one extended
`polynucleotide extending from the surface in the at least one region), paragraph [0419}).
`
` -***-Continued Within the Next Supplemental Box-***-
`
`Form PCT/ISA/237 (Supplemental Box) (January 2015)
`
`

`

`PCT/US2018/056783 20.12.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/US18/56783
`
`In case the space in any of the preceding boxesis not sufficient.
`Continuation of:
`
`-***-Continued from Previous Supplemental! Box-***-
`
`As perclaim 3, Twist discloses a device for polynucleotide synthesis (devices for de novo synthesis of oligonucleotides and
`polynucleotides; abstract; paragraph [0200]; claim 1) comprising: a. a solid support comprising a surface (a solid support comprising a
`surface; claim 1); b. a plurality of structures for polynucleotide extension located on the surface (a plurality of structures for
`polynucleotide extension located on the surface; Figure 1A; claim 1), wherein each structure has a width of about 10 nm to about 1000
`nm (wherein the microchannels have a width of 1-100 um, from a longlist; paragraph [0293]), wherein each structureis in contact with a
`heating unit, and wherein the heating unit comprises at least one electrode (wherein each structure is in contact with a heating unit, and
`wherein the heating unit comprises at least one electrode; paragraph [0356], [(0551]); and c. a solventdistributed acrossthe surface,
`wherein the solvent has a boiling temperature no more than about 82 degreesC (a solvent distributed across the surface, wherein the
`solvent is acetonitrile, which has a boiling point of about 82 C; paragraph {0333)). Twist does not provide a motivation for selecting a
`width of about 10 nm to about 1000 nm.
`It would have been obvious to one of ordinary skill in the art at the time the invention was made
`to disclose about 10 nm to about 1000 nm, since the previous disclosure by Twist includes wherein the microchannels have a width of
`1-100 um,from a longlist (paragraph [0293]), and discovering the optimum value of a result effective variable involves only routine skill
`in the art, and the result would have been a superior configuration for the device.
`
`-***-Continued Within the Next Supplemental Box-***-
`
`As per claims 4/1-3, Twist discloses the device of claims 1-3, and Twist further discloses wherein the surface comprises at least 30,000
`loci for nucleic acid synthesis (the surface comprises at least 100,000 resolvedloci; paragraph [0014]).
`
`As per claims 5/1-3, Twist discloses the device of claims 1-3, and Twist further discloses wherein the surface comprisesat least 50,000
`loci for nucleic acid synthesis (the surface comprises at least 100,000 resolvedloci; paragraph [0014)).
`
`Asperclaims 6/1-3, Twist discloses the device of claims 1-3, and Twist further discloses wherein the surface comprisesatleast
`100,000 loci for nucleic acid synthesis (the surface comprises at least 100,000 resolvedloci; paragraph [0014)).
`
`As per claims 7/1-3, Twist discloses the device of claims 1-3, and Twistfurther discloses wherein the surface comprisesatleast
`100,000loci for nucleic acid synthesis (the surface comprises at least 100,000 resolvedloci; paragraph [0014]). Twist does not disclose
`200,000 loci.
`It would have been obvious to one of ordinary skill in the art at the time the invention was madeto disclose 200,000loci,
`since the previous disclosure by Twist includesat least 100,000 resolved loci (paragraph [0014]), and discovering the optimum value of
`a result effective variable involves only routine skill in the art, and the result would have been a superior configuration for the device that
`permits synthesis of a large quantity of nucleic acids.
`
`As perclaims 8/1-3, Twist discloses the device of claims 1-3, and Twist further discloses wherein the surface comprisesatleast
`100,000