PATENT COOPERATION TREATY
`
`PCT/US2019/012218
`
`From the INTERNATIONAL BUREAU
`
`PCT
`
`
`NOTIFICATION CONCERNING
`TRANSMITTAL OF COPY OF INTERNATIONAL
`
`PRELIMINARY REPORT ON PATENTABILITY
`
`
`.
`(CHAPTER I OF THE PATENT COOPERATION
`WILSONSONSINIGOODRICH & ROSATI
`TREATY)
`
`
`Palo Alto, California 94304
`
`
`Date of mailing (day/month/year)
`ETATS-UNIS D'AMERIQUE
`16 July 2020 (16.07.2020)
`
`
`
`Applicant's or agent's file reference
`IMPORTANT NOTICE
`44854-774601
`
`
`
`
`
`
`
`International application No.
`International filing date (day/month/year)
`Priority date (day/month/year)
`PCT/US2019/012218
`03 January 2019 (03.01.2019)
`04 January 2018 (04.01.2018)
`
`
`
`Applicant
`TWIST BIOSCIENCE CORPORATION
`
`
`The International Bureau transmits herewith a copy of the international preliminary report on patentability (Chapter IT of the Patent
`Cooperation ‘l'reaty)
`
`Agnés Wittmann-Regis Facsimile No. +41 22 338 82 70
`
`The International Bureau of WIPO
`34, chemin des Colombettes
`1211 Geneva 20, Switzerland
`
`Authorized officer
`
`e-mail: pct.team6@wipo.int
`
`Form PC'I/IB/326 (January 2004)
`
`

`

`PATENT COOPERATION TREATY
`
`PCT
`
`INTERNATIONAL PRELIMINARY REPORT ON PATENTABILITY
`(Chapter I of the Patent Cooperation Treaty)
`
`(PCT Rule 44bis)
`
`Applicant’s or agent’s file reference
`44854-774601
`
`FOR FURTHER ACTION
`
`See item 4 below
`
`International filing date (day/month/year)
`International application No.
`03 January 2019 (03.01.2019)
`PCT/US2019/012218
`International Patent Classification (8th edition unless older edition indicated)
`See relevant information in Form PCT/ISA/237
`
`Priority date (day/month/year)
`04 January 2018 (04.01.2018)
`
`Applicant
`TWIST BIOSCIENCE CORPORATION
`
`This international preliminary report on patentability (Chapter I) is issued by the International Bureau on behalf of the
`International Searching Authority under Rule 44 bis.1(a).
`
`This REPORT consists of a total of 8 sheets, including this cover sheet.
`
`In the attached sheets, any reference to the wrilten opinion of the International Searching Authority should be read as a
`reference to the international preliminary report on patentability (Chapter I) instead.
`
`Box No. I
`
`Box No. II
`
`
`
`LI
`
`4 L
`
`I]
`LI
`LI
`
`
`
`This report contains indications relating to the following items:
`Xx
`CI
`Xx
`
`
`
`Box No. I
`
`Box No. IV
`
`Box No. V
`
`Box No. VI
`
`Box No.
`
`Box No.
`
`Basis of the report
`
`Priority
`
`Non-establishment of opinion with regard to novelty, inventive step and industrial
`applicability
`
`Lack of unity of invention
`
`Reasoned statement under Article 35(2) with regard to novelty, inventive step or
`industrial applicability; citations and explanations supporting such statement
`
`Certain documents cited
`
`Certain defects in the international application
`
`Certain observations on the international application
`
`‘Lhe International Bureau will communicate this report to designated Offices in accordance with Rules 44bis.3(c) and 93bis.1
`but not, except where the applicant makes an express request under Article 23(2), before the expiration of 30 months from
`the priority date (Rule 44bis .2).
`
`The International Bureau of WIPO
`34, chemin des Colombcttes
`1211 Geneva 20, Switzerland
`Facsimile No. +41 22 338 82 70
`Form PCT/IB/373 (January 2004)
`
`Date of issuance of this report
`07 July 2020 (07.07.2020)
`Authorized officer
`Agnes Wittmann-Regis
`e-mail: pct.team6@wipo.int
`
`

`

`PCT/US2019/012218 21.03.2019
`
`PATENT COOPERATION TREATY
`
`From the
`INTERNATIONAL SEARCHING AUTHORITY
`
`To: David Harburger
`
`Wilson Sonsini Goodrich & Rosati
`650 Page Mill Road
`Palo Alto, California 94304
`United States of America
`
`PCT
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`(PCT Rule 434is.1) Date of mailing
`
`Applicant’s or agent’s file reference
`44854-774601
`
`2 1 MAR 2019
`(day/month/year)
`FOR FURTHER ACTION
`See paragraph 2 below
`
`
`
`International application No.
`PCT/US19/12218
`
`Internationalfiling date (day/month/year}
`03 January 2019 (03.01.2019)
`
`Priority date (day/month/year)
`04 January 2018 (04.01.2018)
`
`International Patent Classification (IPC) or both national classification and IPC
`IPC - C12N 15/09; G11C 11/00, 11/56; GO1N 27/403 (2019.01)
`CPC -
`
`C12N 15/09, 15/1006; G11C 11/00, 11/56, 11/5664; GO1N 27/403, 27/404
`
`Applicant Twist BIOSCIENCE CORPORATION
`
`Box No. IV__Lack of unity of invention
`
`
`
`1. This opinion contains indications relating to the following items:
`
`Box No. |
`
`Basis of the opinion
`
`Box No. II
`
`Priority
`
`Box No. III Non-establishment of opinion with regard to novelty, inventive step and industrial applicability
`
`LUOKUWOUX Box No. VIII Certain observations on the international application
`
`Box No. VV
`
`Box No. VI
`
`Reasoned statement under Rule 43s. 1(a)(i) with regard to novelty, inventive step and industrial applicability;
`citations and explanations supporting such statement
`Certain documentscited
`
`Box No. VI Certain defects in the international application
`
`2. FURTHER ACTION
`
`If a demand for international preliminary examination is made, this opinion will be considered to be a written opinion of the
`International Preliminary Examining Authority (“{PEA”) 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 notified the International Bureau under Rule 66.1 6/s(b) that written
`opinionsof 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 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 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.
`
`PCT OSP:571-272-7774
`
`Nameand mailing address of the ISA/US| Date of completion of this opinion
`Mail Stop PCT, Attn: ISA/US
`Commissioner for Patents
`P.O. Box 1450, Alexandria, Virginia 22313-1450
`Facsimile No. 571-273-8300
`
`24 February 2019 (24.02.2019)
`
`Authorized officer
`
`Shane Thomas
`PCTHelpdesk: 671-272-4900
`
`Form PCT/ISA/237 (cover sheet) (January 2015)
`
`

`

`PCT/US2019/012218 21.03.2019
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCTIUS19/12218
`
`Box No. I
`
`Basis of this opinion
`
`
`
`
`1. With regard to the language,this opinion has been established on the basis of:
`
`
`[x] the international application in the language in whichit wasfiled.
`a translation of the international application into
`whichis the language ofa translation
`furnished for the purposes of international search (Rules 12.3(a) and 23.1(b)).
`
`
`2. CJ This opinion has beenestablished taking into accountthe rectification of an obvious mistake authorized byor notified to
`this Authority under Rule 91 (Rule 43 dis. 1(a)).
`
`
` 3. CC] With regard to any nucleotide and/or amino acid sequencedisclosed in the international application, this opinion has
`been established on the basis of a sequencelisting:
`
`
`a. C] forming part of the international application as filed:
`[] in the form of an Annex C/ST.25 textfile.
`[] on paperorin the form of an imagefile.
`
`
`b. LJ furnished together with the international application under PCT Rute 13¢er.1(a) for the purposes of international
`search only in the form of an Annex C/ST.25 textfile.
`
`
`c. LJ furnished subsequentto the international filing date for the purposes of international search only:
`[__]
`in the form of an Annex C/ST.25 textfile (Rule 13ser.1(a)).
`[] on paperor in the form of an imagefile (Rule 13¢er.1(b) and Administrative Instructions, Section 713).
`
`
`
` 4, CT] 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 subsequent or additional copies is identical to that forming part of the application as
`filed or does not go beyond the application as fited, as appropriate, were furnished.
`
`Additional comments:
`
`Form PCT/ISA/237 (Box No. 1) (January 2015)
`
`

`

`PCT/US2019/012218 21.03.2019
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/US19/12218
`
`Box No. III
`
`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 examinedin respectof:
`
`[] the entire international application.
`SC]_claimsNos. 5-13, 19-36, 40-46, 51-57, 62-68
`
`because:
`
`the said international application, or the said claims Nos.
`subject matter which does not require an international search (specify):
`
`relate to the following
`
`xX]
`
`the description, claims or drawings (indicate particular elements below) or said claims Nos. 5-13,19-35,40-46,51-57,.62-68
`are so unclear that no meaningful opinion could be formed (specify):
`
`because claims 5-13, 19-35, 40-46, 51-57, 62-68 are dependent claims and are notdrafted in accordancewith the second and third
`sentencesof Rule 6.4(a).
`
`[| the claims, or said claims Nos.
`by the description that no meaningful opinion could be formed (specify):
`
`are so inadequately supported
`
`[] See Supplemental Box for further details.
`
`[| a meaningful opinion could not be formed without the sequencelisting; the applicant did not, within the prescribedtime 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 of the Administrative Instructions, and such listing was not available to the International Searching Authority in the
`form and manneracceptable to it; or the sequence listing furnished did not comply with the standard provided for in
`AnnexC of the Administrative Instructions.
`
`[X<]
`
`_n0 internationalsearch report has been establishedfor said claims Nos. 5-13, 19-35, 40-46, 51-57, 62-66
`
`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. IH) (January 2015)
`
`

`

`PCT/US2019/012218 21.03.2019
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/US19/12218
`
`Box No. V
`
`Reasoned statement under Rule 43d/s.1(a)(i) with regard to novelty, inventive step and industrial applicability;
`citations and explanations supporting such statement
`
`-***-Continued Within the Next Supplemental Box-***-
`
`As per claim 1, Lindsey discloses a device for storing information (high density memory devices; abstract), comprising: a solid support,
`wherein the solid support comprisesa plurality of wells (storage medium is bound to substrate (solid support) comprising storage location
`elements 104; figure 2; column7, lines 45-50; column 11, lines 9-14), wherein each of the wells comprises an addressable locus (each
`storagecell (well) on a chip has storage location element 104 (addressable locus); figure 2; column 10, lines 65-67; column 11, lines
`1-15) comprising: a synthesis surface located in a bottom region of each ofthe wells (storage cell (well) has multiplicity of storage
`molecules 105 (synthesis surface), which can be synthesizedat different oxidation stages, located at the bottom region; figure 1; column
`11, lines 1-15; column 14, lines 10-15); a bottom electrode in addressable communication with the synthesis surface (working electrode
`101 (bottom electrode) located at bottom of the ceil (well); figures 1-2; column 10,lines 65-67; column 11, lines 1-15); and at least one
`sidewall electrode located on a sidewall of each of the wells (reference electrode 103 (sidewall electrode) located on sidewall of well;
`figures 1-2; column 10, lines 65-67; column 11, lines 1-15), wherein the at least one sidewall electrode is 50 nm to 200 nm from the
`bottom region (reference electrode 103 (sidewall electrode) are on the sidewalls of the wells, are located approx. 105 nm above working
`electrodes 101 which are disposed on the bottom of the wells, as observed from figure; figures 1-2; column 10, lines 65-67; column 11,
`lines 1-15).
`
`Statement
`
`Novelty (N)
`
`Inventive step (IS)
`
`Claims
`Claims
`
`Claims
`Claims
`
`1,47, 49
`**Please see below**
`
`NONE
`**Please see below**
`
`Industrial applicability (IA)
`
`Claims
`Claims
`
`“Please see below**
`NONE
`
`Citations and explanations:
`2.
`-***-Continued from Box V.1: Statement-***-
`
`Novelty (N): NO 2-3, 4/1-3, 14-16, 17/14-16, 18/14-16, 36-38, 39/36-38, 48, 50/47-49, 58-60, 61/58-60
`Inventive Step (IS): NO. 1-3, 4/1-3, 14-16, 17/14-16, 18/14-16, 36-38, 39/36-38, 47-49, 50/47-49, 58-60, 61/58-60
`Industrial Applicability (IA): YES 1-3, 4/1-3, 14-16, 17/14-16, 18/14-16, 36-38, 39/36-38, 47-49, 50/47-49, 58-60, 61/58-60
`
`-***-Continued from Box V.2: Citations and explanations-***-
`Claim 1 lacks novelty under PCT Article 33(2) as being anticipated by US 6,728,129 B2 to Lindsey,et al. (hereinafter ‘Lindsey’).
`
`Claims 47 and 49 lack novelty under PCT Article 33(2) as being anticipated by US 2004/0219663 A1 to Page,et al. (hereinafter ‘Page’).
`
`As per claim 47, Page discloses a method for storing information (method of array substrate 10 barcode identifiers carrying information
`which can be stored on computer readable storage medium; paragraphs [0024], [0080]), comprising: a) providing a solid support
`comprising a surface (substrate 10; figure 1; paragraph [0075)); b) depositing at droplet comprising at least one nucleoside on the surface
`(probe precursor drops may be biomonomersuch as a nucleoside; paragraphs [0066], [0074], (0081]), wherein the at least one
`nucleoside couplesto a polynucleotide attached to the surface (one or more arrays 12 arranged onthe substrate 10 contains multiple
`spots 16 of biopolymer/biomonomers, such that probe precursor drops with biomonomers such as nucleosides haslinking groups such
`that polynucleotides can be formed using sequential deposition of different probe precursors; paragraphs [0066], [0074]-[0075]); and c)
`repeating step b) to synthesize a plurality of polynucleotides on the surface (probe precursors, which are nucleosides or polynucleotides,
`are deposited as drops on the surface 11a of arrays 12 on substrate 10; paragraphs [0066], (0074]-[0075], [0081}), wherein the droplet
`has a volume of less than about 100 femtoliters (droplet size is 0.1-1000 pL which is equal to 100-1,000,000 femtoliters; paragraph
`{0099}).
`
`As per claim 49, Page discloses the method of claim 47. Page further discloses wherein the droplet has a volumeof less than about 25
`femtoliters to 100 femtoliters (droplet size is 0.1-1000 pL which is equal to 100-1,000,000 femtoliters; paragraph [0099]).
`
`Claims 2-3, 4/1-3, 14-16, 17/14-16 and 18/14-16 lack an inventive step under PCT Article 33(3) as being obvious over Lindseyin view of
`US 8,500,979 B2 to Elibol, et al. (hereinafter ‘Elibol’).
`
`As per claim 2, Lindsey discloses the device of claim 1. Lindsey does notdisclose wherein the solid support comprises addressableloci
`at a density of at least 100 x10°6 addressableloci per cm2. Elibol discloses wherein the solid support comprises addressable loci ata
`density of at least 100 x10*6 addressable loci per cm2 (arrays of sensors (addressable loci) range from 10°8 to 1000,000,000 for a 1 cm2
`wafer chip, which contain immobilized DNA (polynucleotide) molecules; column6,lines 25-35, 45-60). It would have been obvious to one
`of ordinary skill in the art at the time of the invention to modify the Lindsey invention to provide wherein the solid support comprises
`addressable loci at a density of at least 100x10*6 addressable loci per cm2, as taughtby Elibol, in order to provide minimizing fabrication
`steps to manufacture device and reduce stress induced buckling (Elibo!; column 4, lines 20-40).
`
`Form PCT/ISA/237 (Box No. V) (January 2015)
`
`

`

`PCT/US2019/012218 21.03.2019
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/US19/12218
`
`-***-Continued Within the Next Supplemental Box-***-
`
`As per claim 14, Lindsey discloses a device for storing information (high density memory devices; abstract), comprising: a solid support,
`wherein the solid support comprises a pturality of wells (storage medium is bound to substrate (solid support); figure 2; column7, lines
`45-50; column 11, lines 9-14), wherein each of the wells comprises an addressable locus (each storage cell (well) on a chip has storage
`location element 104 (addressable locus); figure 2; column 10, lines 65-67; column 11, lines 1-15) comprising: a synthesis surface
`located in a bottom region of eachofthe wells (storage cell (well) has multiplicity of storage molecules 105 (synthesis surface), which
`can be synthesized at different oxidation stages, located at the bottom region; figure 1; column 11, lines 1-15; column 14,lines 10-15); a
`bottom electrode in addressable communication with the synthesis surface (working electrode 101 (bottom electrode) located at bottom
`of the cell (welt); figures 1-2; column 10, lines 65-67; column 11, lines 1-15); at least one sidewall electrode located on a sidewall of each
`of the wells (reference electrode 103 (sidewall electrode) located on sidewall of well; figures 1-2; column 10, lines 65-67; column 11,
`lines 1-15). Lindsey does not disclose wherein the synthesis surface at each addressable locus comprisesat least one polynucleotide
`extending from the synthesis surface, and wherein the polynucleotides comprising different sequences onthe solid support are present
`at a density of at least 100 x 10°6 polynucleotides per cm2. Elibo! discloses wherein the synthesis surface at each addressable locus
`comprisesat least one polynucleotide extending from the synthesis surface (arrays of sensors (addressable loci) contain immobilized
`DNA(polynucleotide) molecules within the sensor surface (synthesis surface) onto which other nucleotides attach; column6, lines
`25-35, 45-60), and wherein the polynucleotides comprising different sequences on the solid support are present at a density of at least
`100 x 10*6 polynucleotides per cm2 (arrays of sensors (addressable loci) range from 10*8 to 1000,000,000 for a 1 cm2 wafer chip,
`which contain immobilized DNA (polynucleotide) molecules; column 6, lines 25-35, 45-60). It would have been obvious to one of ordinary
`skill in the art at the time of the invention to modify the Lindsey invention to provide wherein the synthesis surface at each addressable
`locus comprises at least one polynucleotide extending from the synthesis surface, and wherein the polynucleotides comprising different
`sequencesonthesolid support are present at a density of at least 100 x 10*6 polynucleotides per cm2, as taught by Elibol, in order to
`provide minimizing fabrication steps to manufacture device and reducestress induced buckling (Elibol; column 4, lines 20-40).
`
`Supplemental Box
`
`In case the spacein any of the preceding boxesis not sufficient.
`Continuation of.
`
`-"**-Continued from Box V: Citations and Explanations-***-
`As perclaim 3, Lindsey discloses the device of claim 1. Lindsey does not disclose wherein the solid support comprises addressableloci
`at a density of 100 x 10*6 to 100 x 107 addressable loci per cm2. Elibol discloses wherein the density of addressable loci on the solid
`support is 100x 106 to 100 x 10*7 polynucleotides per cm2 (arrays of sensors (addressable loci) range from 108 to 1000,000,000for a
`1 cm2 wafer chip, which contain immobilized DNA (polynucleotide) molecules; column6,lines 25-35, 45-60). It would have been obvious
`to one of ordinary skill in the art at the time of the invention to modify the Lindsey invention to provide wherein the density of addressable
`loci on the solid support is 100x 10*6 to 100 x 10*7 polynucleotides per cm2, as taught by Elibol, in order to provide minimizing
`fabrication steps to manufacture device and reducestress induced buckling (Elibol; column 4, lines 20-40).
`
`Asper claim 4/1, Lindsey discloses the device of claim 1. Lindsey does not disclose wherein the addressable locus comprises a
`diameter up to about 750 nm. Eliboi discloses wherein the addressable locus comprises a diameter up to about 750 nm (arrays of
`sensors (addressable loci) has opening 35 of 5-15 nm;figure 1; column 4, lines 15-25; column6,lines 25-35, 45-60). It would have been
`obviousto one of ordinary skill in the art at the time of the invention to modify the Lindsey invention to provide wherein the addressable
`locus comprises a diameter up to about 750 nm, as taught by Elibol, in order to provide heads larger than the opening diameterin order
`to sealit (Elibol; column 4, lines 15-25).
`
`As per claims 4/2-3, Lindsey and Elibol, in combination, disclose the device of any one of claims 2 to 3. Lindsey does notdisclose
`wherein the addressable locus comprises a diameter up to about 750 nm.Elibo! discloses wherein the addressable locus comprises a
`diameter up to about 750 nm (arrays of sensors (addressable loci) has opening 35 of 5-15 nm; figure 1; column 4, lines 15-25; column 6,
`lines 25-35, 45-60). It would have been obviousto one of ordinary skill in the art at the time of the invention to modify the Lindsey
`invention to provide wherein the addressable locus comprises a diameter up to about 750 nm, as taught by Elibol, in order to provide
`headslarger than the opening diameterin orderto sealit (Elibo!; column 4,lines 15-25).
`
`As per claim 15, Lindsey and Elibol, in combination, disclose the device of claim 14. Lindsey does not disclose wherein the solid support
`comprises polynucleotides of different sequences at a density of at least 100 x 10*7 polynucleotides per cm2. Elibo!l discloses wherein
`the density of addressable loci on the solid support is 100x 10*6 to 100 x 10*7 polynucleotides per cm2 (arrays of sensors (addressable
`loci) range from 10*8 to 1000,000,000 for a 1 cm2 wafer chip, which contain immobitized DNA (polynucleotide) molecules; column 6,
`lines 25-35, 45-60). It would have been obvious to oneof ordinary skill in the art at the time of the invention to modify the Lindsey
`invention to provide wherein the density of addressable loci on the solid support is 100x 10*6 to 100 x 10*7 polynucleotides per cm2, as
`taught by Elibol, in order to provide minimizing fabrication steps to manufacture device and reduce stress induced buckling (Elibol;
`column 4, lines 20-40).
`
`As per claim 16, Lindsey and Elibot, in combination, disclose the device of claim 14, wherein the solid support comprises addressable
`loci at a density of 100 x 10%6 to 100 x 10*7 polynucleotides per cm2. Elibol discloses wherein the density of addressable loci on the
`solid support is 100x 1046 to 100 x 1047 polynucleotides per cm2 (arrays of sensors (addressable loci) range from 108 to 1000,000,000
`for a 1 cm2 wafer chip, which contain immobilized DNA (polynucleotide) molecules; column6, lines 25-35, 45-60). It would have been
`obvious to one of ordinary skill in the art at the time of the invention to modify the Lindsey invention to provide wherein the density of
`addressable loci on the solid support is 100x 10*6 to 100 x 10*7 polynucleotides per cm2, as taught by Elibol, in order to provide
`minimizing fabrication steps to manufacture device and reduce stress induced buckling (Elibol; column 4,lines 20-40).
`
`As per claims 17/14-16, Lindsey and Elibol, in combination, disclose the device of any one of claims 14 to 16. Lindseyfurther discloses
`wherein each of the wells comprises a depth up to about 1000 nm (each storage cell (well) on a chip has depth of approx. 500 nm as
`observedfrom figure 1; figures 1-2, 4; column 10, lines 65-67; column 11, lines 1-15).
`
`As per claims 18/14-16, Lindsey and Elibol, in combination, disclose the device of any one of claims 14 to 16. Lindsey further discloses
`wherein each of the wells comprises a depth of 100 nm to 1000 nm (each storagecell (well) on a chip has depth of approx. 500 nm as
`observed from figure 1; figures 2, 4; column 10, lines 65-67; column 11, lines 1-15).
`
`Form PCT/ISA/237 (Supplemental Box) (January 2015)
`
`

`

`PCT/US2019/012218 21.03.2019
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
` International application No.
`
`
`PCT/US19/12218
`
`Supplemental Box
`
`In case the space in any of the preceding boxesis not sufficient.
`Continuation of:
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`-“"*_Continued from Previous Supplemental Box-***-
`Claims 36-38 and 39/36-38 lack an inventive step under PCTArticle 33(3) as being obvious over US 8,500,979 B2to Elibol, et al.
`
`(hereinafter ‘Elibol’) in view of US 2005/0112679 A1 to Myerson, et al. (hereinafter ‘Myerson’).
`
` As perclaim 36, Elibol discloses a method for storing information (electronic sensor for data collection and output; abstract; column 3,
`lines 10-20), comprising: a) providing a solid support comprising a surface (electronic sensor +0 housed on substrate 15; figure 1;
`
`column3, lines 10-15); to synthesize a plurality of polynucleotides on the surface (arrays of sensors have DNA molecules
`(polynucleotides) immobilized on the surfaces; column 6, lines 20-35; column 9,lines 1-5), wherein polynucleotides on the surface are
`present at a density of at least 100 x10*6 polynucleotides per cm2 (arrays of sensors (addressable loci) range from 108 to
`1000,000,000 for a 1 cm2 wafer chip, which contain immobilized DNA (polynucleotide) molecules; column6, lines 25-35, 45-60). Elibol
`doesnotdisclose b) depositing at least one nucleoside on the surface, wherein the at least one nucleoside couples to a polynucleotide
`attached to the surface; and c) repeating step b) to synthesize a plurality of polynucleotides on the surface, wherein polynucleotides
`having different sequences on the surface. Myersondiscloses b) depositing at least one nucleoside on the surface (nucleosides
`deposited on substrate surface; paragraph [0077]), wherein the at least one nucleoside couples to a polynucleotide attached to the
`surface (nucleosides deposited until polynucleotides are formed by coupling reaction to the polynucleotide chains; paragraph [0077));
`and c) repeating step b) to synthesize a plurality of polynucleotides on the surface (nucleosides deposited till polynucleotides are formed
`by coupling reaction to the polynucleotide chains; paragraph [0077]), wherein polynucleotides having different sequences on the surface
`(polynucleotide array formed on the support surface have different sequences; paragraphs [0077], [0079], [0090]). It would have been
`obviousto one of ordinary skill in the art at the time of the invention to modify the Elibol invention to provide b) depositing at least one
`nucleoside on the surface, wherein the at least one nucleoside couples to a polynucleotide attached to the surface; and c) repeating
`step b) to synthesize a plurality of polynucleotides on the surface, wherein polynucleotides having different sequences on the surface,
`
`as taught by Myerson,in order to provide generating addressable array of polynucleotides on substrate (Myerson; paragraph [0027)).
`
`Asper claim 37, Elibol and Myerson, in combination, disclose the method of claim 36. Elibol further discloses wherein the density of
`addressableloci on the solid support is at least 100 x 10*7 polynucleotides per cm2 (arrays of sensors (addressable loci) range from
`10*8 to 1000,000,000 for a 1 cm2 wafer chip, which contain immobilized DNA(polynucleotide) molecules; column6, lines 25-35, 45-60).
`
`
`As per claim 38, Elibol and Myerson, in combination, disclose the method of claim 36. Elibol further discloses wherein the density of
`addressable loci on the solid support is 100x 106 to 100 x 10°7 polynucleotides per cm2 (arrays of sensors (addressable loci) range
`
`from 10 “8 to 1000,000,000 for a 1 cm2 wafer chip, which contain immobilized DNA (polynucleotide) molecules; column6,lines 25-35,
`
`45-60).
`
`
`
`
`
`
`
`
`Asper claims 39/36-38, Elibol and Myerson, in combination, disclose the method of any oneof claims 36 to 38. Elibo! does not disclose
`wherein the method further comprises cleaving at least one polynucleotide from the surface, wherein the polynucleotide is dissolved in a
`droplet. Myerson discloses wherein the method further comprises cleaving at least one polynucleotide from the surface (following
`synthesis the polynucleotide may be cleaved from the surface; paragraph (0093)), wherein the polynucleotide is dissolved in a droplet
`(dissolving the polynucleotidein ionic liquid in droplet; paragraph [0026]; claims 1, 13). It would have been obvious to oneof ordinary
`skill in the art at the time of the invention to modify the Elibol invention to provide wherein the method further comprises cleaving atleast
`
`
`one polynucleotide from the surface, wherein the polynucleotide is dissolved in a droplet, as taught by Myerson, in order to provide
`
`
`generating addressable array of polynucleotides on substrate (Myerson; paragraph [0027}).
`
`
` Claim 48 lacks an inventive step under PCT Article 33(3) as being obvious over Page in view of US 2015/0293102 A1 (‘SHIM’).
`
`
` As per claim 48, Page discloses the method of claim 47. Page does not disclose wherein the droplet has a volumeof less than about 50
`femtoliters. Shim discloses wherein the droplet has a volumeof less than about 50 femtoliters (microfluidic device able to generate and
`manipulate 1-100 femtoliter sized droplets; paragraph {0035]). It would have been obvious to one of ordinary skill in the art at the time of
`
`
`the invention to modify the Page invention to provide wherein the droplet has a volume of less than about 50 femtoliters, as taught by
`Shim, in order to provide quantification of low abundance biomarkers using microfluidic devices carrying out replicate assays with
`
`smaller sample size (Shim; paragraph ([0035)).
`
`
` Claims 50/47 and 50/49 lack an inventive step under PCT Article 33(3) as being obvious over Page in view of Myerson. As per claims 50/47 and 50/49, Page discloses the method of any one of claims 47 to 49. Page does not disclose wherein the method
`
`
`
`
`
`further comprises cleaving at least one polynucleotide from the surface, wherein the polynucleotide is dissolved in a droplet. Myerson
`discloses wherein the method further comprises cleaving at least one polynucleotide from the surface (following synthesis the
`polynucleotide may be cleaved from the surface; paragraph [0093]), wherein the polynucleotide is dissolved in a droplet (dissolving the
`polynucleotide in ionic liquid in droplet; paragraph [0026]; claims 1, 13). It would have been obviousto oneof ordinary skill in the art at
`
`
`the time ofthe invention to modify the Page invention to provide wherein the method further comprises cleaving at least one
`
`
`polynucleotide from the surface, wherein the polynucleotide is dissolved in a droplet, as taught by Myerson, in order to provide
`
`generating addressable array of polynucleotides on substrate (Myerson; paragraph [0027)).
`
` Claims 58-60 and 61/58-60 lack an inventive step under PCTArticle 33(3) as being obvious over US 2016/0289758 A1 to The Regents
`
`of the University of California (hereinafter ‘Akeson’) in view of Myerson.
`
`
` -**.Continued Within the Next Supplementa! Box-”**-
`
`
`
`Form PCT/ISA/237 (Supplemental Box) (January 2015)
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`

`

`PCT/US2019/012218 21.03.2019
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`
`
`International application No.
`PCT/US19/12218
`
`Supplemental Box
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`in case the space in any of the preceding boxesis not sufficient.
`
`
`
`
`
`Continuation of:
`
`
`
`
`-***-Continued from Previous Supplemental Box-***-
`Asper claim 58, Akeson discloses a methodfor storing information (devices and methodsforfinite state machine that controls
`moleculesin biological nanopore and canstore information gatheredfor retrieval; abstract; paragraph [0137]), comprising: a) providing
`a solid support comprising a surface (semiconductor wafer (solid support) comprising array on one surface; abstract; paragraph [0139]);
`wherein the time to repeat step b) using four different nucleotides is less than about 100 milliseconds (sequencing of polynucleotides at
`the rate of 360 million bases per second (less than 100 milliseconds) for a 1¢m2 semiconductor wafer; paragraph {[0147]). Akeson does
`
`
`not disclose b) depositing at least one nucleoside on the surface, wherein the at least one nucleoside couples to a polynucleotide
`
`
`attachedto the surface; and c) repeating step b) to synthesize a plurality of polynucleotides on the surface. Myersondiscloses b)
`
`
`depos