the priority date (Rule 44his .2).
`
`
`
`
`
`jox No. Tl
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`Bow No.
`
`Box No.
`
`Boa
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`Bon
`
`Bon
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`Sox
`

`

`

`
`No.
`
`No.
`
`No.
`
`No.
`
`PATENT COOPERATION TREATY
`
`PCT
`
`INTERNATIONAL PRELIMINARY REPORT ON PATENTABILITY
`(Chapter I of the Patent Cooperation Treaty)
`
`(PCT Rule 44bis)
`
`Applicant’s ar agent's file reference
`44854-738601
`
`FOR FURTHER ACLION
`
`See item 4 below
`
`International liling dale (diy/menthyyear]
`International application No.
`22 February 2018 (22.02.2018)
`PCT/US2018/019268
`International Patent Classilication (81h edition unless older edition indicated)
`See relevant information in Form PCT/ISA/237
`
`Priority dale fdawmoniivvear)
`22 February 2017 (22.02.2017)
`
`Applicant
`TWIST BIOSCIENCE CORPORATION
`
`Vhis international preliminary report on patentability (Chapler D is issued by dhe Intermativnal Bureau oo behalf af tie
`International Searching Authority under Rule 44 bis.1(a).
`
`This REPORT consists of a total of & sheets, including this cover sheet.
`
`In the attached sheets, any reference to the written opinion of the International Searching Authority should he read as a
`reference Lo the international preliminary report on patentability (Chapter T) instead.
`
`This report contains indications relating lo the [following items:
`
`Sox No.
`
`|
`
`[basis of the report
`
`Prinrity
`
`Non-establishment of opinion with regard to novelly, inventive step and industrial
`applicability
`
`Tack of unity of invention
`
`Reasoned statement under Article 35(2) wilh regard to novelly, inventive slep or
`industrial applicability; citations and explanations supporting such statement
`
`Certain documents cited
`
`Certain delects in the international applicalien
`
`Certain observations on the international application
`
`
`
`The Intermativnal Bureau will communicate Unis cepurt lo desigualed Offices in accordance with Rides 44bis.3¢C) and 93bdis.1
`bul nol, except where the applicant makes an express request under Article 25(2), belore lhe expiralien of 30 months [rom
`
`
`
` e-mail: pcl.leamo@wipoint
`
`Date of issuance of this report
`27 Auqust 2019 (27.08.2019)
`Authorized officer
`
`Simin Baharlou
`
`The International Bureau of WIPO
`34, chewiu des Coluwbettes
`1211 Geneva 20, Swilzerland
`Tacsimile No, +41 22 338 32 70
`
`Form PCWIBS73 (lanuary 2004)
`
`

`

`PCT/US2018/019268 26.06.2018
`
`PATENT COOPERATION TREATY
`
`-
`
`From the
`INTERNATIONAL SEARCHING AUTHORITY
`1: DAVID HARBURGER
`WILSON SONSINI GOODRICH & ROSATI
`650 PAGE MILL ROAD
`PALO ALTO, CA 94304
`
`PCT
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`(PCT Rule 434és.1)
`
`
`
`2OJUN 2018
`
`|
`
` ‘vmnner
`
`
`
`FOR FURTHER ACTION
`
`| Applicant's or agent’s file reference
`
`See paragraph 2 below
`44854-738601
`
`
`
`
`‘day/month/year)
`Priority date fdayimonhyeor)
`International application No.
`International filing date
`
`
`22 February 2017 (22.02.2017}
`PCT/US 18/19268
`22 February 2018 (22.02.2018)
`
`
`International Patent Classification (IPC} or both national classification and IPC
`IPC(g) - GOGF 19/22, B82Y 10/00, G116 14/00 (2018.01)
`
`cpc. G11B 20/0021 ,G11C 13/0009, GO6F 19/10, GO6BN 3/126, GOBN 3/4123
`
`
`
`
`
`
`Applicant TWIST BIOSCIENCE CORPORATION
`
`
`1. This opinion contains indications relating 19 the following items:
`
`Box No.
`
`|
`
`Basis of the opinion
`
`Bax No. I
`
`Priority
`
`Box No. il
`
`Non-establishment of opinion with regard to novelly, invemive step and industrial applicability
`
`Box No. IV
`
`Lack of unity of invention
`
`Box No. ¥_—_-
`
`Reasoned statement under Rule 434s. 1(a}(i) with regard to novelty, inventive step and industrial applicability,
`citations and explanations supporting such statement
`
`Box No. VI
`
`Certain documents cited
`
`Box No. ¥II Certain detects in the international applicalion
`
`Box No. VIN Certain observations on the international application
`
`OooseooR
`
`!
`
`2. FURTHER ACTION
`If a demand for 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 |PEA and the chosen [PEA has notified the International Bureau under Rule 66. 14/s(b) that written
`opinions of this International Searching Authority will not be so considered.
`Ifthis opinionis, as provided above, considered to be a written opinion of the IPEA, the applicant is invited to submit to the IPEA
`a wrilten reply together, where appropriate, with amendments, before the expiration of3 months from the date of mailing of Fonn
`PCTIISA/220 or before the expiration of 22 months from the priority date, whichever expires later.
`For further oplions, see Form PCT/ISA/220.
`
`
`
`
`Mame and mailing address uf the ISA/US|Date of completion ofthis opinion Authorized officer
`Mail Stop PCT, Attn: ISAVUS
`Lee W. Young
`
`
`Commissioner for Patents
` 10 June 2018
`
`POT Helpdesk: 574-272-4300
`P.O. Box 1450, Alexandria, Virginia 22313-1450
`
`PCT OSP: 574-272-7774
`Facsimile No. 571-273-8300
`
`
`Form PCT/ASA&/237 (cover sheet) (January 2015)
`
`

`

`PCT/US2018/019268 26.06.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCTIUS 1819268
`
`Box No. I
`
`Basis of this opinion
`
`1, With repard to the language, this opinion has been established on the basis of:
`[><]
`the international application in the tanguage in which it was filed,
`a translation of the intemational application into
`furnished for the purposes of international search (Rules 12.3(a) and 23.1(b)).
`
`
`
`
`
`
`2, C] This opinion has been established taking into accountthe reetification of an obvious mistake authorized by or noufied to
`this Authority under Rule 91 (Rule 434/s. 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:
`
`
`forming part of the international application as filed:
`Xx]
`inthe form ofan Annex C/ST.25 textfile.
`C] an paper or in the form of an imagefile.
`
`
`b. [| furnished together with the international application under PCT Rule 13ver.1{a} for the purposes of international
`search only in the form of an Annex C/ST.25 textfile.
`
`
`c. [| furnished subsequentto the internationalfiling date for the purposes of international search only:
`[] in the form of an Annex C/ST.25 text file (Rule |3ter. 1{a)).
`
`
`[I on paper or in the form of an image file (Rule [3ter.i(b) and Administrative Instructions, Section 713).
`
`
`
`4. LJ In addition, in the case that more than one version or copy of a sequence listing has been filed or furnished, ihe required
`
`statements that the information in the subsequent or additional copiesis identical to that forming part ofthe application as
`'
`
`whichis the language ofa translalion
`
`a
`
`filed or does not go beyond the application as filed, as appropriate, were fumished. . Additional comments:
`
`Form PCTASA/237 (Box No. 1) Ganuary 2015}
`
`

`

`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`Lack of unity of invention
`
`Box No. IW
`
`PCT/US2018/019268 26.06.2018
`
`
`International application No.
`PCT/US 18/19268
`
`1.
`
`
`
`In responseto the invilalion (Form PCT/ISA/206) te pay additional fees the applicant has, within the applicable linve limit:
`[| paid additional fees.
`["]
`paid additional fees under protest and, where applicable, the protest fee.
`C]
`paid additional fees under protest but the applicable protest fee was not paid.
`(x)
`not paid additional tees.
`2, [_] This Authority found that the requirement ofunity of invention is not complied with and chosesot to invite the applicant to
`pay additional fees.
`3. This Authority considers that the requirementof unity ofinvention in accordance with Rule 13.1, 13.2 and 13.3 is
`[| complied with.
`x not complied with for the following reasons:
`This application cenlains the fallowing inventions or groups of invantions which are not so linked as to form a single general inventive
`cencapt under PCT Rule 13.1. {n orderfor all inventiona to be examined, the appropriate additional examinatian fees must be paid.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Group (+: Claims 1-10, 19-27, drawn te a method/systern for storing ancrypted information. The method/system for bioencryption will be
`searched ta the extent that the bieancryption format encompasses enzymatic based bicencryption. Itis believed that claims 1-3, 9, 19, 19
`-21, 26, 27 ancompassthis first named invention, and thus these claims will be searched withoul fee to the extant that they encompass
`enzymatic based bicencryption. Additional bicencryption formats will be searched upon the payment of additional fees. Applicants must
`specify the claims that encompass any additionally elected bioencryption format. Applicants must furtherindicate,if applicable, the claims
`which ancompass (he first named invention,if different than what was indicated above for this group. Failure to cleanly identify how any
`paid additional invention fees are to ba applied to the "+" group{s) will result In only the first claimed invention te be searched. An
`axemplary election would be a bigancryption format encompassing affinity based bicencrypticn (claims 1, 4-10, 19, 24-27).
`
`Groupt+: Claims 11-14, 28-34, drawn ta a method/system for retrieving ancrypted information, Group |l+ will be searched upon
`paymentof additional faes. Tha mathod/systam may be searched, for example,to the extent that the encrypted informationis retrieved
`using enzymatic based decryption for an additional fee and election as such.Itis beliaved that claims 11-13, 28-30 read on this
`exemplary invention. Additional decryption format{s} will be searched uponthe paymentof additionalfees. Applicants must specify the
`claims that encompass any additionally elected decryption format(s). Failure to clearly identify how any paid additional invention fees ara
`to be applied to the"+" group{s) will result in only the first claimed invention to be searched. Another exemplary election would be a
`decryption format encompasing affinity based decryption {claims 11, 16-18, 28, 34-34).
`
`
`The inventionslisted as Groups I+ and Il+ do not relate to a single generalinventive concapt under PCT Rule 13.1 because, under PLT
`Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
`
`
`Special Technical Features
`
`
`Groups Il+ do not require a mathod/system for storing information in a bigencryption format by converting a digital sequence to a plurality
`of oligonucleotide sequences and synthasizing a plurality of oliganucleotide sequences encodingfor those, as requirad by Groups I+.
`
`
`Groups I+ do not require a method/system for retrieving bioencrypted information by releasing oligonuclectides from a surface, applying
`decryption techniqua thereto, enriching and sequencing the anriched oligonucleotides, as required by GroupsIh.
`
`
`The inventions of Groups |+ each include the special technical feature of bicencrytion formats, recited therein. Each of the inventions of
`Group |+ requires a specific bionencryption format, not required by the other inventions.
`
`
`
`
`
`Tha inventions of Groups Il+ each include the special technical feature of decrytion formats, recited thersin, Each ofthe inventions of
`Group |I+ requires a specific decryption format, not required by the other inventions.
`
`erereeee ctnseee tenner~SEE FIRST SUPPLEMENTAL BOX TO CONTINUE----——----—-=---2---------—
`
`4.
`
`~ Consequently, this opinion has been established in respect of the following parts ofthe international application:
`[| all parts.
`
`the parts relating to claims Nos. 1-3, 9, 10, 19-21, 26, 27limited to enzymatic based bigancryption
`
`
`Form PCTHSA/237 (Box No. {¥) (January 2015)
`
`

`

`PCT/US2018/019268 26.06.2018
`
`WRITTEN OPINION OF THE
`i
`i
`r
`c
`*
`INTERNATIGNAL SEARCHING AUTHORITY
`
`Intemational application No.
`PCT/US 18/19268
`
`Box No. ¥
`
`Reasoned statement under Rule 43dis.1(a)() with regard to novelty, inventive step or industrial applicability;
`citations and explanations supporting such statement
`
`Statement
`
`Novelty (N}
`
`inventive step (15)
`
`Industrial applicability (1A}
`
`Claims
`Claims
`
`2-3, 9, 10, 20-21, 26, 27
`4,75
`
`Claims
`Claims
`
`Claims
`Claims
`
`NONE
`1-3, 9, 10, 19-21, 26, 27
`
`1-3, 9, 10, 19-21, 26, 27
`NONE
`
`anteerentenanennerencenSEE THIRD SUPPLEMENTAL BOX TO CONTINUE----------+--s2rerecene---—--noee
`
`Regarding claim 1, Bharadwaj discloses a methad forstoring information, the method comprising:
`a) receiving at east oneitem of information in a form ofai least one digital sequence (abstract “A methodfor storing information in DNA
`has been daveloped which includes software and a set of schemes to encrypt, store and decrypt information in terms of DNA bases. The
`main advantages of the present method over exiting art is that it addresses complete set of extendad ASCII characters set and thereby,
`ancryption ofall kind of digital information (text, image, audio etc.}. First ofall, information is, encrypted”, thus multiple kinds of digitized
`Information is received lor encryption, see Figs. 2 and 4 for overview);
`i) recelving instructions for selection of at least one bioencryption format, wherein the bioeneryption format is enzymatic based
`biosncryption (para (0017) “plain text/image or any digital informationis encryptedin terms of DNA sequences using encryption key
`(software). If the information overflowsthelimits i.e. it cannot be synthesized in a single piece thenit is encrypted and fragmsnted ina
`number of segments[i.e. aligonucleotides]", para (0019) “the ONA segmentts}is/are flanked by known PCRprimers ... at both the ends
`ia. header primers are attached at the beginning of segment andtail primers ara attached at the end of the segment.”, para [0021] “only a
`recipient knowing the sequences of both the primers (starting andtail] would be able to extract the message, using [enzymatic] PCR to
`isolate & amplify tha encrypted DNA strand),
`:
`¢) converting the at least one digital sequence to a plurality of oligonucleotide sequences based on the selected bioencryption format (para
`(0017) “plain textimage or anydigital information is encrypted in terms of ONA sequences... encrypted and fragmented in a numberof
`segments(i.e, cligonuclectides]", sae Fig. 1B) ;
`3) synthesizing a plurality of oligonucleotides encoding for the oligonucleotide sequences (para [0017] “ Synthesis of encrypted sequence
`(8) is carried out using DNA synthesizer.", see Figs. 4 and 5); and
`e) storing the plurality of oligonucleotides (para [0020] “DNAis then mixed with (he enormous complex denatured DNA strands of genomic
`DNA of human or other organism, As the human genome contains about 3.times.10.sup.9 nucleotide pairs, fragmented & denatured
`human DNA provides a very complex background for storing the encrypted DNA. The DNA can be stored and transported an paper", see
`Figs. 4 and 5).
`
`Citations and explanations:
`2.
`Claims 1 and 19 lack novelty under PCT Article 33(2) as being anticipated by US 2005/0053988 At ta Bharadwaj et al. (hereinafter
`‘Bharadwaj’.
`
`Regarding claim 18, Bharadwal discloses a syslem for storing information (para [0017] “plain textimage or any digital information is
`encrypted in terms of DNA sequences using encryption key (software).", See Fig. 5 for overview of system}, the system comprising:
`a) a receiving unit (.e.computer with software program, see Fig. 2) for receiving machine instructions for at least one ilem of informatian in
`a form ofat least one digital sequence, and machineInstructions for selection of at least one bicencryption format (para [0016] "The
`method anables the storage of information in DNA.In another embodimenta software based on the above method enablesall 256
`Extended ASC characters to be defined in terms of DNA sequences ... Software named as "DNASTORE"has beendeveloped in Visual
`Basic 6.0 for encryption and decryption ofdigital information in terms of DNA bases. Using DNASTORE completa extended ASC!
`character set can be encoded 256 diffarent ways.", See Figs. 4 and 5), wherein the bioencryption formal is enzymatic (para (0019] "the
`DNA segment(s}is/are flanked by known PCR primers ... at both the ends i.e. header primers ara attached at the beginning of segment
`andtail primers are attached at the end of tha segmant.", para [0021] “only a recipient knowing the sequences of both the primers [staring
`andtail] would be able ta extracl the message,using [enzymatic] PCR to isolate & amplify the encrypted DNA strand} |
`b) a processor unit for automatically canverting the at laast one digital sequence to a plurality of oligonuclectide sequences based on the
`selected bioencryption format (para [0017] "plain textfimage or any digital information is ancrypted in terms of ONA sequences...
`encrypted and fragmentedin a number of segments [i.e. cligonucleotides]", see Fig. 4).
`c) a synthesizer unit for receiving machine instructions from the processor unit for synthesizing a plurality of oligonuclectides encoding for
`the aligonucleotide sequences (See Fig. 4 and 5), and
`d) a storage unit for recaiving the plurality of oligonucleotides deposited from the synthesizer unit (para [0020] "DNAis then mixed with the
`enormous complex denatured DNAstrands of genomic DNA of human or other organism, As tha humen genome contains about
`3.times.10.sup.9 nucteotide pairs, fragmented & denatured human ONAprovides a very complex background for storing the encrypted
`DNA. The DNA can be stored and transported on paper’, see Figs. 4 and 5).
`
`Form PCT/ISA/237 (Box No. ¥) (lanuary 2015}
`
`

`

`PCT/US2018/019268 26.06.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`
`international application No.
`PCTIUS 18/19268
`
`Supplemental Box
`
`
`
`In case the space ia any of the preeeding boxcsis not sufficient.
`Continuation of
`Box No. IV (3} Lack of unity of invention:
`
`Common Technical Features
`
`
`The common technical feature shared by Groups [+ and [I+ is a method of managing data comprising encryption/decryption using a
`
`biological based format. However, this shared technical feature does nol represent a contribution over prior art, because the shared
`technical feature is anticipated by the article entitled "New Trandsof Digital Data Storage in DNA by De Silva et al. (hereinafter "de Silva’)
`(BioMed Research International (5 September 2016} Vol 2016, Articia 10 6072463, 14 pages).
`
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`De Silva teachas a method of managing data comprising using a DNAbiological based format (abstract “there emerges a needfor a
`storage medium with high capacity, high storage density, and possibility to withstand extreme environmental conditions. DNA emerges as
`the prospective medium for data storagewithits striking faatures. Diverse encoding models for reading and writing data onto DNA, codes
`for encrypting data ... and approaches for developing cadens and storage styles have been developed”) comprising encrypting and
`decrypting said data (pg, 7, col 2, last 2 para - pg 8, col 1, para 2- "Steganography Technique Using DNA Hybridization. This method
`sffectively uses the advantages offered by the structure of DNA for vast storing capabilities and parallel molecular computation. This
`approach brings out an algorithm for hiding data in DNA in a digital form ... Ona Time Pad (OTP) generated keys are used as encryption
`kay. This key is used just only once for exactly one messages. The used pad is destroyed by the user after encryption. Figure 2
`summarizes the encryption process using hybridization technique", sea Figs. 2-3 for encryption/dacryption, "After decrypting lhe message
`receiver destroys the identical pad which is owned by him. Because of this reason this approachis extramely sacure. In this algonthm
`single stranded ONAis used as the OTP ... Encrypted message is hidden in a microdot. Strand consisting of tha encryptad messageis
`placed between lwo PCRprimer sequences ...Without the knowledge about starl and end primers one will not be able to read the
`message by amplifying."}.
`Another common technical feature shared by Groups [+ and |I+ is a syslem of managing data comprising a storaga unit, a processorunit.
`however this shared technical feature does nol represent a contribution over prior art, because the shared technical feature is mada
`obvious by De Silva. As discussed above, DNAis tha storage unit for DNA, such as a micradot, which is recovered, amplified by
`conventional PCR, and decoded. Far said decoding, an artisan of ordinary skill would have readily appreciated that a computer wilh a
`processor would be used to collect sequence data {invariable generated by a computer conlrolled seugencing device, See diagrams in
`Figs 2 and 3), thus De Silva's stored data would comprise a system and processor(s) to encode data by ONA synthesis and decode data
`by amplification and sequencing.
`
`
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`
`
`Another common technical feature shared by Groups [+ is claims 1 and 19, however,this feature is anticipated by US 2005/0053966 A1 te
`Bharadwaj et al. (hereinafter ‘Bharadwaj’). Bharadwaj teaches {claim 1}. method for storing information, the method comprising:
`a) storing information in a form of at least one digital sequence (abstract "A methodfor stoning information in ONA has bean daveloped
`
`which includes software and a set of schemes to encrypt. stere and decrypt information in terms of ONA bases. The main advantages of
`the present method over exiting art is that it addresses complete set of extended ASCI! characters sel and thereby, ancryption of all kind of
`digital information");
`b} selection of at least one bicencryption format, wherein the bioencryption formatis electromagnetic (computer derived} instruction (para
`[0018] "The method enables tha slorage of information in DNA. ... a software based on the above method enables all 256 Extended ASCII
`
`characters to be defined in terms of DNA sequences. The basic concept used is to take minimum number of bases to define each
`
`Extended ASCII character. ... four bases give 4.times.4.times.4.times.4 = 256 distinct sequences. Therefore, with a set of 4 basas,
`
`complete extended ASCII set has been encoded. Software named as "DNASTORE"has been developed... for encryption and decryption
`
`af digital informationin lerns of DNA bases. Using DNASTORE complete extended ASCII character set can be encoded 256different
`
`ways."};
`
`¢) converting the at least ona digital sequenca to a pluralily of oligonucleotide sequences based on the selacted bioencryption format,
`
`d) synthesizing a plurality of oligonucleotides encodingfor the oligonucleotide sequences (para [0017] “plain texvimage or any digital
`
`information is encrypted in terms of DNA sequences using encryptian key (software).If lhe information overflows the limits i.e. it cannot be
`
`synthesized in a single piece thenil is encrypted and fragmented in a number of segments [i.2. oligonucleotides). Synthesis of encrypted
`
`sequence (s} is carried out using CNA synthesizer.", para [0019] " tha DNA segmenl(s) is/are flanked by known PCRprimers ... at both
`
`the ends i.e. header primers are attached at the beginning af segment and tall plmars are attachedat ihe and of the segmant.") and 4)
`
`storing the plurality of oligonucleotides (para [0020] “DNA is then mixed with the enarmous complex denatured DNA strands of genomic
`
`DNA of hurnan or cthar organism. As the human genomecontains about 3.timas.10.sup.9 nucteotide pairs, fragmented & denatured
`
`human DNA provides a very complex backgroundfor storing the encrypted ONA, The DNA can be stored and transported on paper’).
`
`
`pennant tenementSEE NEXT SUPPLEMENTAL BOX TO CONTINUE-—-----------+
`
`
`
`Form PCTASA/237 (Supplemental Box) (January 2015)
`
`

`

`PCT/US2018/019268 26.06.2018
`
`WRITTEN OPINION GF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCTUS 18/19268
`
`Supplemental Box
`
`In case the space in any of the preceding boxesis not sufficient.
`Cantinuation of:
`/
`Box No. Iv (3) Lack of unity of invention:
`
`Bharadwajfurther teaches (claim 19) system for storing information, the system comprising:
`a) a receiving unit for receiving machine instruciions for at least one item of information in a form ofat least one digital sequence, and
`machine instructions for selection of at least one bioencryption format, wherein the bioancryption format is chemical based bicencryption
`{synthetic DNA sequences) (para [0017] "plain textfimage or anydigital information is encrypted in terms of DNA sequences using
`encryption key (software}."):
`b} a processorunit for automatically converting the at laast one digital sequenceto a plurality of oligonucleotide sequences based on the
`selected bicencryption format;
`c) a synthesizer unit for receiving machine instructions from the processor unit for synthesizing a plurality of oligonucleotides encoding for
`the oligonucleotida saquences (para [0017] "plain text/image or any digital information is encrypted in terms of DNA sequences using
`encryption key (software). If the information overfiows the limits i.e. it cannot be synthesized in a single piece thenit is encrypted and
`fragmented in a number of segments [i.¢. oligonucleotides]. Synthesis of ancrypled sequence {s) is carried out using DNA synthesizer.”,
`para [0019] " the DNA sagmant{s)is/are flanked by known PCRprimers... at both the ands i.e. header primers are attached al the
`baginning of segmentand tail primers are attached at the end of the segment."}, and
`d) a Storage unit for receiving the plurality of oligonucleotides deposited fromthe synthesizer unit (para [0020) “ONA is then mixed with tha
`enormous complex denatured DNA strands of genomic DNA of humanor other organism. As the human genome contains about
`3.times.10.sup.9 nucleotide pairs, fragmented & denatured human DNA provides a very complex background for storing the encrypted
`DNA. The DMA can he stored and transported on paper’).
`
`1
`
`Another common technical feature shared by Groups !I+ is claims 11 and 28, howaver,this feature is anticipated by Bharadwaj. Bharadwaj
`teaches {claims 11 and 28) a method and system for retrieving information comprising
`fa} releasing a plurality of oligonucleotides from a storage unit surface (DNA stored on paper and mixed with human genomic DNA as
`discussed above), and
`b) applying an enzymatic (Polymerase/PCR) decryptionto the plurality of oligonuclectides with a deposition unit (PCR Machine} (see para
`[0020]}, oligonucleotides having primers at each end are stored on paper, para [0017] “digital information is encrypted in terns of DNA
`sequences using encryption key {softwara)."}
`{c) enriching the plurality of oligonucleotides (para (0021) "only a recipient knowing the sequences of both the primers ... would be able 1d
`extract the message, using PCR to isolate & amplify the encrypted DNA strand.”, (2. enrich the oligonucleotides},
`(a) sequencing enriched oligonucleotides fram the plurality of oligonucleotides to ganerate nucleic acid sequences using a sequencing unit
`enriched oligonucleotides from the plurality of oligonucleotides to generate nucleic acid sequences {para [0021] "Isclated and amplified
`DNA can then be sequenced using automated DNA sequencer."} and
`(e) a processorunit for automatically converting the nucleic acid sequences to at least onedigital sequence, wherein the at least one
`digital sequence encadesforat least one item of information (para (0021) "Ths DNA sequence obtained can then be converledinto digital
`massage using encryption/decryption key (software key)."}.
`
`Ag the tachnical features were knownin ihe art at the tima ofthe invention, thay cannol be considered special technical features lhat would
`otherwise unify tha inventions.
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`Groups |+ and (|+ therefore lack unity under PCT Rula 13 because they do not share the same or corresponding special technical feature.
`
`Form PCT/1$A/237 (Supplemental Box) (January 2013)
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`

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`PCT/US2018/019268 26.06.2018
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`International application No.
`PCTIUS 18/19268
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`WRITTEN OPINIGN OF THE
`INTERNATIONAL SEARCHING AUTHORITY
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`Supplemental Box
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`In case the space in any of the preceding boxesis not sufficient.
`Continuation af:
`Box V No. (2) Citations and Explanations:
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`Claims 2 and 20 lack an inventive step under PCT Article 33(3) as being obvious over Bharadwaj
`Bacterla Can Now Slore Data” (Dvorsky}.
`
`in view af the publication entitled "Living
`
`Regarding claims 2 and 20, Bharadwaj teaches a method and a system for storing information that is encrypted as ONA sequence
`comprising , as discussed for claims 1 and 19. Bharadwaj does not expressly teach that the the enzymatic based bisencryption comprises
`CRISPR/Cas based bioencryption, however, Dvorsky teaches storing data in cell DNA using CRISPR/Cas based bioencryption (pg 1 para
`1 "Using the CRISPR gene-editing tool, scientists fram Harvard University have developed a technique that permanently records data into
`living calls.", pg 3, para 1 "During the experiment, loose segments af DNA ware injected into a strain of €. coli bacteria equipped with
`CRISPR/Cas1-Cas?. But these bits of ONA weren't arbitrary- Iney contained specific strings of data that contained specific sequences of
`lattars chosen by the scientists. Thase segments wera introduced one at a time, and the bacteria systematically integrated Ihem ina
`linearly coherent mannerto reflect the order in which they were introduced."). Based on Dvorsky's teaching,it would have been obvious to
`an artisan of ordinary skill to encrypt and store Bharadwai's oligonucleotides using Dvarsky's CRISPRiCas methodof intagrating strings
`(oligonucleotides) of ONA into a bacterial chromosomefor storagashiding, and, for example, recovering said ONA using sequences using
`PCR amplication, because said encryption/storaga methodis a valuable alternative means of storing said encrypted BNA,
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`Claims 3 and 21 lack an inventive step under PCT Articla 33(3) as being obvious over Bharadwaj
`ZHENGZHOU LIGHT IND (hereinafter ' ZhengZhou ’)
`
`in view of CN 104734848 A to UNI
`
`Regarding claims 3 and 21, Bharadwaj teaches a method and a system for storing information that is encrypted as DNA sequence
`comprising , as discussed for claims 1 and 19. Bharadwaj does nat expressly teach that the enzymatic based bioencryption comprises
`instructions for synthesis of the oligonucleotides which are sensitive ta an enzyme (restriction anzymein Table 10), however, ZhengZhou
`teaches encrypting GNA seqments using restriction enzymes (abstract "a recombinant DNAtechnology based information encrypting and
`hiding method and an application. Firstly, a plain text is coded into a GNA sequence, preprocessing is carried out on the DNA sequence by
`adopting the encryption algorithm, and a pseudo-DNA segmentis generated: and then tha pseude-DNA segment and a marker gene
`segmentare connected to a DNA piasmid vector by using the restriction enzyme and the ligase, and an obtained recombinant plasmid is
`further hided into a germ body;finally, a cell which contains confidential information is hided inte a large numberofirrelevant pseudo-cells,
`and the hided calls can ba screened out by the selective cultivation, The encrypting and hiding methodis apptied to the authentication and
`signature technology. Encrypting, hiding and transmitting of the confidential information are achieved", para [0041] "upon receipt of the
`recipient cell containing the recipient cell masquerading according to the type of selective resistance gene,a cell culture received in an
`appropriate selective medium, having a specific resistance by surviving cells and amplified"; para [0042] "The amplified recipient cells for
`extraction and purification of receptors, restriction endgnuclaases will disguise Ihe DNA sequence excised from the plasmid vectors and
`their DNA purified and sequencedafter extraction, to obtain ihe DNA sequence disguised base arrangementinformation"); wherein the
`enzymes are listed in Table 10 (para 0090] The monaclonal colonies were picked, disrupt the cells, centrifuged at high speed, to extract a
`recombinant DNA vector molecule purified smplified dual restriction sites sender design, selection Nde! site and Xhol doula digestion...
`iis sequence obtained by ONA sequencing”). Based on ZhengZhou's teaching,it would have been obvious to an artisan of ordinary skill ta
`experimentwith ZhengZhou's use of restriction enzyme sites flanking encrypted DNA to selactivaly release encrypted sections af DNA
`concealed wilhin a cell or a mixture, because said release and sequencing (e.g. with specific primers thal ligate to the specific cut ends)
`offer another means of encrypting and storing/hiding segments of ONA created using the method of Bharadwaj.
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`Claims 9-10 and 26-27 lack an inventive step under PCT A

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