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
`44854-728601
`
`FOR FURTHER ACTION
`
`See item 4 below
`
`International filing date (day/month/year)
`International application No.
`19 September 2017 (19.09.2017)
`PCT/US2017/052305
`International Patent Classification (8th edition unless older edition indicated)
`See relevant information in Form PCT/ISA/237
`
`Priority date (day/month/year)
`21 September 2016 (21.09.2016)
`
`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 11 sheets, including this cover sheet.
`
`In the attached sheets, any reference to the written opinion of the International Searching Authority should be read as a
`reference to the international preliminary report on patentability (Chapter I) instead.
`
`This report contains indications relating to the following items:
`
`Box \0. I
`
`Basis of the report
`
`Box \0. II
`
`Box \0.
`
`
`
`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 Colombettes
`1211 Geneva 20, Switzerland
`Facsimile NO. +41 22 338 82 70
`Form PCT/IB/373 (January 2004)
`
`Date of issuance of this report
`30 April 2019 (30.04.2019)
`
`AthHZEd officer
`
`-
`XlaOfan Tang
`e—mail; pct.[eam2@wip0.int
`
`
`
`
`
`Box \0.
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`Box \0.
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`Box \0.
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`Box \0.
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`Box \0.
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`E |
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`& g |
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`

`

`PCT/USZO17IO52305 02.02.2018
`
`From the
`INTERNATIONAL SEARCHING AUTHORITY
`
`PATENT COOPERATION TREATY
`
` PCT
`
`To: STEPHANIE DUSABAN GONZALES
`WILSON SONSINI GOODRICH & ROSATI
`
`650 PAGE MILL ROAD
`
`
`PALO ALTO, CA 94304
`
`
`
`
`Date ofmailing
`
`
`(day/month/year)
`O 2 F E B 2018
`
`
`
`FOR FURTHER ACTION
`Applicant’s or agent’s file reference
`
`
`44854-728601
`See paragraph 2 below
`
`
`Intemational application No.
`
`
`International filing date (day/month/year)
`
`
`PCT/US 17/52305
`19 September 2017 (19.09.2017)
`
`21 September 2016 (21.09.2016)
`
`
`
`International Patent Classification (IPC) or both national classification and IPC
`
`”30(3) _ BO1J 19/00, 0120 1/68, C408 40/06, G06F 3/06 (2018.01)
`
`
`0pc _ C120 1/6874, BO1J 19/0046, C12N 15/10, C120 1/6806
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`(PCT Rule 43bis.1)
`
`Priority date (day/manrh/year)
`
`
`
`Applicant TWIST BIOSCIENCE CORPORATION
`
`
`
`I. This opinion contains indications relating to the following items:
`
`Box No.
`
`I
`
`Basis of the opinion
`
`Box No. II
`
`Priority
`
`Box No III Non-establishment of opinion with regard to novelty, inventive step and industrial applicability
`Box No. IV
`Lack of unity ofinvention
`
`Box No. V
`
`Reasoned statement under Rule 43bi's. l (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. VII Certain defects in the international application
`
`Box No. VIII Certain observations on the international application
`
`FURTHER ACTION
`
`Ifa demand for intemational preliminary examination is made, this opinion will be considered to be a written opinion of the
`International Preliminary Examining Authority (“IPEA”) except that this does not apply where the applicant chooses an Authority
`other than this one to be the [PEA and the chosen IPEA has notified the International Bureau under Rule 66.1bis(b) that written
`opinions of this International Searching Authority will not be so considered.
`
`Ifthis opinion is, as provided above, considered to be a written opinion ofthe IPEA, the applicant is invited to submit to the IPEA
`a written reply together, where appropriate, with amendments, before the expiration of 3 months from the date of mailing of Form
`PCT/ISA/220 or before the expiration of 22 months from the priority date, whichever expires later.
`For further options, see Form PCT/ISA/220.
`
`Name and mailing address ofthe ISA/US Date of completion ofthis opinion
`Commissioner for Patents
`Mail Stop PCT, Attn: ISA/US
`PO. Box 1450. Alexandria. Virginia 22313-1450
`Facsimile No. 571 -273-8300
`
`10 January 2018
`
`Authorized officer
`-
`Lee W Young
`For ”sum,“ 3, i-zu-nsuu
`PCT osp: 571-272.7774
`
`Form PCT/ISA/237 (cover sheet) (January 2015)
`
`

`

`PCT/USZO17IO52305 02.02.2018
`
`INTERNATIONAL SEARCHING AUTHORITY
`
` International application No. WRITTEN OPINION OF THE
`
`PCT/US 17/52305
`
`Box No. I
`
`Basis of this opinion
`
`1. With regard to the language, this opinion has been established on the basis of:
`
`
`
`
`
`[XI
`the intemational application in the language in which it was filed
`
` D a translation of the international application into
`which is the language ofa translation
`
`fumished for the purposes of international search (Rules 12.3(a) and 23.1(b)).
` 2. I: This opinion has been established taking into account the rectification of an obvious mistake authorized by or notified to
`this Authority under Rule 91 (Rule 43bl's.l(a)).
` 3.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`filed or does not go beyond the application as filed, as appropriate, were fumished.
`
`[X] With regard to any nucleotide and/or amino acid sequence disclosed in the international application, this opinion has
`been established on the basis ofa sequence listing:
`
`a.
`
`forming part ofthe international application as filed:
`
`Kl in the form ofan Annex C/ST.25 text file.
`E] on paper or in the form ofan image file.
`b. D furnished together with the international application under PCT Rule 131er.l(a) for the purposes of international
`search only in the form of an Annex C/ST.25 text file.
`
`c. D furnished subsequent to the international filing date for the purposes ofintemational search only:
`|:] in the form ofan Annex C/ST.25 text file (Rule 13ter. 1(a)).
`D on paper or in the form ofan image file (Rule 131er.l(b) and Administrative Instructions, Section 713).
`
`4. E] In addition, in the case that more than one version or copy ofa sequence listing has been filed or furnished, the required
`statements that the information in the subsequent or additional copies is identical to that forming part of the application as
`
`Additional comments:
`
`
`
`Form PCT/lSA/237 (Box No. 1) (January 2015)
`
`

`

`PCT/USZO17IO52305 02.02.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`lntemational application No.
`PCT/US 17/52305
`
`Box No. IV
`
`Lack ofunity ofinvention
`
`not complied with for the following reasons:
`
`V
`I. M In response to the invitation (Form PCT/ISA/206) to pay additional fees the applicant has, within the applicable time limit:
`I: paid additional fees.
`
`
`
`
`
`
`
`D paid additional fees under protest and, where applicable, the protest fee.
`
`
`I: paid additional fees under protest but the applicable protest fee was not paid.
`
`
`XI
`not paid additional fees.
`
`
` 2. D This Authority feund that the requirement of unity of invention is not complied with and chose not to invite the applicant to
`pay additional fees.
` 3. This Authority considers that the requirement ofunity ofinvention in accordance with Rule 13.], 13.2 and 13.3 is
`
`
`D complied with.
`V
`
`
`
`This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive
`concept under PCT Rule 13.1. In order for all inventions to be examined, the appropriate additional examination fees must be paid.
`
` Group I: Claims 1-28 and 74. drawn to methods and device for storing and accessing information
`
`Group II: Claims 29-39 and 75, drawn to a method and device for encrypting information
`
`
`Group III: Claims 40-56. drawn to a method for collecting information
`
`Group IV: Claims 57-73, drawn to a nucleic acid library
`
`
`
` Special Technical Features
`
`
`
`
`
`
`
`
`
`Group IV requires a composition comprising a library of nucleic acids. not required by Groups I. ll, Ill.
`Common Technical Features
`
`
`
`The feature shared by Groups I, II, III, and IV is a plurality of polynucleotides for storage of information
`A feature shared by Groups I, II, III is providing a structure comprising a surface.
`
`
`
`———-— Please see continuation In supplemental box -----—
`
`
`The inventions listed as Groups I, II, III and N do not relate to a single general inventive concept under PCT Rule 13.1 because, under
`PCT Rule 13.2. they lack the same or corresponding special technical features for the following reasons:
`
`Group I requires method steps for storing and accessing information comprising selectively transferring a plurality of polynucleotides to a
`receiving unit by application of a force. and a device for carrying out said method steps. not required by Groups II, III. IV.
`
`Group II requires method steps for encrypting information comprising associating each nucleic acid sequence with one of a plurality of
`non«identica| markings on a surface. and a device for carrying out said method. not required by Groups I, III. IV.
`
`Group III requires method steps for collecting information comprising selectively separating a region of a structure comprising a plurality
`of polynucleotides and removing the plurality of polynucleotides from the surface. not required by Groups I, II, N.
`
`
`
`
`Consequently, this opinion has been established in respect of the following parts of the international application:
`El an parts.
`
`
`
`
`IE the parts relating to claims Hos. 1-20 am] 7'4
`
`Form PCT/ISA/237 (Box No. IV) (January 2015)
`
`

`

`PCT/USZO17IO52305 02.02.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`lntematronal application No.
`PCT/US 1752305
`
`Box No. V
`
`Reasoned statement under Rule 43bis.l(a)(i) with regard to novelty, inventive step or industrial applicability;
`citations and explanations supporting such statement
`
`Statement
`
`Novelty (N)
`
`Claims
`
`1-28 and 74
`
`Claims m————*
`
`-------- Please see continuation in supplemental box ---_____
`
`Inventive step (IS)
`
`Claims
`Claims
`
`None
`1-28 and 74
`
`Industrial applicability (IA)
`
`Claims
`Claims
`
`1-28 and 74
`None
`
`Citations and explanations:
`2.
`Claims 10, 14-28, and 74 lack an inventive step under PCT Article 33(3) as being obvious over US 2015/0261664 A1 to Goldman et al.
`(hereinafter 'Goldman').
`
`Regarding claim 10. Goldman discloses a method for storing information (para [0003] - "The disclosure relates to a method and apparatus
`for the storage of digital information in DNA"; para [0012] - "A practical encoding-decoding procedure that stores more information than
`previously handled is described in this disclosure. The inventors have encoded five computer files .
`.
`into a DNA code. The inventors
`subsequently synthesized this DNA, transported the synthesized DNA from the USA to Germany via the UK. sequenced the DNA and
`reconstructed all five computer files with 100% accuracy"). the method comprising:
`a) converting at least one item of informatlon In a form of at least one digital sequence to at least one nucleic acid sequence (para [0012] -
`"The inventors have encoded five computer files .
`.
`into a DNA code"; para [0014] - "The method comprises encoding bytes in the item of
`information. The encoded bytes are represented using a schema by a DNA nucleotide to produce a DNA sequence in-silico"; para [0040]
`"the bytes comprising each computer file 210 were represented in step 720 as a DNA sequence 230"; para [0046] - "The digital
`information encoding in step 720 was carried out as follows. The five computer files 210 of digital information (represented in FIG. 2A)
`stored on a hard-disk drive were encoded using software. Each byte of each one of the five computer files 210 to be encoded in step 720
`was represented as a sequence of DNA bases via base-3 digits ('trits' 0, 1 and 2) using a purpose-designed Huffman code listed in Table
`1 (below) to produce the encoded file 220"):
`b) synthesizing a plurality of polynucleotides having predetermined sequences collectively encoding for the at least one nucleic acid
`sequence (para [0012] - "The inventors subsequently synthesized this DNA"; para [0014] - "the plurality of DNA segments is synthesized";
`para [0051] - "DNA segment designs 240 were synthesized in step 790 in three distinct runs"),
`wherein each polynucleotide comprises:
`I) a plurality ot coding regions, wherein each coding region is identical (para [0014] - "The encoded bytes are represented using a schema
`by a DNA nucleotide to produce a DNA sequence in-silico"; para [0017] - "Multiple copies of the DNA segments can be made using known
`DNA synthesis techniques. This provides an additional degree of redundancy to enable the item of information to be decoded, even if
`some of copies of the DNA segments are corrupted and cannot be decoded"); and
`ii) at least one non-coding region (para [0014] - " indexing information is added to the plurality of DNA segments"; para [0015] - "The
`addition of the indexing information to the DNA segments means that the position of the segments in the DNA sequence representing the
`item of information can be uniquely identified"); and
`c) storing the plurality of polynucleotides (para [0014] - "the plurality of DNA segments is synthesized and stored").
`Goldman does not teach wherein the at least one noncoding region comprises a cleavage region. However. Goldman does suggest that
`the polynucleotide can comprise a cleavage region by teaching that the polynucleotide may be cleaved after it is synthesized (para [0051]
`"Once the DNA synthesis has been completed, the oligonucleotides are then cleaved from the surface"). Given that Goldman teaches that
`non-coding regions can be added to the polynucleotide and that the polynucleotide can be cleaved. one of ordinary skill in the art would
`have found it obvious that non-coding regions that are added to the polynucleotides can further comprise cleavage regions that allow for
`cleavage of the polynucleotides outside of the coding regions.
`
`Regarding claim 14, Goldman discloses the method of claim 10. wherein each coding region comprises 25 to 500 bases in length (para
`[0041] - "The resulting in silico DNA sequences 230 are too long to be readily produced by standard oligonucleotide synthesis. Each of the
`DNA sequences 230 was therefore split in step 730 into overiapping segments 240 of length 100 bases with an overlap of 75 bases").
`
`Regarding claim 15, Goldman discloses the method of claim 10, wherein each coding region comprises 100 to 2000 bases in length (para
`[0041] - "The resulting in silico DNA sequences 230 are too long to be readily produced by standard oligonucleotide synthesis. Each of the
`DNA sequences 230 was therefore split in step 730 into overlapping segments 240 of length 100 bases with an overlap of 75 bases").
`
`Form PCT/ISA/237 (Box No. V) (January 2015)
`
`

`

`PCT/USZO17IO52305 02.02.2018
`
`INTERNATIONAL SEARCHING AUTHORITY
`
`lntcmational application No.
`PCT/US 17/52305
`
`
`
`Supplemental Box
`
`In case the space in any ofthe preceding boxes is not sufficient.
`Continuation of:
`Box No. V2 Citations and Explanations
`
`Regarding claim 16. Goldman discloses the method of claim 10. wherein each non-coding region comprises 1 to 100 bases in length (para
`[0042] - "Each one of the strings of DNA comprised 1 17 nucleotides (encoding original digital information plus indexing information)". 117
`total bases = 100 coding bases + 17 non-coding indexing bases).
`
` WRITTEN OPINION OF THE
`
`
`
`
`
`
`Regarding claim 17, Goldman discloses the method of claim 10, wherein each non-coding region comprises at most 200 bases (para
`[0042] - "Each one of the strings of DNA comprised 1 17 nucleotides (encoding original digital information plus indexing information)", 117
`
`total bases = 100 coding bases + 17 non-coding indexing bases).
`
`
`
` Regarding claim 18, Goldman discloses the-method of claim 10, wherein the plurality of polynucleotides comprises at least 100,000
`polynucleotides (para [0042] - "In total. all of the five computer files were represented by 153335 strings of DNA“).
`
` Regarding claim 19. Goldman discloses the method of claim 10, but does not specifically teach wherein the plurality of polynucleotides
`
`comprises at least 10 billion polynucleotides. However. Goldman does teach that five computer files are represented by 153,335
`
`
`polynucleotides (para [0042] - "In total. all of the five computer files were represented by 153335 strings of DNA"). Given that over 100,000
`
`
`polynucleotides are needed to represent five computer files. one of ordinary skill in the art would have found it obvious that a large number
`of computer files, such as thousands of computer files, would require a large number of polynucleotides, such as at least 10 billion
`polynucleotides.
`
`Regarding claim 21, Goldman discloses the method of claim 10, wherein the at least one item of information is text information, audio
`information or visual information (para [0012] - 'The inventors have encoded five computer files--totaling 757051 bytes (739 1(8) of hard
`disk storage and with an estimated Shannon information of 5.2.tlmes.10.sup.6 bits-~into a DNA code. The inventors subsequently
`synthesized this DNA, transported the synthesized DNA from the USA to Germany via the UK. sequenced the DNA and reconstructed all
`five computer files with 100% accuracy"; para [0013] - "The five computer files included an English language text (all 154 of Shakespeare's
`sonnets). a PDF document of a classic scientific paper, a JPEG colour photograph and an MP3 format audio file containing 26 seconds of
`speech (from Martin Luther King’s "I Have A Dream" speech)“).
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Regarding claim 24, Goldman discloses the method of claim 10, but does not teach wherein a first cleavage region within each
`
`
`
`Regarding claim 20, Goldman discloses the method of claim 10, wherein greater than 90% of the polynucleotides encode for a sequence
`that does not differ from the predetermined sequence (para [0012] - "sequenced the DNA and reconstructed all five computer files with
`
`100% accuracy").
`
`
`
`
`Regarding claim 22, Goldman discloses the method of claim 10, wherein a first non—coding region within each polynucleotide has a
`different sequence than a second non-coding region within each polynucleotide (para [0030] - "The inventors have developed a method
`that uses 'indexing‘ information associated with each one of the DNA segments to indicate the position of the DNA segment in a
`hypothetical longer DNA molecule that encodes the entire message"; para [0041] - "Each segment was then augmented in step 750 with
`an indexing information 250 that permitted determination of the computer file from which the segment 240 originated and its location within
`that computer file 210, plus simple error-detection information. This indexing information 250 was also encoded in step 760 as non-
`repeating DNA nucleotides").
`
`Regarding claim 23, Goldman discloses the method of claim 10. wherein each non-coding region within each polynucleotide has a different
`sequence (para [0030] - "The inventors have developed a method that uses 'indexing' information associated with each one of the DNA
`
`segments to indicate the position of the DNA segment in a hypothetical longer DNA molecule that encodes the entire message"; para
`
`[0041] - "Each segment was then augmented in step 750 with an indexing information 250 that permitted determination of the computer file
`
`from which the segment 240 originated and its location within that computer file 210. plus simple error-detection information. This indexing
`information 250 was also encoded in step 760 as non-repeating DNA nucleotides").
`
`
`
`polynucleotide has a different sequence than a second cleavage region within each polynucleotide. However, Goldman does suggest that
`the polynucleotide can comprise a cleavage region by teaching that the polynucleotide may be cleaved after it is synthesized (para [0051]
`"Once the DNA synthesis has been completed, the oligonucleotides are then cleaved from the surface"). Goldman further teaches that
`each non-coding region within each polynucleotide has a different sequence (para [0030] - "The inventors have developed a method that
`uses 'indexing' information associated with each one of the DNA segments to indicate the position of the DNA segment in a hypothetical
`
`
`longer DNA molecule that encodes the entire message": para [0041] - "Each segment was then augmented in step 750 with an indexing
`
`
`information 250 that permitted determination of the computer file from which the segment 240 originated and its location within that
`
`
`computer file 210. plus simple error-detection information. This indexing information 250 was also encoded in step 760 as non-repeating
`
`
`DNA nucleotides"). Given that Goldman teaches that non-coding regions having different sequences can be added to the polynucleotide
`
`
`and that the polynucleotide can be cleaved, one of ordinary skill in the art would have found it obvious that the non-coding regions that are
`
`
`added to the polynucleotides can further comprise cleavage regions that allow for cleavage of the polynucleotides outside of the coding
`
`
`regions. and that each cleavage region within each polynucleotide has a different sequence.
` ----——— Please see continuation ln next supplemental box —--—---—
`
`
`
`Form PCT/ISA/237 (Supplemental Box) (January 2015)
`
`

`

`PCT/USZO17IO52305 02.02.2018
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`
`Intematlonal applicatlon No.
`PCT/U5 17/52305
`
`Supplemental Box
`
`In case the space in any ot‘the preceding boxes is not sufficient.
`Continuation of:
`_
`Box No. V2 Citations and Explanations
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Regarding claim 25. Goldman discloses the method of claim 10. but does not teach wherein each cleavage region within each
`polynucleotide has a different sequence. However. Goldman does suggest that the polynucleotide can comprise a cleavage region by
`teaching that the polynucleotide may be cleaved after it is synthesized (para [0051] "Once the DNA synthesis has been completed, the
`oligonucleotides are then cleaved from the surface"). Goldman further teaches that each non-coding region within each polynucleotide has
`a different sequence (para [0030] - "The inventors have developed a method that uses 'indexing' information associated with each one of
`the DNA segments to indicate the position of the DNA segment in a hypothetical longer DNA molecule that encodes the entire message";
`
`
`para [0041] - "Each segment was then augmented in step 750 with an indexing information 250 that permitted determination of the
`
`
`computer file from which the segment 240 originated and its location within that computer file 210. plus simple error—detection information.
`
`
`This indexing information 250 was also encoded in step 760 as non-repeating DNA nucleotides"). Given that Goldman teaches that non-
`
`
`coding regions having different sequences can be added to the polynucleotide and that the polynucleotide can be cleaved, one of ordinary
`
`
`skill in the art would have found it obvious that the non-coding regions that are added to the polynucleotides can further comprise cleavage
`regions that allow for cleavage of the polynucleotides outside of the coding regions. and that each cleavage region within each
`
`
`polynucleotide has a different sequence.
`
`
`Regarding claim 26, Goldman discloses the method of claim 10. but does not teach wherein a.number of cleavage regions within each
`polynucleotide is at least 1. 2. 3. 4. or 5. However. effective parameters, such as the number of cleavage regions is a parameter that a
`
`
`person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a
`person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal number
`
`of cleavage regions. such as 1, 2. 3. 4, or 5, needed to achieve the desired results.
` Regarding claim 27. Goldman discloses the method of claim 26, but does not teach wherein a sequence for the number of cleavage
`regions is different. However, Goldman does suggest that the polynucleotide can comprise a cleavage region by teaching that the
`polynucleotide may be cleaved after it is synthesized (para [0051] "Once the DNA synthesis has been completed. the oligonucleotides are
`
`then cleaved from the surface"). Goldman further teaches that each non-coding region within each polynucleotide has a different sequence
`
`(para [0030] - "The inventors have developed a method that uses 'indexing' information associated with each one of the DNA segments to
`
`
`indicate the position of the DNA segment in a hypothetical longer DNA molecule that encodes the entire message": para [0041] - "Each
`
`
`segment was then augmented in step 750 with an indexing information 250 that permitted determination of the computer file from which
`
`
`the segment 240 originated and its location within that computer file 210, plus simple error-detection information. This indexing information
`
`
`250 was also encoded in step 760 as non-repeating DNA nucleotides"). Given that Goldman teaches that non-coding regions having
`
`
`different sequences can be added to the polynucleotide and that the polynucleotide can be cleaved, one of ordinary skill in the art would
`
`
`have found it obvious that the non-coding regions that are added to the polynucleotides can further comprise cleavage regions that allow
`for cleavage of the polynucleotides outside of the coding regions. and that each cleavage region within each polynucleotide has a different
`
`sequence.
`
`Regarding claim 28, Goldman discloses the method of claim 10, but does not specifically teach wherein each polynucleotide comprises a
`
`tether region. However, Goldman does teach that when each polynucleotide is synthesized. they are tethered to a 20 planar surface and
`
`later released once the DNA synthesis has been completed (para [0051] - "The inkjet printing within an anhydrous chamber allows the
`delivery of very small volumes of phosphoramidites to a confined coupling area on a 2D planar surface, resulting in the addition of
`hundreds of thousands of bases in parallel. Subsequent oxidation and detritylation are carried out in a flow cell reactor. Once the DNA
`synthesis has been completed, the oligonucleotides are then cleaved from the surface and deprotected"). Given that Goldman does teach
`that the polynucleotide was tethered to a 2D surface during synthesis. one of ordinary skill in the art would have found it obvious to include
`a tether region on each polynucleotide.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
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`Regarding claim 74. Goldman discloses a device for storing information (para [0051] - "DNA segment designs 240 were synthesized in
`step 790 in three distinct runs .
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`. Agilent Technologies adapted the phosphoramidite chemistry developed previously' and employed inkjet
`printing and flow cell reactor technologies in Agilent's SurePrint in situ microarray synthesis platform"). the device comprising:
`a) a stmcture having a surface (para [0051] - "The inkjet printing within an anhydrous chamber allows the delivery of very small volumes of
`phosphoramidites to a confined coupling area on a 20 planar surface"); and
`b) a plurality of discrete regions on the surface for synthesizing a plurality of polynucleotides having predetermined sequences collectively
`encoding for at least one nucleic acid sequence (para [0051] - "The inkjet printing within an anhydrous chamber allows the delivery of very
`small volumes of phosphoramidites to a confined coupling area on a 20 planar surface. resulting in the addition of hundreds of thousands
`of bases in parallel. Subsequent oxidation and detritylation are carried out in a flow cell reactor"),
`wherein each polynucleotide comprises:
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`i) a plurality of coding regions. wherein each coding region is identical (para [0014] - '"l’he encoded bytes are represented using a schema
`by a DNA nucleotide to produce a DNA sequence in-silico"; para [0017] - "Multiple copies of the DNA segments can be made using known
`DNA synthesis techniques. This provides an additional degree of redundancy to enable the item of information to be decoded. even if
`some of copies of the DNA segments are cormpted and cannot be decoded"); and
`ii) at least one non-coding region (para [0014] - " indexing information is added to the plurality of DNA segments"; para [0015] - "The
`addition of the indexing information to the DNA segments means that the position of the segments in the DNA sequence representing the
`item of information can be uniquely identified"); and
`[continued]
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` —--—--- Please see continuation in next supplemental box --——-—-
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`Form PCT/lSA/237 (Supplemental Box) (January 2015)
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`

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`PCT/USZO17IO52305 02.02.2018
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`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
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` International application No.
`PCT/US 17/52305
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`Supplemental Box
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`In case the space in any ofthe preceding boxes is not sufficient.
`Continuation of:
`Box No. V2 Citations and Explanations
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`[claim 74 continued] wherein the at least one nucleic acid sequence encodes for at least one item of information (para [0012] - "The
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`inventors have encoded five computer files .
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`into a DNA code": para [0014] - "The method comprises encoding bytes in the item of
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`information. The encoded bytes are represented using a schema by a DNA nucleotide to produce a DNA sequence in-silico"; para [0040]
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`"the bytes comprising each computer file 210 were represented in step 720 as a DNA sequence 230"; para [0046] - "The digital information
`encoding in step 720 was carried out as follows. The five computer files 210 of digital information (represented in FIG. 2A) stored on a hard
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`-disk drive were encoded using software. Each byte of each one of the five computer files 210 to be encoded in step 720 was represented
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`as a sequence of DNA bases via base-3 digits ('trits' 0, 1 and 2) using a purpose-designed Huffman code listed in Table 1 (below) to
`produce the encoded file 220").
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`Goldman does not teach wherein the at least one noncoding region comprises a cleavage region. However. Goldman does suggest that
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`the polynucleotide can comprise a cleavage region by teaching that the polynucleotide may be cleaved after it is synthesized (para [0051]
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`"Once the DNA synthesis has been completed. the oligonucleotides are then cleaved from the surface"). Given that Goldman teaches that
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`non-coding regions can be added to the polynucleotide and that the polynucleotide can be cleaved, one of ordinary skill in the art would
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`have found it obvious that non-coding regions that are added to the polynucleotides can further comprise cleavage regions that allow for
`cleavage of the polynucleotides outside of the coding regions.
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`Claims 1-9 lack an inventive step under PCT Article 33(3) as being obvious over Goldman in view of US 5,863,801 A to Southgate et al.
`(hereinafter ‘Southgate').
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`Regarding claim 1 , Goldman discloses a method for storing and accessing information (para [0003] - "The disclosure relates to a method
`and apparatus for the storage of digital information in DNA"; para [0012] — "A practical encoding-decoding procedure that stores more
`information than previously handled is described in this disclosure. The inventors have encoded five computer files .
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`into a DNA code.
`The inventors subsequently synthesized this DNA, transported the synthesized DNA from the USA to Germany via the UK. sequenced the
`DNA and reconstructed all five computer files with 100% accuracy"), the method comprising:
`a) converting at least one item of information in a form of at least one digital sequence to at least one nucleic acid sequence (para [0012] -
`"The inventors have encoded five computer files .
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`Into a DNA code"; para [0014] - "The method comprises encoding bytes in the item of
`information. The encoded bytes are represented using a schema by a DNA nucleotide to produce a DNA sequence in-silico"; para [0040]
`"the bytes comprising each computer file