PATENT COOPERATION TREATY
`
`PCT
`
`INTERNATIONAL PRELIMINARY REPORT ON PATENTABILITY
`(Chapter Hf of the Patent Cooperation Treaty}
`
`(PCT Article 36 and Rule 70)
`
`} Applicant’s or agent’s file reference
`See Form PCT/IPEA/416
`FOR FURTHER ACTION
`i
`} 1080-G-01PCT
`| International application No.
`international filing date (day/month/year)
`Priotity date (day’monti'vear)
`| PCT/IL2012/000326
`30 Aug 2012
`O1 Sep 2011
`
`Iniernational Patent Classification (IPC) or national classification and IPC
`TPC (2013.01) GO6F 19/22 GO6F 19/26
`
`
`
`This report is also accompanied by ANNEXES, comprising:
`a total of 25ee sheets, as follows:
`sent to the applicant and to the International Bureau)
`[x] sheets of the description, claims and/or drawings which have been amended and/or sheets containing rectifications
`authorized by this Authority, unless those
`sheets were superseded or cancelled, and any accompanying letters (sce
`Rules 46.5, 66.8, 70.16, 91.2, and Section 607 of the Administrative instructions).
`‘a sheets containing rect
`Hons, where the decision was made by this Authority not to take them into account becanse
`they were not authorized by or notified to this Authorityat the time when this Authority began to draw upthis report,
`and ary accompanying letters (Rules 66.4 bis, 70.2(8), 76.16 and 91.2).
`superseded sheets and any acconmanying letters, where this Authority either considers that the superseding sheets
`conlain an amendment that goes beyond the disclosure in the intemational application as filed, or the superseding
`sheets were not accompanied bya latter indicating the basis for the amendments in the application as filed, as indicated
`in iiem 4 of Box No. [ and the Supplemental Box (see Rule 70.160).
`b. [| (sent
`fo the International Bureau only) a total of (indicate type and mumberof electronic carrier(s)}
`containing a sequencelisting, in electronic form only, as indicated in the Supplemental
`Box Relating to Sequence Listing (see paragraph 3bis of Annex C of the Administrative Instructions).
`
`| Applicant
`| GENOME COMPILER ISRAEL LTD. et al
`
`Phis report is the international prelimmnary examiat.
`Authority under Article 35 and transmitted to the applicant according to Article 36.
`
`This REPORT consists of a total
`
`of
`
`4
`
`sheets, including this cover sheet.
`
`This report contains indicationsrelating to the following items:
`as Box No. }
`Basis of the report
`| Box Ne.
`Priority
`Box No.
`Non-cstablishment of opinion with regard to novelty, inventive step and industrial applicability
`
`Box No.
`
`Box No.
`
`[J Box No.
`| Box No.
`[| Box
`
`Lack of unity of invention
`
`Reasoned staiement under Article 35@2) with regard to novelty, inventive siep and industrial applicability;
`citations and explanations supporting suchstatement
`Certain documents cited
`Certain defects in the international application
`Certain observations on the international! application
`
`Date of submission of the demand
`
`Date of completion of this report
`
`06 Jun 2013
`
`i
`
`05 Dec 2013
`
`| Name and mailing address of the IPEA/
`| Israel Patent Office
`
`| Authorized officer
`MOSKOVICHElad
`
`Facsimile No, 972-2-5651616
`
`FormPCT/IPEA/409 (coversheet) July 2011)
`
`| Telephone No, 972-2-5651607
`
`

`

`INTERNATIONAL PRELIMINARY REPORT ON PATENTABILITY
`
`[ International application No.
`PCT/IL2012/000326
`
`i. With regard to the language, this report is based on:
`
`the international application in the language in whichit was filed.
`J a tianslation of the international application into
`translation furnishedfor the purposes of:
`j international search (Rules 12.3(a} and 23. 1(b)).
`[|
`publicationof the international application (Rule 12.4(a)).
`tj international preliminary examination (Rules 55.2{a) and/or 55.3(a} and (b)).
`
`whichis the language of a
`
`2. With regard to the elements of the utternational application, this report is based on=(replacement sheets which have been
`Jurnished to the receiving Office in responseto an invitation under Article 14 are referred to in this report as “originallyfiled”
`and are not ainexedto this report) «
`| the international application as originally filed/furnished.
`the description:
`
`pages All as originallyHled/furnished.
`
`pages *
`received by this Authority on
`
` * Ifitem 4 applies, some orall ofthose sheeis may be marked
`
`report has been established:
`taking into account the rectification of an obvious mistake authorizcd by ornotificd to this Authority under
`Rule 91 (Rules 66, i(d- dis} and 70.2(e}).
`without taking into account the rectification of an obvious mistake authorized byor notificd to this Authority
`under Rule 9i(Rules 66.4 bis and 70.2¢e)).
`Supplementary international search report(s) from Authority(ies)
`has/have been teceitved and taken into account in establishing this report (ule 45 is.8¢b) and (c)).
`“superseded.”
`
`
`
`pages *
`
`received bythis Authority on
`
`
`
`the claits:
`
`
`pages
`
`as originally filed/furnished.
`
`pages*
`_ as amended(together with any statement) under Article 19
`
`pages * 40 - 54 received bythis Authority on 96 Jun 2013
`
`pages*
`received by this Authority on
`
`the drawings:
`pages AllPo as originallyfiled/furnished.
`
`
`pages *
`received by this Authority on
`
`received bythis Authority on
`
`pages *
`
`a sequence listing - see Supplemental Box Relating to Sequence Listing.
`
`The amendments have resulted in the cancelation of:
`
`the description, pages _
`
`the claims, Nos.
`
`the drawings, sheeis/figs
`
`
`
`the sequence hsting (speci
`
`This report has been established as if (some of) the amendments annexed to this report and listed below had not heen
`made, since either they ate considered to go beyond the disclosure as filed, or they were not accompaniedbyaletter
`indicating the basis for the amendments in the application as filed, as indicated in the Supplemental Box (Rules 70.2{c¢
`and (c-bis)i:
`the description, pages
`
`
`
`
`the claims, Nos.
`
`the drawings, sheets/figs
`
`
`
`the sequence listing (specif):
`
`P]
`
`Form PCTAPEA/409 (Box No. D Ghily 20135
`
`

`

`INTERNATIONAL PRELEMINARY REPORT ON PATENTABILITY
`
`International apphcation Ne.
`
`PCT/IL2012/000326
`
`Box No. V
`
`Reasoned statement under Article 35(2)} with regard to novelty, inventive step and industrial applicability;
`citations and explanations supporting such statement
`
`Statement
`
`Novelty (N)
`
`Claims
`Claims
`
`
`
`
`Inventive step (IS)
`
`Claims
`Claims
`
`Industrial applicability (IA)
`
`Claims
`Claims
`
`
`
`associated with harmful products are maliciously or accidentally designed.
`
`Document D1 teaches of a methods for designing oligonucleotides. A set of sequence elements 1s
`defined. Each sequence element represents an amino acid sequence segment or a nucleic acid sequence
`scgment. The sct of sequence clements collectively represcnt a design nucleic acid scqucncc. The sct of
`sequence elements are displayed as a plurality icons in a linearor a near linear arrangement such that
`each respective icon in the plurality of icons uniquely represents a corresponding sequence elementin
`the set of sequence elements. In this representation, neighboring icons inthe plurality of icons represent
`neighboring sequence elements in the set of sequence elements. Each respective icon in the plurality of
`icons depicts a directional property for the corresponding sequence elementin the set of sequence
`elements. An oligonucleotide selection module is used to identify oligonucleotides in the design nucleic
`acid scquencce.
`
`Citations and explanations (Rule 70.7)
`
`1. Reference is madeto the following documents:
`
`D1 US2007043516 (Al) GUSTAFSSONetal. [US] 2007-02-22
`
`D2 W02010141433 (A2) DING SHOU-WEI[US] 2010-12-09
`
`D3 W00227638 (Al) ROGNES TORBJOERN [NO] 2002-04-04
`
`2. Novelty and Inventive step
`
`Claims 1-135 meetthe criteria set out in PCT Articles 33(2) and 33(3) because the prior art does not
`tcach or suggests everylimitation of the claims.
`
`Document D2 teaches of a methods and systems for identifying viral nucleic acids in a sample. In
`another embodiment the invention provides methods for viral genome assembly and viral discovery
`using, small inhibitory RNAs, or "small silencing," RNAs (siRNAS), micro-RNAs (miRNAs) and/or
`PIWI-interacting RNAs (piRNAs), including siRNAS, miRNAsand/or piRNAsisolated or sequenced
`from invertebrate organismssuch as insects (Anthropoda), nematodes (Nemapoda), Mollusca, Porifera,
`and other invertebrates, and/or plants, fungi or algae, Cyanobacteria and the like.
`
`None of the documents D1 or D2 teach or fairly suggest detecting and notifying when sequences
`
`Porm PCT/APEA/409 (Box No. ¥) Gruly 2010)
`
`

`

`INTERNATIONAL PRELIMINARY REPORT ON PATENTABILITY
`
`International apphcation Ne.
`
`PCT/IL2012/000326
`
`Consequently, the solution proposed in claims 1-135 ofthe present application are considered as new
`and involving an inventive step (Article 33(2) and 33(3) PCT).
`
`Claims 1-135 are industrially applicable under PCT Article 33(4).
`
`3. Industrial Applicability
`
`Porm PCT/APEA/409 (Box No. ¥) Gruly 2010)
`
`

`

`Dr Eyal Bressler INTELLECTUAL PROPERTY
`
`OURREF
`
`1080-G-01-PCT
`
`YOUR REF
`
`nev
`
`:a0n
`
`Date
`
`Page
`
`06/06/13
`
`PIN
`
`-1-
`
`: Tiny
`
`Dr. Eyal Bressler Ph.D.!3
`Patent Attorney, INTA AIPPIIAPA
`Adv. , LLB
`B.Sc. (Biochem., F. Technol.)
`M.Sc. (Appl. Chem.)
`Ph.D, (Biotechnology)
`Patents
`Partners
`
`Dr. Joseph I. Wyse PhD, AIPPI
`Dr. Lior Itzhaki PhD, AIPPI
`
`(Genetics)
`(Chem)!
`
`(Immuno-bio.)
`Dr. Yael Uziel PhD
`Phys.)!
`Dr. Michael Meyklyar PhD.
`(Mol.Bio.}
`Dr. Keren Hagai PhD
`Dr. Richard H. Schultz PhD (Chem)! ?
`Dr. Stuart Weisrose PhD
`(Physics)!
`Maya Basanchik B.Ac.
`(Comp.-Sci. Math,)!
`Eva Soller M.Sc.
`Biolo)”
`IL Patent Attorney
`I
`2 US Patent Agent
`Malka Guttman, Department Coordinator
`mall
`bressler.co.il
`
`Legal
`Dana Grinberg, Adv. LLB 3
`dan.
`ressler,co.
`il
`Liat Galily Perel, Adv. LLB?
`lia
`il
`Einat Hay Zemach,paralegal
`paralegal@pbressler.co.il
`Gil Tessler, paralegal
`Paralegal-2@bressler.co.il
`3 Member of IL Bar
`
`Industrial Designs
`Dr. Smadar Bressler PhD (Phys. Chem.)
`design@bressler.co.i
`
`Of counsel
`Raffi Goren, Ph.D.
`James de Rothschild Professor of Horticulture
`
`Administration
`Hadar Daniel
`reception@bressler.co.if
`
`Accounts
`Pnina llani, MA; CFO
`accounts@bressler.co.il
`Miri Hershkovitch
`Acet3@bressler,co.it
`Joyce Framowitz, BA
`Acct4@bressler.co.il
`
`Dr. Eyal Bressler Ltd.
`Offices and Postal Address
`Lazrom House, || Tuval Street
`Ramat Gan 52522Israel
`Tel: (972)-3-5765555
`Fax: (972)-3-5765566
`main@bressler.co.il www.bressler.co.il
`Bank Details:
`
`Account name
`Bank Name
`Branch No,
`Account No.
`Swift No. IBAN
`
`Or Eyal Bressler Led.
`Bank Hapoalim (42)
`537
`222294
`Poalilit
`IL-81-0125-3700-0000-0222-294
`
`Israel Patent Office
`The Technology Park, Bldg 5, Malcha,
`Jerusalem 96951
`Israel
`Newman Baruch (Barry)
`Authorized Officer
`Fax: +972-2-5651616
`
`
`
`
`
`
`
`PCT mvIveN OWI)
`
`06 -06- 2013
`
`Re: Demand for IPRP
`SYSTEM FOR POLYNUCLEOTIDE CONSTRUCTDESIGN,
`VISUALIZATION AND TRANSACTIONS
`TO MANUFACTURE THE SAME
`IL/2012/000326
`Inventors: AMIRAV DRORI Omri, DR.et al
`Applicant: GENOME COMPILER ISRAEL LTD.
`Priority Claim: United States Pat Appl. 61/530,384 dated
`01/09/2011
`International Filing Date: 30/08/2012
`
`Dear Sir/ Madam,
`
`Please find enclosed a 24 page Demand under Article 31 of the
`
`the
`Patent Cooperation Treaty: The undersigned requests that
`international
`application specified above be the subject of
`international preliminary. examination according to the Patent
`
`Cooperation Treaty.
`
`If anything further is needed from us, please advice.
`
`Kindly acknowledge receipt of this fax by return fax to +972-
`
`5765555
`
`Yours sincerely,
`
`Adv. Omri Sega
`
`

`

`Dr. Eyal BresslerSiCo.
`
`BOUTIQUE IP FIRM
`
`PCTAL2012/
`06 JUN he fr
`
`326
`Group
`
`Dr. Eyal Bressler Ph.D. '3
`Patent Attorney,
`INTA AIPPIIAPA LES
`Ady. , LLB
`B.Sc. (Biochem., F. Technol.)
`M.Sc. (Appl. Chem.)
`Ph.D. (Biotechnology)
`
`Patent Department
`Partners
`
`Dr. Joseph |. Wyse, PhD AIPP!
`Dr, Lior Itzhaki, PhD AIPP!
`
`(Genetics)!
`(Chemistry)!
`
`Ms. Sigalit Avraham, M.Sc.
`Dr. Jeannette M. Fine, PhD
`Dr. Keren Hagai, PhD
`Dr. Dana Levanony, PhD
`Dr. Iris Dejmal Mahrer, PhD
`Dr. Michael Meyklyar, PhD
`Dr. Richard H. Schuitz, PhD
`Dr. Maya Amit, PhD
`
`1
`2.
`
`IL Patent Attorney
`‘US Patent Agent
`
`(Chemistry)
`(Physics)
`(Mol. Biology)!
`(Physics)
`(Engineering)
`(Physics)!
`(Chemistry)'?
`(BioChemistry)
`
`Dr. Neil J. Wilkof, Adv.
`wilkof@bressler.co.il
`Trademarks & Licensing Partner
`
`Ph.D., J.D3¢
`
`Legal Department
`Dana Grinberg-Matsliah, Adv. LLB >
`
`OUR REF
`YOUR REF
`
`1080-G-01-PCT
`
`1L2012/000326
`
`:n790n
`spoon
`
`Date
`Page
`
`06/06/13
`
`4.
`
`xn
`emmy
`
`Fax: +972-2-5651616
`
`Israel Patent Office
`The Technology Park, Bldg 5, Malcha,
`Jerusalem 96951
`Israel
`Newman Baruch (Barry)
`Authorized Officer
`
`DemandunderArticle 31 of the Patent Cooperation Treaty:
`The undersigned requests that the international application
`specified below be the subject of an international preliminary
`examination according to the Patent Cooperation Treaty.
`
`Applicant: GENOME COMPILER ISRAEL LTD..
`
`PCTapplication no. IL/2012/000326
`PCTpublication no. WO 2013/030827
`
`SYSTEM FOR POLYNUCLEOTIDE CONSTRUCT DESIGN,
`VISUALIZATION AND TRANSACTIONS TO
`MANUFACTURE THE SAME
`
`Dear Baruch,
`
`The applicant hereby files a Demandfor International Preliminary
`
`Examinationin this file.
`
`Please find below our reply to the Search Report and Written
`
`Opinion of January 29, 2013.
`
`General remarks:
`
`1.
`
`The subject matters taught in claims 133, 135 is held by the
`
`in the sense of Article 33(2) PCT.
`to be novel
`applicant
`Arguments for novelty of the examined claims are presented.
`
`WE
`CLAIM
`success®
`
`LLB?
`
`LLM?
`LLB >
`
`i
`
`Einat Zemach Rodman, Adv, LLM *
`Einar@bressler.co.il
`Aviv N.Pollak, Adv.
`lak@bressler.co.il
`Cyril Clerget, Adv.
`Jegal-8
`Dalia Haberman, Adv.
`legal-'
`ressler.co.il
`Jonathan Kafri
`aralegal-
`ressler.co.il
`Yair Shwarts
`legal-4@pbressler.co.il
`Gilad Ben-Joya
`legal-
`ressier.co.il
`Omry Segal
`paralegal-7@pbressler.co.il
`Rachel Nissim
`legal-2@bressler.co.il
`
`LLM
`
`3) Memberof IL Bar
`4 Member of OH Bar (USA) (INACTIBE)
`Head of Administration
`Gal Moran
`reception@bressler.co.il
`Sara Rutstein
`reception2@bressler.co,j
`
`Accounting Department
`Pninallani, MA; CFO
`accounts@bressler.co.il
`Miri Hershkovitch, B.A.
`Acct3@bressfer.co.il
`Joyce Framowitz, B.A.
`Acct4@bressier.co.il
`
`Dr. Eyal Bressler Ltd.
`Offices and Postal Address
`Lazrom House,
`1
`| Tuval Street
`Ramat Gan 52522 Israel
`Tel: (972)-3-5765555
`Fax: (972)-3-5765566
`main@bressler.co.il www.bressler.co.il
`
`Bank Details:
`Account name
`DrEyal Bressler Ltd.
`Bank Name
`Bank Hapoalim (12)
`Branch No.
`537
`Account No.
`222294
`Swift No. IBAN
`Poaiilit41 AINE 37AN AAAA ANID AAA
`
`

`

`Dr. Eyal BresslerSlCo.
`
`BOUTIQUE 1P FIRM
`
`PCTNL2012/000326
`06 JUN 2013
`
`OURREF
`YOURREF
`
`“90n
`1080-G-01-PCT
`IL/201 2/000326 Men
`
`Date
`Page
`
`96/06/13 wan
`-2-
`Ty
`
`2.
`
`To meet the requirements of Article 33(3) PCT, claim 1 is amended and arguments for
`inventive steps are disclosed supporting the patentability of claims 1 and 134.
`
`3.
`
`The new set of amended claimsis attached.
`
`WE
`CLAIM
`SUCCESS
`
`

`

`Dr. Eyal BresslerS1Co.
`
`BOUTIQUE IP FIRM
`
`PCT/NL2012/000326
`06 JUN 9973
`
`OURREF__180OCT ‘A90n Date 06/063 NN
`
`YOUR REF
`1L/201'2/000326
`pon
`Page
`-3-
`rTmay
`
`Arguments againstallegation of lack of novelty under Article 33(2) of the PCT:
`
`Claim 133
`
`The Examiner finds claim 133 of the current application to lack novelty in view of D3
`
`(W000227638).
`
`D3 relates to a sequence similarity searching method that computes an alignment score that
`represents the degree of similarity between a query sequence and a database sequence (D3, page
`
`10-11).
`
`Claim 133 of the current application does not rank similarity between sequences as done in D3,
`but rather discloses a method for assessing the quality of a nucleotide sequence. In this method it
`
`is assessed how many times the nucleotide sequence is represented in the database. The greater
`the number of times the sequence is represented in the database, the higher ranking quality will
`be received. This method is purposed for deciding what sequence to order when there is more
`than one option. It harnesses the "wisdom of the masses" as a check for quality of the designed
`sequence. The person designing the sequence can get an idea from the ranking system how many
`times his sequence was previously selected and by that decide if he is making the right choice.
`
`Scoring a sequence according to similarity to other sequences in a database as done in D3 is an
`entirely different method than scoring a sequence according to the number of times it is
`represented in a database as suggested in the current application. The use of the D3 similarity
`alignment within the present invention would not achieve the desired resultatall.
`
`In view ofthis, the applicant respectfully requests that claim 133 will be recognized as novel in
`
`light of D3.
`
`Claim 135
`
`The Examiner finds claim 135 of the current application to lack novelty in view of D1
`
`(US2007/00435 16).
`
`1.
`
`D1 relates to a system for representing a nucleotide sequence by icons. D1 further explains
`
`how the icons are arranged and viewed (D1; paragraph 97):
`
`WE
`CLAIM
`SUCCESS
`
`

`

`Dr. Eyal BresslerSo.
`
`BOUTEQUE IP FIRM
`
`PCT/IL2012/000326
`|
`06 JUN 2019
`
`OURREF
`YOURREF
`
`1080-G-01-PCT
`IL/20 12/000326
`
`:mpon
`n90n
`
`Date
`Page
`
`96/06/13 KN
`-4-
`Tiny
`
`"Icons can be displayed in an icon view or a sequence view. When the icons
`are displayed in icon view, a graphical depiction of each sequence element
`represented by the icons is displayed as illustrated in FIG. 6. When icons are
`displayed in sequence view, a sequence represented by each icon is displayed,
`as illustrated, for example, in FIG. 7. In icon view, each sequence element can
`
`be represented by an icon. The order of the icons can be altered using, for
`
`example, mouse drag operations."
`
`Claim 135 of the current application describes a system for visualizing biological
`
`information by zooming through a plurality of resolution layers. These layers are further
`
`described in the embodiments (page 33; lines 12-16):
`
`"In various embodiments, the dynamic zoom function ofthe systems and method of
`
`the invention switches the display on a user interface between various views, such
`
`as gene view, metabolic simulation view, protein view, cellular view, organism
`
`view, organ view, complex organism view, for example yeast, plant, animal,
`
`human, gender specific view or any other suitable view knownin the art."
`
`Although both patent applications, D1 and the current application,
`
`relate to the
`
`visualization of information there is no resemblance between the two systems. D1 relates
`
`to a specific way of representing DNA sequences with icons, while Claim 135 of the
`
`present application describes the representation of biological information well beyond the
`
`one dimensional sequence described in D1 . claim 135 is directed to providing layers
`
`reflecting the abstraction levels of biological organization, such as gene, protein, metabolic
`
`pathways, cell, organism, organ and complex organism. The layers of the present invention
`
`provide far more utility to the invention by means of the layer features. The same
`
`visualization quality would not have been achievedif the icons of D1 were used to replace
`
`the visualization system of Claim 135. There would be no option of visualization beyond
`the single dimension DNA sequence if the system of D1 was implied in the current
`application.
`
`2.
`
`In D1 the database providing the information for the visual display is a library of sequence
`
`elements and projects (D1; paragraph 88).
`
`WE
`CLAIM
`SUCCESS
`
`

`

`Dr. Eyal BresslerSLCo.
`
`BOUTIQUE IP FIRM
`
`PCT/ALZ012/000326
`06 JUN 9973
`
`OURREF Date_06/06/131080-G-01-PCT sa90n atarel
`
`
`
`
`YOURREF
`1172012000326
`‘gon
`Page
`-5-
`Try
`
`In Claim 135 the database providing the information for the visual display includes various
`pieces of biological information. The data which is included in the biological information
`is elaborated in the embodiments (page 32; line 23-26).
`
`"Im some
`
`embodiments,
`
`the various visual
`
`representations of biological
`
`information relate to an abstraction level. The abstraction levels can be chosen to
`optimally represent biological information in desired sufficiency, for example
`various abstraction levels of the invention can correspond to organism, genome,
`
`system, metabolic pathway, protein, genetic sites, amino acids, or nucleic acid
`
`level detail."
`
`It can be seen that the databases described in D1 and claim 135 of the current
`
`application are completely different. D1 describes a database including only DNA
`sequences, while the database of Claim 135 includes a much broader spectrum of
`biological information including such as proteins, amino acid sequences, genome
`systems and metabolic pathways. The database of D1 can replace the database of
`Claim 135 without having a large impact on the quality on the visualization system.
`
`Since the visualization system of Claim 135 is entirely different than the system of D1 and
`
`the content of the database of Claim 135 includes much more additional types of non-
`
`obvious information in comparison to the database described in D1, the applicant requests
`
`that Claim 135 will be recognized as novel in view of D1.
`
`Arguments and amendments against allegation of lack of inventive steps under Article
`33(3) of the PCT:
`
`Claim 1
`
`Amended Claim 1:
`
`A computerized
`
`system for designing nucleic
`
`acid sequences
`
`for gene
`
`expression
`
`comprising;
`
`a.
`
`a server [103] for hosting a database [106]
`
`WE
`CLAIM |
`SUCCESS
`
`

`

`Dr. Eyal BresslerSLCo.
`
`BOUTIQUE IP FIRM
`
`PCT/IL2012/000326
`06 JUN 9973
`
`OUR REF
`YOURREF
`
`1080-G-01-PCT
`11/201 2/000326
`
`:n90n
`‘gon
`
`Date
`Page
`
`96/06/13 An
`-6-
`Ty
`
`b.
`
`¢.
`
`anetwork connection [102]
`
`acomputer readable medium [101] comprising functional modules including:
`
`i. adesign module for enabling designing of nucleic acid constructs;
`
`ii.
`
`interactive user interface module for visualizing biological information relating to design
`
`operations;
`
`iii.
`
`transaction module for purchasing a user-designed or pre-stocked nucleic acid
`
`constructs
`
`bmhex a detecting module for detecting designed nucleic acid sequences associated with
`
`harmful products;
`
`wherein said system is operating in a methodof:
`
`d._-visualizing biological information;
`
`e.
`
`f.
`
`g.
`
`designing nucleic acid sequences;
`
`detecting and notifying when sequences associated with harmful products are designed;
`
`providing means for transactions regarding ordering and purchasing said synthesized
`
`nucleic acids
`
`Claim 1 was amendedto meet the requirements of an inventive step. Amendments were carried
`
`out according to Exemplary Module 2 of the current application (page 19, lines 12-18) which
`
`states:
`
`"In some embodiments, a database is compiled representing a list of harmful
`
`products, such as toxins, viruses, bacteria, pathogens, and more.The database
`
`can contain nucleic acid sequences
`
`strongly
`
`associated with harmful
`
`products."
`
`Claims 104, 106, 117, 118, 132 and 133 were also amended to suit the change of claim 1 by
`
`replacing the phrase “harmful sequences" with "sequences associated with harmfulproducts".
`
`WE
`CLAIM
`SUCCESS
`
`

`

`Dr. Eyal BresslerSiCo.
`
`BOUTIQUE IP FIRM
`
`PCTAL2Z012/000326
`
`Q6 JUN 2913
`
`OURREF
`YOURREF
`
`1080-G-01 -PCT
`IL/2012/000326
`
`“son
`-s790n
`
`Date
`Page
`
`06/06/13
`-7-
`
`"NAN
`my
`
`Further arguments to the amended claim 1 are as follows:
`
`Claim 1 was found by the examiner to be obvious in view of D1 (US2007/0043516) over D2
`
`(W00227638).
`
`D1 describes a computer system and program for designing oligonucleotides (D1; abstract). D2
`describes a method for identifying viral or microorganism genome, nucleic acid or protein
`
`encoding sequence, or sequences thereof, having significant homology to the assembled
`
`contiguous unit (D2; page 4,lines 4-5).
`
`Claim 1 recites a system for designing nucleic acid sequences for gene expression that detects
`
`and notifies when sequences associated with harmful products are designed (see below amended
`
`Claim 1). The current application further explains what harmful products are: toxins, viruses,
`
`bacteria, pathogens (Claim 109),
`
`The applicant wishes to commentthat there is an extensive difference between identifying DNA
`
`sequences comprising the genomesof viruses and microorganisms (D2) and between identifying
`
`sequences associated with harmful products (current application) for two main reasons:
`
`1.|Sequences which are homologousto viral and microorganisms genomesare not necessarily
`
`harmful and in most cases are innocuous. Many viruses and microorganisms are not
`
`harmful and therefore their genomes are not harmful as well.
`
`2.
`
`Notall parts of the genomeof harmful viruses and microorganismsare harmful.
`
`to genomes of viruses and
`In D2 a method for generally identifying sequences identical
`microorganisms is presented. If the method of D2 was replaced with the method of Claim 1 in
`
`the current application not only sequences associated with harmful products were detected but
`
`rather all DNA sequences appearing in viruses and microorganisms whether harmfulor not.
`
`The method of Claim 1 in the current application is focused on detecting and notifying when
`
`sequences associated with harmful products when such sequences are maliciously or accidentally
`
`designed. The invention of D2 does not enable or motivate towards this. Therefore the method of
`
`WE
`CLAIM
`SUCCESS
`
`

`

`Dr. Eyal BresslerSlCo.
`
`BOUTIQUE IP FIRM
`
`PCT/NL2012/000326
`06 JUN 2973
`
`OUR REF
`YOURREF
`
`1080-G-01-PCT
`11/201 2/000326
`
`‘on|0n
`yon
`
`Date
`Page
`
`06/63
`-8-
`
`van
`‘tny
`
`identifying sequences associated with harmful products in the current application cannot be
`inferred from D1 in combination with D2 without undue burden.
`
`In view of the above comments and amendmentsto claim 1, the applicant is of the opinion that
`
`the claim involves an inventive step in view of the documents cited in the ISR, separately and in
`combination.
`
`Claim 134
`
`
`Claim 134 was found by the examinerto be obvious in view of D1 over D3.
`
`D1, as already described, discloses a computerized method for designing a polynucleotide
`construct. However, the method does not include a step _of quality ranking of the designed
`
`polynucleotide as suggested in the current application.
`
`D3 relates to a sequence similarity searching method that computes an alignment score that
`
`represents the degree of similarity between a query sequence and a database sequence (D3, page
`
`10-11).
`
`The current application relates in Claim 134 to a method of ranking designed sequences
`
`according to the numberof times the sequence was represented in the database.
`
`Therefore, we respectfully disagree with the Examiner's suggestion of obviousness of Claim 134
`in view of D1 over D3. D1 relates to a computer program for designing oligonucleotides that
`
`does not involve quality ranking and D3 generally relates_to ranking sequence_alignment,
`
`whereas the current application offers a quality ranking system of designed polynucleotides
`
`according to a database of previously received sequences that has a specific aim of assisting the
`
`user in making the right choice when choosing a sequence. Therefore it seems unlikely that a
`
`person skilled in the art will find obvious directives in view of references D1 and D3 for
`
`detecting and notifying when sequencesassociated with harmful products.
`
`WE
`CLAIM
`SUCCESS
`
`

`

`Dr. Eyal BresslerSiCo.
`
`BOUTIQUE IP FIRM
`
`PCT/ILZ012/000326
`06 JUN 9913
`
`OURREF
`YOURREF
`
`1080-G-01-PCT
`|
`2
`1/2012/000326
`yon
`
`Date
`Page
`
`08/06/13 ny
`-9-
`Tiny
`
`Best regards,
`
`‘
`Dr. Keren’
`
`Hagai
`
`Dr. Maya Amit
`
`WE
`CLAIM
`SUCCESS
`
`

`

`PCT/NL2012/000326
`06 JUN 2013
`
`AMENDED CLAIMS
`
`1.
`
`A computerized system for designing nucleic acid sequences for gene expression
`
`comprising;
`
`h.
`
`aserver [103] for hosting a database [106]
`
`i.a network connection [102]
`
`j.a computer readable medium [101] comprising functional modules including
`
`i. adesign module for enabling designing of nucleic acid constructs;
`
`ii.
`
`interactive user interface module for visualizing biological information relating to design
`
`operations;
`
`iii.
`
`transaction module for purchasing a user-designed or pre-stocked nucleic acid
`
`constructs
`
`iv. a detecting module for detecting designed nucleic acid sequences associated with
`
`_ harmful products;
`
`wherein said system is operating in a methodof:
`
`k. visualizing biological information;
`
`|. designing nucleic acid sequences;
`
`m.detecting and notifying when sequences associated with harmful products
`
`are designed;
`
`n. providing means for transactions regarding ordering and purchasing said
`
`synthesized nucleic acids.
`
`2. The system of claim 1, wherein said computerized system is configured to be a software
`
`application and/or a web site running on a computerized device.
`
`4o
`
`AMENDED SHEET
`
`

`

`
`
`PCT/NL2012/000326
`06 JUN 2913
`
`N
`
`_ ae
`
`—
`
`3. The system of claim 2, wherein said application is installed on a computerized device selected
`
`from a group consisting of: a telephone, a handheld device, and any suitable computerized device
`
`knownin theart.
`
`4. The system of claim 1, wherein the nucleic acid is selected from a group consisting of DNA,
`
`RNAand any combination thereof.
`
`5. The system of claim 1, wherein said computer readable medium further comprises an access
`
`module to enable access for users to modules at different levels, access to different levels of
`
`functionality within a module and any combination thereof,
`
`said access defined by a
`
`predetermined variable
`
`6. The system of claim 5, wherein said predetermined variable is selected from a group
`
`consisting of: different pay grades, user type, and user skill-level and any combination
`
`thereof.
`
`7. The system of claim 1, wherein said a design module is further configured to enable a user to
`
`edit said nucleic acid sequence andto use. a different predetermined controls in said design.
`
`8. The system of claim 7, wherein said controls are selected from a group consisting of: alteration
`
`of methylation sites, protein level changes and/or metabolic level changes.
`
`9. The system of claim 7 wherein said editing nucleic acid sequence comprises editing the
`
`incorporation of non-natural amino acid and other conventional molecule coding sequences
`
`selected from a group consisting of heavy metals, markers, encoded data and/or any other
`
`suitable molecule known in the art, in relevant translation systems.
`
`10. The system of claim 1, wherein said design module is further configured to enable a user to
`
`create a nucleic acid design from genetic elements selected from a group consisting of:
`
`transcription promoters,
`
`ribosome binding sites, genes, and terminators and any other
`
`conventional genetic elements knownintheart.
`
`11. The system of claim 1, wherein said design module is further configured to enable a user to
`stitches said nucleic acid constructs from a building blocks that are available through said
`
`41
`
`AMENDED SHEET
`
`

`

`PCTAL2012/000326
`06
`JUN
`29173
`JU
`
`
`
`NN
`
`interactive user interface module.
`
`12.
`
`The system of claim 11, wherein said building block is selected from a group consisting of a
`
`promoter, an open reading frame, a terminator, a Shine-Dalgarno sequence or an expression
`
`system equivalent thereof.
`
`13.
`
`The system of claim 1, wherein said design module is further adapted for optimizing said
`
`designed nucleic acid construct according to various requirements.
`
`14.
`
`The system of claim 13, wherein said various requirements are related to codon usage, GC
`
`content and CpG content, while on the other hand, substantially avoiding problems associated
`
`with DNA motifs and sequence repeats and inverse complementary sequencerepeats.
`
`15.
`
`The system of claim 1, wherein said design module is further configured to utilize various
`
`computer-assisted methods for ascertaining an optimal codon sequence.
`
`16.
`
`The system of claim 15, wherein said optimal codon sequenceis in relation to the protein
`
`expression level in relevant expression systems.
`
`17.
`
`The system of claim 16, wherein said expression system determined based on the nucleic acid
`
`sequence entered by a user.
`
`18.
`
`The system of claim 17, wherein said determining said expression system is based on
`
`recognizing tRNA sequences.
`
`19.
`
`The system of claim 16, wherein said expression system is selected from a group consisting of: a
`
`cell, a cell-free system,
`
`in vitro system, a prokaryotic expression system and, eukaryotic
`
`expression system may.
`
`20.
`
`The system of claim 16, wherein said expression system further selected from a group consisting
`
`of: bacterial cells,
`
`insect cells, e.g. Baculovirus expression systems, SF9 cells, Drosophila-
`
`Schneider cells, plant cells, yeasts, e.g. Saccharomyces Cerevisiae, Pichia angusta, Pichia
`
`pastoris and the like; as well as also algae, e.g. Chlamydomonas. Examples of possible plant
`expression systems include Arabidopsis
`thaliana, Zea mays
`(com), Nicotiana tobacco
`(tobacco), Oryza sativa (rice), Hordeum vulgare (barley), Glicine max (soya) and, Brassica
`
`42.
`
`AMENDED SHEET
`
`

`

`
`
`PCT/NL2012/000326
`06 JUN 2013
`
`sp. (cabbage) and an