PA'E‘ENT CGOPERATIGN TREATY
`
`i3C?
`
`INTERNA TEGNAL PRELlh/HN ARY REPGRT 9N PATENTABHJTY
`
`(Chapter ll of the Patent Cooperation Treaty)
`
`(PCT Article 36 and Rule ‘70)
`
`Applicant’s or agent’s file reference
`
`;
`;
`
`FGR FURTHER ACTEGN
`
`See Form FC’l‘x’lPEA/4 to
`
`lOSO-G-O lPCT
`
`International application No,
`international filing date {dqw'monlii/ycar)
`Priority date (day'filonmfvcaiil
`PCT/IL2012/000326
`30 Aug 2012
`01 Sep 2011
`
`international Patent Classification (LDC) or national classificaLion and lPC
`1PC(2013t01) G06F19/22 G06F 19/26
`
`Applicant
`GENOME COMPILER ISRAEL LTD. et a1
`
`15 report is the international preliminary examinati
`.
`Authority tinder Article 35 and transmitted to the applicant according to Article 36,
`
`This REPORT consists of a total
`
`1’
`
`4
`
`streets, inch (ling this cover sheet,
`
`This report is also accompanied by ANNEXES. comprising:
`
`VIOSKOVICH Elad
`
`a total or?7777777777777777777 sheets, as follows:
`sent {To the applicant and to the Mmrnartonai Bureau)
`EX! sheets of the description, claims and/or drawings which have been amended and/or sheets containing rectifications
`authorized by this Authorinr, unless those
`eets were superseded or cancelled, and any accompanying letters (see
`Rules 46.5, one, rate, 91.2, and Section so? of the Administrative instructions).
`
`ty not to rake then} into accounthecause
`ions, where the decision was made by this Anthi
`E sheets containing rect
`they were not authe- zed by or notified to this Autlio tits at the time when this Authority began to draw up nis report,
`and any accompanying letters (Roles 56.4 his, 702$), 7G. to and 9 l 2).
`:1 superseded sheets and any accompanying
`rs, where this Authority either considers that the superseding sheets
`contain an amendment that goes beyond the hisclosnre in the intetnational application as filed, or the snpersetling
`sheets were not c ccompmiied by a latter indicating the basis for the amendments in the application as filed, as indicated
`in item of Box No, l and the Supplemental Box (see Rule ‘70. loll)».
`
`'
`
`i {:3 {sent
`
`to the [filerflailwiai Bureau new a total of (indicate type and number of electronic carrier‘tsl)
`containing a sequence listing, in electronic form only, as indicated in the Supplemental
`Box Relating to Sequence Listing (see paragraph 32m of Aimex C of the Administrative instructions},
`
`This report contains indications relating to the following items:
`
`Basis ot’the report
`
`Priority
`
`Non—establishment of opinion with regard to novelty, inventive step and indus trial applicability
`
`Lacl< of unity of invention
`
`Reasoned statement under Article 35(2) with regard to novelty, invenLive step and industrial applicability;
`citations and explanations supporting such statement
`Certain documents cited
`
`Certain defects in the international application
`
`Ceitain observations on the inter
`
`onai application
`
`Date of sobnnssron or tne demand
`06 Jun 2013
`
`1
`
`Date or" completion or this report
`05 Dec 2013
`
`Name and mailing address of the lPEA/
`Israel Patent Office
`
`Authorized officer
`
`Facsimile No 9724-5651615
`
`Form PCT/'lPEA/409 (cover sheet) (July 2011)
`
`3 Telephone No 9724-5651607
`
`

`

`ENTERNATEGNAL PRE LEMENARY REPQRT 0N FATENTABILETY
`
`PCT/IL20 12/0003 26
`
`International application No.
`
`With regard to the language, this report
`
`Jased on:
`
`the international application in the lan. .tage in Which it was filed.
`
`U a translation of the international application into
`translation 1“- rnished for the purposes of:
`
`which is the language of a
`
`{3 international search (Rules 12.3(a) and 2.3. ltb».
`E publication of the international application (Rule 12.4(a)).
`E international preliminary examination {Rules 55.2{a) and/or 55.3(a) and (bl).
`
`(replach/zcm‘ sheets which have been
`2. With regard to the elements ol‘ the international application, this report is based on
`fiu‘nished m the receiving ()zjfice in response to an invitation under Amide M are referred to in {his report as ”originallyfiied "
`and are not armexed to this report) :
`if]
`the international application as originally filed/furnished.
`the description:
`
`as originally filed‘furnished.
`pages All
`
`pages *
`received by this Authority on
`
`
`received by this Authority on
`
`
`
`pages *
`
`the claims:
`
`
`pages
`
`as originally filed‘furnished.
`
`
`
`A
`
`4
`
`as amended (together with any statement) under Article 19
`
`
`received by this Authority on 06 Jun 2013
`pages * 40 ' 54
`
`pages i‘
`received by this Authority on
`
`the drawings:
`
`pages All_______________________________________________________________________________________________________________________________________________ as originally iiled/furnished.
`
`received by this Authotr y on
`
`received by this Authority on
`
`a sequence listing -= see Supplement ‘ Box Relating to Sequence Listing.
`
`Tia: amendments have resulted in the cancellation of:
`
`
`
`B the description, pages _
`
`E the claims, Nos
`[:3
`the drawings, sheets/figs
`a the sequence listing (spec/i
`This report has been established as if (some 00 t, e amendments annexed to this report and listed below had not been
`made, since either they are considered to go beyond the disclosure as filed, or they were not accompanied by a letter
`indicating the basis for the amendments in the application as filed. as indicated in the Supplemental Box (Rules 70.2(c)
`and (is—bis»:
`[:3
`the description. pages
`
`[:5
`the claims? Nos.
`
`3 the drawings sheets/figs
`E the sequence listing (specgficl: __________________________________________________________________________
`E This report has been established:
`E taking into account the rectification of an obvious mistake authorized by or notified to this Authority under
`Rule 9l (Rules 66. ltd» his) and 70.2telt).
`E Without taking into account the rectification of an obvious mistake authorized by or notified to this Authority
`under Rule {lltRules 66.4 his and 70.2te}).
`
`
`
`E Supplementary inter ational search reportts) front Anthorityties)
`leis/have been received and taken into account in establishing this report (late 4:? bisfit’b) and (cl).
`*[fltem 4’ applies. some or all offizose Shier may be nmrked
`“superseded. "
`
`Form PC'i‘t’li‘EA/flO‘) (Box No i) (July 2(li l)
`
`

`

`INTERNATIGNAL PRELIIVHNARY REPGRT 8N PATENTABILETY
`
`International application No.
`
`PCT/ILZOIZ/000326
`
`Box No. V
`
`Reasoned statement nniler Article 35(2) with regard to novelty, inventive step and industrial applicability;
`citations and explanations supporting such statement
`
`State me in
`
`Novelty (N)
`
`Claims
`Claims
`
`
`
`
`inventive step (IS)
`
`Claims
`Claims
`
`Industrial applicability (EA)
`
`Claims
`Claims
`
`
`
`
`
`Citations and explanations (Rule 70.7)
`
`1. Reference is made to the following documents:
`
`Dl US2007043516 (Al) GUSTAFSSON et al. [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 meet the criteria set out in PCT Articles 33(2) and 33(3) because the prior art does not
`teach or suggests every limitation of the claims.
`
`Document Dl teaches of a methods for designing oligonueleotides. A set of sequence elements is
`defined. Each sequence element represents an amino acid sequence segment or a nucleic acid sequence
`segment. The set of sequence elements collectively represent a design nucleic acid sequence. The set of
`sequence elements are displayed as a plurality icons in a linear or a near linear arrangement such that
`each respective icon in the plurality of icons uniquely represents a corresponding sequence element in
`the set of sequence elements. In this representation, neighboring icons in the 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 element in the set of sequence
`elements. An oligonucleotide selection module is used to identify oligonucleotides in the design nucleic
`acid sequence.
`
`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
`PlWI-interacting RNAs (piRNAs), including siRNAS, miRNAs and/or piRNAs isolated or sequenced
`from invertebrate organisms such 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
`associated with harmful products are maliciously or accidentally designed.
`
`Form PCT/{PEA/lei? (Box No. V) (July lelll)
`
`

`

`INTERNATIGNAL PRELEB’HNARY REPGRT 8N PATENTABILETY
`
`International application No.
`
`PCT/[LZOIZ/000326
`
`3. Industrial Applicability
`
`Consequently, the solution proposed in claims 1-135 of the 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).
`
`Perm PCT/{PEN'ALGQ {Box No. V) (July 20M)
`
`

`

`Dr Eyal Bressler INTELLECTUALFROM
`
`OUR REF
`
`1080-G—01-PCT
`
`YOUR REF
`
`:msvn
`
`2'DDDD
`
`Date
`
`Page
`
`06/06/1 3
`
`: 1mm
`
`- l '
`
`mm:
`
`Dr. Eyal Bressler Ph.D. "3
`Patent: Attorney, INTA AIPPI IAPA
`Adv. , LLB
`B.Sc. (Biochem.. F. Technol.)
`M.Sc. (Appl. Chem.)
`Ph.D. (Biotechnology)
`Patents
`Partners
`
`Dr. Joseph I. Wyse PhD, AIPPI
`Dr. Liorltzhaki PhD, AIPPI
`
`(Genetics)
`(Chem.)'
`
`(Immune-bio.)
`Dr. Yael Uziel PhD
`Dr. Michael Meyklyar PhD (Phys.)'
`Dr. Keren Hagai PhD
`(Mol,Bio.)
`Dr. Richard H. Schultz PhD (Chem.)l'2
`Dr. Stuart Weisrose PhD
`(Physics)l
`Maya Basanchik B.Ac.
`(Comp—Sci. Mach)I
`Eva Soller M.Sc.
`(Biolo.)2
`IL Patent Attorney
`I
`2 US Patent Agent
`Malka Guttman, Department Coordinator
`mil
`bresslar.c .il
`
`‘
`Legal
`Dana Grinberg, Adv. LLB 3
`d n
`re I r
`'|
`
`Liat Galily Perel, Adv. LLB 3
`Iia
`r
`'
`Einat Hay Zemach, paralegal
`paralegal@bre§§|gr.cg.il
`Gil Tessler, paralegal
`Paralegal-2@bressler.co.il
`3 Member of IL Bar
`
`Industrial Designs
`Dr. Smadar Bressler PhD (Phys. Chem.)
`design@bressler.coti
`
`Of counsel
`Raffi Goren. PhD.
`James de Rothschild Professor of Horticulture
`
`Administration
`Hadar Daniel
`[eception@br§§sler.co.il
`
`Accounts
`Pnina llani. MA; CFO
`accounts@bres:ler.go.‘l
`Miri Hershkovitch
`Acct3
`ressle co.il
`loyce Framowitz, BA
`Ac :4
`bressler.coil
`
`Dr. Eyal Bressler Ltd.
`Offices and Postal Address
`Lazrom House, |
`| Tuval Street
`Ramat Gan 52522 Israel
`Tel: (972)-3-5765555
`Fax: (972)-3-5765566
`main@bressler.co.il www.bressler.co.il
`Bank Qetails:
`
`Account name
`Bank Name
`Branch No.
`Account No,
`Swift No. IBAN
`
`Dr Eyal Bressler Ltd.
`Bank Hapoalim (12)
`537
`222294
`Poalilll
`IL-8 l -0 l 25—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
`
`Re: Demand for IPRP
`
`
`
`
`
`
`
`PCT mommies
`
`00 -08- 2W3
`
`SYSTEM FOR POLYNUCLEOTIDE CONSTRUCT DESIGN,
`VISUALIZATION AND TRANSACTIONS
`TO MANUFACTURE THE SAME
`IL/2012/000326
`
`Inventors: AMIRAV DRORI Omri, DR. et a1
`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
`
`Patent Cooperation Treaty: The undersigned requests that
`
`the
`
`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 So a
`
`
`
`

`

`Dr. Eyal Bressler&Co.
`
`BOUTEQUE 1P FIRM
`
`P61791301 2/
`05 JUN mime :
`
`3 2 3
`
`Group
`
`OUR REF
`
`YOUR REF
`
`I080-G-0l -PCT
`
`| U20 l 2/000326
`
`:moon
`
`qweon
`
`Date
`
`Page
`
`06/06/13
`
`— 1 -
`
`:Tnxn
`
`:‘nnu
`
`Israel Patent Office
`
`The Technology Park, Bldg 5, Malcha,
`Jerusalem 96951
`Israel
`-
`
`Fax: +972-2-5651616
`
`Newman Baruch (Barry)
`Authorized Officer
`
`Demand under Article 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..
`
`PCT application no. IL/2012/000326
`PCT publication no. WO 2013/030827
`
`SYSTEM FOR POLYNUCLEOTIDE CONSTRUCT DESIGN,
`VISUALIZATION AND TRANSACTIONS TO
`MANUFACTURE THE SAME
`
`Dear Baruch,
`
`The applicant hereby files a Demand for International Preliminary
`
`Examination in 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
`
`applicant
`
`to be novel
`
`in the sense of Article 33(2) PCT.
`
`Arguments for novelty of the examined claims are presented.
`
`WE
`cum
`succsss®
`
`Dr. Eyal Bressler Ph.D. '3
`Patent Attorney,
`lNTA AIPPI IAPA LES
`Adv. . LLB
`B.Sc. (Biochem.. F. Technol.)
`MSC, (Appl. Chem.)
`PhD. (Biotechnology)
`
`Patent Department
`Partners
`
`Dr. Joseph l. Wyse. PhD AIPPI
`Dr. Lior ltzhaki. PhD AIPPI
`
`(Genetics)I
`(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. Schultz, PhD
`Dr. Maya Amit, PhD
`
`IL Patent Attorney
`l
`2 US Patent Agent
`
`(Chemistry)
`(Physics)
`(Moi. Biology)I
`(Physics)
`(Engineering)
`(Physics)l
`(Chemistry)"2
`(BioChemistry)
`
`Dr. Neil ]. Wilkof, Adv.
`milkgf@_br§§§ler,5g.il
`Trademarks & Licensing Partner
`
`Ph.D., ].D.3 ‘
`
`Legal Department
`Dana Grinberg-Matsliah, Adv. LLB 3
`
`Einat Zemach Rodman. Adv. LLM a
`
`WA
`
`viv N. Pollak, Adv.
`| k
`r
`ler oil
`
`LLB 3
`
`LLM 3
`LLB 3
`
`LLM
`
`Cyril Clerget, Adv.
`MW
`Dalia Haberman. Adv.
`|
`l-
`r
`| r
`.il
`Jonathan Kafri
`arale
`-
`r ssler.coil
`Yair Shwarcs
`I M r
`Gilad Ben-Joya
`
`|
`
`r.
`
`.il
`
`Omry Segal
`WE
`Rachel Nissim
`|
`l-2
`r
`l
`r.
`H
`
`3 Member of IL Bar
`4 Member of OH Bar (USA) (INACTIBE)
`Head of Administration
`Gal Moran
`reception@bressler.co.il
`Sara Rutstein
`sceptionZQbresslergo,‘
`
`Accounting Department
`Pnina llani, MA; CFO
`accounBQbresslgncoJI
`Miri Hershkovitch, B.A.
`Acct3@bressler.co.il
`Joyce Framowitz. B.A.
`Accl‘i
`bressier.co.il
`
`Dr. Eyal Bressler Ltd.
`Offices and Postal Address
`Lazrom House,
`I
`| 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
`Dr Eyal Bressler Ltd.
`Bank Name
`Bank Hapoalim (l2)
`Branch No.
`537
`Account No.
`222294
`Swift No. IBAN
`Poalih't
`u a: an: 37M nnM m-n non
`
`

`

`Dr. Eyal Bressler&Co.
`
`SOUTEQUE l? FIRM
`
`PCT/lLZUlZ/UDUBZB
`85 JUN 2013
`
`OUR REF
`
`l080-G-0 [ 'PCT
`
`YOUR REF
`
`lL/20l 2,0003%
`
`:Inson
`
`mson
`
`Date
`
`Page
`
`06/06/13
`
`21-1101
`
`- 2 -
`
`mm:
`
`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 claims is attached.
`
`WE
`cum
`SUCCESS®
`
`

`

`DnEyal Bressler&Co.
`
`BOUTiQUE 2? FSRM
`
`PCT/lLZU12/000326
`05 JUN 2073
`
`OUR REFw ”“90“
`
`Date fl :‘mxn
`
`YOUR REF
`
`”'n'm ”000326
`
`moon
`
`Page
`
`- 3 ~
`
`:1an
`
`Argpments against allegation of lack of novelfl 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
`
`(WOOO227638).
`
`_D_3: relates to a sequence similarifl searching method that computes an aligpment 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 m 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 result at all.
`
`In View of this, 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
`
`(USZOO7/0043516).
`
`1.
`
`D_1 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
`succsss®
`
`

`

`Dr.Eyal Bressler§QCQ
`
`BOUTEQUE t? FIRM
`
`PCTNLZUiZ/UDUBZB
`“5 JUN 2013
`
`OUR REF
`
`IOSO‘G‘O I ‘PCT
`
`YOUR REF
`
`|LI20|2I000326
`
`IITIDOYJ
`
`:Tlson
`
`Date fl :111xn
`
`Page
`
`_ 4 _
`
`:"rmu
`
`”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 throqu a plurality of resolution layers. These layers are further
`
`described in the embodiments (page 33; lines 12-16):
`
`”In various embodiments, the dynamic zoom @nction 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 known in 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. _D_1 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 achieved if 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 E the database providing the information for the visual display is a library of seguence
`
`elements and projects (D1; paragraph 88).
`
`we
`cum
`success®
`
`

`

`Dr.Eyal Bressler&Co.
`
`BOUTEQUE l? FlRM
`
`PCT/ILZUlZ/UUU326
`05 JUN 2mg
`
`OUR REF
`
`I080-G-0I 'PCT
`
`YOUR REF
`
`IL/2012/000326
`
`:meon
`
`:1190):
`
`Date
`
`Page
`
`06/06/13
`
`:‘mxn
`
`- 5 -
`
`mm!
`
`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).
`
`”In 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 sufiiciency, 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. m 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
`3313! 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
`cum
`s’uccsss‘®
`
`

`

`Dr. Eyed Bressier§LCQ
`
`BOUTEQUE l? FiRM
`
`PCT/IL2012/000326
`05 JUN 2013
`
`OUR REF
`
`I080-G—Ol _PCT
`
`YOUR REF
`
`IUZOIZ/OOO326
`
`:mson
`
`2119010
`
`Date
`
`Page
`
`06/06/13
`
`nmm
`
`- 6 -
`
`:‘rmv
`
`b.
`
`c.
`
`a network connection [102]
`
`a computer readable medium [101] comprising functional modules including:
`
`i. a design 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 pro-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 method of:
`
`d.
`
`visualizing biological information;
`
`e.
`
`f.
`
`designing nucleic acid sequences;
`
`detecting and notifying when sequences associated with harmful products are designed;
`
`g.
`
`providing means for transactions regarding ordering and purchasing said synthesized
`
`nucleic acids
`
`Claim 1 was amended to 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 se uences stronl
`
`associated with harm ul
`
`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 harmful products ”.
`
`WE
`cum
`success®
`
`

`

`Dr. Eyal BressleréLCo.
`
`EOUTIQUE 3P FIRM
`
`PCT/ILZUlZ/000326
`
`05 JUN 2013
`
`OUR REF
`
`|080-G-0l-PCT
`
`YOUR REF
`
`|L/20l2/000326
`
`:moon
`
`21190,:
`
`Date
`
`Page
`
`06/06/13
`
`nmm
`
`_ 7 _
`
`”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 (U82007/0043516) over D2
`
`(W00227638).
`
`D_1 describes a computer system and progxam for desigping oligonucleotides (D1; abstract). Q2
`
`describes a method for identimng 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 desigping nucleic acid sequences for gene expression that detects
`
`and notifies when sequences associated with harmful products are desigped (see below amended
`
`Claim 1). The current application fiirther explains what harmful products are: toxins, Viruses,
`
`bacteria, pathogens (Claim 109).
`
`The applicant wishes to comment that there is an extensive difference between identiffl'ng DNA
`
`sguences comprising the genomes of viruses and microorganisms (D2) and between identifying
`
`sequences associated with harmful products (current application) for two main reasons:
`
`1.
`
`Sequences which are homologous to viral and microorganisms genomes are 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.
`
`Not all parts of the genome of harmful Viruses and microorganisms are harmful.
`
`In D2 a method for generally identifying sequences identical
`
`to genomes of Viruses and
`
`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 harmful or 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
`cum
`succrss®
`
`

`

`Dr. Eyal BressteréSLCo.
`
`BOU‘FEQUE i? FIRM
`
`PCT/lLZUlZ/UUUSZB
`”5 JUN 2073
`
`OU R REF
`
`”80-6-0 l 'PCT
`
`YOUR REF
`
`NEH/000326
`
`:moon
`
`mason
`
`Date
`
`Page
`
`06/06/13
`
`:‘1 '1xn
`
`— 8 -
`
`:‘rmv
`
`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 amendments to 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 examiner to be obvious in view of D1 over D3.
`
`m, as already described, discloses a computerized method for desigping a polmucleotide
`
`construct. However, the method does not include a step of quality ranking of the designed
`
`polynucleotide as suggested in the current application.
`
`m relates to a sequence similarig searching method that computes an aligpment score that
`
`represents the degpee 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 seguences
`
`according to the number of 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 desigping oligonucleotides that
`
`does not involve quality ranking and D3 generally relates to ranking seguence 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 sequences associated with harmful products.
`
`we
`cum
`sweetss®
`
`

`

`Dr.Eyal Bressier§LCa
`
`BOUTEQUE {P FIRM
`
`PCT/ILzmz/anuna
`05 JUN 2013
`
`OUR REF
`
`YOUR REF
`
`l080-G-OI-PCT
`I
`2
`L/20|2l0003 6
`
`”mom
`
`mson
`
`Date
`
`Page
`
`06/06/13 mun
`
`— 9 -
`
`mm;
`
`Best regards,
`
`N
`
`Dr. K e
`
`agai
`
`Dr. Maya Amit
`
`WE
`CLAEM
`succsss®
`
`

`

`PCT/1L2012/000326
`
`UBJUN 2013
`
`AMENDED CLAIMS
`
`1.
`
`A computerized system for designing nucleic acid sequences for gene expression
`
`comprising;
`
`h.
`
`a server [103] for hosting a database [106]
`
`i. a network connection [102]
`
`j. a computer readable medium [101] comprising functional modules including
`
`i. a design 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 method of:
`
`k. visualizing biological information;
`
`1. designing nucleic acid sequences;
`
`1n.detecting and notifying when sequences associated with harmful products
`
`are designed;
`
`11. 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.
`
`40
`
`AMENDED SHEET
`
`

`

`
`
`\
`
`PCT/IL2012 Ianuszfi
`Baum 2013
`
`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
`
`known in the art.
`
`4. The system of claim 1, wherein the nucleic acid is selected from a group consisting of DNA,
`
`RNA and 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 and to 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 known in the art.
`
`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
`
`44
`
`AMENDED SHEET
`
`

`

`PCT/51.2012 / U
`00325
`
`flN2 1 3
`UBJU
`
`
`
`\,
`
`interactive user interface module.
`
`12.
`
`13.
`
`14.
`
`15.
`
`16.
`
`17.
`
`18.
`
`19.
`
`20.
`
`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.
`
`The system of claim 1, wherein said design module is further adapted for optimizing said
`
`designed nucleic acid construct according to various requirements.
`
`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 sequence repeats.
`
`The system of claim 1, wherein said design module is further configured to utilize various
`
`computer-assisted methods for ascertaining an optimal codon sequence.
`
`The system of claim 15, wherein said optimal codon sequence is in relation to the protein
`
`expression level in relevant expression systems.
`
`The system of claim 16, wherein said expression system determined based on the nucleic acid
`
`sequence entered by a user.
`
`The system of claim 17, wherein said determining said expression system is based on
`
`recognizing tRNA sequences.
`
`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.
`
`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 w