Trademark Trial and Appeal Board Electronic Filing System. http://estta.uspto.gov
`ESTTA999791
`09/05/2019
`
`ESTTA Tracking number:
`
`Filing date:
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`BEFORE THE TRADEMARK TRIAL AND APPEAL BOARD
`
`Notice of Opposition
`
`Notice is hereby given that the following party opposes registration of the indicated application.
`
`Opposer Information
`
`Name
`
`Entity
`
`Address
`
`Generation Bio Co.
`
`Corporation
`
`301 Binney Street, Suite 401
`Cambridge, MA 02142
`UNITED STATES
`
`Citizenship
`
`Delaware
`
`Attorney informa-
`tion
`
`Michael J. Bevilacqua
`Wilmer Cutler Pickering Hale and Dorr LLP
`60 State Street
`Boston, MA 02109
`UNITED STATES
`whiptrademark@wilmerhale.com, michael.bevilacqua@wilmerhale.com, bar-
`bara.barakat@wilmerhale.com
`617-526-6448
`
`Applicant Information
`
`Application No
`
`88093870
`
`Publication date
`
`08/06/2019
`
`Opposition Filing
`Date
`
`International Re-
`gistration No.
`
`Applicant
`
`09/05/2019
`
`NONE
`
`Touchlight IP Limited
`40 Queen Anne Street
`London, W1G9EL
`UNITED KINGDOM
`
`Opposition Peri-
`od Ends
`
`International Re-
`gistration Date
`
`09/05/2019
`
`NONE
`
`Goods/Services Affected by Opposition
`
`Class 001. First Use: 0 First Use In Commerce: 0
`All goods and services in the class are opposed, namely: Chemical preparations, enzymes and DNA
`for the preparation of nucleic acid for scientific research; chemicals for use in the preparation and cre-
`ation of DNA extracts and cassettes for scientific and industrial purposes; enzymes for use in the pre-
`paration and creation of DNA extracts and cassettes for scientific and industrial purposes; DNA ex-
`tracts and cassettes for scientific and research use; DNA extracts for use in agri-biotechnology and
`nanotechnology other than for medical and veterinary purposes; nucleic acids comprising natural and
`unnatural nucleotides for use in nanotechnology applications including data storage, data retrieval
`and computing other than for medical and veterinary purposes; nucleic acidanalogues comprising
`synthetic backbones or a mixture of natural and synthetic backbones for use in nanotechnology ap-
`plications including data storage, data retrieval and computing other than for medical and veterinary
`purposes; compositesof nucleic acids or nucleic acid analogues with organic and inorganic chemic-
`alsfor use in nanotechnology applications including data storage, data retrieval and computing other
`than for medical and veterinary purposes; nucleic acid analogues with organic and inorganic chemic-
`
`

`

`alsfor laboratory use in labeling, imagingand sensing applications; nucleic acid analogues with organ-
`ic and inorganic chemicals for laboratory use in smart materials; two-dimensional and three-di-
`mensional nucleic acid analogues with organic and inorganic chemicals for laboratory use in creating
`nanostructures and scaffolds
`
`Class 005. First Use: 0 First Use In Commerce: 0
`All goods and services in the class are opposed, namely: Vaccines; DNA based vaccines; DNA ex-
`tracts, namely, nucleic acid sequences and chemical reagents for medical use; therapeutic DNA,
`namely, nucleic acid sequences and chemical reagents for medical andveterinary purposes; nucleic
`acids comprising natural and unnatural nucleotidesfor medical and veterinary purposes; nucleic acid
`analogues comprising synthetic backbones or a mixture of natural and synthetic backbones for med-
`ical and veterinary purposes; composites of nucleic acids or nucleic acid analogues with organic and
`inorganic chemicals for medical and veterinary purposes; nucleic acid analogues with organic and in-
`organic chemicals for medical and veterinary purposesin labeling, imaging and sensing applications;
`nucleic acid analogues with organic and inorganic chemicals for medical and veterinary purposes in
`smart materials; two-dimensional and three-dimensional nucleic acid analogues with organic and in-
`organic chemicals for medical and veterinary purposes in creating nanostructures and scaffolds
`
`Grounds for Opposition
`
`The mark is merely descriptive
`
`Failure to function as a mark
`
`Trademark Act Section 2(e)(1)
`
`Trademark Act Sections 1, 2 and 45
`
`Attachments
`
`cedna NOP 88093870.pdf(109709 bytes )
`Exhs A and B.pdf(1390158 bytes )
`Exhibits CEDNA nop Exhibits D thru H.PDF(1768348 bytes )
`Ex C part 1.pdf(3892003 bytes )
`Ex C part 2.pdf(3355902 bytes )
`
`Signature
`
`/barbara a. barakat/
`
`Name
`
`Date
`
`Barbara A. Barakat
`
`09/05/2019
`
`

`

` 
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE 
`BEFORE THE TRADEMARK TRIAL AND APPEAL BOARD 
` 
`In the matter of Application Serial No. 88093870 
`Published in the Official Gazette at TM 1381 on August 6, 2019    
` 
`__________________________________________ 
`Generation Bio  Co.,  
` 
`       
` 
`) 
` 
` 
` 
` 
` 
` 
` 
`) 
`Opposer 
` 
` 
` 
` 
` 
`) 
` 
` 
` 
` 
` 
` 
` 
`) 
`v. 
` 
` 
` 
` 
` 
` 
`) 
` 
` 
` 
` 
` 
` 
` 
`) 
`Touchlight IP Limited, 
` 
` 
` 
`) 
` 
` 
` 
` 
` 
` 
` 
`) 
`Applicant 
` 
` 
` 
` 
` 
`) 
`__________________________________________) 
` 
` 
`
`Opposition No. 
`
`NOTICE OF OPPOSITION 
`
` 
` 
`
`Generation Bio Co. (hereinafter “Opposer”), a corporation duly organized 
`
`and existing under the laws of the State of Delaware and located and doing 
`
`business at 301 Binney Street, Suite 401, Cambridge, Massachusetts 02142 
`
`believes that it will be damaged by the registration of the mark “CEDNA” as 
`
`shown in Application Serial No. 88093870 filed August 27, 2018 by Touchlight IP 
`
`Limited  (hereinafter “Applicant”), and hereby opposes the same. 
`
` 
`
` 
`
`As grounds for opposition, it is alleged that: 
`
`1. 
`
`Applicant seeks registration on the Principal Register of the mark 
`
`“CEDNA” for use in connection with “Chemical preparations, enzymes and 
`
`DNA for the preparation of nucleic acid for scientific research; chemicals for use 
`
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`in the preparation and creation of DNA extracts and cassettes for scientific and 
`
`industrial purposes; enzymes for use in the preparation and creation of DNA 
`
`extracts and cassettes for scientific and industrial purposes; DNA extracts and 
`
`cassettes for scientific and research use; DNA extracts for use in agri‐
`
`biotechnology and nanotechnology other than for medical and veterinary 
`
`purposes; nucleic acids comprising natural and unnatural nucleotides for use in 
`
`nanotechnology applications including data storage, data retrieval and 
`
`computing other than for medical and veterinary purposes; nucleic acid 
`
`analogues comprising synthetic backbones or a mixture of natural and synthetic 
`
`backbones for use in nanotechnology applications including data storage, data 
`
`retrieval and computing other than for medical and veterinary purposes; 
`
`composites of nucleic acids or nucleic acid analogues with organic and inorganic 
`
`chemicals for use in nanotechnology applications including data storage, data 
`
`retrieval and computing other than for medical and veterinary purposes; nucleic 
`
`acid analogues with organic and inorganic chemicals for laboratory use in 
`
`labeling, imaging and sensing applications; nucleic acid analogues with organic 
`
`and inorganic chemicals for laboratory use in smart materials; two‐dimensional 
`
`and three‐dimensional nucleic acid analogues with organic and inorganic 
`
`chemicals for laboratory use in creating nanostructures and scaffolds” in 
`
`international class 1 and “Vaccines; DNA based vaccines; DNA extracts, namely, 
`
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`nucleic acid sequences and chemical reagents for medical use; therapeutic DNA, 
`
`namely, nucleic acid sequences and chemical reagents for medical and veterinary 
`
`purposes; nucleic acids comprising natural and unnatural nucleotides for 
`
`medical and veterinary purposes; nucleic acid analogues comprising synthetic 
`
`backbones or a mixture of natural and synthetic backbones for medical and 
`
`veterinary purposes; composites of nucleic acids or nucleic acid analogues with 
`
`organic and inorganic chemicals for medical and veterinary purposes; nucleic 
`
`acid analogues with organic and inorganic chemicals for medical and veterinary 
`
`purposes in labeling, imaging and sensing applications; nucleic acid analogues 
`
`with organic and inorganic chemicals for medical and veterinary purposes in 
`
`smart materials; two‐dimensional and three‐dimensional nucleic acid analogues 
`
`with organic and inorganic chemicals for medical and veterinary purposes in 
`
`creating nanostructures and scaffolds” in international class 5.  
`
` 
`
`2. 
`
`Application Serial No. 88093870 for registration of the mark 
`
`“CEDNA” was filed on August 27, 2018 based upon the priority of a European 
`
`application filed February 28, 2018 and an intention to use the mark.  
`
` 
`
`3. 
`
`Opposer is now, and has been for some time, engaged in the 
`
`business of scientific and medical research related to the diagnosis and treatment 
`
`of genetic diseases, development and provision of pharmaceuticals and genetic 
`
`medicines with drug like properties that enable people born with genetic 
`
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`diseases to live long, full lives and product development and consultancy in the 
`
`fields of biotechnology, biologics, pharmaceutics, medical science, chemistry and 
`
`biochemistry, (collectively, “Opposer’s Goods and Services”).  
`
` 
`
`4. 
`
`Since long prior to the August 27, 2018 filing date of Applicant’s 
`
`United States application, and the February 28, 2018 filing date of Applicant’s 
`
`European priority application, the term “ceDNA” has been used as an acronym 
`
`for “closed‐ended(or closed‐end) DNA.”  
`
` 
`
`5. 
`
`The attached exhibits show that the term “ceDNA” has been used 
`
`as an acronym for closed‐ended (or close‐end) DNA in the medical and scientific 
`
`fields of the Applicant for many years and certainly prior to the date Applicant 
`
`filed for protection of this mark.  Exhibits A and B are articles from third party 
`
`websites ResearchGate and What‐When‐How.com which describe “cedna” as a 
`
`type of chemical, gene, enzyme, or DNA for various scientific, industrial, and 
`
`medical uses.  The attached Exhibit C is a copy of a third party’s (University of 
`
`Massachusetts’) patent application publication, published September 8, 2017, 
`
`with an inventor named Robert Kotin, that refers to closed‐ended DNA as 
`
`“ceDNA ” throughout the document.   
`
` 
`
`6. 
`
`Since at least as early as January 2018, Opposer has also used the 
`
`acronym “ceDNA” to  refer to “closed‐ended DNA” in association with its 
`
`scientific and medical research related to the diagnosis and treatment of genetic 
`
`
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`diseases, and development and provision of pharmaceuticals and genetic 
`
`medicines, since long before the Applicant adopted this mark.  The attached 
`
`Exhibit D is an article dated January 4, 2018 from Business Wire discussing the 
`
`launch of Opposer’s business utilizing Dr. Kotin’s discoveries from that patent 
`
`application in Exhibit C.  The attached Exhibit E is a copy of an article dated 
`
`January 4, 2018 from Endpoint News, about Dr. Kotin and the formation of 
`
`Generation Bio, and his use of close‐ended DNA (ceDNA) for gene transfer.  
`
`Exhibit F is a copy of an article on PharmacyChoice dated January 4, 2018 about 
`
`the formation of Opposer’s company and its platform to develop gene therapies 
`
`delivered via closed‐ended DNA (ceDNA).  Exhibit G is a copy of an article from 
`
`Insights.bio regarding Cell & Gene Therapy which discusses the Opposer and its 
`
`use of closed ended DNA (ceDNA).  Exhibit H shows copies of the Opposer’s 
`
`website dated December 11, 2018 which were cited by the Examining Attorney 
`
`during the prosecution of Applicant’s trademark application Serial No.  
`
`88093870, illustrating Opposer’s prior use of the term “ceDNA” in a descriptive 
`
`manner.   
`
` 
`
`7. 
`
`The goods identified in Application Serial No. 88093870 include 
`
`DNA backed chemicals, vaccines and extracts, the exact goods in connection 
`
`with which Opposer uses the acronym “ceDNA. ”   
`
` 
`
`8. 
`
`The goods other than DNA backed chemicals, vaccines and extracts 
`
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`

`identified in Application Serial No. 88093870 are identical to or closely related to 
`
`Opposer’s Goods and Services. 
`
` 
`
`9. 
`
`On information and belief the goods identified in Application Serial 
`
`No. 88093870 will be marketed through the same or similar channels of trade to 
`
`the same class of consumers as Opposer will market Opposer’s Goods and 
`
`Services. 
`
` 
`
`10. 
`
`The term “ceDNA” gives direct information about the goods 
`
`covered under Application Serial No. 88093870, namely, it tells the purchasing 
`
`public that the goods utilize, incorporate, or were formed with closed‐ended 
`
`DNA.  
`
` 
`
` 
`
`11.  Applicant’s Mark is not unique. 
`
` 
`
`12.  Applicant’s registration of the mark “CEDNA” on the Principal 
`
`Register of the United States Patent and Trademark Office Grant will prevent 
`
`Opposer, and others, from fairly describing its goods and services. 
`
` 
`
`13.  Applicant’s registration of the mark “CEDNA” on the Principal 
`
`Register of the United States Patent and Trademark Office will prevent Opposer, 
`
`and others, from communicating with their customers to a significant degree.  
`
` 
`
`14. 
`
`Based upon the foregoing, Applicant’s registration of the mark 
`
`“CEDNA” on the Principal Register of the United States Patent and Trademark 
`
`Office would clearly cause injury and damage to Opposer. 
`
`
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`

` 
` 
` 
` 
` 
` 
`
` 
` 
`
` 
` 
`
` 
` 
`
` 
` 
`
` 
`
` 
`
` 
`
`WHEREFORE, Opposer prays that this opposition be sustained and that 
`
`registration of the mark “CEDNA” as shown in Application Serial Number 
`
`88093870 be refused. 
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
`Respectfully submitted, 
`
`GENERATION BIO CO. 
`
`/barbara a. barakat/ 
`_________________________________ 
`Michael J. Bevilacqua 
`Reg. No. 31,091 
`Barbara A. Barakat 
`Reg. No. 32,190 
`Attorneys for Opposer 
` 
`Wilmer Cutler Pickering Hale and Dorr LLP 
`60 State Street 
`Boston, Massachusetts  02109 
`(617) 526‐6000 
`Date:  September 5, 2019 
` 
`
` 
`
`
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`

`EXHIBIT A
`
`

`

`Researchcate
`
`Q
`
`Jolnrorlree
`
`Logln
`
`3“ a" ’
`11 Citations
`
`See all ’
`18 References
`
`&, Cox: nioad citation
`
`Share v
`
`Request fulHext
`
`Linear closed mini DNA generated by the prokaryotic cleaving-joining enzyme TelN
`is functional in mammalian cells
`
`Article --7 Journal oi Molecular Medicine sorrows-54 - Novemberzooz .
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`Abstract
`
`Show more authors
`
`For application of DNA in gene medicine plasmid or viral DNA is usually used as a vector for the gene of interest. To generate DNA with a
`minimum of loreign DNA sequences. we used the prokaryotic telomerese. protelomerase T l
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`15. This is a novel
`
`enzyme with cleaving-Joining activity‘ which is required forthe formation oflinearprophagm lysogenic bacteria.
`
`in 0 near covelen y closed dumbbell—shaped
`Acting on e telomere resolution site teiRL. the protelomerase converts circular plasmid D
`molecules ("doggybones") In a single-step enzyme reaction. TWO such sites were inserted into an expression plasmid flanking a gene of
`interest. This is cleaved and Joined by means ofthe protelomerase. yielding linear closed m‘ni DNA coding for green fluorescent protein
`(EGFP) or interleukin-12 (lL-12). Upon transient transfection of human embryonal kidney cells. EGFP was expressed at higher levels from
`linear closed molecules than from linear open molecules generated by restriction endonucleases tor comparison. The ievel of transcription
`was comparable to that obsen/ed for the parental plasmid DNA To test whether the linear closed mini DNA molecules are functional in vivo
`the B16F10/C57BL/6 melanoma metastasis model was applied. where injection of lL-12~expressing DNA inhibits metastasis formation in the
`lung. The anti-metastatic effect of the lbw-expressing linear closed DNA was equal or higher than that ofthe parental plasmid DNA.
`Therefore. the TelNl teiRL system is well su'tod to generate iinear closed mini DNAw'th high stability and a minimum of foreign nucleotide
`sequences.
`
`Do you want to road the rest ofthis article?
`
`Request fulletext
`
`
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`
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`httpsiMwwreeearcngalemetipublicatim’t1068242_Lineaii_;dostd_mnnii_ Wgermmed(mutterW_diewwmnm_ewne,fm_is_mnml,in_Mimi-Miran
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`

`

`See a")
`11 Citations
`
`See a" i
`18 References
`
`35 Download citation
`
`Share v
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`
`Citations (11)
`
`References {18)
`
`Highty et'ncaclous gene therapeutics demand contributions from sound design of both the synthetic vector as well as the enclosed DNA
`cargo. Conventional recombinant plasmid DNA (pDNA) employed in non-viral gene delivery typically consists of two essential components:
`i) an eukaryotic expression cassette for the expression of the gene of interest. and ii) a prokaryotic backbone with an origin of replication
`for plasmid amplification and an antibiotic resistance gene cassette for selection [21L While safer than their viral counterparts. non-viral
`delivery of such circular covalently closed (CCC) pDNA vectors. alone or packaged within synthetic vectors . offers a limited safety profile
`as they often result in the transfer of antibiotic resistance genes as well as other unwanted prokaryotic sequences with CpG motifs.
`
`Unmethylated CpG dinucleotides. or CpG motifs. have the potential for eliciting immunostimulatory responses which reduce the efficacy
`of the gene therapeutic and may induce detrimental effects in the treated host22232425 , Hence. the removal of the prokaryotic backbone
`in the generation of linear covalently closed (LCC) DNA minlvectors serves the dual purpose of enhancing the safety of the delivered
`vector while Improving the delivery process through the formation of smaller vectors that increase extracellular and intracellular
`bioavailabillty [21, 26]. Lcc DNA mlnivectors are small. dumbbell shaped vectors possessing hairpin ends enclosing an eukaryotic
`expression cassette.
`
`Physical Characterization oi Gemini Surfactant-Based Synthetic Vectors for the Delivery of Linear Covalently Closed (LCC) DNA
`Mlnistrlngs
`Article
`Full-text available Nov 2015-ELQS_QN.E
`
`fl Chi Hong Sum -Q Naflseh Nafissi -. Shawn Wettig w. Roderick A Slavcev
`
`View
`
`Show abstract
`
`DNA vaccination: An immunological perspective
`Article
`.lah ZOO-l
`
`Sharmaine Moreno - Marcos Timon
`
`View
`
`Show abstract
`
`Novel synthetic plasmid and Doggybone’“ DNA vaccines induce neutralizing antibodies and provide protection from lethal influenza
`challenge in mice
`Article
`Full-textavailabie
`
`Jun 20i5
`
`3 Daniel 0 Villarreal ~ Veronica L Scott ~
`
`Amt Patel t; David 8 Weiner
`
`View
`
`Show abstract
`
`impact of DNA Vector Topology on Nominal Geno Mum: Safety and Efficacy
`Article
`Full-text available Jun 2014 @jlfifigfim
`
`& Chi Hang Sum ~. ShevmWettig -. RoderickASievcev
`View
`Showabstract
`
`Comparative analysis oi enzymatienity produocd navet linear DNA cmuotsvdlh Maids for use as DNA vocoims
`Nude inay :-.'-i-I
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`Adam A. Walters -
`
`Ekaterina Kinnear fl Room Shaaock
`
`John S Tnegontng
`
`View
`
`Showabstract
`
`Both generate a 3'-phosphotyrosine DNA htermeoiate that emceesthe covenant rejoining oi cieaved DVA strands united! the use. 62‘ a
`high-energy cofactois (Valentin and Rybchin 1999). TelN Cmmffltflmfl actively is tumor-tar in the essence of any one? N t S-encodod
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`factors» and oun‘tied TelN is the ante omtein reouied to convert circular W amazes oossessino tineteiRL seams to the linear
`hflps:iiuwwtreeeazchMeneWeatim’t 1068242_um_ciosed_mmgw_gemewmdgay;tire premier: gcieevnc-lommenmgmis_moMLii\_itnnmtuait
`_ceil's
`3:30:44 PM tar-memo
`
`

`

`595 9“ f
`11 Citations
`
`See all ’
`18 References
`
`,i Download citation
`
`Share v
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`Request full—text
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`Both generate a 3'-phosphotyrosine DNA intermediate that enables the covalent rejoining or cleaved DNA strands without the use of a
`high-energy cofactors (Valentin and Rybchin 1999). TelN cleaving-joining activity ls functional in the absence of any other N15-encoded
`factors, and purified TelN is the uni
`roteln required to convert circular DNA substrates possessing the telRL sequence to the linear
`
`molecule with covalentl
`Heinrich at al. 2002). in vitro studies on the functionality of purified TeiN demonstrate that in the
`
`presence of the 56—bp t
`nd in particular the 22—bp telO target site. purified TelN processes circular and linear pDNA in vitro
`
`with the same covalently
`topology as was observed In vlvo (Deneke et al. 2000).
`
`TeIN protelomerase represents a significant addition to the repertoire of exploitable enzymes in biotechnology with respect to its unique
`property In iinearlzlng the plasmids carrying its target telRL site. The "pJAZZ" series of transcription-tree. linear cloning vectors and "linear
`mlniplasmids" are N15-based linear cloning systems that facilitate cloning of up to 30-kb DNA sequences including AT-rlch inserts or
`inverted repeats. which are very difficult to clone by standard methods into plasmid Heinrich et al. 2002) vectors (Ravin et al. 2000).
`TelN/teIRL cleaving-Joining activity has also been applied to enhance in vitro production of LCC DNA vectors (Fig. 3), where LCC DNA
`vectors demonstrate heightened and sustained expression of a gene of interest both in vitro and in vivo ( Heinrich at al. 2002).
`
`The "pJAZZ" series of transcription-free. linear cloning vectors and “linear miniplasmids“ are Ntsbased linear cloning systems that
`facilitate cloning of up to 30-kb DNA sequences. Including AT-rich inserts or inverted repeats. which are very difficult to clone by standard
`methods into plasmid Heinrich et al. 2002) vectors (Ravin et al. 2000). TeletelRL cleaving-joining activity has also been applied to
`enhance in vitro production of LCC DNA vectors (Fig. 3). where LCC DNA vectors demonstrate heightened and sustained expression of a
`gene of interest both in vitro and in vivo ( Heinrich at al. 2002).
`
`Bacteriophage recombination systems and biotechnical applications
`Article
`Full-text available
`Jan 2014 Appl_Michbigl Eigiechngl
`
`m Naflseh Nafissl w. Roderick A Slavcev
`
`View
`
`Show abstract
`
`E. coil phage N15 was the first discovered phage to exist in its tysogenic (prophage) state as a linear covalently closed (Icc) plasmid [17]
`that is actively partitioned to daughter cells [18]. The lcc conformation is conferred by the cleaving-ioining activity of the protelomerase
`protein (Prokaryotic Telemerase). TeIN (~72 kDa). acting upon the 56 bp telRL target sequence that is entirely sufficient to confer TelN-
`mediated processing and Iinearization both in vivo and in vitro [19. 20]. Similarly. phage PY54. isolated from Yersinia enterocolitica.
`maintains its prophage as a linear, circularly permuted, and covalently closed plasmid with telomere hairpin ends and a genome size of 46
`kb.
`
`upercoiled plasmid DNA containing the identified target site. teiRL. to produce linear
`Purified TelN was shown to roc
`lc: and mini lcc DNA vectors produced in vitro by recombinant TelN have been
`double-stranded
`n gene e very experiments. and showed higher and more durable expression of the gene of interest in targeted
`successfully app
`human cells [20. 21]. in contrast. to the best of our knowledge. there are no reported applications of the Tel-pal system.
`
`Construction and Characterization of an ln-vlvo Linear Covalently Closed DNA Vector Production System
`Article
`Full-text available Dec 2012 ~MlCROB CELL FACT
`
`& Nafiseh Nafissi a, Roderick A Slavcev
`
`View
`
`Show abstract
`
`Linear Plasmids and Prophages in Gram-Negative Bacteria
`
`Chapter Jun 2007
`
`Stefan Hertwtg
`
`\flew
`
`Show abstract
`
`In combination. the existing studies employing lcc DNA systemsW that ice DNA is smasher to lo DNA in inflection efficiency. and
`to ccc DNA lntransgene expression. PwifledmN (closely nlatodto‘hliwaspnvlowynpomdtogomatolccplasmldslnmmlpal
`related) telRL-dependent manner and was shown to successfuly deliver EGFP to human entryonal kidney cells it vitro as well as lL~12
`in an untargeted manner to inhibit metastasis formation in BtSFtOGflBLaS mama model mice in vivo (Heinrich at d. 2000 ). At
`present. our laboratory is hvorved in des'gn. and construction of bacterizphageencodad recombination systems to generate linear
`covalently closed (lccl DNA minivectors .
`
`Nanomedicine Based Approaches to Cancer Diagonsis and My
`
`,
`
`httpstliwmvresearchgalenetl‘publoatiom 1068242~Linear__ciosed_huiii_DNA_gemated_by_new”Mmmm_m~ls_mml_infimmim
`“ceills
`3:31:10 PM 112911¥2018
`
`

`

`See all >
`11 Citations
`
`See all >
`18 References
`
`Gupta
`
`Full-textavailable Nov2011
`
`Q Shawn Wettlg ~Q Tranum Kaur a" Roderick A Slavcev
`VI ew
`
`3;. Download citation
`
`Share v
`
`Request full-text
`
`These are also employed as an intermediate step prior to the final vector of choice. as demonstrated by the linear expression element
`approach for relevant antigen identification [43]. Other variation from the same theme comes from studies led by Heinrich et at.
`[44.]
`employing the TeIN protelomerase from bacteriophage N15 for generating the doublestranded linear covalently closed dumbbell~shaped
`DNA molecule in vitro. It comprises exclusively the expression cassette and the remaining recombination strand-end signals (Fig 3c).
`although selective purification from DNA molecule‘s mixes is still required as in the MIDGE and minicircle systems.
`
`Nonvlral DNA vectors for immunization and therapy: Design and methods for their obtention
`
`‘ Full-text available Sep 2004 ‘J MOL MED-JMM
`Article
`Emesto Galban Rodriguez
`
`View
`
`Show abstract
`
`Show n are
`
`Recommended publications
`
`Discover more publications. questions and projects in \firal DNA
`
`Alida
`
`Amos
`
`The protelomerase of temperate Escherichia
`coli phage N15 has cleaving-joining activity
`August 2300 Proceedmgs of the National Academy of SCIEHCCS
`GN Ziegelin ~Jan Deneke Erich Lanka‘
`Rudi Luz
`
`ESChEllulla colt phage ms encodes he 5! ghtly acidic. 530<IESICU€ protein
`01 72 2 kDa called protelomerase tTelN) TelN is a component of the N15
`
`'
`replication system r
`use to be involve
`in the
`ration of the linear
`prophage UNA
`he
`reaction converting circular plasmids lnio linear molecules was catalyzed ttl
`wtro. We demonstrate that
`.. [Show tull abstract]
`
`The protelomerase of the phage-plasmid N15 is
`responsible for its maintenance in linear form
`November 2001
`Journal of Molecular Biology
`Nikolai V Ravin ~Ta‘sia S Stralthova Victor V. Kuprianov
`
`The propnage of :oliphage N15 IS not Integratec min the bacterial
`chromosome but exrsts as a linear plasmid moleculeWill'—
`n inlection afar. Estnerichia "DH cell, the nhage DNA Circularises
`vra cohesrve ends, A phage-encoded enzyme, protelomerase then CLts at
`another Site telRL‘ and forms hairpin ends (telon‘ieres‘i
`l .e demonstrate
`that this enzyme acts n «we on ,V [Show full abstract]
`
`Read more
`
`A!”
`
`PY54, alinear plasmid ro ha
`of Yersinia
`enterocolmcawn&
`June JUCB lllcierular itlrcrcrrclog)
`
`Rudi Lurz ~Bomd Appol -lrls Klein -[...] ~
`
`Stefan HM
`
`PYFA Is a temperan- phage isolated from Yersmra enierocolnica Lysoge'iic
`Versinlu strains harbour thc PY‘4 l-
`:phagc as a plasmid (p‘l‘éd) The
`plasmid has the same srle (46 KM as the PY54 genome isolated from
`pha Tc pirtrrles By electron microscopy restriction analysis and DNA
`sequencmg. it was demonstrated mm the phage and the plasmid DNAs are
`true .:. circularly permuted molecules
`. [Show lull abstract]
`
`Read more
`
`Read more
`
`More
`
`Full-text available
`
`tumor regggion of human and murine
`mglanw after intratumoral iniection of lL-12—
`encodingplasmid...
`
`
`Jovan Pavlovic Reinhard 0m . Lucie
`Hoinzerting ~[. .] Karin Hauling
`
`DNA cod nr- ‘or marine interleu- in ‘2 {IL-12} Drew-.nts the formation of [51'3-
`mei mania rr 'tr-strr5is then avini-nisterea inn tfllliSCUIdl-Y Here the
`alltltul'l‘ \r L.-E< to IL 12-encoding MA on established mouse Br
`melrncnia and human melanoma tunmis was mves'lgated in "NO using
`two amn‘zl n‘it tots 816 rrelanoma in £97816 mice . no human melanoma
`in nude mice In 816 melanoma .ilratunioral .nioriions st. . [Show fu'l
`abstract]
`
`View hill~text
`
`researchgatenet/"J11273528_Tumor_mgrcssion_of_hum
`
`v
`
`hm:m.mmmam't1068242_Lmeaino’oeedkmtmDNA_gerriemted_w_ilre_wkmmm_omuwmm_mgis_mnml_tmmummies
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`what-when-how
`in Depth Tutorials and information
`
`Transformation (Molecular Biology)
`
`(50lethth n
`
`SAMSUMB
`
`SAMSUNL
`‘II o.
`
`Many bacteria can bind naked DNA to their surface. transport it through the cell wall. and incorporate it into their genomes. This
`phenomenon is called transtomiation. Typically, transforming DNA substitutes for a homologous segment of the host chromosome
`by recombination. although plasmids usually resume their autonomous existence. The term transformation originally referred only to
`the alteration in behavior and appearance of one pneumococcal strain upon mixing with neat-killed cells of another (1 ). but it has
`since come to signify the entire DNA-uptake process.
`
`To import DNA, bacteria must be in a particular physiological state. usually transitory. termed competence. Only then are the genes
`that code for the DNA uptake apparatus turned on Competence occurs naturally in many species. but far from all. However, the
`capacity for DNA uptake can often be induced by laboratory manipulation of bacteria that do not display natural competence. Two
`examples of competence, one natural and one artificial, transformed biology itself: Natural transformation of Pneumococcus (now
`Streptococcus pneumoniae) was the experimental procedure used by Avery and his colleagues to demonstrate that DNA is the
`genetic material (2). and calcium treatment of normally noncompetent Escherichia coli was crucial to the emergence of recombinant
`DNA technology (3, 4). Our intention here is less ambitious: to show how transformation takes place and to consider its function in
`nature.
`
`
`
`1. The Basic Process
`
`Nearly everything we know about transformation and competence comes from experiments carried out on four species: S.
`pneumoniae, Bacillus subtilis. Haemophtlus influenzae. and Neisseria gonorrhoeae. These studies suggest that whereas induction
`of competence is idiosyncratic. possibly reflecting the diversity of natural habitats in which naked DNA is encountered (see
`Competence). the basic mechanisms of transformation are similar in all naturally transformabie bacteria. Thus we can View the
`process of transformation as passing through four stages: (l) Competent cells sporting a limited number of DNA~binding receptor:
`attach duplex DNA to the cell surface. (it) The DNA is processed by endonucleoiytic cleavage and. usualty, by exonucieolytic
`removal at one of the strands. (iii) The other strand is drawn through a pore into the cytoplasm. possibly in concert with the
`exonucleolytic degradation. (iv) The entering single strand of DNA undergoes homologous recombination with the chromosome.
`creating a new recombinant if the recombining partners carry dittorent alleles. We shall look at how each of the tour bacterial
`species works its variations on this theme.
`
`1.1. B, Subtiiis
`
`As cells become competent. transcription of the “late“ commence genes begins. One of these transcription units. come,
`specifies five small proteins tCornGC to 66) that appear to term ammal receptors tor DNA, as well as two larger proteins
`(ComGA GB) that probably anchor the receptors to the morons (Fig. 1,). Each competent cell has about 50 ot these receptors.
`as measured by saturation of binding capacity tor radioactively labeled DNA (5. 6). When transforming DNA is added. the receptors
`a
`bind it rapidly and without regard to sequence (unlike H. influenzae and N. gonorrhoeae; see text below)‘ and for about 30 seconds
`
`mumsmmm-biobgymmohmmm
`3281)!) PM 12?“th
`
`

`

`AS ueus ueuume UUIIIPBIUIII, llfllliullpllull Ul lliU Illa UUlllPBlUllCe genes Degllili. Ulle Ul muse llullSCllpllUll Ulllls. Culllu.
`specifies five small proteins ((30ch to 66) that appear to form external receptors for DNA. as well as two larger proteins
`(ComGA, GB) that probably anchor the receptors to the membrane (Fig. 1). Each competent cell has about 50 oi these receptors.
`as measured by saturation of binding capacity for radioactively labeled DNA (5. 6). When transforming DNA is added. the receptors
`blnd it rapidly and without regard to sequence (unlike H. influenzae and N. gonorrhoeae: see text below). and for about 30 seconds
`the DNA remains on the surface. susceptible to added nucleases but not removable by washing.
`
`Figure 1. The apparatus of DNA uptake during transformation of i a) B. subtilis and (b) H. influenzae. The locations and
`presumed roles of several of the proteins shown are partly speculative, but the overall mechanisms depicted are based on
`good evidence. The B. subtilis Com proteins are described in the text; Nuc denotes nucleases that cut bound DNA and
`degrade the 5'-ended strand: A shows RecA protein. mediating invasion of the resident chromosome. The appearance of
`the H. infl