Dkt. 62239-BZA7/JPW/AC
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Applicant
`
`The Trustees of Columbia University in the City
`of New York
`
`Inventors
`
`Jingyue Ju et al.
`
`U.S. Serial No.
`
`15/167,917
`
`Examiner: Jezia Riley
`
`Filed
`
`May 27, 2016
`
`Group Art Unit: 1637
`
`Conf. No.
`
`1260
`
`For
`
`MASSIVE PARALLEL METHOD FOR DECODING DNA AND RNA
`
`30 Rockefeller Plaza
`20th Floor
`New York, NY 10112
`November 4, 2016
`
`BY EFS
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`COMMUNICATION IN RESPONSE TO JULY 20, 2016 OFFICE ACTION
`AND SUMMARY OF OCTOBER 27, 2016 INTERVIEW WITH EXAMINER RILEY
`
`This Communication is submitted in response to the Office Action
`the above-identified
`in connection with
`2016
`issued July 20,
`application. A response to the July 20, 2016 Office Action was due
`October 20, 2016 and applicant is concurrently filing a Petition for
`A One Month Extension of Time. Accordingly, a response is now due
`November 20, 2016 and this Communication is being timely filed.
`
`Remarks begin on page 2 of this paper.
`
`Page 1
`
`Illumina Ex. 1062
`IPR Petition - USP 10,435,742
`
`

`

`Applicant
`
`The Trustees of Columbia University in the City
`of New York
`U.S. Serial No.: 15/167,917
`May 27, 2016
`Filed
`Page 2 of 9 of Communication in Response to July 20, 2016 Office
`Action and Summary of October 27, 2016 Interview with Examiner Riley
`
`REMARKS
`
`Claim 49 is the sole claim pending in the subject application and is
`not being amended in response to the July 20, 2016 Office Action;
`
`As an initial matter, applicant wishes to express its gratitude to
`Examiner Riley for the in person interview held October 27, 2016 at
`the U.S. Patent and Trademark Office in Alexandria, Virginia. This
`interview was attended by the first named inventor, Dr. Jingyue Ju a
`the
`professor at Columbia University in the City of New York,
`assignee of the subject application, and the undersigned. Applicant
`thinks the interview was most helpful in terms of clarifying the
`scope of claim 4 9 and the content of the references cited in the
`July 20, 2016 Office Action. Applicant attaches as Exhibit A hereto
`the
`to Examiner Riley at
`the Claim Chart provided
`copy of
`a
`beginning of the interview. The remarks which follow were discussed
`with Examiner Riley during the interview.
`
`I. Neither Tsien nor Seela discloses
`multiple features required by claim 49.
`
`As discussed during the October 27, 2016 interview and as shown in
`there are multiple features recited in
`the attached Claim Chart,
`claim 49 which are not disclosed in either Tsien or Seela. Among
`these features are the foll?wing:
`
`A.
`
`B.
`
`chemically
`a
`(Tag)
`attached via
`label
`fluorescent
`a
`the 7-position of a
`linker
`cleavable, chemical
`to
`deazaguanine deoxyribonucleotide analogue;
`
`(Y)
`
`(R) capping the oxygen
`a small, chemically cleavable group
`the 7-
`the deoxyribose of
`3' position of
`the
`at
`resulting
`analogue
`the
`nucleotide
`and
`deazaguanine
`structure OR not being either a methoxy group or an ester
`group; and
`
`Page 2
`
`

`

`Applicant
`
`The Trustees of Columbia University in the City
`of New York
`U.S. Serial No.: 15/167,917
`May 27, 2016
`Filed
`Page 3 of 9 of Communication in Response to July 20, 2016 Office
`Action and Summary of October 27, 2016 Interview with Examiner Riley
`
`C.
`
`7-deazaguanine
`the
`claimed
`of
`ability
`the
`deoxyribonucleotide analogue with features A and B to:
`1. be recognized as a substrate by a DNA polymerase;
`2. be incorporated at the end of a growing DNA strand
`during a polymerase reaction;
`3. produce a 3'-OH group on the deoxyribose upon cleavage
`of R;
`4. no longer include a tag on the base upon cleavage of Y;
`and
`5. be capable of forming hydrogen bonds with cytosine or a
`cytosine nucleotide analogue.
`
`In view of the absence of these features from both Tsien and Seela,
`the 7-
`render obvious
`references can
`these
`no combination of
`deazaguanine deoxyribonucleotide analogue recited in claim 49.
`
`chemically
`a
`(Tag)
`attached via
`label
`fluorescent
`A. A
`the 7-position of a
`to
`(Y)
`linker
`cleavable, chemical
`deazaguanine deoxyribonucleotide analogue.
`
`the
`top of page 3,
`the July 20, 2016 Office Action at the
`In
`Examiner acknowledged that Tsien does not disclose "deazaguanine as
`label
`a base". This is correct. Tsien also does not disclose a
`attached via a cleavable linker to the 7-posi tion of a guanine.
`Tsien discloses attachment of a label to a purine at the "ideal" 8-
`lines 3-4; structure on page 30) Substituting
`position (page 29,
`deazaguanine for guanine would result in a deazaguanine with a label
`attached at the 8-position, not the claimed 7-deazaguanine with a
`label attached at the 7-position via a cleavable linker.
`
`the Examiner asserts on page 3 of the July 20,
`Turning to Seela,
`2016 Office Action that Seela "discloses nucleotides comprising 7-
`deazapurine base having a label attached via a linker. And that said
`nucleotide can be used in nucleic acid sequencing (see col 15-16) ."
`Seela discloses the addition of a label to an
`This is not correct.
`7-deazaguanine
`claimed
`applicant's
`not
`oligonucleotide,
`
`Page 3
`
`

`

`Applicant
`
`The Trustees of Columbia University in the City
`of New York
`U.S. Serial No.: 15/167,917
`May 27, 2016
`Filed
`Page 4 of 9 of Communication in Response to July 20, 2016 Office
`Action and Summary of October 27, 2016 Interview with Examiner Riley
`
`deoxyribonucleotide analogue molecule which includes a label on the
`col 17, line
`7-deazaguanine (see col 15, line 64; col 16 line 65
`a 7-deazaguanine
`Formula VI of Seela does not encompass
`4).
`deoxyribonucleotide analogue having the structure Y-Tag attached at
`in
`Seela' s substituent R1s
`the deazaguanine.
`the 7-position of
`Formula VI is not a Y-Tag structure, and there is no disclosure in
`the 7-position of a 7-
`to
`Seela of such a structure attached
`deazaguanine deoxyribonucleotide analogue.
`
`7-deazaguanine
`discloses
`Seela
`nor
`neither Tsien
`Since
`a
`fluorescent label attached at
`deoxyribonucleotide analogue with a
`let alone attached via a
`the 7-deazaguanine,
`the 7-position of
`chemically cleavable linker, no combination of the disclosures of
`these references can render obvious applicant's claimed compound.
`
`(R) capping the oxygen
`B. A small, chemically cleavable group
`at the 3' position of the deoxyribose of a 7-deazaguanine
`deoxyribonucleotide wherein the resulting structure OR is
`not a methoxy group or an ester group.
`
`At the bottom of page 2 of the July 20, 2016 Office Action the
`compounds
`Examiner stated that "Tsien disclose 3'-blocked DNTP
`that can be
`label and a blocking group
`comprising fluorescent
`different than methoxy or ester (see pages 20-21, 24-25) .u Although
`this statement is correct, Tsien does not disclose the species of
`Tsien does not disclose the
`blocking group recited in claim 4 9.
`requirement that the blocking group be small and in fact discloses
`that it can be large, including, for example, a fluorescent label or
`an enzyme. Moreover, Tsien does not require that the structure OR
`To the contrary, Tsien
`not be a methoxy group or an ester group.
`discloses that such groups may be used, disclosing methoxy on page
`li'ne 15 and esters as preferred blocking groups on page 21,
`21,
`lines 12-14 and 20-24. As discussed during the interview it is the
`inventors' insight and conception that R must be small and OR must
`not be either a methoxy group or an ester group that has resulted in
`the compound
`a compound useful in sequencing by synthesis, namely,
`
`;
`
`Page 4
`
`

`

`Applicant
`
`The Trustees of Columbia University in the City
`of New York
`U.S. Serial No.: 15/167,917
`Filed
`May 27, 2016
`Page 5 of 9 of Communication in Response to July 20, 2016 Office
`Action and Summary of October 27, 2016 Interview with Examiner Riley
`
`As further discussed during the interview,
`recited in claim 49.
`in the subject application small, cleavable
`applicant discloses
`ethers other than methoxy as examples of the OR structure needed to
`successfully accomplish sequencing by synthesis.
`
`Turning to Seela, applicant notes that the R13 of Formula VI may be
`large such as C1s-alkoxy and can be a methoxy group
`( a C1-alkoxy -
`col 15, line 37). There is no disclosure in Seela that the capping
`group be small or that the structure OR not be a methoxy group or an
`ester group.
`
`Importantly, and contrary to the Examiner's assertion in the July
`20, 2016 Office Action that the compounds of Formula VI may be used
`in sequencing, Seel a explicitly states that for sequencing R13 must
`be either H or OH
`(col 16,
`lines 45-46).
`Thus, Seela does not
`disclose a
`chemically cleavable group capping
`the 3'-0 of
`the
`deoxyribose of a 7-deazaguanine deoxyribonucleotide analogue for use
`in sequencing as required by claim 49.
`
`Since neither Tsien nor Seela disclose the species of Rand of OR
`recited in claim 49, no combination of Tsien and Seela can render
`claim 49 obvious.
`
`C. The ability of a 7-deazaguanine deoxyribonucleotide with
`the features discussed in preceding sections A and B to:
`1. be recognized as a substrate by a DNA polymerase;
`2. be incorporated at the end of a growing DNA strand
`during a polymerase reaction;
`3. produce a 3'-0H group on the deoxyribose upon cleavage
`of R;
`4. no longer include a tag on the base upon cleavage of Y;
`and
`5. be capable of forming hydrogen bonds with cytosine or a
`cytosine nucleotide analogue.
`
`As discussed during the interview the provision of a nucleotide
`
`Page 5
`
`

`

`Applicant
`
`The Trustees of Columbia University in the City
`of New York
`15/167,917
`U.S. Serial No. :
`May 27, 2016
`Filed
`Page 6 of 9 of Communication in Response to July 20, 2016 Office
`Action and Summary of October 27, 2016 Interview with Examiner Riley
`
`having the five properties enumerated above is critical to enable
`
`sequencing by synthesis. Neither Tsien nor Seela disclose features
`
`required
`
`by
`
`claim
`
`49
`
`that
`
`result
`
`in
`
`a
`
`7-deazaguanine
`
`deoxyribonucleotide analogue having the five properties recited in
`
`claim 49.
`
`Tsien suggests the goal of sequencing by synthesis but fails to
`
`disclose features required to achieve the goal. Tsien also fails to
`
`disclose a
`
`chemical synthesis
`
`to make
`
`a nucleotide having
`
`the
`
`recited features.
`
`Seela discusses
`
`sequencing only
`
`in
`
`two contexts:
`
`(a) Sanger
`
`sequencing using dideoxyribonucleotides as irreversible terminator
`
`or uncapped deoxyribonucleotides, neither of which are compatible
`
`with
`
`sequencing by synthesis or
`
`(b)
`
`sequencing using
`
`labeled
`
`oligonucleotide probes which are not useful
`
`for sequencing by
`
`synthesis. In contrast, applicant defines essential features of a
`
`nucleotide analogue required to achieve sequencing by synthesis and
`
`provides synthetic schemes to make such nucleotide analogues.
`
`The
`
`lack of relevance of Seela is underscored by the fact that
`
`Formula VI
`
`relates only
`
`to nucleotides produced by
`
`adding
`
`triphosphates to previously known nucleosides (see col 17, lines 15-
`
`22)
`
`No nucleosides having the features of claim 49 are disclosed
`
`in the prior art. Furthermore,
`
`the lack of relevance of Seela is
`
`shown by the inclusion of alkynyl groups as possible R1 5 groups.
`
`Such groups could only be cleaved by harsh conditions which would
`
`damage DNA and destroy the ability of the nucleotide compound to
`
`form hydrogen bonds with a cytosine or cytosine analogue (required
`
`property 5 of claim 49 discussed above).
`
`Solely based on the lack of recited features in either Tsien or
`
`Seela
`
`the Examiner has not made out a prima facie showing of
`
`obviousness. Nevertheless, applicant comments on other shortcomings
`
`of the Examiner's prima facie case of obviousness.
`
`Page 6
`
`

`

`Applicant
`
`The Trustees of Columbia University in the City
`of New York
`U.S. Serial No.: 15/167,917
`Filed
`May 27, 2016
`Page 7 of 9 of Communication in Response to July 20, 2016 Office
`Action and Surmnary of October 27, 2016 Interview with Examiner Riley
`
`II. Lack of Motivation.
`
`On pages 3 and 4 of the July 20, 2016 Office Action the Examiner
`
`asserts that a motivation to combine the references and make the
`
`claimed compound is to avoid "band compression" associated with
`
`Sanger sequencing. However,
`
`the claimed compound is a reversible
`
`terminator, not an irreversible/terminator, and a person skilled in
`
`the art would not have made the claimed compound to address "band
`
`compression", a phenomenon not relevant to sequencing by synthesis
`
`which does not involve the use of gel electrophoresis. Therefore,
`
`the motivation to avoid "band compression" would have led a skilled
`
`person
`
`to make an
`
`irreversible
`
`terminator,
`
`not
`
`the reversible
`
`terminator of claim 49.
`
`A further reason given for combining the references is a quotation
`
`from Seela (col 16-17 bridging paragraph) which concerns adding a
`
`fluorescent label to an oligonucleotide synthesized using nucleotide
`
`analogues of Formula VI. This disclosure of the use of a
`
`labeled
`
`oligonucleotide would not provide a reason to place a fluorescent
`
`label on a 7-deazaguanine deoxyribonucleotide analogue at all, let
`
`alone via a cleavable linker.
`
`Thus,
`
`the reasons given by the Examiner for combining Tsien and
`
`Seela to obtain the invention of claim 49 do not support doing so, a
`
`further flaw in the Examiner's prima facie case of obviousness.
`
`III. Lack of Expectation of Success of Obtaining
`A Compound Having Claimed Properties (i) to (v).
`
`The Examiner asserts simply that combining the cited references in
`
`the manner of
`
`the claims would achieve
`
`the expected benefits,
`
`optimizations and/or expanded applications as this is well known
`
`practice in the art. The question of reasonable expectation of
`
`success needs to be addressed by reference to the claimed invention
`
`Page 7
`
`

`

`Applicant
`
`The Trustees of Columbia University in the City
`of New York
`U.S. Serial No.: 15/167,917
`Filed
`May 27, 2016
`Page 8 of 9 of Communication in Response to July 20, 2016 Office
`Action and Summary of October 27, 2016 Interview with Examiner Riley
`
`including
`
`particularly
`
`the
`
`five
`
`properties
`
`of
`
`the
`
`7-
`
`deazadeoxyribonucleotide analogue recited in claim 49. There is no
`
`evidence that a person skilled in the art would, or could, have had
`
`a reasonable expectation that a compound having the features recited
`
`in claim 49 would have had each of the five properties recited in
`
`claim 49. Thus, once again there is a flaw in the Examiner's prima
`
`facie case of obviousness.
`
`IV. Objective Indicia of Non-Obviousness.
`
`Further support for the non-obviousness of the invention recited in
`
`claim 49
`
`is provided by objective
`
`indicia of non-obviousness
`
`including long felt need, commercial success, praise, and unexpected
`
`results. By way of example,
`
`the 10-year gap between
`
`(1)
`
`the
`
`publication of Tsien suggesting the goal of sequencing by synthesis
`
`and a myriad of possible approaches to achieving this goal and (2)
`
`the filing of the subject application disclosing the first viable
`
`approach to actually performing sequencing by synthesis is clear
`
`evidence of long felt need and non-obviousness.
`
`In summary, the Examiner has not made out a prima facie case of the
`
`obviousness of claim 49 and applicant respectfully requests that the
`
`Examiner reconsider and withdraw this rejection, the sole ground of
`
`rejection raised against claim 49.
`
`If a
`
`telephone
`
`interview would be of assistance
`
`in advancing
`
`prosecution of
`
`the subject application, applicant's undersigned
`
`attorney
`
`invites
`
`the Examiner
`
`to
`
`telephone him at
`
`the number
`
`provided below.
`
`Page 8
`
`

`

`Applicant
`
`The Trustees of Columbia University in the City
`of New York
`U.S. Serial No.: 15/167,917
`Filed
`May 27, 2016
`Page 9 of 9 of Communication in Response to July 20, 2016 Office
`Action and Summary of October 27, 2016 Interview with Examiner Riley
`
`No fee is deemed necessary in connection with the filing of this
`
`Communication. However,
`
`if any fee is required, authorization is
`
`hereby given to charge the amount of any such fee to Deposit Account
`
`No. 03-3125.
`
`Respectfully submitted,
`
`Certificate of Transmission
`hereby
`certify
`that
`this
`I
`correspondence
`is
`being
`transmitted via
`the Electronic
`Filing System
`(EFS)
`to the U.S.
`Patent
`and Trademark Office on
`November 4, 2016.
`
`Registration No. 28,678
`Attorney for Applicant
`Cooper & Dunham LLP
`30 Rockefeller Plaza
`20 th Floor
`New York, New York 10112
`(212) 278-0400
`
`Jon P. White
`~ ,678
`
`Page 9
`
`

`

`October 26, 2016
`
`62239-BZA7 Claim
`A guanine deoxyribonucleotide analogue having the
`structure:
`
`No
`
`Tsien
`
`See/a
`
`No
`
`CLAIM CHART
`
`Does not disclose:
`1) a deazaguanine nucleotide
`2) a 7-deazaguanine nucleotide
`3) a purine labeled at the 7 position
`'4) a 7-deazaguanine labeled at the 7 position
`
`Discloses 7-deazaguanine and 8-deazaguanine
`nucleotide analogues.
`
`Contrary to the Examiner's assertion on page 3 of the
`Office Action, does not disclose a 7-deazaguanine
`nucleotide analogue containing the structure
`
`wherein R
`(a) represents a small, chemically cleavable chemical
`group capping the oxygen at the 3' position of the
`deoxyribose of the deoxyribonucleotide
`
`No
`
`No
`
`Does not mention, let alone require, a small R cap on
`the 3'-0.
`
`Does not require a small R cap on the 3'-0.
`
`Discloses that R can be large, e.g., a fluorophore.
`(P. 26, L. 28-32).
`
`(b) does not interfere with recognition of the analogue I Yes1
`as a substrate by a DNA polymerase
`
`Explicitly disclosed on P. 24, L. 1.
`
`(c) is stable during a DNA polymerase reaction
`
`Yes1
`
`Formula VI (referred to by the Examiner on page 3 of
`the Office Action) discloses large R caps on the 3'-0,
`e.g., C1-C1s-alkoxy. (Col. 15, L. 37).
`
`For sequencing, discloses that there is no 3' -0 cap R,
`stating there is a 3' H or OH (Col. 16, L. 45-46) which is
`in the passage cited by the Examiner.
`No
`
`Does not disclose use of a 3'-0 cap R in sequencing;
`only 3'H or OH. (Col 16, L. 45-46).
`No
`
`Impliedly discloses this feature by disclosing that R
`(the 3' -0 cap) is removed after incorporation of the
`nucleotide analogue. (P. 23, L. 28-32).
`
`Does not disclose use of a 3' -0 cap R in sequencing;
`therefore does not disclose cap R must be stable
`during polymerase reaction.
`
`1 Qualified by fact that reference doesn't disclose a compound
`having other features of the claimed structure or a rationale to
`use or achieve the specific feature in question
`
`Pagel of 4
`Cooper & Dunham LLP
`
`Applicant: The Trustees of Columbia University
`in the City of New York
`U.S. Serial No.: 15/167,917
`Filed: May 27, 2016
`Exhibit A
`
`Page 10
`
`

`

`October 26, 2016
`(d) does not contain a ketone group
`
`No
`
`Discloses an R containing a ketone -NHCOCH3. (P. 21,
`L. 15)2
`
`wherein OR is not a methoxy group
`
`No
`
`Discloses that OR may be methoxy. (P. 21, L. 15).
`
`or an ester group
`
`No
`
`Discloses that esters are among the most common R
`caps on 3'-Os (P. 21, L. 12-14) and that "preferred
`embodiments focus on ester blocking groups",
`suggesting several specific esters. (P. 21, L. 20-24).
`wherein the covalent bond between the 3' -oxygen and Yes1
`R is stable during a DNA polymerase reaction
`
`No
`
`Does not disclose that R should not contain a ketone.
`(However, formula VI does not encompass any R
`containing a ketone.)
`No
`
`In formula VI, R may be methoxy. (Col. 15, L. 37,
`wherein R13 ,of "formula VI" is a C1-alkoxy).
`No
`
`Does not disclose that OR should not be an ester.
`(However, formula VI does not encompass an OR
`which is an ester.)
`
`No
`
`Impliedly discloses this feature by disclosing removal
`of R (the 3'-0 cap) after incorporating the nucleotide
`analogue into a growing strand. (P. 23, L. 28-32).
`
`Does not disclose use of a 3'-0 cap R in sequencing,
`only 3'H or O_H. Therefore, does not disclose R must be
`stable during polymerase reaction.
`
`wherein tag represents a detectable fluorescent
`moiety [as part of structure
`attached to
`the 7-position of a deazaguanine nucleotide analogue] Only discloses attaching fluorescent labels via linkers
`to the 8-position of non-deaza purine bases, referring
`to the 8-position as the "ideal position for attachment
`of a label." (P. 29, L. 3-4).
`
`No
`
`'
`
`No
`
`Does not disclose a label attached via a linker to the 7-
`position of a 7-deazaguanine nucleotide analogue;
`rather discloses a label can be attached to a
`substituent on the 7-position of a deazaguanine after
`incorporation of the nucleotide analogue into an
`oligonucleotide. (Col 16, L. 65 - Col. 17, L. 4).
`
`1 Qualified by fact that reference doesn't disclose a compound
`having other features of the claimed structure or a rationale to
`use or achieve the specific feature in question
`2 Assuming definition of a ketone is a carbonyl group present in a
`compound
`
`Page 2 of 4
`Cooper & Dunham LLP
`
`Page 11
`
`

`

`October 26, 2016
`wherein Y represents a chemically cleavable, chemical No
`linker
`
`which (a) does not interfere with recognition of the
`analogue as a substrate by a DNA polymerase
`
`Yes1
`
`Does not require that a linker Y be a chemically
`cleavable, chemical linker; only discloses that such a
`linker "can be cleavable if desired." (P. 28, L. 22)
`
`No
`
`Does not disclose a chemically cleavable, chemical
`linker at the 7-position of a deazaguanine as part of a
`~ structure.
`No
`
`structure on a 7-
`Does not disclose a
`deazaguanine nucleotide analogue.
`
`No
`
`Does not disclose a~ structure on a 7-
`deazaguanine nucleotide analogue.
`
`No
`
`Discloses only that non-deaza nucleotide analogue
`labeled via a linker will not interfere with the action of
`a polymerase. (P. 28; L. 31-35).
`Yes1
`
`Impliedly discloses that the linker attached to
`non-deaza base be stable during a polymerase
`reaction in that the linker survives a polymerase
`reaction and is removed prior to subsequent
`incorporations. (P. 28, L. 23-25).
`No
`
`and (b) is stable during a DNA polymerase reaction
`
`; and
`
`wherein the [7-deaza]guanine deoxyribonucleotide
`analogue:
`i)
`
`is recognized as a substrate by a DNA
`polymerase,
`
`ii)
`
`is incorporated at the end of a growing
`strand of DNA during a DNA polymerase
`reaction,
`
`Does not disclose a 7-deazaguanine
`deoxyribonucleotide at all {let alone one containing
`the structure ~ ) .
`
`Does not disclose a 7-deazaguanine
`deoxyribonucleotide analogue containing the
`structure [])-[Tog].
`
`Does not disclose that DNA polymerase would
`recognize such an analogue.
`No
`
`Does not disclose that DNA polymerase would
`recognize such an analogue.
`No
`
`Does not disclose a 7-deazaguanine
`deoxyribonucleotide at all (let alone one containing
`the structure ~ ) .
`
`Does not disclose a 7-deazaguanine
`deoxyribonucleotide analogue containing the
`structure [])-[Tog].
`
`Does not disclose incorporating such a nucleotide
`analogue at the end of a growing strand.
`
`Does not disclose incorporation of such a nucleotide
`analogue at the end of a growing strand.
`
`1 Qualified by fact that reference doesn't disclose a compound
`having other features of the claimed structure or a rationale to
`use or achieve the specific feature in question
`
`Page 3 of 4
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`

`

`October 26, 2016
`iii)
`produces a 3' -OH group on the
`deoxyribose upon cleavage of R,
`
`No
`
`No
`
`Does not disclose a 7-deazaguanine
`deoxyribonucleotide at all (let alone one containing
`the structure ~ ) .
`
`Does not disclose a 7-deazaguanine
`deoxyribonucleotide analogue containing the
`structure ~ .
`
`iv)
`
`v)
`
`Does not disclose producing a 3' -OH group on such an
`analogue upon cleavage of R.
`no longer includes a tag on the base upon No
`cleavage of Y, and
`
`- Does not disclose producing a 3' -OH group on such a
`compound upon cleavage of R.
`No
`
`Does not disclose a 7-deazaguanine
`deoxyribonucleotide at all (let alone one containing
`the structure
`
`Does not disclose a 7-deazaguanine
`deoxyribonucleotide analogue containing the
`structure~-
`
`Does not disclose what would happen upon cleavage
`of a linker Y attached to such an analogue
`is capable of forming hydrogen bonds with No
`cytosine or a cytosine nucleotide
`analogue.
`
`Does not disclose a 7-deazaguanine
`deoxyribonucleotide at all (let alone one containing
`the structure ~ ) .
`
`Does not disclose what would happen upon cleavage
`of a linker Y attached to such an analogue.
`No
`
`Does not disclose a 7-deazaguanine
`deoxyribonucleotide analogue containing the
`structure IYJ--CTog].
`
`Does not disclose the ability of such an analogue to
`form hydrogen bonds with cytosine or a cytosine
`analogue.
`
`Does not disclose the ability of such an analogue to
`form such hydrogen bonds with cytosine or a cytosine
`analogue.
`
`1 Qualified by fact that reference doesn't disclose a compound
`having other features of the claimed structure or a rationale to
`use or achieve the specific feature in question
`
`Page 4 of 4
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`
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`