DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claims dated 2/13/2026 are under consideration.
The amendments and arguments presented in the papers filed 2/13/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 8/13/2025 listed below have been reconsidered as indicated.
a) The objection to the drawings are withdrawn in view of the replacement drawings.
b) The amendments to the specification addressing nucleotide sequence disclosure requirements are acknowledged.
c) Any objection or rejections of claims 8-11, 14, 17 and 20 are withdrawn as being moot in view of the cancellation of the claims.
d) The rejections of claims 2-4, 6 and 20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in view of the amendments to the claims.
e) The rejections of: claim(s) 1-7, 9-11 and 15-17 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ortac (WO 2018/112412 A1); claim(s) 1-7, 9-11 and 15-17 under 35 U.S.C. 102(a)(2) as being anticipated by Ortac ‘000 (US 11,486,000 B2); and claim(s) 1-7, 9-11 and 15-17 under 35 U.S.C. 102(a)(2) as being anticipated by Ortac ‘038 (US 2019/0360038 A1), are withdrawn in view of the amendments to claim 1 requiring aspects of claim 18.
f) The rejections of: claims 1-3, 5-7, 9-11 and 15-17 on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,486,000 B2; and claim 4 on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,486,000 B2 in view of Ortac (WO 2018/112412 A1), are withdrawn in view of the amendments to claim 1 requiring aspects of claim 18.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Election/Restrictions
Applicant elected without traverse Group I, claims 1-11 and 14-20, in the reply filed on 7/14/2025.
Claims 21 and 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/14/2025.
The election of dATP-7-deaza-7-propargylamino-BHQ2-Alexa-546 without traverse is acknowledged.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or cited on a submitted IDS, they have not been considered.
Drawings
High resolution copies of the drawings may be accessed via PAIR/Patent Center Retrieval using the Supplemental Content tab.
Specification
The use of terms that are trade names or marks used in commerce, such as Alexa®, BHQ™, Black Hole Quencher™, etc., has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-7, 15-16 and 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ortac (WO 2018/112412 A1; previously cited) in view of Williams (US 2008/0241833 A1; previously cited).
The following new rejections are over the generic scope of the claims.
Regarding claims 1 and 18-19, Ortac teaches providing a “sequencing mixture” comprising:
(i) a polymerase as a “polymerase enzyme”;
(ii) a “template nucleic acid” to be sequenced and a “primer oligonucleotide” complementary to a segment of the template nucleic acid; and
(iii) a “polymerase reagent solution” having the components for carrying out template directed synthesis of a growing nucleic acid strand. See para. 8 and Figure 2A.
Ortac further teaches the “polymerase reagent solution” includes ATP Sulfurylase and APS as a “component for a requenching reaction” and quenched deoxyribonucleotides as a “plurality of types of quenched nucleotide analogs”. See para. 8 and 40; and Figure 2A-2C.
Ortac further teaches each type of quenched nucleotide analog has a labeled leaving group that is cleavable by the polymerase, and each type of quenched nucleotide analog has a different label. Ortac teaches the labeled leaving group is cleaved upon polymerase-dependent binding of a respective nucleotide analog to the template strand. See para. 8.
Ortac further teaches carrying out nucleic acid synthesis such that a plurality of quenched nucleotide analogs are added sequentially to the template whereby:
a) a nucleotide analog as a “quenched nucleotide analog” associates with the polymerase;
b) “the quenched nucleotide analog” is incorporated on the template strand by the polymerase when the labeled leaving group on that nucleotide analog is cleaved by the polymerase, wherein the labeled leaving group generates light as a “signal” upon cleavage; and then
c) the labeled leaving group on the nucleotide analog is “requenched” by the requenching reaction. See para. 9 and Fig. 2B, 2C and 2D.
Ortac further teaches detecting light as a “signal” from the labels while nucleic acid synthesis is occurring, and using the “signal” detected in the time between step b) when the labelled leaving group is cleaved, and step c) in which the labeled leaving group is requenched, to determine a sequence of the template nucleic acid. See para. 9.
See also, Figure 3 and the claims of the Ortac reference.
Regarding claims 2 and 3, Ortac teaches the nucleotide analog has a fluorophore attached to a terminal phosphate (para. 17 and Claim 2).
Regarding claim 4, Ortac teaches exciting the sequencing mixture with only low intensity excitation light, which advantageously reduces photobleaching of the fluorophores and reduces the denaturing of the polymerase enzyme (para. 44 and 58).
Regarding claims 5 and 6, Ortac teaches the cleavable leaving group is a fluorophore labeled pyrophosphate (para. 18; and Fig. 2B).
Regarding claim 7, Ortac teaches there is a unique colored fluorophore for each class of nucleotide analog dNTPs, such that each type of nucleotide analog has a different label (para. 19; and Fig. 2C).
Regarding claim 15, Ortac teaches the polymerase enzyme is a DNA polymerase (para. 24).
Regarding claim 16, Ortac teaches types of nucleotide analogs comprise dATP, dTTP, dGTP, dCTP and dUTP (claim 10).
Ortac does not teach a non-removable quencher molecule permanently attached to the nucleotide analog (amended claim 1) or the additional elements specifically required by claims 18 and 19.
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However, Williams teaches that labeled nucleotides are well-known in the field.
Regarding claims 18-19, Williams teaches the following labeled nucleotides:
Williams teaches the “dye” is tetramethylrhodamine/TMR, Cy3 or Cy5 (p. 5-6, Table I). Willaims teaches the quencher is covalently attached to the base (para. 52 and 54) as encompassed by claims 18-19.
It would have been prima facie obvious to the ordinary artisan at the time of filing that the nucleotide analogs of Williams could be used in the method of Ortac. Ortac teaches generic nucleotide analogs and Williams teaches specific examples with the scope of the genus described by Ortac. Furthermore, Williams teaches covalently attaching the quencher to base results in the quencher remaining at every incorporated base (para. 52). The ordinary artisan would recognize that having the quencher remain incorporated into the synthesized strand results in a “polymerase reagent solution” in which only the fluorophore is diffused within the solution and with the quencher being localized to the complex of the template nucleic acid and extended primer oligonucleotide. Instead of having a homogenous mixture of quencher and fluorophore as taught by Ortac, the modification results in a solution in which only the fluorophore is homogeneously dispersed and having less interaction with and less fluorescent quenching by the quencher, as quenching is related to distance between fluorophore and quencher as taught by Willaims (para. 49). The ordinary artisan would appreciate that the average distance between fluorophores and quenchers in a homogenous mixture of both is less than the average distance between fluorophores and quenchers in a homogenous mixture of fluorophores and sequestered quenchers.
Claim(s) 1-7, 15-16 and 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ortac (WO 2018/112412 A1; previously cited) in view of Williams (US 2008/0241833 A1; previously cited) and Almogy (WO 2018/213787 A1; previously cited).
The rejections are over the elected species of dATP-7-Deaza-7-propargylamino-BHQ2-ALEXA-546.
Regarding claims 1 and 18-19, Ortac teaches providing a “sequencing mixture” comprising:
(i) a polymerase as a “polymerase enzyme”;
(ii) a “template nucleic acid” to be sequenced and a “primer oligonucleotide” complementary to a segment of the template nucleic acid; and
(iii) a “polymerase reagent solution” having the components for carrying out template directed synthesis of a growing nucleic acid strand. See para. 8 and Figure 2A.
Ortac further teaches the “polymerase reagent solution” includes ATP Sulfurylase and APS as a “component for a requenching reaction” and quenched deoxyribonucleotides as a “plurality of types of quenched nucleotide analogs”. See para. 8 and 40; and Figure 2A-2C.
Ortac further teaches each type of quenched nucleotide analog has a labeled leaving group that is cleavable by the polymerase, and each type of quenched nucleotide analog has a different label. Ortac teaches the labeled leaving group is cleaved upon polymerase-dependent binding of a respective nucleotide analog to the template strand. See para. 8.
Ortac further teaches carrying out nucleic acid synthesis such that a plurality of quenched nucleotide analogs are added sequentially to the template whereby:
a) a nucleotide analog as a “quenched nucleotide analog” associates with the polymerase;
b) “the quenched nucleotide analog” is incorporated on the template strand by the polymerase when the labeled leaving group on that nucleotide analog is cleaved by the polymerase, wherein the labeled leaving group generates light as a “signal” upon cleavage; and then
c) the labeled leaving group on the nucleotide analog is “requenched” by the requenching reaction. See para. 9 and Fig. 2B, 2C and 2D.
Ortac further teaches detecting light as a “signal” from the labels while nucleic acid synthesis is occurring, and using the “signal” detected in the time between step b) when the labelled leaving group is cleaved, and step c) in which the labeled leaving group is requenched, to determine a sequence of the template nucleic acid. See para. 9.
See also, Figure 3 and the claims of the Ortac reference.
Regarding claims 2 and 3, Ortac teaches the nucleotide analog has a fluorophore attached to a terminal phosphate (para. 17 and Claim 2).
Regarding claim 4, Ortac teaches exciting the sequencing mixture with only low intensity excitation light, which advantageously reduces photobleaching of the fluorophores and reduces the denaturing of the polymerase enzyme (para. 44 and 58).
Regarding claims 5 and 6, Ortac teaches the cleavable leaving group is a fluorophore labeled pyrophosphate (para. 18; and Fig. 2B).
Regarding claim 7, Ortac teaches there is a unique colored fluorophore for each class of nucleotide analog dNTPs, such that each type of nucleotide analog has a different label (para. 19; and Fig. 2C).
Regarding claim 15, Ortac teaches the polymerase enzyme is a DNA polymerase (para. 24).
Regarding claim 16, Ortac teaches types of nucleotide analogs comprise dATP, dTTP, dGTP, dCTP and dUTP (claim 10).
Williams teaches that labeled nucleotides are well-known in the field.
Regarding claims 18-19, Williams teaches the following labeled nucleotides:
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Williams teaches the “dye” is tetramethylrhodamine/TMR, Cy3 or Cy5 (p. 5-6, Table I). Willaims teaches the quencher is covalently attached to the base (para. 52 and 54) as encompassed by claims 18-19.
It would have been prima facie obvious to the ordinary artisan at the time of filing that the nucleotide analogs of Williams could be used in the method of Ortac. Ortac teaches generic nucleotide analogs and Williams teaches specific examples with the scope of the genus described by Ortac. Furthermore, Williams teaches covalently attaching the quencher to base results in the quencher remaining at every incorporated base (para. 52). The ordinary artisan would recognize that having the quencher remain incorporated into the synthesized strand results in a “polymerase reagent solution” in which only the fluorophore is diffused within the solution and with the quencher being localized to the complex of the template nucleic acid and extended primer oligonucleotide. Instead of having a homogenous mixture of quencher and fluorophore as taught by Ortac, the modification results in a solution in which only the fluorophore is homogeneously dispersed and having less interaction with and less fluorescent quenching by the quencher, as quenching is related to distance between fluorophore and quencher as taught by Willaims (para. 49). The ordinary artisan would appreciate that the average distance between fluorophores and quenchers in a homogenous mixture of both is less than the average distance between fluorophores and quenchers in a homogenous mixture of fluorophores and sequestered quenchers.
Ortac and Williams do not specifically teach the elected species.
Almogy teaches that substrates for making nucleotide analogs are known.
Almogy teaches that DABCYL and BHQ2 are obvious variants of one another (para. 72).
Almogy teaches that Alexa Fluor 546 and Cy3/Cy5 are obvious variants of one another (para. 71).
Almogy further teaches that 7-deaza-7-Propargylamino-2'- deoxyadenosine-5' -Triphosphate is a well-known nucleotide analog that may be used and conjugated with labels/quenchers (para. 73).
Thus, in view of Almogy, the elected species of dATP-7-Deaza-7-propargylamino-BHQ2-ALEXA-546 is an obvious variant of that taught by Williams. The elected species may be arrived upon based on design choices.
Examiner’s response to the traversal of the 103 rejections
The Remarks argue applicant’s invention distinguishes over the combination of Ortac and Williams, by requiring a method for sequencing a nucleic acid template comprising in part: the quenched nucleotide analogs comprise a non-removable quencher molecule permanently attached to the nucleotide analog, wherein the component for the requenching reaction is selected from a quencher molecule permanently attached to APS and an ATP sulfurylase enzyme; a quencher molecule permanently attached to AMP and a PPDK enzyme; or a quencher molecule permanently attached to ADP-G and an AGPase enzyme; and the non-removable quencher molecule remains with the incorporated dNMP after cleavage of the labeled leaving group (p. 11-12).
It is the Examiner’s position as described in the above rejections that the combination of Ortac and Williams teaches all the required elements of the generic amended claims.
The Remarks ague the Examiner concedes Ortac does not teach the elements of claim 8, 14 and 18-20 and further argues that Ortac does not disclose or suggest that the quenched nucleotide analogs comprise a non-removable quencher molecule permanently attached to the nucleotide analog, wherein the component for the requenching reaction is selected from a quencher molecule permanently attached to APS and an ATP sulfurylase enzyme; a quencher molecule permanently attached to AMP and a PPDK enzyme; or a quencher molecule permanently attached to ADP-G and an AGPase enzyme; nor wherein the non-removable quencher molecule remains with the incorporated dNMP after cleavage of the labeled leaving group, as required by Applicant's claims as amended (p. 12).
The arguments have been fully considered but are not persuasive. Ortac does teach APS with a covalently attached quencher molecule (paara. 37) that is used with an ATP sulfurylase enzyme in requenching steps. While Ortac does not teach a non-removable quencher molecule permanently attached to the nucleotide analog, this element is taught by Williams as described above.
The Remarks argue Williams does not teach any information regarding requenching, nor a reason or need for a permanently attaching a quencher molecule to APS for use with the ATP sulfurylase enzyme; a quencher molecule to AMP for use with the PPDK enzyme; or a quencher molecule to ADP-G for use with the AGPase enzyme, as required in the claimed "component for a requenching reaction." (p. 12).
The arguments have been fully considered but are not persuasive. While Williams may not teach the above elements, those elements are clearly taught by Ortac.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The elements argued to be missing in one of the reference by the Remarks are clearly taught in the other reference.
The Remarks argue there is no reason nor motivation to combine Ortac with Williams because combining these references would require modifying Ortac's fundamental requenching mechanism in a manner not suggested by Ortac or Williams (p. 12).
The arguments have been fully considered but are not persuasive. It is unclear how the requenching mechanism of Ortac would have to be modified and the arguments to do provide any explanation of why. The requenching process of Ortac is based on using ATP Sulfurylase and APS permantently quenched, to quench fluorescent released pyrophosphate. By incorporating the quenched nucleotides of Williams a fluorescent pyrophosphate would still be released, detected and then quenched by a reaction mediated by an ATP sulfurylase enzyme and APS with a covalently attached quencher molecule.
The Remarks rely on the above arguments also in the context of the rejections of the elected species over Ortac, Williams and Almogy (p. 13-14). The Remarks further argue Almogy does not remedy the alleged deficiency of Ortac and Williams (p. 14).
The arguments have been fully considered but are not persuasive. It is the Examiner’s position that the combination is not deficient for the reasons provided above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7, 15-16 and 18-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,486,000 B2 in view of Williams (US 2008/0241833 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the present application and claims 1, 7 and 8 of the ‘000 patent are nearly identical. The only difference is the present claim 1 requires “a primer oligonucleotide complementary to a segment of the template nucleic acid” and a nucleotide with a permanently attached quencher. However, including a “sequencing primer” in a sequencing-by-synthesis (the basis of the ‘000 patent method”) is well-known in order to prime base incorporation to determine the sequence of the template.
Claim 2 of the ‘000 is encompassed by present claims 2-3.
Claim 3 of the ‘000 is encompassed by present claim 5.
Claim 4 of the ‘000 is encompassed by present claim 6.
Claim 5 of the ‘000 is encompassed by present claim 7.
Claim 9 of the ‘000 is encompassed by present claim 15.
Claim 10 of the ‘000 is encompassed by present claim 16.
Williams teaches that labeled nucleotides are well-known in the field.
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Regarding claims 8, and 18-20, Williams teaches the following labeled nucleotides:
Williams teaches the “dye” is tetramethylrhodamine/TMR, Cy3 or Cy5 (p. 5-6, Table I), as encompassed by claim 8. Willaims teaches the quencher is covalently attached to the base (para. 52 and 54) as encompassed by claims 18-19.
It would have been prima facie obvious to the ordinary artisan at the time of filing that the nucleotide analogs of Williams could be used in the method of the ‘000 claims. The ‘000 claims require generic nucleotide analogs and Williams teaches specific examples with the scope of the genus described by ‘000 claims.
Regarding claim 14, it would have been prima facie obvious to have used the same quencher on the APS using the ATP sulfurylase enzyme as used on the nucleotide analog. Thus, it would have been prima facie obvious to have used DABCYL as quencher on APS.
Claim 4 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,486,000 B2 in view of Williams (US 2008/0241833 A1) and Ortac (WO 2018/112412 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 4 of the present application and claims of the ‘000 patent are nearly identical. The only difference the ‘000 method claims do not require the elements specific to claim 4.
However, regarding claim 4, Ortac teaches a sequencing mixture used requires only low intensity excitation light, which advantageously reduces photobleaching of the fluorophores and reduces the denaturing of the polymerase enzyme (para. 44 and 58).
It would have been prima facie obvious to the ordinary artisan that the light source of Ortac may be used to excite the label such that is emits a signal in the context of the ‘000 claims.
Examiner’s response to the traversal of the double patenting rejections
The Remarks argue the Examiner’s acknowledges the ‘000 method claims do not require the elements specific to dependent claims 8, 14 and 18-20 and further argue the '000 method claims 1-13 do not disclose or suggest that the quenched nucleotide analogs comprise a non-removable quencher molecule permanently attached to the nucleotide analog, wherein the component for the requenching reaction is selected from a quencher molecule permanently attached to APS and an ATP sulfurylase enzyme; a quencher molecule permanently attached to AMP and a PPDK enzyme; or a quencher molecule permanently attached to ADP-G and an AGPase enzyme; nor wherein the non-removable quencher molecule remains with the incorporated dNMP after cleavage of the labeled leaving group, as required by Applicant's claims as amended. Contrary to Applicant's claimed invention, the '000 method claims 1-13 explicitly discloses "wherein a removable quencher molecule is attached to the nucleotide analog through electrostatic interaction or hydrogen bonding." See p. 15-17.
The arguments have been fully considered but are not persuasive. The elements lacking from the ‘000 method are taught by Williams and any elements lacking from Williams are required by the ‘000 method claims.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682