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 .
Election/Restrictions
Restriction to one of the following inventions is required under 35 U.S.C. 121:
I. Claims 1-10 and 17-20, drawn to a nucleic acid sequencing method, classified in C12Q1/6869.
II. Claims 11-16, drawn to a nucleic acid sequencing apparatus, classified in G01N27/3278.
The inventions are independent or distinct, each from the other because:
Inventions I and II are related as process and apparatus for its practice. The inventions are distinct if it can be shown that either: (1) the process as claimed can be practiced by another and materially different apparatus or by hand, or (2) the apparatus as claimed can be used to practice another and materially different process. (MPEP § 806.05(e)). In this case, the apparatus as claimed can be used to practice another materially different process such as sequencing a template nucleic acid without binding complementary nucleotides.
Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because one or more of the following reasons apply:
The inventions require a different field of search (searching for different classes/subclasses or electronic resources, or employing different search strategies or search queries). Group I would require a search in at least CPC C12Q1/6869, along with a unique text search. Group II would not be searched as above and would require a search in at least CPC G01N27/3278, along with a unique text search.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
During a telephone conversation with Juliet Kavanaugh on March 19, 2026 a provisional election was made without traverse to prosecute the invention of Group I, claims 1-10 and 17-20. Affirmation of this election must be made by applicant in replying to this Office action. Claims 11-16 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 16/169,756, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, the instant limitations “the polymerase attached to the two electrodes by two linkers” (claims 1 and 18), “the linkers are peptide linkers” (claim 2), “binding the linkers to self assembled monolayers” (claim 6), and “said nucleotide is unlabeled” (claim 10) do not have support in the disclosure of the prior-filed application. The prior-filed application discloses that the polymerase may be disposed on a surface of at least one of an at least two electrodes (para. [0015] of the US PGPub of the prior-filed application), but there is no support for attachment of the polymerase to the two electrodes by two linkers. The prior-filed application discloses that the linker may comprise an amino acid polymer (para. [0268] of the US PGPub of the prior-filed application), which is a polypeptide, but there is no support for the linker being a peptide. The prior-filed application discloses that self assembled monolayers utilize a linker bound to a 3′ end of a hybridization oligo and may be bound to one electrode of an electrode pair, while a linker which may be bound to a 5′ end of a hybridization oligo may be bound to another electrode of an electrode pair (para. [0173]-[0174] of the US PGPub of the prior-filed application), but there is no support for the same linkers from instant claim 1 binding to self assembled monolayers on the two electrodes while also binding polymerase. The prior-filed application discloses that some nucleobases may be unlabeled (para. [0223], [0232], [0235], [0260] of the US PGPub of the prior-filed application), but there is no support for the unlabeled nucleotides binding to a complementary base being interrogated as required by instant claim 1. Accordingly, claims 1-10 and 17-20 are not entitled to the benefit of the prior application.
This application repeats a substantial portion of prior Application No. 16/169,756, filed October 24, 2018, and adds disclosure not presented in the prior application. Because this application names the inventor or at least one joint inventor named in the prior application, it may constitute a continuation-in-part of the prior application. Should applicant desire to claim the benefit of the filing date of the prior application, attention is directed to 35 U.S.C. 120, 37 CFR 1.78, and MPEP § 211 et seq. The presentation of a benefit claim may result in an additional fee under 37 CFR 1.17(w)(1) or (2) being required, if the earliest filing date for which benefit is claimed under 35 U.S.C. 120, 121, 365(c), or 386(c) and 1.78(d) in the application is more than six years before the actual filing date of the application.
Information Disclosure Statement
The information disclosure statements filed January 17, 2025 fail to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 1 is objected to because of the following informalities: in line 6, “during binding” should read “during the binding”. Appropriate correction is required.
Claim 2 is objected to because of the following informalities: in line 1, “the linkers” should read “the two linkers”. Appropriate correction is required.
Claim 3 is objected to because of the following informalities:
In line 3, “said gap” should read “said non-conductive gap”.
In line 3, “said electrodes” should read “said two electrodes”.
Appropriate correction is required.
Claim 4 is objected to because of the following informalities: in line 1, “the gap” should read “the non-conductive gap”. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: in line 2, “the linkers” should read “the two linkers”. Appropriate correction is required.
Claim 17 is objected to because of the following informalities: in line 6, “during binding” should read “during the binding”. Appropriate correction is required.
Claim 18 is objected to because of the following informalities: in line 1, “the linkers” should read “the two linkers”. Appropriate correction is required.
Claim 19 is objected to because of the following informalities:
In line 2, “said gap” should read “said non-conductive gap”.
In line 3, “said electrodes” should read “said two electrodes”.
Appropriate correction is required.
Claim 20 is objected to because of the following informalities: in line 4, “a 10 nm” should read “10 nm”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10 and 17-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation “identifying a nucleotide” in line 7 of the claim. It is unclear whether “a nucleotide” in line 7 refers to the previously recited “a base being interrogated of a sample nucleic acid” in line 3 of the claim. For the purpose of examination, Examiner interprets them to be the same. Claims 2-10 are rejected as dependent thereon.
Claim 1 recites the limitation “the complementary base” in line 7 of the claim. It is unclear whether “the complementary base” in line 7 refers to the previously recited “a nucleotide complementary” in lines 2-3 of the claim. For the purpose of examination, Examiner interprets them to be the same. Claims 2-10 are rejected as dependent thereon.
Claim 4 recites the limitation "the width" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 recites the limitation "the size" in line 3 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 17 recites the limitation “at least one of tunneling current and hopping current” in line 5 of the claim. It is unclear whether this limitation means: (a) at least one of a tunneling current or a hopping current, or (b) at least one tunneling current and at least one hopping current. For the purpose of examination, Examiner interprets the limitation to mean at least one of a tunneling current or a hopping current. Claims 18-20 are rejected as dependent thereon.
Claim 17 recites the limitation “a matching nucleobase on a single stranded portion of the sample nucleic acid” in lines 8-9 of the claim. It is unclear whether “a matching nucleobase” in line 8 refers to the previously recited “an interrogated base of a sample nucleic acid” in line 3 of the claim. For the purpose of examination, Examiner interprets them to be the same. Claims 18-20 are rejected as dependent thereon.
Claim 17 recites the limitation “electron current measurement” in line 9 of the claim. It is unclear whether this limitation refers to the previously recited “at least one of tunneling current and hopping current” in line 5 of the claim. For the purpose of examination, Examiner interprets them to be the same. Claims 18-20 are rejected as dependent thereon.
Claim 19 recites the limitation "the non-conductive gap" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the non-conductive gap" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation “said non-conductive gap may be etched to a depth of a 10 nm or less” in lines 3-4 of the claim (emphasis added by Examiner). It is unclear whether or not this limitation is required because it recites “may be”.
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.
Claims 1-7, 10, and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (US 2018/0180567 A1) in view of Nishida et al. (US 2015/0050644 A1).
Regarding claim 1, Li teaches a nucleic acid sequencing method (a method for analysis of the sequence of a nucleic acid molecule, Li, para. [0078]-[0079], [0111]), comprising:
using a polymerase attached to two electrodes on a substrate to bind a nucleotide complementary to a base being interrogated of a sample nucleic acid (immobilizing a polymerase on each guiding electrode 501 of a microwell electrode 100, wherein the microwell electrode 100 comprises a first electrode 301, a second electrode 303 arranged opposite to the first electrode 301, and the guiding electrodes 501 on a substrate 101, Li, Figs. 1A-1B, para. [0033], [0081], [0103]-[0104], [0178]-[0180]; hybridizing the nucleic acid molecule to be tested with a primer to form a complex, and in the presence of the polymerase, incorporating one of the molecules into the primer to form an extension product complementary to the nucleic acid molecule to be tested, Li, para. [0082]-[0083], [0097]-[0098]).
Li teaches that methods for immobilizing polymerase are well known in the art (Li, para. [0107]). Li teaches that a linking molecule or molecule-binding region may be provided between the insulated layer and the polymerase (Li, para. [0109]). Li fails to teach wherein the polymerase is attached to the two electrodes by two linkers.
Nishida teaches a method for performing DNA sequencing with polymerase (Nishida, abstract). Nishida teaches that the polymerase is immobilized on the electrically conductive support by a peptide tag having binding affinity (Nishida, para. [0058], [0122], [0127]). Nishida teaches that the electrically conductive support is an electrode (Nishida, para. [0042]). Nishida teaches that on the electrode 401, a self-assembled monolayer 402 of a compound containing a boronic acid group is immobilized by a thiol, and a polymerase 404 can be immobilized on the electrode 401 through binding between a peptide tag 403 and the compound containing the boronic acid group 402 (Nishida, Fig. 4, para. [0092], [0097], [0100], [0138]).
It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the immobilization of the polymerase of Li to be immobilized on the two guiding electrodes by two peptide linkers bound to self-assembled monolayers bound by thiol on the electrodes as taught by Nishida in order to yield the predictable result of immobilizing polymerase on the electrodes for DNA sequencing. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP § 2143(I)(A).
Modified Li teaches measuring a tunneling current between the two electrodes caused by a conformational change of the polymerase during binding of the nucleotide (detecting a tunneling current between the guiding electrodes 501 when the polymerase acts as a catalyst to form an extension product complementary to the nucleic acid molecule to be tested, Li, Figs. 1A-1B, para. [0065], [0071], [0083]-[0084], [0088]); and
identifying a nucleotide from the binding of the complementary base to the base being interrogated, as a function of the tunneling current measurement (identifying the type of the nucleotide to be tested by using the tunneling current detected between the guiding electrodes 501, and determining the base at the corresponding position of the nucleic acid molecule to be tested according to the principle of complementary base pairing, Li, Figs. 1A-1B, para. [0064]-[0067], [0085], [0087]-[0088]).
Regarding claim 2, Modified Li teaches wherein the linkers are peptide linkers (peptide linkers, Nishida, [0058], [0122], [0127], [0138], see modification supra).
Regarding claim 3, Modified Li teaches wherein prior to using the polymerase, the method further comprises disposing the polymerase in a non-conductive gap (the polymerase is disposed in a chamber or channel of the microwell electrode 100 which is formed on an insulating layer 102, Li, Figs. 1A-1B, para. [0081], [0103]-[0104], [0185]), wherein said gap is etched down between said electrodes to a depth of 10 nm or more (the channel 601 has a depth of 0-10 µm, Li, para. [0022], [0217]). Generally, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Regarding claim 4, Modified Li teaches wherein the gap has a wider portion that is greater than the width of the polymerase and a smaller portion which is smaller than the size of the polymerase (the inlet port of the channel 601 may be designed in a funnel shape to hold the polymerase, Li, Figs. 1A-1B, para. [0103], since the funnel shape holds the polymerase, Examiner interprets the funnel shape to have a wider portion that is greater than the width of the polymerase and a smaller portion which is smaller than the size of the polymerase in order to hold the polymerase).
Regarding claim 5, Modified Li teaches wherein prior to using the polymerase, the method further comprises disposing the polymerase over a non-conductive gap (the polymerase is disposed in a chamber or channel of the microwell electrode 100 which is formed on an insulating layer 102, Li, Figs. 1A-1B, para. [0081], [0103]-[0104], [0185]), wherein said non-conductive gap is smaller than a size of the polymerase (the inlet port of the channel 601 may be designed in a funnel shape to hold the polymerase, Li, Figs. 1A-1B, para. [0103], since the funnel shape holds the polymerase, Examiner interprets the funnel shape to have a smaller portion which is smaller than the size of the polymerase in order to hold the polymerase) and wherein said non-conductive gap is etched to a depth of 10 nm or less (the channel 601 has a depth of 0-10 µm, Li, para. [0022], [0217]). Generally, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Regarding claim 6, Modified Li teaches wherein prior to using the polymerase, the method further comprises respectively binding the linkers to self assembled monolayers on the two electrodes (the peptide linkers are bound to self-assembled monolayers on the electrodes in order to immobilize the polymerase, Nishida, Fig. 4, para. [0097], [0100], [0138], see modification supra).
Regarding claim 7, Modified Li teaches wherein each of the self assembled monolayers is bound by a thiol to a respective one of the two electrodes (the self-assembled monolayers are bound by a thiol on the electrodes, Nishida, Fig. 4, para. [0092], [0097], [0100], [0138], see modification supra).
Regarding claim 10, Modified Li teaches wherein said nucleotide is unlabeled (the nucleotide is not modified by a label, Li, para. [0067], [0097]).
Regarding claim 17, Li teaches a nucleic acid sequencing method (a method for analysis of the sequence of a nucleic acid molecule, Li, para. [0078]-[0079], [0111]), comprising:
using a polymerase attached to two electrodes on a substrate to bind a nucleobase complementary to an interrogated base of a sample nucleic acid (immobilizing a polymerase on each guiding electrode 501 of a microwell electrode 100, wherein the microwell electrode 100 comprises a first electrode 301, a second electrode 303 arranged opposite to the first electrode 301, and the guiding electrodes 501 on a substrate 101, Li, Figs. 1A-1B, para. [0033], [0081], [0103]-[0104], [0178]-[0180]; hybridizing the nucleic acid molecule to be tested with a primer to form a complex, and in the presence of the polymerase, incorporating one of the molecules into the primer to form an extension product complementary to the nucleic acid molecule to be tested, Li, para. [0082]-[0083], [0097]-[0098]).
Li teaches that methods for immobilizing polymerase are well known in the art (Li, para. [0107]). Li teaches that a linking molecule or molecule-binding region may be provided between the insulated layer and the polymerase (Li, para. [0109]). Li fails to teach wherein the polymerase is attached to the two electrodes by two linkers.
Nishida teaches a method for performing DNA sequencing with polymerase (Nishida, abstract). Nishida teaches that the polymerase is immobilized on the electrically conductive support by a polypeptide tag having binding affinity (Nishida, para. [0058], [0122], [0127]). Nishida teaches that the electrically conductive support is an electrode (Nishida, para. [0042]). Nishida teaches that on the electrode 401, a self-assembled monolayer 402 of a compound containing a boronic acid group is immobilized by a thiol, and a polymerase 404 can be immobilized on the electrode 401 through binding between a polypeptide tag 403 and the compound containing the boronic acid group 402 (Nishida, Fig. 4, para. [0092], [0097], [0100], [0127], [0138]).
It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the immobilization of the polymerase of Li to be immobilized on the two guiding electrodes by two polypeptide linkers bound to self-assembled monolayers bound by thiol on the electrodes as taught by Nishida in order to yield the predictable result of immobilizing polymerase on the electrodes for DNA sequencing. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP § 2143(I)(A).
Modified Li teaches measuring at least one of tunneling current and hopping current between the two electrodes caused by a conformational change of the polymerase during binding of the nucleobase (detecting a tunneling current between the guiding electrodes 501 when the polymerase acts as a catalyst to form an extension product complementary to the nucleic acid molecule to be tested, Li, Figs. 1A-1B, para. [0065], [0071], [0083]-[0084], [0088]); and
identifying a matching nucleobase on a single stranded portion of the sample nucleic acid based on electron current measurement (identifying the type of the nucleotide to be tested by using the tunneling current detected between the guiding electrodes 501, and determining the base at the corresponding position of the single-stranded nucleic acid molecule to be tested according to the principle of complementary base pairing, Li, Figs. 1A-1B, para. [0064]-[0067], [0085], [0087]-[0088], [0105]).
Regarding claim 18, Modified Li teaches wherein the linkers are polypeptide linkers (polypeptide linkers, Nishida, [0058], [0122], [0127], [0138], see modification supra).
Regarding claim 19, Modified Li teaches the polymerase to be disposed in the non-conductive gap (the polymerase is disposed in a chamber or channel of the microwell electrode 100 which is formed on an insulating layer 102, Li, Figs. 1A-1B, para. [0081], [0103]-[0104], [0185]), wherein said gap is etched down between said electrodes to a depth of 10 nm or more (the channel 601 has a depth of 0-10 µm, Li, para. [0022], [0217]). Generally, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Regarding claim 20, Modified Li teaches that non-conductive gap is smaller than a size of the polymerase and configured for the polymerase to be disposed over the non-conductive gap (a chamber or channel of the microwell electrode 100 which is formed on an insulating layer 102, Li, Figs. 1A-1B, para. [0081], [0103]-[0104], [0185]; the inlet port of the channel 601 may be designed in a funnel shape to hold the polymerase, Li, Figs. 1A-1B, para. [0103], since the funnel shape holds the polymerase, Examiner interprets the funnel shape to have a smaller portion which is smaller than the size of the polymerase in order to hold the polymerase), wherein said non-conductive gap may be etched to a depth of 10 nm or less (the channel 601 has a depth of 0-10 µm, Li, para. [0022], [0217]). Generally, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Nishida as applied to claim 1 above, and further in view of He et al. (US 2011/0312529 A1).
Regarding claim 8, Modified Li teaches said nucleotide (the primer comprising the complementary nucleotides having a 3’ end, Li, para. [0116], [0124]). Modified Li fails to teach wherein said nucleotide further comprises a terminator, of instant claim 8, and wherein said terminator is bound to the 3’ of the ribose, of instant claim 9.
He teaches a method of determining a sequence of nucleotides for a nucleic acid template using polymerase and at least four different nucleotide species (He, abstract). He teaches that at least one of the nucleotide species has a reversible terminator moiety at the 3' position of the ribose moiety (He, para. [0072], [0107], [0122]-[0124]). He teaches that the incorporation of the nucleotide species having the reversible terminator can be distinguished from the other nucleotide species based on the termination in extension that occurs for the nucleic acid, which helps determine the sequence of nucleotides for the nucleic acid sample (He, para. [0122]-[0123]).
It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the primer comprising the nucleotides of Modified Li to have a reversible terminator moiety at the 3' position of the ribose as taught by He because the incorporation of the nucleotide species having the reversible terminator can be distinguished from the other nucleotide species based on the termination in extension that occurs for the nucleic acid, which helps determine the sequence of nucleotides for the nucleic acid sample (He, para. [0122]-[0123]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VIVIAN A TRAN whose telephone number is (571)272-3232. The examiner can normally be reached Mon - Fri 9am-5pm.
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/V.T./ Examiner, Art Unit 1794
/JAMES LIN/ Supervisory Patent Examiner, Art Unit 1794
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