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 .
Claims 126-145 are pending and are being examined on the merits.
Information Disclosure Statement
The Information Disclosure Statement submitted June 18, 2023 has been considered.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference sign(s) mentioned in the description: Para. 86 recites reference nos. 901, 902 and 903, however these reference nos. do not appear in the Fig. 9 drawing.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. Specifically, the instant claims are not directed to methods for nucleic acid sequencing.
The disclosure is objected to because of the following informalities: Para. 1 of the specification should be updated to indicate that the parent application, US Serial No. 16/525,826, has issued into US Patent No. 11,649,493.
Appropriate correction is required.
The use of the terms for various reporter and quencher molecules, which are trade names or marks used in commerce, 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.
Specifically, the trademarks appear as follows in the specification, at least, at paras. 50-51, 54: Cy[X], BHQ-[X], Alexa Fluor [X], QSY [X], ATTO [X], YOYO-1, SYBR Green, EvaGreen.
Claim Objections
Claims 126, 130, 134 and 139-145 are objected to because of the following informalities:
In claim 126, the phrase “nucleotides analogs” in l. 2 should be “nucleotide analogs”.
The same informality appears in claim 130 (l. 2) and claim 141 (l. 6), and each instance should be corrected accordingly.
In claim 134, the phrase “double stranded” in l. 1 should be hyphenated. The same informality appears in claim 139 (l. 2) and it should be corrected accordingly.
In claim 139, the phrase “single stranded” in l. 2 should be hyphenated. The same informality appears in claim 140 (l. 2) and it should be corrected accordingly.
Claims 142-145 are objected to for incorporating the informality of claim 141.
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 126-140 and 144 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 126 recites the limitation “all other nucleotides or nucleotide analogs in said
mixture”, the meaning of which is unclear. Specifically, claim 126 recites a reaction space comprising a plurality of nucleic acid molecules and a mixture of nucleotides or nucleotide analogs. It is not clear if the “all other nucleotides” refers to only the nucleotides or nucleotide analogs that are in solution in the reaction mixture, or if it additionally requires the nucleotides or nucleotide analogs comprised within the plurality of nucleic acid molecules. Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite. Claims 130 and 144 recite the same limitation, each instance of which is rejected with corresponding reasoning.
Claims 127-129 depend from claim 126, and consequently incorporate the indefiniteness issues of claim 126.
Claims 131-140 depend directly or indirectly from claim 130, and consequently incorporate the indefiniteness issues of claim 130.
Claim 139, which incorporates the limitations of claim 134, recites the limitations “said
reaction space is replenished with an additional plurality of nucleic acid molecules … [and] by denaturation of said double-stranded nucleic acid molecules and removal of resultant single-stranded nucleic acid molecules”, the meaning of which is unclear. Specifically, it is unclear if these limitations are intended to be two separate replenishing steps, or if they are intended to be a single step. If it is the former, the sequence of the two steps is unclear. If it is the latter, it is not clear how both actions (addition and denaturation/removal) can occur at the same time. Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is unclear.
Claim 140 depends from claim 139, and consequently incorporates the indefiniteness issues of claim 139.
Prior Art and Allowable Subject Matter
Claims 126-145 are free of the art.
The closest prior art is Stromberg1 (US 2018/0305749 A1, filed March 15, 2018), Bebenek (The effects of dNTP pool imbalances on frameshift fidelity during DNA replication, J Biol Chem, 267(6): 3589-3596, 1992), and Cadwell (Randomization of Genes by PCR Mutagenesis, PCR Methods Appl, 2(1): 28-33, 1992).
Stromberg is directed to contacting a primed nucleic acid sequence with a series of mixtures of nucleotides and then monitoring incorporation of the nucleotides to determine the nucleic acid sequence. Regarding independent claim 126, Stromberg teaches using mixtures of different types of nucleotides, but does not teach or suggest selecting a subset of nucleotides and incorporating nucleotides into the nucleic acid molecule that do not correspond to the subset in such a way as to increase the percentage of the subset nucleotides relative to the non-subset nucleotides in the mixture, nor does it teach or suggest incorporating nucleotides into a nucleic acid molecule in the absence of sequencing the nucleic acid molecule.
Regarding independent claim 130, Stromberg also does not teach or suggest selecting a subset of nucleotides and incorporating nucleotides into the nucleic acid molecule that correspond to the subset in such a way as to decrease the percentage of the subset nucleotides relative to the non-subset nucleotides in the mixture, nor does it teach or suggest incorporating nucleotides into a nucleic acid molecule in the absence of sequencing the nucleic acid molecule.
Regarding independent claim 141, Stromberg also does not teach or suggest selecting a subset of nucleotides and incorporating nucleotides into the nucleic acid molecule that correspond to the subset, thereby generating a remainder of nucleotides, where the remainder of nucleotides are used to perform nucleic acid synthesis, nor does it teach or suggest incorporating nucleotides into a nucleic acid molecule in the absence of sequencing the nucleic acid molecule.
Bebenek is directed to examining nucleotide pool bias effects on frameshift fidelity during DNA synthesis. Bebenek teaches applying mixtures of different types and amounts of nucleotides to nucleic acid molecules, and teaches doing so in a context that does not involve sequencing the nucleic acid molecule. Specifically, instead of sequencing, Bebenek is using a frameshift fidelity assay to determine nucleotide incorporation into the target nucleic acid molecule. However, Bebenek does not remedy the other deficiencies of Stromberg, discussed above.
Cadwell is directed to PCR mutagenesis of genes using nucleotide pools with various proportions of nucleotides. Cadwell teaches applying mixtures of different types and proportions of nucleotides to nucleic acid molecules to induce mutagenesis, and then detects the mutated nucleic acid with sequencing. However, Cadwell does not remedy the deficiencies of Stromberg, discussed above.
Claims 141-143 and 145 are objected to, but are otherwise directed to allowable subject matter.
Conclusion
Claims 126-145 are being examined. Claims 126-140 and 144 are rejected. Claims 126, 130, 134, 139-140 and 144 are objected to. Claims 141-143 and 145 are objected to, but are otherwise directed to allowable subject matter. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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/CAROLYN L GREENE/Examiner, Art Unit 1681
1 Stromberg was cited in the Information Disclosure Statement filed June 18, 2023.