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 .
Priority
This application 18/252,524filed on 05/10/2023 is a 371 national phase of PCT/GB2021/053036 filed on 11/24/2021, and claims the benefit of GB Patent Application No. 2018476.8, filed on 11/24/2020.
The priority date of claims 1 and 8 and their dependent claims is determined to be 11/24/2020, the filing date of GB Patent Application No. 2018476.8.
Status of Claims
Applicant’s amendments to claims filed 02/27/2026 in response to the Non-Final Rejection mailed 12/01/2025 are acknowledged.
Claims 2-5 and 19 are amended.
Claims 1-25 are pending and under examination.
Response to Remarks filed 02/27/2026
The amendments and arguments presented in the papers filed 02/27/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 12/01/2025 listed below have been reconsidered as indicated.
a) The objections to the specification regarding the use of trade names or marks are withdrawn in view of the amendments to the specification.
b) The objection to claim 19 for informalities has been withdrawn in view of the amendments to the claim.
c) The 35 USC 112(b) indefiniteness rejections of claims 3 and 19-25 have been withdrawn in view of the amendments to the claims.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Claim Interpretation
Claim 3 recites the limitation “using a blunt/non-cohesive end-generating endonuclease prevents the need for end-repair of the fragmented nucleic acid molecules”. The claims do not require any specific structural features to accomplish “prevent[ing] the need for end-repair of the fragmented nucleic acid molecules” and it is interpreted as any method that uses a blunt/non-cohesive end-generating endonuclease meets the limitation.
Claim 10 recites the limitation “wherein introducing dideoxy nucleotides at internal nick sites in step (ii) prevents extension of the internal nick and results in an unamplifiable nucleic acid strand”. The claims do not require any specific structural features to accomplish “prevent[ing] extension of the internal nick and result[ing] in an unamplifiable nucleic acid strand” and it is interpreted as any method that introduces dideoxy nucleotides at internal nick sites meets the limitation.
Claim Rejections - 35 USC § 112(b) - updated
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.
Claim 24 remains/is 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.
This maintained rejection has been modified to address claim amendments filed on 02/27/2026.
Regarding claim 24, it is not clear how the recited preamble is intended to breathe life and meaning into the claim. The preamble of the claim recites “A method of diagnosing disease in a human or animal subject”. However, the method steps in the claim only require “detecting the presence and/or identity of a mutation in a single DNA molecule according to the method of claim 19” and “using the presence and/or identity of the mutation as an indicator of disease in the human or animal subject.”. Claims 17 and 19 recite limitations directed to detecting mutations. Thus, it is unclear if applicant intends to cover any method of the active method steps of claims 17 and 19, or if the method is intended to somehow require more to accomplish the goal set forth in the preamble. If it is the later, then it appears that the claims are incomplete, as they fail to provide any active steps that clearly accomplish the goal of diagnosing disease as set forth by the preamble of the claim. Claims should be amended to include an active process step directed towards diagnosing a disease on the basis of the detected mutations. It is unclear how the detecting the presence and/or identity of a mutation could be used as an indicator of disease. No guidance is provided regarding what disease would be diagnosed or what particular mutations would diagnose particular diseases. It is also unclear how the presence of a mutation without an identity (presence and/or identity) would allow diagnosing disease.
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.
Claims 1-5, 10, 11, 17, 19, 20, and 25 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Dellaporta et al. (US2016215331, on IDS dated 08/09/2023) in view of Cao et al. (Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage. 2020. Nucleic Acids Research., 48: 6715–6725. Published 06/02/2020).
Regarding claim 1, Dellaporta teaches a method of sequencing that comprises (i) cutting genomic DNA into blunt-ended fragments using a blunt-cutting restriction endonuclease enzyme, (ii) dA tailing the fragments and (iii) ligating the dA tailed fragments to universal sequencing adapters (Abstract and Fig. 12) to generate a sequencing library.
Dellaporta teaches the concept of dideoxy chain termination method for sequencing, but does not teach introducing dideoxy nucleotides at internal nick sites present in the fragmented nucleic acid molecules.
Cao teaches a method for mapping of DNA modifications at single-nucleotide resolution comprising a step of adding ddNTPs after fragmentation to block any pre-existing strand-break sites (p. 6716 col.1 to col. 2) before adding sequencing adapters (Fig. 1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta and Cao to arrive at the instantly claimed invention. The modification would have entailed performing the step of adding ddNTPs to the nucleic acid fragments of Dellaporta. One would have been motivated to add the step in order to ensure that only the desired fragment ends were extended by the addition of sequencing adapters. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 2, Dellaporta teaches cutting genomic DNA into blunt-ended fragments using a blunt-cutting restriction endonuclease enzyme (Abstract).
Regarding claim 3, Dellaporta teaches restriction enzymes that generate blunt ended-fragments, rather than ones with staggered ends enable preparation of a genomic DNA fragment library without an end-repair step (para 72).
Regarding claim 4, Dellaporta teaches using restriction endonuclease having a 4 base-pair recognition site, e.g. AluI,HpyCH4V, RsaI (para 187).
Regarding claim 5, Dellaporta teaches using AluI or HpyCH4V as the restriction endonuclease (para 187).
Regarding claim 10, Dellaporta does not teach introducing dideoxy nucleotides at internal nick sites in step (ii) prevents extension of the internal nick and results in an unamplifiable nucleic acid strand.
Cao teaches a method for mapping of DNA modifications at single-nucleotide resolution comprising a step of adding ddNTPs after fragmentation to block any pre-existing strand-break sites (p. 6716 col.1 to col. 2) before adding sequencing adapters (Fig. 1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta and Cao to arrive at the instantly claimed invention. The modification would have entailed performing the step of adding ddNTPs to the nucleic acid fragments of Dellaporta. One would have been motivated to add the step in order to ensure that only the desired fragment ends were extended by the addition of sequencing adapters. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 11, Dellaporta does not teach any of the claimed limitations.
Cao teaches the addition of ddNTPs, which comprise dideoxy non-A nucleotides.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta and Cao to arrive at the instantly claimed invention. The modification would have entailed performing the step of adding ddNTPs to the nucleic acid fragments of Dellaporta. One would have been motivated to add the step in order to ensure that only the desired fragment ends were extended by the addition of sequencing adapters. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 17, Dellaporta and Cao teach generating a nucleic acid library using the method of claim 1.
Dellaporta further teaches enriching and sequencing the library (Abstract and Fig. 12) and using computer programs to determine sequence identity (para 55).
Regarding claim 19, Dellaporta and Cao teach method of claim 1 as described above, thus satisfying the requirements of performing the method of claim 1.
Regarding claim 20, Dellaporta teaches obtaining nucleic acid samples from tissues, which reads on a polyclonal population (para 74).
Regarding claim 25, Dellaporta and Cao teach performing the method of claim 1 described above, which reads on detecting the presence and/or identity of a mutation in a single DNA molecule according to the method of claim 19.
Dellaporta further teaches a sample for nucleic acids can be whole cell samples (para 177) and a cell can be in vitro (para 60).
Claim 18 remains/is rejected under 35 U.S.C. 103 as being unpatentable over Dellaporta et al. (US2016215331, on IDS dated 08/09/2023) in view of Cao et al. (Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage. 2020. Nucleic Acids Research., 48: 6715–6725. Published 06/02/2020) as applied to claims 1-5, 10, 11, 17, 19, 20, and 25 above, and further in view of Kennedy et al. (Detecting ultralow-frequency mutations by Duplex Sequencing.2014 Nat Protoc. 9: 2586–2606).
Regarding claim 18, Dellaporta teaches aligning reads to a reference genome (para 148) and determining a Phred score (a base call quality score) (paras 148, 283) but does not teach (i) grouping reads limitations of the claim and (ii) filtering false positive base calls at reference and mutated positions.
Cao also does not teach grouping reads using the limitations of the claim and filtering false positive base calls at reference and mutated positions.
Kennedy teaches a method of detecting mutations by duplex sequencing, the method comprising aligning reads to a reference genome, (i) grouping reads that share the same tag sequence and genomic coordinates (p. 2589, col. 1), which reads on the embodiment grouping reads of the sequencing data based on the position in the reference genome to which they correspond and/or the nucleic acid fragment from which they derive, and (ii) removing sequencer-derived false positives (i.e. false positive base calls in reference and mutated positions).
Kennedy states an advantage of the method is superior accuracy (p. 2587, col. 2).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta and Cao with Kennedy to arrive at the instantly claimed invention. The modification would have entailed analysis of the reads of the Dellaporta sequencing library that incorporates grouping reads to form consensus sequences and decrease false positives in order to increase accuracy of mutation detection. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Claims 6-9, 12-15, and 21-24 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Dellaporta et al. (US2016215331, on IDS dated 08/09/2023) in view of Cao et al. (Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage. 2020. Nucleic Acids Research., 48: 6715–6725. Published 06/02/2020) as applied to claims 1-5, 10, 11, 17, 19, 20, and 25 above, and further in view of Salk (WO 2020081743).
Regarding claim 6, neither Dellaporta nor Cao teach removing overhangs from the fragmented nucleic acid molecules using one or more exonuclease enzymes to generate fragmented nucleic acid molecules with blunt ends.
Salk teaches using a single-stand specific nucleases such as mung bean nuclease to destroy single-stranded portions of a duplex molecule (i.e. remove overhangs) (para 75).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta and Cao with Salk to arrive at the instantly claimed invention. The modification would have entailed using the exonuclease of Salk to achieve the blunt ends desired for the method of Dellaporta and Salk. One would have been motivated to make the modification in the process of routine optimization towards generating the desired blunt ends for the addition of sequencing adapters using a method known to remove single stranded sequences. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 7, Dellaporta teaches genomic DNA and dsDNA libraries created by mechanical cleavage of genomic DNA (para 177).
Regarding claims 8 and 9, Dellaporta teaches a method of sequencing that comprises (i) cutting genomic DNA into blunt-ended fragments using a blunt-cutting restriction endonuclease enzyme, (ii) dA tailing the fragments and (iii) ligating the dA tailed fragments to universal sequencing adapters (Abstract) to generate a sequencing library.
Dellaporta further teaches genomic DNA and dsDNA libraries created by mechanical cleavage of genomic DNA (para 177), which reads on fragmenting by sonication.
Dellaporta does not teach (ii)introducing dideoxy nucleotides at internal nick sites present in the fragmented nucleic acid molecules (claim 8)
Cao teaches a method for mapping of DNA modifications at single-nucleotide resolution comprising a step of adding ddNTPs after fragmentation to block any pre-existing strand-break sites (p. 6716 col.1 to col. 2) before adding sequencing adapters (Fig. 1).
Neither Dellaporta nor Cao teach (i) removing overhangs from the fragmented nucleic acid molecules using one or more exonuclease enzymes to generate fragmented nucleic acid molecules with blunt ends (claim 8), or the one or more exonuclease enzymes is Mung Bean nuclease (claim 9).
Salk teaches using a single-stand specific nucleases such as mung bean nuclease to destroy single-stranded portions of a duplex molecule (i.e. remove overhangs) (para 75), which satisfies the requirements of removing overhangs from the fragmented nucleic acid molecules using one or more exonuclease enzymes in claim 8 and the one or more exonuclease enzymes is Mung Bean nuclease in claim 9.
Salk states that this method helps prevent pseudo-duplex errors (para 75).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta and Cao with Salk to arrive at the instantly claimed invention. The modification would have entailed (i) using the method of Salk to generate blunt ended fragments. One would have been motivated to use the method for the advantage of decreasing errors as stated in Salk. The modification would further have entailed (ii) performing the step of adding ddNTPs to the nucleic acid fragments of Dellaporta. One would have been motivated to add the step in order to ensure that only the desired fragment ends were extended by the addition of sequencing adapters. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claims 12 and 13, neither Dellaporta nor Cao teach the sequencing adaptors are duplex sequencing adaptors comprising a barcode sequence (claim 12) or the nucleic acid library is for duplex sequencing (claim 13).
Salk teaches duplex sequencing (Abstract, para 68) of libraries using adapter molecules with an indexing sequence (barcode) (para 15 and Fig. 1). Salk states that duplex sequencing reduces sequencing errors of double-stranded nucleic acid molecules by multiple orders of magnitude (para 117) and that indexing allows pooling for multiplexed sequencing, thereby reducing expense and time involved in library preparation (para 2).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta and Cao with Salk to arrive at the instantly claimed invention. The modification would have entailed using the indexed adapters of Salk for duplex sequencing in the sequencing library preparation of Dellaporta. One would have been motivated by the improved accuracy of sequencing provided by the duplex sequencing method of Salk. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 14 and 15, neither Dellaporta nor Cao teach (i)selectively enriching nucleic acids corresponding to one or more genomic region of interest to generate an enriched nucleic acid library(claim 14) or the one or more genomic region of interest is one or more coding sequences (CDSs) of coding genes (claim 15).
Salk teaches (i) selectively enriching one or more targeted genomic regions prior to sequencing (para 6). Salk further teaches (ii) the one or more targeted genomic regions comprise genes known to harbor disease-causing mutations.(para 6) and a gene includes coding sequence (para 154).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta and Cao with Salk to arrive at the instantly claimed invention. The modification would have entailed enriching genomic regions of interest such as known cancer drivers in the sequencing library before sequencing. One would have been motivated to add the enriching step in order to increase the likelihood of detection of known disease drivers. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claims 21-23, Dellaporta does not teach the population of cells is an aged population of cells or a diseased population of cells (claim 21); the mutation present in a single DNA molecule is a driver mutation (claim 22); or the driver mutation is involved in an ageing process or is a disease driver mutation (claim 23).
Salk teaches performing the method on nucleic acids from a subject suffering from a disease (para 63), which reads on diseased population of cells, and detecting cancer driver mutations (para 142).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta and Cao with Salk to arrive at the instantly claimed invention. The modification would have entailed applying the method of Dellaporta and Cao to samples from a subject with a disease in order to identify mutations driving cancer in the subject. One would have been motivated to do so in order to use the mutation detecting method of Dellaporta and Coa in a medical or diagnostic context. Although neither Dellaporta nor Cao did not teach direct application of the method to diseased samples and the discovery of driver mutations, both Dellaporta (para 64) and Cao (p. 6715, col. 2) recognized the importance of mutations in disease. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 24, Dellaporta and Cao teach performing the method of claim 1, which satisfies the requirement of detecting the presence and/or identity of a mutation in a single DNA molecule according to the method of claim 19.
Neither Dellaporta nor Cao teach (ii) using the presence and/or identity of the mutation as an indicator of disease in the human or animal subject.
Salk teaches screening human patients for a rare genetic disorder or disease (para 143) by screening for variant alleles correlating or causative of rare genetic disease (para 117), and identifying a patient having a rare variant allele among a population of patients (para 18).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta and Cao with Salk to arrive at the instantly claimed invention. The modification would have entailed obtaining nucleic acids from a human or animal subject as in Salk for the method of Dellaporta and Cao. The method would further have entailed using the method of Salk to identify mutations in the human or animal nucleic acid sequencing. One would have been motivated to do so in order to apply the method of Dellaporta and Cao. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Claim 16 remains/is rejected under 35 U.S.C. 103 as being unpatentable over Dellaporta et al. (US2016215331, on IDS dated 08/09/2023) in view of Cao et al. (Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage. 2020. Nucleic Acids Research., 48: 6715–6725. Published 06/02/2020) further in view of Salk (WO 2020081743) as applied to claims 6-9, 12-15, and 21-24 above, and further in view of Jarosz et al. (US 20160122817).
Regarding claim 16, neither Dellaporta, Cao, nor Salk teach using oligonucleotide probes which bind to the coding sequences (CDSs).
Jarosz teaches methods for targeted nucleic acid sequencing, including targeting the coding region (CDS) of a genome with exome sequencing (para 3), the method comprising hybridizing oligonucleotide probes that are complementary to the targeted regions to genomic fragment libraries (para 90).
Jarosz states that exome sequencing is less expensive, faster and easier to analyze (para 3)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Dellaporta Cao and Salk with Jarosz to arrive at the instantly claimed invention. The modification would have entailed using the method of Jarosz for targeted exome enrichment as the method for coding sequence analysis as in Salk. The enrichment method would have been applied to the sequencing library generated by Dellaporta and Cao. One would have been motivated to so for the benefits of a cheaper and easier to analyze dataset. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Response to Arguments against Claim Rejection - 35 U.S. C § 103
The response asserts that each of the 103 rejections involves relying on the disclosures of Dellaporta and Cao to allegedly teach the feature of introducing dideoxy nucleotides (ddNTPs) at internal nick sites but that a person of ordinary skill in the art starting from Dellaporta, or even Dellaporta and Cao together, would not have arrived at the presently claimed invention without the impermissible benefit of hindsight, using the present claims as a template (p. 18). The response asserts that, as conceded by the Office, Dellaporta fails to suggest introducing dideoxy nucleotides at internal nick sites present in the fragmented nucleic acid molecules and submits that Cao's disclosure is directed to a distinct method of mapping DNA modifications across a genome with single nucleotide resolution and differs from the present invention wherein the genomic sequence is determined-with very low error rates-to facilitate the reliable detection of mutations in single DNA molecules (p. 18).
Applicant's arguments have been fully considered but are not persuasive.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., that the methos is performed with very low error rates-to facilitate the reliable detection of mutations in single DNA molecules) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
The response asserts that instead of introducing ddNTPs at internal nick sites to prevent extension and result in an unamplifiable nucleic acid strand, Cao blocks the ends of fragments using ddNTPs (p. 19). The response further asserts that Cao converts modifications in the genomic fragments to strand breaks which are equivalent to the internal nicks of the instant invention. The nicks of Cao are not subjected to any further ddNTP blocking but are subjected to nick translation (NT). Accordingly, a person of ordinary skill would understand Cao to be inapposite to the present invention and would, in fact, be unsuitable to the technical solution to be achieved by the present invention (p. 19).
Applicant's arguments have been fully considered but are not persuasive.
The instant claims do not require that ddNTPs be guided or targeted to internal nick sites. Adding, dideoxy nucleotides as in Cao would have the effect of introducing dideoxy nucleotides at internal nick sites present in the fragmented nucleic acid. The structure of the ddNTP and lack of a 3’OH would prevent addition of nucleotides at the internal nick sites, thereby blocking the sites, preventing extension and resulting in an unamplifiable strand. Therefore, the teaching of Cao adding ddNTPs after fragmentation would achieve the goal of blocking internal nick sites.
Furthermore, it is noted that the internal nicks of Cao are generated after fragmentation and ddNTP blocking and therefore do not appear to be equivalent to the internal nick sites present in the fragmented nucleic acid molecules of the claims.
Conclusion
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.
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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