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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 12, 2025 has been entered.
Specification
The disclosure is objected to because of the following informalities:
The use of the following trade names or marks in the specification, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
At page 12, lines 28-29, "Triton" (serial # 71464446)
At page 12, line 31, "Tween" (serial # 76451302)
At page 12, line 30, "IGEPAL" (Serial # 71397707)
Regarding the terms above, trademark symbols are not used to denote the tradenames and should be added. Further, each letter in the trademark should be capitalized.
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.
Status of claims / Response to Amendment
This office action is in response to an amendment filed on November 12, 2025.
Claims 1, 5-8, 13-22, 24 and 26-27 were previously pending. Applicant amended claim 1, and added new claim 28.
Claims 1, 5-8, 13-22, 24 and 26-28 are currently pending and under consideration.
Improper Amendment to the Claims:
Claim 1 is improperly amended for having incorrect status identifier. While the claim is amended with markups, it is incorrectly identified as "previously presented" when "currently amended" should be used. Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c)(2) which states: "When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims."
In the interest of compact prosecution, however, the examiner will consider the claim listing on its merits. MPEP 714.03 (“Where an amendment substantially responds to the rejections, objections, or requirements in a non-final Office action (and is a bona fide attempt to advance the application to final action) but contains a minor deficiency . . . , the examiner may simply act on the amendment and issue a new (non-final or final) Office action.”) The examiner reserves the right to send a PTOL-324 Notice of Noncompliant Amendment in the event of more severe deficiencies, which may result in loss of patent term.
Missing Terminal Disclaimer: The Applicant's Remarks at page 5 indicate the submission of a Terminal Disclaimer directed to U.S. Pat. 11,174,509. However, there is no Terminal Disclaimer filling in the Applicant's response on November 12, 2025 (see Electronic Filing System Acknowledgment Receipt - 11/12/2025).
All of the amendment and arguments have been thoroughly reviewed and considered. All of the previously presented rejections have been withdrawn as being obviated by the amendment of the claims, which added new limitations to the claims, that were not considered in the previous rejections.
Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
This office action contains new grounds for rejection necessitated by amendment.
Priority
For the instant claims 1, 5-8, 13-22, 24 and 26-28 in this application, the applicant claims priority of US provisional application NO. 61/915,435, which has a filling date on 12/12/2013.
Claim Interpretation -- Updated
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP§ 2111.
Regarding all claims, terms such as "first" and "second" are interpreted as adjectives for identification purposes to distinguish between repeated instances of an element or limitation, and do not impose any additional features, such as any specific temporal limitation, any sequential order of steps, or any structural or composition differences. See 3M Innovative Props. Co. v. Avery Dennison Corp., 350 F.3d 1365 (Fed. Cir. 2003)1.
For the purpose of applying prior art, claim 1 recites "first unique sequence tag" and "second unique sequence tag," which are terms not expressly defined by the application's disclosure. The specification does not provide any definition for the term "unique sequence tag" or any description of structural features, that can distinguish this term from any sequence known in the art.
Thus, under BRI, the term "unique sequence tag" is interpreted to encompass any sequence, such as a barcode sequence.
For the purpose of applying prior art, claim 8 recites "wherein the forward and reverse strand amplicons further comprise a pool identification tag and a first universal portion."
The application's disclosure does not define the terms "pool identification tag" and "first universal portion" with any structural feature or characteristics that could distinguish these terms from any sequences or molecular biology assay elements, that can be comprised by "forward and reverse strand amplicons" (interpreted under BRI as any nucleic acids).
Therefore, under BRI, the terms "pool identification tag" and "first universal portion" are interpreted to encompass any nucleic acid sequences or elements that can be comprised by or attached to a nucleic acid molecule (e.g. biotin tag, linker, etc. )
For the purpose of applying prior art, claim 1 has been amended to recite:
"conducting a first amplification reaction in the first pool to enrich for forward strand amplicons" and
"conducting a second amplification reaction in the second pool to enrich for reverse strand amplicons."
The application's disclosure does not expressly define the term "enrich." Thus, under BRI and based on the commonly understood meaning by those skilled in the art, the term "enrich" is understood to encompass any approach that increases the presence of targets of interest in a sample. This can be achieved by increase the number of targets, such as through target amplification 2; isolating targets from non-targets, such as via hybridization capture 2; or depleting non-targets to reduce background 3.
Claim Rejections - 35 USC § 112(b) -- New
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.
Claims 1, 5-8, 13-22, 24 and 26-28 are rejected under 35 U.S.C. 112(b), 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 steps of conducting amplification to
"enrich for forward strand amplicons comprising a first unique sequence tag without substantially enriching for reverse strand amplicons" and
"enrich for reverse strand amplicons comprising a second unique sequence tag without substantially enriching for forward strand amplicons."
This claim language is indefinite because it is unclear how to determine whether an amplicon is "enriched" or "substantially enriched." The term "substantially enriching" appears to imply a greater degree of enrichment than "enriching," but the application's disclosure does not define the terms "enrich" and "substantially enriching," nor does it provide any guidance as to what threshold or quantitative difference qualifies as "substantial," rendering the scope of the limitation unclear 4.
For the purpose of compact prosecution and applying prior art under 35 USC§ 102 and 103, the phrase "enrich for forward strand amplicons comprising a first unique sequence tag without substantially enriching for reverse strand amplicons" is interpreted to mean that reverse strand amplicons are not enriched to a greater extent than forward strand amplicons. Accordingly, this interpretation encompass scenarios in which both forward and reverse strand amplicons are enriched to a similar extent, without one being more enriched over the other.
The same interpretation regarding "enrich for A… without substantially enriching for B" also applies to the recitation "enrich for reverse strand amplicons comprising a second unique sequence tag without substantially enriching for forward strand amplicons."
Claims 5-8, 13-22, 24 and 26-28 are rejected for depending from claim 1 and not remedying the indefiniteness.
Claim Rejections - 35 USC § 103 – New
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, 5-8, 13-22, 24 and 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Samuels (WO2012112804A1- Compositions and methods for molecular labeling; Published August 23 2012), in view of
Meacham (Meacham et al. Identification and correction of systematic error in high-throughput sequence data. BMC Bioinformatics 12, 451 (2011). doi.org/10.1186/1471-2105-12-451).
A) Samuels teaches methods for analyzing biological samples by compartmentalizing samples (e.g., droplet encapsulation) with barcode libraries, followed by analysis approaches such as sequencing (entire document; summary of the invention).
Regarding claim 1, Samuels teaches the method steps of:
providing amplicons of a sample nucleic acid molecule in a first pool and a second pool (Figure 13; page 11“Figure 13 shows barcode addition for amplification-based single molecule haplotyping with universal PCR barcodes.”);
conducting a first amplification reaction in the first pool to enrich for forward strand amplicons comprising a first unique sequence tag (Figure 13-14; page 52, para 2, lines 1-3; unique barcode: page 52, para 2, lines 6-9; page 41, para 2; page 51, para 3), without substantially enriching for reverse strand amplicons in the first pool (Figure 13-14, the forward and reverse strands are equally enriched);
conducting a second amplification reaction in the second pool to enrich for reverse strand amplicons comprising a second unique sequence tag (Figure 13-14; ; page 52, para 2, lines 1-3; unique barcode: page 52, para 2, lines 6-9; page 41, para 2; page 51, para 3), without substantially enriching for forward strand amplicons in the second pool (Figure 13-14, the forward and reverse strands are equally enriched);
sequencing the forward strand amplicons to produce forward strand sequence reads and sequencing the reverse strand amplicons to produce reverse strand sequence reads (page 52, para 2, lines 6-7; page 11, lines 3-4 “schematic depicting an example of barcode labeled strands in a droplet before sequencing (in droplet) and after sequencing (in bulk)”; page 47, para 4, lines 4-5, barcode that will enable post-sequencing correlation to the target strand); and
identifying a true variant based on barcoded sequencing reads (page 70-71; Fig. 43 ).
Samuels teaches strand-specific labeling of nucleic acids for sequencing (page 52, para 2, lines 6-7; page 11, lines 3-4 “schematic depicting an example of barcode labeled strands in a droplet before sequencing (in droplet) and after sequencing (in bulk)”; page 47, para 4, lines 4-5, barcode that will enable post-sequencing correlation to the target strand); it also teaches identifying a true variant (page 70-71; Fig. 43 ) by teaching highly accurate nucleic acid sequencing, particularly by enabling the discrimination between true SNPs and sequencing errors.
Specifically, Samuels teaches using barcodes on differently labeled molecules to determine whether a detected base change is real or an artifact of some kind. For instance, on the same strand of the same molecule (e.g., top strand of Fragment A in Fig. 43), the nucleotide base at a specific position should be the same (e.g., base “C” at position X). Therefore, if reads with the same molecule barcode presents a small fractions of reads with different nucleotide base at a specific position, it is likely not a true variant but rather a technical error.
While Samuels teaches nucleic acid molecule-specific barcoding in high accuracy sequencing method for detecting single-nucleotide variants such as SNP, it focuses on distinguishing reads between nucleic acid fragments which could comprise both strands, and does not explicitly teach specifically investigating variants in both the forward and reverse stands.
B) Meacham teaches an improved approach for the identification and correction of systematic errors in sequencing data analysis, specifically applicable to the identification of SNP variants (entire document, Abstract for example).
Regarding claim 1, Meacham teaches finding a variant in the forward strand sequence reads and the reverse strand sequence reads; and identifying the variant as a true variant (page 3, left-hand col, lines 11-17).
Meacham specifically highlights types of errors in sequencing (Figure 1), including systemic error that affects SNP calling methods as this type of error escapes traditional error identification approaches and cannot be distinguished from true SNPs:
"Systematic error manifests as many individual base-call errors from separate sequence reads occurring at the same genomic position (Figure 1). Thus, a systematic error comprises many individual base-call errors (from different reads) that fall at the same genomic location. These errors have the potential to be especially troublesome because they can confound methods that identify errors based on their sparsity among reads. For example, we show systematic errors affect current SNP (Single-Nucleotide Polymorphism) calling methods, where the first step involves computing the posterior probability for a SNP at every site based on relative nucleotide counts [6]. Although filters based on the depth of reads are frequently applied (mostly to screen for indels, copy number variants, or other structural variation) [7,8], most existing approaches will not identify systematic errors, or distinguish them from true SNPs.
Similarly, the detection of RNA editing sites in RNASeq data is complicated by systematic error, because an accumulation of errors at a transcriptome site can appear to be an edit event when compared with a reference genome that may have been sequenced using another technology [9]. " (page 2)
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Meacham then teaches a solution to address the false-positive problem in SNP calling, by comparing sequencing reads from both strand directions:
"Due to the small fragment size in methyl-Seq experiments many of the mate-pair reads overlapped, providing for each such location two base calls sequenced from the same DNA molecule (Figure 1) albeit from different directions. We made use of this to distinguish between base-call errors and true heterozygosity calls in the following manner: each pair of bases originating from a single mate-pair and sequencing the same position was denoted a reference-pair if both calls agreed with the reference genome, a SNP-pair if both calls disagreed with the reference genome and agreed among themselves, and an error-pair if one of the calls agreed with the reference genome but the other did not." (page 3, left-hand col)
Therefore, 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 droplet-based nucleic acid sequencing method with strand-specific labeling for SNP analysis, taught by Samuels, with the teachings of Meacham regarding the improved method to more accurately identity true variants through strand-based comparison of sequencing reads, because both references are in the same or overlapping fields of sequencing-based SNP detection and provide complementary teachings related to variant identification.
Samuels teaches sequencing methods for SNP identification with labeling schemes that preserve strand-specific information, while Meacham teaches an improved, sequencing data analysis approach for identifying systematic errors in SNP calling by comparing the two strands at the same genomic location, thereby improve SNP calling accuracy. Therefore, a skilled artisan would have readily applied Meacham's analysis method to the strand-specific sequencing reads generated using Samuels's teaching as a logical extension to reduce false positives in SNP calling.
The person of ordinary skill would have had a reasonable expectation of success in combining these teachings because they are technically compatible and address the same goal ꟷ SNP identification from sequencing data. Samuels already enables strand-resolved analysis by preserving strand-specific information in sequencing reads, which supports the strand-based variant comparison taught by Meacham. Meacham teaches its data analysis approaches in detail, further supporting the feasibility of such combination. Moreover, both references describe sequencing workflows that are well-established in the field (e.g. Illumina sequencing). Doing so would have yielded the predictable result of improved SNP calling accuracy by identifying and filtering out false variants that exhibit strand-specific bias, as suggested by Meacham.
The skilled artisan would have been motivated to combine these teachings to enhance the reliability of SNP detection, and address the shortcomings in conventional analysis pipelines that are prone to false positives due to systematic errors, as suggested by Meacham.
Additionally, this combination would have been obvious as it represents the KSR principle of predictable use of prior art elements (i.e., strand-based variant comparison for error identification of Meacham) according to a known method (i.e., strand-specific sequencing of Samuels) to yield predictable results (i.e., more accurate SNP calling). (See MPEP §2143).
C) Regarding claims 5-6, Samuels teaches exponential amplification comprises PCR (Figure 14, PCR).
Regarding claim 7, Samuels teaches the forward and reverse strand products are produced by a polymerase extension reaction (Figure 12; page 51-52).
Regarding claim 8, Samuels teaches wherein the forward and reverse strand products further comprise a pool identification tag (page 52, para 2, lines 6-9; page 41, para 2; page 51, para 3; page 48, para 2, as the forward and reverse primer each has barcode, this unique pair of barcodes labels the pool or droplet) and a first universal portion (Figure 14, “universal ends”; Page 8, para 3, unique N-mer and functional N-mer, functional N-mer comprise: sequence specific primers, random N-mer (pool identification), universal primer ; page 4, para 1).
Regarding claim 13, Samuels teaches wherein the variant is associated with a disease (page 62, para 3, disease-associated copy number variation).
Regarding claim 14, Samuels teaches wherein the disease is cancer (page 70, para 2).
Regarding claim 15, Samuels teaches incorporating sequencing adaptors into the forward and reverse strand amplicons (page 70, lines1-2, page 69, para 4).
Regarding claim 16, Meacham teaches identifying a variant as a false variant when the variant is found among one of, but not the other of, sequence reads from the forward strand and sequence reads from the reverse strand (Figure 1, systematic error).
Regarding claim 17, Meacham teaches wherein the second variant is an amplification or sequencing error (Figure 1) .
Regarding claim 18, it is obvious over the combined teachings of Samuels and Meacham because it does not further limit the claimed method.
Claim 18 recites :"wherein the sample nucleic acid molecule is derived from formalin-fixed, paraffin-embedded tissue."
Per MPEP 2111.04, a wherein clause can limit a method claim if it contributes meaning and purpose to the manipulative steps. In this instant case, the wherein clause does not limit the method claim because the base claim 1 does not recite any step of obtaining or deriving nucleic acid molecules. As such, this clause merely describes a source of the nucleic acid molecules, without modifying any step of the claimed method. Therefore, this claim language is interpreted as descriptive statement without any associated active steps and do not distinguish the claims from the prior art.
Regarding claim 19, Samuels teaches the amplicons are produced by linear amplification (page 55, para 4, lines6-9).
Regarding claim 20, Meacham teaches the sequencing step comprises detecting a third variant (Figure 1).
Regarding claim 21, Meacham teaches identifying a variant as a genetic mutation when the variant is found among sequence reads from the forward strand and sequence reads from the reverse strand (page 3, left-hand col, lines 9-17).
Regarding claim 22, Samuels teaches sequencing-by- synthesis (page 8, para 2, lines1-2).
Regarding claim 24, Samuels teaches wherein the nucleic acid molecule is from a blood sample (page 2. Para 2) .
Regarding claim 26, Samuels teaches the first unique sequence tag identifies the forward strand sequence reads and the second unique sequence tag identifies the reverse strand sequence reads (page 109, lines 3-6, barcodes that enable post-sequencing correlation to target strand).
Regarding claim 27, Samuels teaches the first unique sequence tag and the second unique sequence tag identify the forward and reverse strand sequence reads as corresponding to the sample nucleic acid molecule (page 52, para 2, lines 6-9; FIG 43).
Regarding claim 28, Samuels teaches the forward strand amplicons comprises first double-stranded nucleic acids and wherein the reverse strand amplicons comprise second double- stranded nucleic acids (Figs 13B and 14A, PCR amplification in droplets; page 34, lines 1-5, PCR amplification produces double-stranded nucleic acids).
Double Patenting- Obvious Type -- New
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, 13-15, 18-19, 20-22 and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-8, 12-13, and 15-16 of U.S. Patent No.11174509B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over claims of the '509 patent.
Instant claim 1 recites:
A method comprising the steps of:
providing amplicons of a sample nucleic acid molecule in a first pool and a second pool (‘509 Patent, claims 15, 1);
conducting a first amplification reaction in the first pool to enrich for forward strand amplicons comprising a first unique sequence tag without substantially enriching for reverse strand amplicons in the first pool (‘509 Patent, claims 15, 1, 4);
conducting a second amplification reaction in the second pool to enrich for reverse strand amplicons comprising a second unique sequence tag without substantially enriching for forward strand amplicons in the second pool (‘509 Patent, claims 15, 1, 4);
sequencing the forward strand amplicons to produce forward strand sequence reads and sequencing the reverse strand amplicons to produce reverse strand sequence reads (‘509 Patent, claims 15, 1, 4);
finding a variant in the forward strand sequence reads and the reverse strand sequence reads (‘509 Patent, claims 15-16); and
identifying the variant as a true variant (‘509 Patent, claims 15-16).
Therefore, instant claim 1 is anticipated by claims 1, 4 and 15-16 of the '509 patent. Instant claims 7, 19; 13-15; 18; 20-21; 22; and 24 are anticipated by claims 2; 5-7; 12; 16; 8; and 13 of the '509 patent, respectively.
Prior Art
For the purpose of compact prosecution, the examiner has reviewed the application's entire disclosure, but has not readily identified any subject matter that is not taught or suggested by the prior art, or combined in a non-obvious way. However, the examiner remains open to considering any aspect of the invention that the applicant believes may be allowable. To advance prosecution, Applicant is advised to amend the claims in their response, to focus on what they consider as the inventive concept in the present disclosure.
Other prior art also teach performing strand-specific amplification (e.g., asymmetric PCR, in which a great excess of primers for a chosen strand is used) in pools or partitions (e.g. droplets):
WO2010036352A1;
US20130210638A1;
US20130084572A1;
US20110092392A1;
US20130295567A1.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIAN NMN YU whose telephone number is (703)756-4694. The examiner can normally be reached Monday - Friday 8:30 am - 5:30 pm.
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/TIAN NMN YU/Examiner , Art Unit 1681 /AARON A PRIEST/Primary Examiner, Art Unit 1681
1 Holding that "first pattern" and "second pattern" is equivalent to "Pattern A" and "Pattern B": The use of the terms "first" and "second" is a common patent-law convention to distinguish between repeated instances of an element or limitation. See, e.g., Anchor Wall Sys., Inc. v. Rockwood Retaining Walls, Inc., 340 F.3d 1298, 1304 (Fed. Cir. 2003) ("first and second sidewall surfaces"); Springs Window Fashions LP v. Novo Indus., L.P., 323 F.3d 989, 992 (Fed. Cir. 2003) ("first and second opposed ends"). In the context of claim 1, the use of the terms "first . . . pattern" and "second . . . pattern" is equivalent to a reference to "pattern A" and "pattern B," and should not in and of itself impose a serial or temporal limitation onto claim 1."
2 see Tewhey et al. Microdroplet-based PCR enrichment for large-scale targeted sequencing. Nat Biotechnol 27, 1025–1031 (2009), (introduction);
See also Ware et al., Next generation sequencing for clinical diagnostics and personalised medicine: implications for the next generation cardiologist. Heart. 2012 Feb;98(4):276-81. doi: 10.1136/heartjnl-2011-300742. Epub 2011 Nov 29. PMID: 22128206. (Fig 2)
3 see Feehery et al. A method for selectively enriching microbial DNA from contaminating vertebrate host DNA. PLoS One. 2013 Oct 28;8(10):e76096. doi: 10.1371/journal.pone.0076096. PMID: 24204593; PMCID: PMC3810253 (entire document).
4 It is noted that Applicant's Remarks filed on Nov 12, 2025 has been thoroughly considered. However, it also does not provide any definition for the terms, nor does it clearly set forth any difference in scope between the terms "enrich" and "substantially enriching."