DETAILED ACTION
The applicant’s response, from 16 June 2026, has been fully considered. Amendments to the claims, from 16 June 2026, were received and entered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status
Claims 1-20 are currently pending and under examination herein.
Claims 1-20 are rejected.
Priority
The instant application claims priority to Application No. 15958376 filed on 04/20/2018, Application No. 14089720 filed on 11/25/2013, Application No. 12940992 filed on 11/05/2010, Provisional Application No. 61360399 filed on 06/30/2010, and Provisional Application No. 61259076 filed on 11/06/2009. In this action, claims 1-20 are examined as though they had a priority date of 06 November 2009. In future actions, the date of one or more claims may change, due to amendments to the claims, or further analysis of the disclosure(s) of the priority application(s).
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 16 July 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings filed 12 May 2022 are accepted.
Claim Rejections - 35 USC § 112
The previously issued 35 USC 112 second paragraph rejections are withdrawn in response to the amended claims overcoming the rejections for claims 1, 5, 6. Regarding the 112 second paragraph rejections for claims 7 and 16, the examiner agrees with the applicant’s arguments (Page 8, Paragraphs 1-2 of remarks). The limitations recited by the claims are broad but definite when considered in light of the specification/art.
Claim Rejections - 35 USC § 101
The previously issued 35 USC 101 rejection is withdrawn in response to applicant’s arguments (Page 12, Paragraphs 3-4 of remarks). Particularly, the examiner is convinced based on the presented arguments and section from the specification cited that the invention represents an improvement to the technology/field of diagnosing genetic disorders over the state of the field at the time of the priority date (2009).
Claim Rejections - 35 USC § 103
Arguments associated with the previously issued 35 USC 103 rejection are considered persuasive. Particularly, the examiner agrees that Fan et al. does not teach single molecule sequencing (Page 14, Paragraph 3-4 of remarks) and Lampaire et al. does not teach the nature of the sample as claimed (Page 15, Paragraphs 2-3 of remarks). However, the following rejection is reiterated and newly modified (this action is non-final).
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Fan et al. (2008, PNAS, Vol. 105, No. 42: 16266–16271, Cited by previous office action), in view of Lapaire et al. (2007, Clinical Chemistry, Vol. 53, No. 3: 405–411, Cited by previous office action), and in further view of Clarke et al. (2009, Nature Nanotechnology, Vol. 4: 265-270, Cited by previous office action). Italicized text from reference art. Underlined text correspond to amendment.
Applicable claims include:
Claim 1. A method for performing prenatal diagnosis of a sequence imbalance in a biological sample obtained from a female subject pregnant with a fetus, (Claim 1.i) wherein the biological sample includes blood, plasma, serum, saliva, or urine, and wherein the biological sample includes a mixture of cell-free DNA molecules that are part of DNA sequences of a human genome, the biological sample including DNA molecules from the fetus and the female subject, the method comprising: for each of a plurality of the DNA molecules in the biological sample: (Claim 1.ii) measuring a size of the DNA molecule, wherein measuring the size of the DNA molecule comprises: (Claim 1.iii) performing single-molecule sequencing of the DNA molecule to obtain a read of the DNA molecule; (Claim 1.iv) identifying which nucleic acid sequence in the human genome the DNA molecule is derived from, wherein identifying which DNA sequence the DNA molecule is derived from includes: (Claim 1.v) aligning, by a computer system, at least a portion of the read to the human genome; (Claim 1.vi) calculating, by the computer system, a first statistical value from the sizes of DNA molecules from a first sequence; (Claim 1.vii) comparing the first statistical value to a threshold value; and (Claim 1.viii) determining a classification of whether a sequence imbalance exists for the first sequence based on a comparison of the first statistical value to the threshold value.
Claim 2. The method of claim 1, wherein the single-molecule sequencing comprises nanopore sequencing.
Claim 3. The method of claim 1, wherein the single-molecule sequencing comprises single-molecule, real time sequencing.
Claim 4. The method of claim 1, further comprising extracting the mixture of cell-free DNA to obtain the biological sample.
Claim 5. The method of claim 1, wherein the threshold value is determined using a different haplotype.
Claim 6. The method of claim 1, wherein the threshold value is determined using another sample, wherein the other sample is a euploid sample.
Claim 7. The method of claim 1, wherein comparing the first statistical value to the threshold value comprises: calculating, by the computer system, a second statistical value from the sizes of DNA molecules from one or more reference sequences; and determining the threshold value using the second statistical value.
Claim 8. The method of claim 1, wherein the first statistical value includes the median or average size of the measured sizes for the DNA molecules from the first sequence.
Claim 9. The method of claim 1, wherein the first sequence is a chromosome and the sequence imbalance is a fetal chromosomal aneuploidy.
Claim 10. The method of claim 9, wherein the threshold value is determined using one or more reference sequences, and the one or more reference sequences comprise one chromosome.
Claim 11. The method of claim 9, wherein the threshold value is determined using one or more reference sequences, and the one or more reference sequences are a plurality of chromosomes.
Claim 12. The method of claim 1, wherein the biological sample includes blood, plasma, serum, maternal blood containing fetal cells, fetal cells obtained from maternal blood, urine, saliva, or uterine lavage fluid.
Claim 13. The method of claim 1, wherein the plurality of the DNA molecules includes at least one million DNA molecules.
Claim 14. The method of claim 1, further comprising: collecting a blood sample from the female subject, and extracting plasma from the blood sample to obtain the biological sample.
Claim 15. The method of claim 1, further comprising displaying, by the computer system, the classification of whether the sequence imbalance exists for the first sequence.
Claim 16. The method of claim 1, further comprising: (Claim 16.i) determining a first amount of sequences identified as aligning to the first sequence of the human genome determining a second amount of sequences identified as aligning to one or more second sequences; (Claim 16.ii) using the first amount and the second amount to determine another parameter; and (Claim 16.iii) comparing the other parameter to one or more second cutoff values to determine another classification of whether the sequence imbalance exists for the first sequence.
Claim 17. The method of claim 16, further comprising: comparing the classification determined using the first statistical value and the threshold value to the other classification determined using the first amount and the second amount.
Claim 18. The method of claim 1, wherein the threshold value is determined using one or more reference sequences, and the one or more reference sequences have a GC content that is similar to a GC content of the first sequence.
Claim 19. The method of claim 18, further comprising: calculating the GC content of the one or more reference sequences; and calculating the GC content of the first sequence.
Claim 20. The method of claim 18, wherein the GC content of the one or more reference sequences and the GC content of the first sequence are obtained for a particular sequencing platform.
Regarding Claim 1, Fan et al. teach (Claim 1.i) wherein the biological sample includes blood, plasma, serum, saliva, or urine, and wherein the biological sample includes a mixture of cell-free DNA molecules that are part of DNA sequences of a human genome, the biological sample including DNA molecules from the fetus and the female subject, (Page 16266, Column 2, Paragraph 2: Cell-free plasma DNA from 18 pregnant women were sequenced; Page 16270, Column 2, Paragraph 4: peripheral blood drawn from each subject and donor was collected). Fan et al. teach (Claim 1.ii) measuring a size of the DNA molecule (Page 16269, Column 1, Paragraph 2: observations of the size distribution of cell-free plasma DNA; Page 16270, Column 1, Paragraph 1: The size distributions of the sequencing libraries were analyzed). Fan et al. teach (Claim 1.iii) performing sequencing of the DNA molecule to obtain a read of the DNA molecule (Page 16270, Column 2, Paragraph 5: cell-free plasma DNA samples, including from pregnant women sequenced on the Solexa/Illumina platform). Fan et al. teach (Claim 1.iv) identifying which nucleic acid sequence in the human genome the DNA molecule is derived from (Page 16271, Column 1, Paragraph 3: reads were uniquely mapped to the human genome). Fan et al. teach (Claim 1.v) aligning, by a computer system, at least a portion of the read to the human genome (Page 16271, Column 1, Paragraph 3: reads were uniquely mapped to the human genome; Page 16271, Column 2, Paragraph 2: reads were aligned to the human genome; Page 16271, Column 2, Paragraph 1: All analyses were done with Matlab). Fan et al. teach (Claim 1.vi) calculating a first statistical value from the sizes of DNA molecules from a first sequence (Page 16268, Column 2, Paragraph 3: The peak fragment size was, on average, 261 bp (range: 256–264 bp)). Fan et al. teach (Claim 1.vii) comparing the first statistical value to a threshold value (Page 16268, Column 2, Paragraph 3: To verify that the size distribution observed in the electropherograms is not an artifact of PCR, we also sequenced cell-free plasma DNA from a pregnant woman carrying a male fetus by using the 454 platform. The size distribution of the reads mapped to unique locations of the human genome resembled those of the Solexa sequencing libraries). Fan et al. teach (Claim 1.viii) determining a classification of whether a sequence imbalance exists for the first sequence based on a comparison values (Page 16271, Column 1, Paragraph 3: We estimated fetal DNA fraction from chromosome 21 for T21 cases, chromosome 18 from T18 cases, chromosome 13 from T13 case, and chromosomes X and Y for male pregnancies; Page 16270, Column 2, Paragraph 2: we demonstrated the use of sequencing to detect fetal aneuploidy noninvasively with maternal cell-free plasma DNA).
Regarding Claim 4, Fan et al. teach extracting the mixture of cell-free DNA to obtain the biological sample (Page 16270, Column 2, Paragraph 4: DNA was extracted from cell-free plasma).
Regarding Claim 5, Fan et al. teach the threshold value is determined using a different haplotype (Page 16268, Column 2, Paragraph 4: fetal DNA has size range of that of mononucleosome, whereas maternal DNA is longer).
Regarding Claim 6, Fan et al. teach the threshold value is determined using another sample, wherein the other sample is a euploid sample (Page 16268, Column 2, Paragraph 4: fetal DNA has size range of that of mononucleosome, whereas maternal DNA is longer).
Regarding Claim 7, Fan et al. teach calculating, by the computer system, a second statistical value from the sizes of DNA molecules from one or more reference sequences; and determining the threshold value using the second statistical value (Page 16268, Column 2, Paragraph 3: Subtracting the total length of the Solexa adaptors (92 bp) from 261 bp gives 169 bp as the actual peak fragment size. we also sequenced cell-free plasma DNA from a pregnant woman carrying a male fetus by using the 454 platform). Data from multiple sequencing techniques were analyzed to generate multiple statistical values and compared. Additionally, it is obvious to repeat steps (calculating a value from a separate sample or group) to generate a value to compare.
Regarding Claim 8, Fan et al. teach the first statistical value includes the median or average size of the measured sizes for the DNA molecules from the first sequence (Page 16268, Column 2, Paragraph 3: The peak fragment size was, on average, 261 bp).
Regarding Claim 9, Fan et al. teach the first sequence is a chromosome and the sequence imbalance is a fetal chromosomal aneuploidy (Page 16267, Column 2, Paragraph 1: Detection of Fetal Aneuploidy - The distribution of chromosome 21 sequence tag density for all nine T21 pregnancies is clearly separated from that of pregnancies bearing disomy 21 fetuses).
Regarding Claim 10, Fan et al. teach the threshold value is determined using one or more reference sequences, and the one or more reference sequences comprise one chromosome (Page 16267, Column 2, Paragraph 1: The coverage of chromosome 21 for T21 cases is 4–18% higher than that of the disomy 21 cases). Also see Page 16267, Figure 1. Sequences are aligned so it is known which sequences come from which chromosome including those used as the reference.
Regarding Claim 11, Fan et al. teach the threshold value is determined using one or more reference sequences, and the one or more reference sequences are a plurality of chromosomes (Page 16271, Column 2, Paragraph 1: Chromosomes X and Y are considered). Also see Page 16267, Figure 1. Sequences are aligned so it is known which sequences come from which chromosome including those used as the reference.
Regarding Claim 12, Fan et al. teach the biological sample includes blood, plasma, serum, maternal blood containing fetal cells, fetal cells obtained from maternal blood, urine, saliva, or uterine lavage fluid (Page 16266, Column 2, Paragraph 2: Cell-free plasma DNA from 18 pregnant women were sequenced; Page 16270, Column 2, Paragraph 4: peripheral blood drawn from each subject and donor was collected).
Regarding Claim 13, Fan et al. teach the plurality of the DNA molecules includes at least one million DNA molecules (Page 16266, Column 2, Paragraph 2: Approximately 50% (i.e., 5 million) of the reads mapped uniquely to the human genome).
Regarding Claim 14, Fan et al. teach collecting a blood sample from the female subject, and extracting plasma from the blood sample to obtain the biological sample (Page 16270, Column 2, Paragraph 4: Peripheral blood drawn from each subject and donor was collected. Blood was centrifuged. Plasma was transferred and centrifuged to remove residual cells).
Regarding Claim 15, Fan et al. teach displaying, by the computer system, the classification of whether the sequence imbalance exists for the first sequence (See Page 16267, Figure 1). Fan et al. determining sequence imbalance exists on a computer (see above). It would be obvious to have the computer the display the result as shown in the figure.
Regarding Claim 16, Fan et al. teach (Claim 16.i) determining a first amount of sequences identified as aligning to the first sequence of the human genome and determining a second amount of sequences identified as aligning to one or more second sequences (Page 16266, Column 2, Paragraph 2: An average of sequence tags mapped to chromosomes 13, 18, and 21, respectively. The number of sequence tags for each sample is detailed in supporting information (SI) Table S1. We observed a nonuniform distribution of sequence tags across each chromosome). Fan et al. teach (Claim 16.ii) using the first amount and the second amount to determine another parameter (Page 16266, Column 2, Paragraph 3: We applied a sliding window of 50 kb across each chromosome and counted the number of tags falling within each window. The median count per 50-kb window for each chromosome was selected; Page 16266, Column 2, Paragraph 3: The median count for each chromosome was selected. The median of the autosomal values was used as a normalization constant). Fan et al. teach (Claim 16.iii) comparing the other parameter to one or more second cutoff values to determine another classification of whether the sequence imbalance exists for the first sequence (Page 1626, Columns 1 and 2: normalized values were used for comparing different samples and for subsequent analysis including detection of fetal aneuploidy; Page 16267, Column 2, Paragraph 1: The distribution of chromosome 21 sequence tag density for all nine T21 pregnancies is clearly separated from that of pregnancies bearing disomy 21 fetuses). Tag density was used to determine the sequence imbalance. Regarding Claim 17, Fan et al. teach comparing the classification determined using the first statistical value and the threshold value to the other classification determined using the first amount and the second amount (Page 16267, Column 2, Paragraph 1 and Page 16268, Column 2, Paragraph 3 demonstrate tag density and size frequency are each used for exploring differences between samples).
Regarding Claim 18, Fan et al. teach the threshold value is determined using one or more reference sequences (see above for Fan et al. teaching of a threshold (whatever sequence is compered to is interpreted as a reference sequence)). Fan et al. teach the one or more reference sequences have a GC content that is similar to a GC content of the first sequence (Page 16267, Column 1, Paragraph 1: Fan et al. suggest the one or more reference sequences have a GC content that is similar to a GC content of the first sequence). Fan et al. also suggest the one or more reference sequences have a GC content that is similar to a GC content of the first sequence (Page 16270, Column 1, Paragraph 2: The results were influenced by a GC bias indicating that utilizing a refence with a similar GC would remove the bias).
Regarding Claim 19, Fan et al. teach calculating the GC content of the sequences (Page 16271, Column 2, Paragraph 2: information regarding GC content were obtained).
Regarding Claim 20, Fan et al. teach the GC content of the sequences are obtained for a particular sequencing platform (Page 16270, Column 2, Paragraph 5: sequenced on the Solexa/Illumina platform; Page 16271, Column 2, Paragraph 2: information regarding GC content were obtained). Additionally, the sequencing data from the particular seducing platform include the base call information, therefore it would be obvious that the GC would be known for the sequenced DNA because GC content was explicitly obtained.
Fan et al. does not explicitly teach the single molecule sequencing (Claims 1.iii, 2 and 3). Fan et al. does not explicitly teach determining a sequence imbalance by comparing values based on size (Claim 1.viii).
Regarding Claim 1, Lapaire et al. teach (Claim 1.vi) calculating a first statistical value from the sizes of DNA molecules from a first sequence (Page 407, Column 2, Paragraph 2: Descriptive statistics, including medians, were generated for all study variables (fragment size was a variable)). Lapaire et al. teach (Claim 1.vii) comparing the first statistical value to a threshold value (Page 408, Column 2, Paragraph 2: The median AUCs for DNA fragments of different lengths was determined. Statistical analysis showed highly significant differences in AUC among euploid and aneuploid samples). Lapaire et al. teach (Claim 1.viii) determining a classification of whether a sequence imbalance exists for the first sequence based on a comparison of the first statistical value to the threshold value (Page 408, Column 2, Paragraph 2: The median AUCs for DNA fragments of different lengths was determined. Statistical analysis showed highly significant differences in AUC among euploid and aneuploid samples; Page 409, Column 2, Paragraph 2: We observed striking differences in cffDNA fragment sizes and their characteristic distributions as a function of karyotype).
Regarding Claim 4, Lapaire et al. teach extracting the mixture of cell-free DNA to obtain the biological sample (Page 406, Column 2, Paragraph 4: measure the amount of the extracted cffDNA).
Regarding Claim 5, Lapaire et al. teach the threshold value is determined using a different haplotype (Page 408, Column 2, Paragraph 2: Statistical analysis showed highly significant differences in AUC among euploid and aneuploid samples).
Regarding Claim 6, Lapaire et al. teach the threshold value is determined using another sample, wherein the other sample is a euploid sample (Page 408, Column 2, Paragraph 2: Statistical analysis showed highly significant differences in AUC among euploid and aneuploid samples).
Regarding Claim 7, Lapaire et al. teach calculating, by the computer system, a second statistical value from the sizes of DNA molecules from one or more reference sequences; and determining the threshold value using the second statistical value (Page 408, Column 2, Paragraph 2: The median AUCs for DNA fragments of different lengths were determined for fresh and frozen euploid samples, as well as for aneuploid samples). See above for how the different samples used as a threshold (i.e. determining significant differences). The methods were performed with a computer (Page 407, Column 2, Paragraph 3: All statistical analyses were performed using SAS/STAT software). Additionally, it is obvious to repeat steps to generate a value to compare.
Regarding Claim 8, Lapaire et al. teach the first statistical value includes the median or average size of the measured sizes for the DNA molecules from the first sequence (Page 407, Column 2, Paragraph 2: Descriptive statistics, including medians, were generated for all study variables (fragment size was a variable)).
Regarding Claim 9, Lapaire et al. teach the first sequence is a chromosome and the sequence imbalance is a fetal chromosomal aneuploidy (Page 408, Column 1, Paragraph 5: The small number of fresh aneuploid samples included trisomy 21, triploidy, and monosomy X samples).
Regarding Claim 10, Lapaire et al. teach the threshold value is determined using one or more reference sequences, and the one or more reference sequences comprise one chromosome (Page 407, Column 2, Paragraph 2: compare unadjusted GAPDH concentrations between trisomy 18, trisomy 21, and euploid pregnancies). Reference sequences comprised at least one chromosome.
Regarding Claim 11, Lapaire et al. teach the threshold value is determined using one or more reference sequences, and the one or more reference sequences are a plurality of chromosomes (Page 407, Column 2, Paragraph 2: compare unadjusted GAPDH concentrations between trisomy 18, trisomy 21, and euploid pregnancies). Reference sequences comprised multiple chromosomes.
Regarding Claim 15, Lapaire et al. displaying, by the computer system, the classification of whether the sequence imbalance exists for the first sequence (Page 408, Column 1, Paragraph 6: After gel electrophoresis, scanning, and software analysis, we observed unique qualitative patterns for euploid and each aneuploidy, which we termed “fragmentation signatures” (Figs. 1 through 4)). Lapaire et al. teach determining sequence imbalance on a computer (see above). It would be obvious to have the computer the display the result as shown in the figure.
Regarding Claim 16, Lapaire et al. teach determining a first amount of sequences identified as aligning to the first sequence of the human genome and determining a second amount of sequences identified as aligning to one or more second sequences; using the first amount and the second amount to determine another parameter; and comparing the other parameter to one or more second cutoff values to determine another classification of whether the sequence imbalance exists for the first sequence (Page 407, Column 2, Paragraph 4: Fragmentation signatures were analyzed using the trapezoid methods. Area under the curve (AUC) was calculated separately for each sample using all available signal readings).
Regarding Claim 17, Lapaire et al. teach comparing the classification determined using the first statistical value and the threshold value to the other classification determined using the first amount and the second amount (Page 407, Column 2, Paragraph 3: The effect of interaction between the karyotype and gestational age on the logarithmically transformed GAPDH concentrations was assessed using multiple linear regression analyses). Additionally both Fan et al. Lapaire et al. compare results between different metrics. Therefore it would be obvious to compare the classification using the two methods.
Lapaire et al. does not explicitly teach the single molecule sequencing (Claims 1.iii, 2 and 3).
Regarding Claim 1, Clarke et al. (Claim 1.iii) performing single-molecule sequencing of the DNA molecule to obtain a read of the DNA molecule (Page 267, Column 2, Paragraph 2: continuous detection of nucleotides was achieved with a single nanopore; Page 268, Column 2, Paragraph 2: single molecule events that could be unambiguously assigned to a particular base).
Regarding Claim 2, Clarke et al. teach the single-molecule sequencing comprises nanopore sequencing (Page 267, Column 2, Paragraph 2: continuous detection of nucleotides was achieved with a single nanopore).
Regarding Claim 3, Clarke et al. teach the single-molecule sequencing comprises single-molecule, real time sequencing (Page 269, Column 2, Paragraph 1: the simple signal from the nanopore requires little processing, allowing base assignment in real time).
Regarding Claim 5, Clarke et al. suggest the threshold value is determined using a different haplotype (Page 269, Column 2, Paragraph 1: direct information on haplotypes).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to combine Lapaire et al. with Fan et al. Lapaire et al. teach novel methods and finding that highlight the impotence of fragment size in cell free DNA for determining aneuploidy (Page 409, Column 2, Paragraphs 1-2: The most intriguing finding of our study, however, is the novel fragmentation signature pattern of AF cffDNA. We observed striking differences in cffDNA fragment sizes and their characteristic distributions as a function of karyotype. Our results show that there is a unique and consistent qualitative pattern of AF cffDNA fragments in euploid and aneuploid fetuses), which is a focus of Fan et al. and the instant application. They also suggest their methods can have important clinical applications (Page 409, Column 2, Paragraphs 1-2: These results may have clinical application in the rapid triaging of AF. Furthermore, the ability to statistically analyze the data from each sample provides a novel tool for a predictive model of aneuploidy in prenatal diagnosis). Furthermore, one of ordinary skill in the art would predict that the methods could be readily combined with a reasonable expectation of success because both are within the same technical field – utilizing sequence data to investigate fetal genetic disorders.
It would have been further obvious to one of ordinary skill in the art at the time of the effective filing date to combine Clarke et al. with Lapaire et al. and Fan et al. Clarke et al. teach single molecule sequencing with nanopores offer numerous advantages over other sequencing techniques (Page 269, Column 1, Paragraph 3: The sequencing of single molecules removes the need for amplification of the target DNA, lowering the time and cost of sample preparation and avoiding amplification errors. The nanopore approach will not require expensive fluorescent labels or imaging technologies, further reducing the overall cost and workflow time. In addition, certain exonucleases have high processivity, which will allow long read lengths that will simplify sequence alignment and reassembly and offer additional benefits such as direct information on haplotypes), sequencing being a critical step in Fan et al. and the instant application. Furthermore, one of ordinary skill in the art would predict that the methods could be readily combined with a reasonable expectation of success because the sequence data once generated, is the same across all methods (sequence of DNA bases) and therefore capable of being utilized by any downstream analysis that takes a genetic sequence as an input.
Double Patenting
The previously issued double patenting rejections over US patents 8620593, 9982300, 11365448 are withdrawn in view of the terminal disclosure filed 16 June 2026. No new double patenting issues are identified.
Conclusion
No Claims are allowed.
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/B.H.E./Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
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