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 .
Claim Status
Original claims 1-20 filed 10/11/2022 are pending.
Priority
This application filed 10/11/2022 is a continuation of 13/952761, filed 7/29/201, now US Patent 11,468970; and
is a continuation of 14/489198, now US Patent 11,475980 filed 9/17/2014 (which is the parent to PCT/US15/48082, filed 9/2/2015) which also is a CIP of applications 13/952761, filed 7/29/201, now US Patent 11,468970; and
is related to PCT/US14/27582 through parent 13/952761 (Abn); which is a continuation of 13/834830 (Abn).
Examiner note: There appears to be an inconsistency in the claim of priority to 13/952761 because the instant application claims benefit as a continuation to both 13/952761 and 14/489198, but 14/489198 is indicated to be a continuation in part of 13/952761 implying a difference is the disclosures.
Examiner has performed a review for support of the instant claims through the claimed chain of applications, and the instant claims have been found to be supported.
Information Disclosure Statement
The five information disclosure statements (IDS) submitted between 8/15/2023 and 2/19/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
It is noted that the IDSs contain office actions from other US Applications and from related to foreign applications, but do not provide a context or specific claims or references that are discussed in the actions (see for example 2/19/2026 IDS citation #1 for 16/654094 where PTAB affirmed 101 rejection, 8/15/2023 IDS citation #s 44, 48). These have been reviewed for what is provided within them, but the relevant application material such as specification, claims and cited references have not been used for the review.
Double Patenting
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 claims at issue 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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent Application No. 13/952761 now US Patent 11,468970. Although the claims at issue are not identical, they are each provide the same analysis steps of comparing and distinguishing alleles based on difference between the sequences and abundance of the text/read sequences in the data provided. The claims of ‘761 provide additional steps for amplifying sequences from a sample and using a MPS platform to provide the text strings for analysis, but are clearly implied in the present claims for the source of plurality of text strings first selected. A copy of the allowed claim is provided for completeness and comparison to the instant claims.
An allelotyping method comprising:
amplifying one or more nucleotide sequences corresponding to a particular locus using a PCR amplification process to produce an amplified sample, wherein the amplified sample produced comprises the one or more nucleotide sequences that correspond to the particular locus and one or more erroneous nucleotide sequences that do not correspond to the particular locus, wherein the one or more erroneous nucleotide sequences are introduced during the PCR amplification process;
using a massively parallel sequencing (MPS) instrument to read the one or more nucleotide sequences and the one or more erroneous nucleotide sequences of the amplified sample and to generate a plurality of text strings quantifying the reads of the one of the nucleotide sequences and the one or more erroneous nucleotide sequences of the amplified sample;
comparing the plurality of text strings to one another using a text string matching routine to determine an abundance count for each text string included in the plurality of text strings;
distinguishing each text string quantifying one of the nucleotide sequences from each text string quantifying one of the erroneous nucleotide sequences based upon their relative abundance counts; and
determining one true allele for the particular locus by identifying the text string having a highest abundance count from among the plurality of text strings.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent Application No. 14/489198 now US Patent 11,475980. Although the claims at issue are not identical, they are each provide the same analysis steps of comparing and distinguishing alleles based on difference between the sequences and abundance of the text/read sequences in the data provided. The claims of ‘761 provide additional steps for amplifying sequences from a sample and using a MPS platform to provide the text strings for analysis, but are clearly implied in the present claims for the source of plurality of text strings first selected. A copy of the allowed claim is provided for completeness and comparison to the instant claims.
A method comprising:
amplifying nucleotide sequences in a sample using a PCR amplification process to produce an amplified sample;
using a massively parallel sequencing (MPS) instrument to read the nucleotide sequences of the amplified sample and generate a first plurality of text strings based on the amplified sample, wherein the first plurality of text strings comprises at least ten thousand text strings;
selecting, with a processor, a second plurality of text strings from the first plurality of text strings generated by the MPS instrument, wherein each of the selected second plurality of text strings represents a nucleotide sequence that corresponds to a first target locus in the amplified sample;
comparing, with the processor, the selected second plurality of text strings to one another to determine an abundance count for each unique text string included in the selected second plurality of text strings;
identifying, with the processor, a first number of unique text strings included in the selected second plurality of text strings as representing noise responses; and
determining, with the processor, a method detection limit (MDL) as a function of the abundance counts for the first number of unique text strings identified as representing noise responses.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) are: “a massive parallel sequencing (MPS) instrument’ which was used to provide a ‘read’ of nucleotide sequences and which also provides for ‘abundance count’ (in claim 1). Review of the specification provides literal support for the term MPS instrument, but no definition, description or example of such an instrument is provided. A search of the relevant art identifies Shendure et al. for the teaching that MPS is generally considered a technology, noting for example that “Although these platforms are quite diverse in sequencing biochemistry as well as in how the array is generated, their work flows are conceptually similar” and the overview provided in (Fig. 1b). Shendure et al. teach that there are a varied number of types and formats of sequencing reactions are performed by second generation sequencing machines (see Table 1 for specific formats) and the sequencing instruments are capable of providing sequence read data in the form of text strings. Shendure et al. teaches that there are advantages and disadvantages to the data produced which can affect downstream data management (page 1141, first column). Finally, Shendure et al. teach that once the sequence data is obtained from the instrument, software and standards for the generated data are necessary in addressing challenges for bioinformatics (page 1141 second column).
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter because the claimed invention is not directed to patent eligible subject matter.
Claim analysis
Claim 1 is generally drawn to a method of determining a allotype by examining alleles in sequence read data. More specifically, claim 1 requires selecting text strings representing locus in a genome, comparing the selected text strings to each other and assessing abundance based on the number of unique text strings present in the data selected in the first step, and determining what alleles are present based on the number of unique text strings representing sequences that were selected. Claims 15-20 provide for the claimed method steps stored on a computer readable medium computer file. In view of the specification, while text strings representing a sample can be obtained through amplification using PCR methodology and sequence information (‘read strings’) of the resulting amplified sample and obtained by massively parallel sequencing, the claims broadly provide for only data and no physical steps to generating the data. For the analysis required of the claims, ‘a plurality of text strings’ are required and the comparing and analysis of the text strings are then compared relative to one another to determine an abundance count and using the abundance count to identify alleles based on the differences and the identification being considered ‘allelotyping’ set forth in the preamble.
For step 1 of the 101 analysis, the claim is found to be in a statutory category as it is directed to a process and product.
For step 2A of the 101 analysis, the judicial exception of the claims is the steps of analyzing sequence read data, specifically the steps of ‘selecting’, ‘comparing’, and ‘determining’ a detection limit by aligning and comparing the number of sequence reads represented by text strings which were previously obtained from the steps of amplifying and sequencing with MPS. It is noted that these steps of analysis indicated as the judicial exception are practiced after the sequence data is obtained, and given the guidance of the specification do not require simultaneous practice of obtaining and analysis, and the judicial exception could be practiced with any sequence data, that is as a product by process of the data could be obtained with any other methodology besides MPS for providing a plurality of text strings. The judicial exception of the claim is the instructions and abstract steps of analyzing data from PCR/MPS to arrive at a value representing an allele.
Recent guidance from the office requires that the judicial exception be evaluated under a second prong to determine whether the judicial exception is practically applied. In the instant case, the claims do not have an additional element to which the allelotyping is applied, nor does it require a physical step for obtaining the text string which is analyzed. This judicial exception requires steps recited at high level of generality and are only stored on a non-transitory, and is not found to be a practical application of the judicial exception as broadly set forth.
For step 2B of the 101 analysis, the additional elements of the claim implied by using MPS are two steps for 1) amplifying a sequence by PCR and 2) sequencing the amplified sequences with MPS to obtain nucleotide sequence reads represented by text strings of data given the guidance of the specification for locus specific sdquences A search of the relevant art prior to effective filing date (2014) has identified Kinde et al. (Detection and quantification of rare mutations with massive parallel sequencing, PNAS June 2011) where they perform PCR and use MPS to obtain reads to quantitate/analyze the reads for sequence differences. Kinde et al. identify different unique sequences, and quantitate and characterizing the sequence reads as variants/mutations in the sequence data that was obtained. More generally, a review article by Day et al. (Role of digital PCR in the era of next-generation/whole genome sequencing
Jan 2013) provide for the same method steps discussed above, and provide a more general overview of the existing technology for obtaining sequence data. Specifically, Day et al. teach that there “has been a huge increase in the use and breadth of applications of next generation sequencing technology in the last three years” of which the use of MPS as a NGS is discussed. Further, the advantages of obtaining multiple reads are discussed in that the “number of reads per locus affords the potential for data from targeted resequencing protocols to be used to estimate copy-number variation”. In view of the art of record, the steps of both amplification by PCR and the use of MPS to obtain sequence read data appear to be known and conventional method steps of obtaining nucleic acid sequence data for further analysis.
The judicial exception of the claim is the instructions and abstract steps of analyzing data from PCR/MPS to arrive at a value representing an allele. The claim provides for the additional elements of performing PCR and massive parallel sequencing of the PCR product to obtain sequence information about the sample, however these steps are well known and considered conventional steps of obtaining sequence information about a sample as evidenced above. In review of the specification, the art of record and arguments in prosecution it does not appear that these steps alone or in combination provide for significantly more to obviate the basis of the 101. The additional element steps are claimed broadly, and it does not appear that any new or unobvious method for these steps are provided in the disclosure, and are implemented consistent with the art to obtain sequence information about a sample. Further, the steps of obtaining sequence read data of the additional element are separate and independent from the analysis steps, and the analysis does not feed back into the practice of the additional elements and simply provides the analysis of the data obtained from this methodology. What is left is the judicial exception, which is a series of steps that instruct to use the sequence information in the form of ‘text strings’ to compare the abundance of each text strings to identify text strings representing noise responses and determining effectively as a function of the abundance. These steps are considered abstract instructions that analyze sequence data and result in identification of an allele based on the presence in the data.
In this case, each of the steps of the judicial exception are set forth broadly as 'comparing' to obtain an abundance count, identifying unique sequences as noise, and 'determining’ a method detection level. None of these steps appear to provide a technical improvement to conventional methodology of used in the analysis of data obtained from massive parallel sequencing experiments. The claims as broadly set forth encompass providing data and verifying the data to corresponding reference sequence data. Dependent claims set forth that the unique sequences could be SNPs or STRs, however there are no specific steps in the claims and upon review of the specification there are no improvements to comparison steps or identification steps that result in any more than validation of the data. The specification provides guidance that PCR can produce copies that contain errors, however this is known by the skilled artisan and it would be understood that variations in a set of compiled sequences would have to be verified back to the starting sample or that the few random differences obtained from MPS represent these PCR variant sequences. In the instant case, the claims as stated are drawn to a method which recites abstract instructional steps for analyzing sequence read data, in which a nucleotide sequence is obtained and analyzed based on the presence or change in a sequence compared to a another reference sequence. The recited process involves obtaining sequence information and resolving the obtained sequence information in order to determine an abundance based in part on quantitating the number of reads in a sample. These analysis steps only require sequence read data, and are separate from the process in which they are obtained. Further, they information obtained from the analysis is not used to inform or change the process of obtaining the sequences, and appears to be two separate methods. As such, the judicial exception of the instant claims are drawn only to an abstract process that only manipulates data and, therefore, are not directed to patent eligible subject matter. With regards to the claims being directed to a process implemented on a computer system or embedded on a computer readable medium comprising instructions for carrying out the method, it is the underlying invention that is analyzed to determine subject matter eligibility, not just the use of a computer system or computer program product. In the instant case, the claims are directed to only the manipulation of data as described above. The method steps themselves are considered to be an abstract idea because they do not purport to improve the functioning of the computer itself, there is no specific or limitation recitation of improved computer technology, nor do they effect an improvement in any other technology or technical field. As evidenced above by the teaching of Kinde et al. and Day et al. the methodology of using PCR to amplify a target and sequence the amplified target by MPS (or any NGS) were known and appear to be conventional steps used in obtaining and quantitating sequence reads from a sample. No additional steps are recited in the instantly claimed invention that would amount to significantly more than the judicial exception. Without additional limitations, a process that employs mathematical algorithms to manipulate existing information to generate additional information is not patent eligible. Furthermore, if a claim is directed essentially to a method of calculating, using a mathematical formula, even if the solution is for a specific purpose, the claimed method is non-statutory. In other words, patenting abstract ideas cannot be circumvented by attempting to limit the use [the idea] to a particular technological environment. In the instant claims, dependent claim 16 claims that the system can be a human since the functions are performed by a human being, the computer recited in claim 15 is a program/product that amount to mere instruction to implement the abstract idea. The hardware recited by the system claims do not offer a meaningful limitation beyond generally linking “the use of the method to a particular technological environment,’ that is, implementation via computers.” see Alice Corp v. CLS Bank Int’l 573 U.S. (2014).
Claim Rejections - 35 USC § 103
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Walsh et al. (Sequence analysis and characterization of stutter products at the tetranucleotide repeat locus vWA, 1996), Reiss et al (The effect of replication errors and the mismatch analysis of PCR amplified DNA 1990), Bornman et al (Short-read, high-throughput sequencing technology for STR genotyping, published online April 2012), Gymrek et al. (lobSTR: A short tandem repeat profiler for personal genomes April 2012, cited in IDS) and Quail et al. (A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers, 2012).
Independent claim 1 requires selecting text strings representing locus in a genome, comparing the selected text strings to each other and assessing abundance based on the number of unique text strings present in the data selected in the first step, and determining what alleles are present based on the number of unique text strings representing sequences that were selected. Claims 15-20 provide for the claimed method steps stored on a computer readable medium computer file. In view of the specification, while text strings representing a sample can be obtained through amplification using PCR methodology and sequence information (‘read strings’) of the resulting amplified sample and obtained by massively parallel sequencing, the claims broadly provide for only data and no physical steps to generating the data. For the analysis required of the claims, ‘a plurality of text strings’ are required and the comparing and analysis of the text strings are then compared relative to one another to determine an abundance count and using the abundance count to identify alleles based on the differences and the identification being considered ‘allelotyping’ set forth in the preamble. One means provided by the specification for specific locus are the steps of using a PCR amplification process to produce a particular locus which can be a STR or SNP. In view of the specification, the first and second reads that are obtained and analyzed are: for the first read set the total number of reads that align with a given target (that was amplified); and for the second read set it is the subset of this total that represents total number of reads that are exactly the same (i.e. without any base errors) as the expected given target.
At the time of filing, it was known that PCR and sequencing could introduce a variety of issues based on stutter over repeats or lack of fidelity in base pairing during the amplification process. For example Walsh et al. provide a detailed analysis of the issue of stutter in the analysis of STR. Walsh et al. teach that the result is a relationship of stutter produce and the number of repeats where the ranges of allele size result in a range of stutter observed, as well as affected by the polymerase used. Walsh et al. demonstrate that minor bands representing an artifact can be distinguished from that of the major band, and also teach that one possible approach would be to use quantitative methods and could be filtered and confidence evaluated would be interpreted based in part on the amount of data. In all, Walsh et al. provide the teaching that the process of PCR can introduce errors in the resulting data, and that simply by determining the minor amount present (that is the ‘noise’ represented by the aberrant sequences), the true represented sequence can be determined and provide for a ‘detection level’ for a given method, specific primers, templates and methodology used, in particular for simple samples where there is knowledge and expectation of the allele being analyzed such that provided in the stutter of STR analysis. Walsh et al provide a basis for a visual quantification, and do not specifically sequence the smaller band or any of the amplified sequence in a way that one could provide a representative number of clones/reads that adequately represent the quantity of sequences in each of these two bands. Reiss et al. has been provided to demonstrate that many factors can affect the amount of errors that PCR can introduce and implications in statistical approaches for analysis and the expectation of thresholds for properly addressing the resulting data.
Bornman et al. (Biotech Rapid Dipateches 2012) provides for methods of PCR amplification the use and comparison of several NGS platforms to demonstrate short-read length technology could be applied in determining alleles present in a sample, such as analysis of locus representing STR-typing analysis. Bornman et al. provide a detailed analysis of the read data with respect to the starting sample, for example in STR profiling by NGS. Bornman et al. provide a heuristic decision model based on Fisher’s Exact Test was applied to evaluate the magnitude of reads mapping to each allele. A probability score was generated for each allele in the in silico genome based on: (i) the number of reads mapping to the allele, (ii) the total number of reads mapping to locus, (iii) the number of reads aligning to the in silico genome, and (iv) the total number of reads generated for a particular sample; and in Sensitivity analysis provide a simulated analysis was performed to estimate the confidence of STR genotyping calls as related to number of reads. In the results section, Bornman et al. provide a discussion of the importance of accuracy ant that the high number of reads allowed for a high level of stringency in accurately calling alleles, noting known issues with stutter and sequencing errors that can occur in the steps used to obtain the read data (see also Table 3). Gymrek et al. provide a similar analysis for the analysis of STR using data from MPS, and provide a detailed discussion on the importance of alignment in the analysis of reads which provided for the methodology performed by lobSTR in the analysis of STRs. Several filters were tested, including BLAT which provided the top hit read data in the pipeline used to analyze samples. Both Bornman et al. and Gymrek et al. provide analysis of STR, however the use of MPS to analyze SNPs was also known as evidenced by Quail et al. in the analysis of three different platforms of MPS.
Given the evidence and guidance of Walsh et al. demonstrate that minor bands representing an artifact can be distinguished from that of the major band, it would have been appreciated that the quantity would have been represented as differences in the number of reads represented in each, and it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to analyze and filter the reads in MPS wherein the more abundant band represents the unique sequence present in the sample that was amplified. This analysis clearly applies to simple samples representing one allele or STR or SNP, however in mixed samples or the analysis of multiple alleles, while the analysis becomes more challenging, the principle remains the same, and given the guidance of Bornman et al. and Gymrek et al. the analysis can be adapted to MPS data with adequate coverage. With the advent of MPS and whole genome sequencing and more generally the ability to use MPS to obtain greater sequence reads for a given sample, one having ordinary skill in the art would have been motivated to use the observations of Walsh et al. who suggest using quatitative methods when providing the analysis or filters of data as provided by Bornman et al. and Gymrek et al. As evidenced by Reiss et al. there are multiple factors that can contribute to the introduction of errors in the read data of amplified samples, however there would have been a reasonable expectation of success given the level of skill and knowledge as evidenced by the results of Bornman et al. and Gymrek et al. demonstrating the versatility of their analysis tools in physical and in silico analysis of mixed samples which would provide for the steps of using sequence read data to determine the error rate or expectation of ‘noise’ representing sequences that contain artifacts for a given specific workflow, target, primers and instrument.
Thus, the claimed invention as a whole was clearly prima facie obvious.
Conclusion
No claim is allowed.
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/Joseph Woitach/Primary Examiner, Art Unit 1687
Prosecution Insights