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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/15/2026 has been entered.
Applicants Amendment
Applicant’s amendment filed 7/15/2026 has been received and entered. Claims 16-29, 31-77 have been cancelled, no amendments to the other claims have been made.
Claims 1-15, 30, 78-79 are pending.
Election/Restriction
Applicant’s election of Group I in the reply filed on 6/5/2025 was acknowledged, and claims directed to non-elected groups were cancelled.
In view of prosecution, Applicant are reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Additionally, the examiner had required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. However, it is noted that the claims directed to the method have been cancelled. In order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Claims 1-15, 30, 78-79, drawn to a system that generates a graphic representation of aligned sequences for the determination of haplotypes that may exist in the sequence data are currently under examination.
Priority
This application filed 12/10/2021 claims benefit to US Provisional application 63/124622 filed 12/11/2020; and
is related to PCT/US21/62963 filed 12/10/2021 by claim to the same US provisional application.
Applicants did not make any comments to the summary in the instant response.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/15/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 1-15, 30, 78-79 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claim analysis
Independent claim 1 has not been amended and is generally drawn to a system that generates a graphic representation of aligned sequences for the determination of haplotypes. Regarding requirements of the claim, in step a) one must first ‘align a plurality of sequence reads’ to a reference that provides ability to analyze a haplotype that might be represented in the read, and dependent claims set forth the reference is a genomic region with 1000 alignment positions (claim 2), some which can be alleles (claim 5) and/or comprises repeat regions (claim 4). There is no specific number of reads beyond a ‘plurality’ or how they are obtained, and no specific means of aligning but convention would provide aligning homologous regions where the read aligns with a reference. Once aligned, step b) provides ‘estimating an alignment score’ and given the broad ‘score’ given the guidance of the specification and convention of the art of record, the score represents an estimate of the distribution of the reads to a reference, and where step c) provides that multiple reads and reference locations can be assessed by aligning and estimating. Again, the claims are directed to a system product and there are no steps on how the reads are made, and broadly provide for reads from a data source and comparison of the reads to a reference source. The claims imply that the reads and reference that are chosen comprise information about ‘haplotypes’ and so prior knowledge of the reads and reference are required to practice the claims practically. Final steps d) and e) provide for selecting ‘alignment positions’ ‘satisfying criteria relating to evenness of read distribution’ and then displaying a graphic of the read alignments, i.e. ‘pileup’. The claims encompass a set of instructions to align read and reference sequences, assess how the reads ‘distribute’ over the reference and based on the alignment display in graphic form how the reads align with the reference. The claims only require that a plurality of reads be assessed and aligned, with no specific requirement but implied that the reads and reference comprise informative allele information representing haplotypes.
Generally, the claims provides five steps comprising aligning sequence reads to a genomic region, estimating or providing an assessment of the alignment, reiterating the steps for the sequence again or for a multiple of other sequences, based on the alignment assessment score provide a graphic representation of a plurality of reads that were processed for alignment to show haplotypes that may exist in the read data that was aligned. The process the system provides for ‘a computer graphic representing sequence reads aligned to haplotypes of a genomic region’ which is just a visualization of the alignment or homology of the reads and some reference. Other dependent claims set forth possible types of ‘haplotypes’ that may be represented in the data or the genomic region of interest, such as an ‘allele’, ‘SNP’ or other structural variations such as ‘ deletions, duplications, copy-number variants, insertions, inversions, translocations’ (claim10) or any combination thereof, and specific steps for providing alignment where read data from pair end sequencing, that is sequences between two defined primers, is aligned to a region at both ends and fragment length or other possible features between them are assessed (claim 13). Importantly for the complexity of the read data which is analyzed, while step a) indicates the source of the reads are from ‘whole genome sequencing’, the step of a) requires a simple alignment of a ‘plurality’ of reads and does not appear to materially affect the reads or the data in general which is being compared/aligned and assessed for the distribution relative to the reference even when a NGS platform is used.
Response to Applicants arguments
Applicants argue that the claims do not comprise a mathematical concept, and that there is no indication which limitation of claim 1 recites a mathematical concept.
In response, claim 1 requires that one ‘estimate an alignment score’ of which estimate and providing a score appears to fall into the category of mathematical concepts. It is acknowledged that there is no specific equation or algorithm and that ‘estimating’ broadly encompasses a best guess looking at alignments of step a), however for completeness of the analysis these limitations were noted as both mathematical for estimating a score and abstract as they can be performed without the use of a computer and could be performed using one’s mind. The guidance of the MPEP, examples of the Kim memo are acknowledged, however these general guidance are concerning claims which encompass mathematical concepts, whereas here upon review of the teaching of the specification and requirements of the claims, it is noted that claim 1 step a) requires aligning ‘a plurality of sequence reads’ and does not appear to provide any new complexity or specific requirement, and once aligned the data is ‘scored’ which appears to be mathematical, even though there is no specific algorithm set forth in the claims.
Applicants argue that the claims do not encompass a mental process and that it is not possible to practice the steps of claim 1 noting step a) for aligning a plurality of sequences. Applicants note that aligning 100 sequence reads would take about 229 days if done manually, as provided ad supported in the SMED of Dr. Vitor Onuchic, and is impossible for a human to perform. Further, it is argued that it is not possible to estimate an alignment score as required in step b).
In response, the difference of using a computer and doing the steps manually are acknowledged, however the time that it takes to perform a step is not the criteria of the 101 analysis, rather it is what is required of the steps. Here, sequences can be aligned and the alignment distribution can be estimated, and there is no evidence that these steps are so complex that the artisan could not perform these. Again, it is acknowledged that a computer can perform many tasks more quickly than a human, but what is being assessed is not the speed but what is required of the claims. Looking to the figures, for example figure 21, it appears straightforward to align a plurality of read sequences with a reference, the assess and estimate how many align with certain regions of the reference. Claim 1 is very broad and generic in what is required for steps a and b, and providing an alignment which for a plurality of sequences is a ‘pileup’ representation and providing the assessment as a graphic in the final step appears to be instructions for aligning and assessing read versus read data for possible allele information, and clearly fall into the a category of abstract concepts for data analysis which can be performed in one’s mind or using paper and pen. As noted throughout, he source of the ‘plurality’ is noted, however the requirement for analysis previous analyzed does not appear to be affected by the source or platform used to generate the data. While dependent claims provide the size of the reference of 1000 bases and number of iterations that should be performed for example claim 2 requires that the number of alignment positions is 1000, and claim 30 provides that there are 10,000 iterations of step c) which indicates to align and estimate an alignment score, in view of the teachings of the specification and generality of the claims it appears only an indication to repeat the steps, however steps a) and b) are generic alignment and estimating which appear to be simple steps that can be performed mentally. Providing that simple steps be performed multiple times does not appear to be complex nor introduce a complexity such that the claims are patent eligible.
Applicants argue that there is a significant advancement in the technical field of bioinformatics as supported by the statements in the SMED. Providing a visual assessment of an accuracy of a genotype call is argued to be an improvement, comparing the present fact pattern to Core Wireless.
In response, the statements are noted, however the steps of aligning and assessing, i.e. scoring homology between the reference and read data are well known. Providing a graphic display to a physician does not appear to be an improvement, rather it appears to broadly be simply a different way of display what was observed in the alignment of the reads. The claims do not require any increase in accuracy that appear to flow from the broad requirements of aligning and estimating recited and required of the steps of the claims. The claims generically provide for a resulting graphic and do not appear to be a technological means or necessarily an improved visualization since a generic graphic would or could lose or hide important sequence specific information that would inform the user, for example when an informative allele like BRCA1/2 is observed at the base level and not easily determined in a simple pileup of the reads as a display of the data.
Therefore, for the reasons above and of record, the rejection is maintained.
The analysis under 101 is provided below for completeness of the record.
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a product.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of assessing sequence read data for similarity or differences between themselves and possible a reference genome sequence of interest, wherein the sequences are aligned/processed using a computer The step of aligning and comparing sequence to arrive at the identification of similarities and differences between sequence reads are instructional steps. In view of the guidance of the specification and art of record, the claim requires computing similarity scores based on sequence homology with the broad steps of receiving data, compute a similarity score and thus determine any possible differences among the sequence read data forms. Claim 1 is directed to identifying ‘haplotypes’ however the claims broadly provide for any structural difference to be identified and in part do not provide ‘haplotype’ but rather more broadly a structural comparison of two or more sequences where the differences are displayed and termed haplotypes. The judicial exception is a set of instructions for analysis of sequence data and fall into the category of Mathematical Concepts, that is mathematical formulas or equations or mathematical calculations for providing ‘alignment scores’ and to the category of a Mental Processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion), where here sequences can easily be aligned and difference between them identified and represented.
The breadth of “align”, “estimate”, and “generate” a graphic of the analysis encompasses non-transformative visual assessment of read data. Recognizing and terming the differences seen as a ‘haplotype’ is consistent with any difference between the sequence read data that can be seen and as set forth in dependent claims such as ‘allele’, ‘SNP’ or other structural variations such as ‘ deletions, duplications, copy-number variants, insertions, inversions, translocations’
These limitations and generic breadth which is all relative to the input of the data which is not defined except it was from a ‘sample’ origin does not impose a meaningful limit on the claim scope, such that all others are not precluded from using the natural principle of comparing sequence data. Although the claims recite ‘computer graphic’, the courts have also identified limitations that did not integrate a judicial exception into a practical application; for example, merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f). Computing, constructing datasets and using statistical models was well understood, conventional, and routinely performed in the art at the time the application was filed. The claims appear to fall into the category of Mathematical Concepts, as it applies the use of statistics and mathematical relationships in analyzing probabilities related to a alignment score generically required of the claims, and also into the category of mental processes, as concepts performed in the human mind (including an observation, evaluation, judgment, opinion) because there is no apparent complexity to or amount of data that is collected and analyzed as presently claimed.
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 analysis is applied, except to say it is graphically displayed using a computer. This judicial exception or the steps implemented by the computer requires steps recited at high level of generality and the instructions necessary to process using a computer are only stored on a non-transitory medium possibly, and is not found to be a practical application of the judicial exception as broadly set forth.
For step 2B of the 101 analysis, each of the independent claims recites additional elements and are found to be the steps of obtaining and assessing sequence data. As such, the claims do not provide for any additional element to consider under step 2B. It is noted that in explaining the Alice framework, the Court wrote that "[i]n cases involving software innovations, [the step one] inquiry often turns on whether the claims focus on the specific asserted improvement in computer capabilities or, instead, on a process that qualifies as an abstract idea for which computers are invoked merely as a tool." The Court further noted that "[s]ince Alice, we have found software inventions to be patent-eligible where they have made non-abstract improvements to existing technological processes and computer technology." Moreover, these improvements must be specific -- "[a]n improved result, without more stated in the claim, is not enough to confer eligibility to an otherwise abstract idea . . . [t]o be patent-eligible, the claims must recite a specific means or method that solves a problem in an existing technological process." As indicated in the summary of the judicial exception above and in view of the teachings of the specification, the steps are drawn to analysis of sequence data. While the instruction can be stored on a medium and could be implemented on a computer, together the steps do not appear to result in significantly more than a means to compare sequences. The judicial exception of the method as claimed can be performed by hand and in light of the previous claims to a computer medium and in light of the teaching of the specification on a computer. In review of the instant specification the methods do not appear to require a special type of processor and can be performed on a general purpose computer. Dependent claims set forth additional steps which are more specifically define the considerations and steps of calculating, and comparing, and do not add additional elements which result in significantly more to the claimed method for the analysis. 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 (aligning sequences) to manipulate existing information (identify a difference such as a SNP, a deletion or insertion) 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 idea (designing probes to a target sequence) cannot be circumvented by attempting to limit the use to a particular technological environment or purpose and desired result.
One way to overcome a rejection for non-patent-eligible subject matter is to persuasively argue that the claimed subject matter is not directed to a judicial exception. Another way for the applicants to overcome the rejection is to persuasively argue that the claims contain elements in addition to the judicial exception that either individually or as an ordered combination are not well understood, routine, or conventional. Another way for the applicants to overcome the rejection is to persuasively argue that the claims as a whole result in an improvement to a technology. Persuasive evidence for an improvement to a technology could be a comparison of results of the claimed subject matter with results of the prior art, or arguments based on scientific reasoning that the claimed subject matter inherently results an improvement over the prior art. The applicants should show why the claims require the improvement in all embodiments.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims are 1-15, 30, 78-79 rejected under 35 U.S.C. 103 as being unpatentable over Bakker et al., McKenna et al. and Zielenzinski et al. is withdrawn.
Response to Applicants arguments
Upon review of the claim requirements, in particular the requirement of scoring ‘evenness of the read distribution’ in claim 1 and evaluation of the art of record, it is agreed that none of the references provide for assessment of read distribution and the evenness of the read provided. While the art of record does provide for consideration of alterations in the read data that might be introduced during the sequencing process and that confirmation of specific alleles or SNPs would require assessment of multiple clones/reads, the art fails to provide for estimating a score of the distribution required of the claims.
Conclusion
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
The art of record provides evidence that the analysis and characterization of haplotypes in genes of interest was well known and an active area of study. Bakker et al. provide an in depth study and a high-resolution of HLA and SNP haplotype map for disease association studies in the extended human MHC. Bakker et al provide multiple starting sequences and compare them to a reference and then graphically provide the relationship of the various sequences analyzed as demonstrated in figure 3 for example:
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Bakker et al. use the process of PCR-SSOP for HLA analysis and typing, and Bifucator to illustrate the relationship of the sequences analyzed. Further, many types of tools for aligning were known, for another example McKenna et al. was provided an overview of a genome analysis toolkit or GATK which is a MapReduce framework for analyzing next-generation DNA sequencing data. The program is capable of comparing an aligning sequences which have insertions and/or deletions, and to graphically provide read based and locus based traversals of reference target sequences as illustrated in figure 1:
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It is noted that in both Baker et al. and McKenna et al. read data relative to a reference and allele information is provided as a pileup graphic. However, none of the references indicate to estimate a score for the distribution of the reads.
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Joseph T Woitach whose telephone number is (571)272-0739. The examiner can normally be reached Mon-Fri; 8:00-4:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz R Skowronek can be reached at 571 272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Joseph Woitach/Primary Examiner, Art Unit 1687
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