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 .
Applicants Amendment
Applicant’s amendment filed 12/17/2025 has been received and entered. Claims 1, 2, 30 have been amended, claims 78-79 have been added, and claims 16-29, 31-77 have been cancelled.
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.
Newly added claims 78-79 are consistent with the examined invention.
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elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder.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prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues.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 summary.
Information Disclosure Statement
It was noted that the listing of references in the specification is not a proper information disclosure statement citing for example [0069]. No new IDS or comments were made in the instant response.
37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-15, 30 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn.
The amendment to the claims have clarified the issue as to what is meant by alignment positions and why a plurality of positions are required when a sequence is aligned.
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 stand and newly added claims 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 been amended and still is generally drawn to a system that generates a graphic representation of aligned sequences for the determination of haplotypes. Steps a), b) and d) have been amended to provide wherein clauses that describe in more detail how alignment, estimation and selection of possible alignment positions are performed and in final step e) that the graphic is a ‘read pileup associated with the selected set of alignment positions’ Generally, the claims still 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 provides for ‘a computer graphic representing sequence reads aligned to haplotypes of a genomic region’ and 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). While step a) indicates the source of the reads are from whole genome sequencing, the step of a) requires a simple alignment.
Response to Applicants arguments
Applicants summarize the basis of the 101 analysis citing MPEP 2106.04 and noting the claims require that the reads are produced by whole genome sequencing.
In response, upon review of the teaching of the specification and requirements of the claims as amended, it is noted that claim 1 step a) requires aligning ‘a plurality of sequence reads’ and does not appear to provide any new complexity. The 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.
Applicants note that claim 2 and 30 introduce an amount of complexity that would incorporate elements of complexity that would be impossible to perform in the human mind.
In response, claim 2 has been amended to require 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.
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 stand and newly added claims 78-79 are rejected under 35 U.S.C. 103 as being unpatentable over Bakker et al., McKenna et al. and Zielenzinski et al.
Response to Applicants arguments
Applicants note the amendments to the claims and argue that none of the references teach ‘for a set of alignment positions’ and ‘select[ing] a set of alignment positions…based on the plurality of alignment scores’ as amended.
In response, the claims provide generically for estimating a score, which broadly and practically is an assessment of homology when sequences are aligned. The assessment is based on how each consecutive base aligns with the aligned sequences. In view of the art, clearly multiple sequences are aligned and compared, which appears to make obvious that each of the positions were assessed. It is acknowledged that in the alignment the references do not teach that each base or position is ‘scored’ however given the generic breath a simple assessment if they match or not appears to be encompassed by a score of match or no match. Moreover, it would be obvious when comparing similar sequences for differences and similarities, and in creating a phylogenetic tree such as provided by Bakker et al. one would assess every position for conservation or branching of the compared set of sequences. Given the breadth of the claims and the high level of skill in the art for alignment and assessing homology, and methods of providing pileup sequences of reads and references, the claims appear to provide obvious high-level descriptions of considerations when assessing sequences.
Therefore, for the reasons above and of record, the rejection is maintained.
Claim 1 sets forth 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. Broadly this provides for providing known sequence reads from a specific genomic region of interest, using a computer alignment tool or simply aligning the sequences with their respective reference, then based on matches and mismatches providing a % homology or % identity or defining other differences between a sequence read from a target genome then indicating in the align sequences identity, mismatches, deletions,… which structurally as defined by the dependent claims encompass haplotypes after making the comparison. The process provides for ‘a computer graphic representing sequence reads aligned to haplotypes of a genomic region’ and 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’ 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.
The analysis and characterization of haplotypes in genes of interest was well known and an active area of study. For example, 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, but many methods of providing, comparing and aligning sequences were well known and could be used. McKenna et al. provide 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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Zielezinski et al. is provided as additional evidence for alignment-free sequence comparison where the reads are compared one to another instead of only a reference of interest, and teaches the benefits, applications, and tools in the analysis of read data. In particular, Zielezinski et al. provide for query sequences and word size iterative search parameters in the comparison and alignment of sequences.
Given the detailed teaching for the use of the various alignment tools and the illustration of the application to a variety of types of structural differences that could exist and represent a haplotype, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to use alignment tools to compare read data from a variety of sources and compare it to its correspond reference to identify informative alleles and haplotypes that may exist in the data. As demonstrated by Bakker et al. showing the application to various informative haplotypes, one having ordinary skill in the art would have been motivated to align sequences to identify informative haplotypes that might exist. Given the results of all three over Bakker et al., McKenna et al. and Zielenzinski et al. there would have been a reasonable expectation of success to use known alignment tools to identify similarities and differences between a read data and reference sequences and to display the results of the analysis based on the homology and differences observed.
Thus, the claimed invention as a whole was clearly prima facie obvious.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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