DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendments and remarks, filed on 05/30/2025, are acknowledged. Applicant's arguments have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn.
Status of Claims
Claims 1-20, 22, 24, 26-29, 31 are cancelled.
Claims 21, 23, 25, 30, 32-34 are under examination.
Priority
This application claims priority under 35 U.S.C. § 120 and is a continuation of U.S.
Application Serial No. 14/517,513, filed October 17, 2014, which claims priority to U.S. Patent Application No. 61/892,661 filed on October 18, 2013.
Withdrawn Rejections
The rejection of claims 21, 23, 24, 25, 33, 34 under 35 U.S.C. 103 as being unpatentable over Lee et al. (Bioinformatics, 2002, Vol. 18, No. 3, pp. 452-464) in view of Medvedev (Genome Graphs, Thesis, 2010, pp. 1-99) is withdrawn in view of applicant’s amendments.
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.
The following rejection is modified in view of applicant’s amendments.
Claims 21, 23, 25, 30, 32-34 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.
The United States Patent and Trademark Office published revised guidance on the application of 35 U.S.C. § 101. USPTO’s 2019 Revised Patent Subject Matter Eligibility Guidance (“Guidance”). Under the Guidance, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes) (Guidance Step 2A, Prong 1); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)) (Guidance Step 2A, Prong 2).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that are not “well-understood, routine and conventional in the field” (see MPEP § 2106.05(d)); or 2019 Revised Patent Subject Matter Eligibility Guidance, 84 Fed. Reg. 50-57 (January 7, 2019).
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.(Guidance Step 2B). See Guidance, 84 Fed. Reg. at 54-56.
Guidance Step 1:
The instantly claimed invention (claims 21, 33, 34 being representative) is directed to a method/system for aligning sequence reads to a reference sequence construct. Thus, the claim is directed to one of the statutory categories of invention. MPEP 2106.03.
A. Guidance Step 2A, Prong 1:
As discussed in the MPEP, abstract ideas include mathematical concepts (mathematical relationships, mathematical formulas or equations, mathematical calculations; see MPEP § 2106.04(a)(2), subsection I); certain methods of organizing human activity (see MPEP § 2106.04(a)(2), subsection II); and mental processes (concepts performed in the human mind including an observation, evaluation, judgment, opinion; see MPEP § 2106.04(a)(2), subsection III). In this case, the claimed steps that are part of the abstract idea are as follows:
aligning each of a plurality of paired sequence reads to the reference sequence construct representing the at least 1,000,000 nucleotides and embodied in the DAG data structure, the plurality of paired sequence reads including a first paired sequence read having a first sequence read and a second sequence read comprising at least a portion of a first repetitive nucleic acid sequence within the genome, the second sequence read being within a known distance of the first sequence read, wherein aligning each of the plurality of paired sequence reads to the reference sequence construct comprises:
aligning the first sequence read of the first paired sequence read to the reference sequence construct at least in part by:
creating a plurality of matrices representing a comparison between…respective nodes...in the reference sequence construct; evaluating a first plurality of scores corresponding to a respective first plurality of alignments between the first sequence read and the reference sequence construct by comparing the first sequence read to nucleotide sequences represented by nodes of the reference sequence construct based on degrees of overlap indicated in the matrices; and identifying…a first location of the reference sequence construct to which to align the first sequence read of the first paired sequence read;
aligning, using the first location and the known distance, the second sequence read of the first paired sequence read to the reference sequence construct at least in part by comparing the second sequence read to the reference sequence construct at a second location of the reference sequence construct determined using the first location and the known distance;
identifying, based on locations to which the first sequence read and second sequence read were aligned to the reference sequence construct, the first repetitive nucleic acid sequence as present in the genetic sample.
Mathematical Concept
In this case, above aligning, creating, and evaluating steps require using a DAG for relating data, generating matrices for relating data, and calculating scores and values. Notably, a mathematical relationship is a relationship between variables or numbers, and may be expressed in words or using mathematical symbols. See MPEP 2106.04(a)(2). As such, these steps require mathematical concepts and/or mathematical calculations. In this case, the scores are a mathematical relationship (in words) based on a degree of overlap between reads (which is a numerical operation). Moreover, the specification specifically teaches specific alignment algorithms that includes creating matrices using mathematical equations [page 3]. Therefore, when read in light of applicant’s own specification, the claims are directed to a mathematical concept. See MPEP 2106.04 and 2106.05(II).
In addition, as discussed above, the aligning steps rely upon the use of a “directed acyclic graph” (DAG) and one of ordinary skill in the art of graph theory would recognize that DAGs are a fundamental mathematical concept, with a precise mathematical structure consisting of a set of vertices and edges connecting them as well as associated matrices, used for modeling relationships and graphically organizing information. This position is supported by Bondy et al. (Graph Theory With Applications, 1976, pp.1-115, see at least Sections 1.1 through 1.6), which teaches that directed graphs are typically represented using nodes, edges, and/or symbols, are associated with matrices, and are a systematic means for organizing information and mathematically relating data. Therefore, to the extent that the recited DAG data structure is involved in the aligning steps, it is nothing more than another way of describing the manipulation of abstract ideas by organizing and/or mathematically relating data (via nodes and edges). See also MPEP 2106.04 and 2106.05(II). For these reasons, the claims are directed to one or more judicial exceptions. [Step 2A, Prong 1: YES].
Mental Processes
Under its broadest reasonable interpretation when read in light of the specification, the above “aligning” and “identifying” steps encompass mental observations or evaluations that are practically performed in the human mind. For example, the claimed “aligning” requires comparing sequence read data to reference sequence data (embodied in a generically recited DAG data structure), wherein in the aligning additionally includes steps for calculating scores and identifying specific locations using these scores. Applicant is reminded that the Office's eligibility guidance does not set limit on the number of calculations that can or cannot be performed mentally. MPEP § 2106.04(a)(2)III. As such, but for the recitation of a computer processor, these steps fall within the “mental processors” grouping of abstract ideas as they require performing evaluation, judgment, and opinion to make a determination about sequence read data. See MPEP 2106.04(a)(2), subsection III. [Step 2A, Prong 1: YES].
B. Guidance Step 2A, Prong 2
This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. In this case, the claimed steps that are not part of the abstract idea are as follows:
obtaining, from at least one non-transitory computer-readable storage medium, the reference sequence construct embodied in a directed acyclic graph (DAG) data structure, the reference sequence construct representing at least 1,000,000 nucleotides and comprising a plurality of nodes representing respective nucleotide sequences of one or more nucleotides stored as respective strings of one or more symbols in the at least one non-transitory computer-readable storage medium, wherein at least one node…is stored in the memory as a string of a plurality of symbols and a set of parent nodes;
In this case, the above step requires obtaining a “reference sequence construct” (embodied in a DAG data structure) which broadly encompasses obtaining a particular data source or type of data to be manipulated by the abstract idea. Therefore, this step amounts to insignificant extra-solution activity and is not indicative of an integration into a practical application. See MPEP 2106.05(g). With regards to the “DAG data structure”, although this limits the identified judicial exception, this type of limitation merely confines the use of the abstract idea to a particular technological environment (i.e. a computer) and thus fails to add an inventive concept to the claims. See MPEP 2106.05(h). With regards to the computer processor and computer readable medium, these are recited at a high level of generality and are merely used as a tool to perform generic computer functions, as discussed above in Step 2A, Prong One. Therefore, the above step amounts to no more insignificant extra-solution activity and/or mere instructions to apply the exception using a generic computer. See MPEP 2106.05(f). Even when viewed in combination, these additional elements do not integrate the recited judicial exception into a practical application (Step 2A, Prong Two: NO), and the claim is directed to the judicial exception. [Step 2A, Prong 2: NO]
C. Guidance Step 2B:
Under the 2019 PEG, a conclusion that an additional element is insignificant extra-solution activity in Step 2A should be re-evaluated in Step 2B. In this case, the claims do not include additional steps and/or elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s) for the following reasons:
As discussed above, the above non-abstract steps (including the full limitations and not just the verbs) amount to nothing more than insignificant extra-solution activity and/or instructions to “apply” the exception in a generic way. In this case, the specification teaches routine and conventional computer hardware and quantitative analysis software for carrying out the claimed invention [see at least pages 19, 20] and that DAGs can be easily assembled from known sequence databases [page 7]. Moreover, Shaffer et al. (A Practical Introduction to Data Structures and Algorithm Analysis, Copyright 2009, pp. 1-620) teaches that graph structures are routine and conventional means for organizing information and necessarily include the use of edges, nodes, and directed graphs (i.e. mathematical constructs) for relating data (See at least Sections II and IV). See also Hernandez et al. (Bioinformatics, 2014, Vol. 30 no. 1, pages 40–49, Early Pub. Date: 10/15/2013), which teaches sequence alignment and assembly methods using paired-end reads and directed graph search trees. In other words, there is nothing unconventional with regards to the use of DAGs for storing sequence data (including paired-end reads). With regards to the claimed processor and storage medium, as explained with respect to Step 2A Prong 2, this limitation is at best the equivalent of merely adding the words “apply it” to the judicial exception.
In addition, to the extent that the DAG is stored on the computer, the courts have held that a claim defining storing data in a "data structure" does not define a "particular machine," and does not distinguish from "manipulation of abstract ideas" and therefore does not satisfy the requirements of 35 USC 101. See Ex Parte Wasynczuk, No. 2008-1496 (2 June 2008) and Ex Parte Langemyr, No. 2008-1495 (28 May 2008). Mere instructions to apply an exception cannot provide an inventive concept, and the courts have also explained that the use of generic computer elements do not alone transform an otherwise abstract idea into patent-eligible subject matter. See DDR Holdings (Fed. Cir. 2014). Therefore, even when viewed as a combination, there is nothing unconventional with regards to the above steps/elements and applicant has not provide any evidence to the contrary. Thus, the independent claim(s) as a whole do not amount to significantly more than the exception itself. For these reasons, the claim(s) is/are not patent eligible. [Step 2B: NO].
D. Dependent Claims
Dependent claims 23, 25, 30, 32 have also been considered under the two-part analysis but do not include additional steps/elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s) for the following reasons. In particular, claims 23, 25, 30, 32 further limit the specificity of the abstract idea or the data used by the abstract idea and therefore are also directed to an abstract idea for reasons discussed above (Step 2A, prong 1 analysis). Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea (and/or natural correlation) without significantly more.
Response to Arguments
Applicant’s arguments, filed 05/30/2025, have been fully considered but are not persuasive for the following reasons.
Applicant argues that the claimed invention does not recite any mental steps because the human mind cannot practically access a directed acyclic graph representing 1,000,000 nucleotides of the human genome. In response, applicant is again reminded that the Office's eligibility guidance does not set limit on the number of calculations that can or cannot be performed mentally. MPEP § 2106.04(a)(2)III. In addition, while the reference sequence construct ‘represents at least 1,000,000 nucleotides’, it comprises a plurality of nodes representing ‘one or more nucleotides’ and the claims do not impose any boundary on the number of paired sequence reads (being aligned). Under the BRI, the claimed steps require analyzing reference data (in the form of a directed acyclic graph or DAG) and sequence data, generating scores, and generating additional information (genotyping) based on said scores. The courts are clear that an invention directed to the “collection, manipulation, and display of data” is an abstract process. See Intellectual Ventures, 850 F.3d at 1340; see generally id. at 1340-41. The specification also provides sufficient evidence that the claims are directed to an abstract idea since the specific descriptions provided for accomplishing these tasks include only data analysis methods [pages 6, 7]. Accordingly, these steps are properly classified under the “mental process” category for reasons discussed above (Step 2A, prong 1). See MPEP 2106.04(a)(2), subsection III [Step 2A, Prong 1: YES].
Applicant additionally argues that the claims do not recite a mathematical concept. In response, this argument is also not persuasive. In this case, for reasons discussed above (Step 2A, prong 1), the claimed aligning, creating, and evaluating steps require using a DAG for relating data, generating matrices for relating data, and calculating scores and values. Notably, a mathematical relationship is a relationship between variables or numbers, and may be expressed in words or using mathematical symbols. See MPEP 2106.04(a)(2). As such, these steps require mathematical concepts and/or mathematical calculations. In this case, the scores are a mathematical relationship (in words) based on a degree of overlap between reads (which is a numerical operation). Moreover, the specification specifically teaches specific alignment algorithms that includes creating matrices using mathematical equations [page 3]. Therefore, when read in light of applicant’s own specification, the claims are directed to a mathematical concept. See MPEP 2106.04 and 2106.05(II). In addition, as discussed above, the aligning steps rely upon the use of a “directed acyclic graph” (DAG) and one of ordinary skill in the art of graph theory would recognize that DAGs are a fundamental mathematical concept, with a precise mathematical structure consisting of a set of vertices and edges connecting them as well as associated matrices, used for modeling relationships and graphically organizing information. This position is supported by Bondy et al. (Graph Theory With Applications, 1976, pp.1-115, see at least Sections 1.1 through 1.6), which teaches that directed graphs are typically represented using nodes, edges, and/or symbols, are associated with matrices, and are a systematic means for organizing information and mathematically relating data. Therefore, to the extent that the recited DAG data structure is involved in the aligning steps, it is nothing more than another way of describing the manipulation of abstract ideas by organizing and/or mathematically relating data (via nodes and edges). See also MPEP 2106.04 and 2106.05(II). For these reasons, the examiner maintains that the claims are indeed directed to a mathematical concept. [Step 2A, Prong 1: YES].
Applicant additionally argues that the claimed invention takes advantage of the fact that paired-end sequence reads are within a known distance of each other in order to “greatly reduce the number of co-alignments” as compared to state-of-the-art methods (Specification, para. 21). In response, the limitations set forth above have been interpreted as part of the abstract idea (Step 2A, prong 1). Accordingly, applicant is essentially arguing that the inventive concept is the abstract idea (and that the abstract idea is being used to obtain “better data”). However, Applicant is reminded that “[i]t has been clear since Alice that a claimed invention’s use of the ineligible concept to which it is directed cannot supply the inventive concept that renders the invention ‘significantly more’ than that ineligible concept.” BSG Tech LLC v. BuySeasons, Inc., 899 F.3d 1281, 1290 (Fed. Cir. 2018). On this point, the courts have recently instructed that “[t]he different use of a mathematical calculation, even one that yields different or better results, does not render patent eligible subject matter.” Board Of Trustees Of Leland Stanford Junior University, 991 F.3d 1245, 1251 (Fed. Cir. 2021). In addition, there is also case law supporting the determination that claims that merely provide efficiency or accuracy increases over mental calculations do not recite eligible subject matter. See Bancorp Servs., L.L.C. v. Sun Life Assurance Co. of Can. (US.), 687 F.3d 1266, 1279 (Fed. Cir. 2012) ("Using a computer to accelerate an ineligible mental process does not make that process patent-eligible.").
To the extent that applicant is arguing that the claimed invention provides an improvement to a specific machine, the claimed invention is directed to a method for aligning paired sequence reads. The claim relies on a computer hardware processor that is recited at a high level of generality and the specification teaches these are generic computer hardware elements performing routine and conventional functions [pages 18-20]. Applicant does not contend that it invented any of the claimed components or their basic functions or that those components, claimed generally, were unknown in the art as of time of the invention. Accordingly, the claimed processor has been reasonably interpreted as conventional computer elements and using a computer as a tool to perform an abstract idea. As such, the claimed invention does not improve any specific machine. Unlike the McRO decision, for example, where the ultimate product produced was a synchronized computer animation that was itself the transformative use, the result of the presently claimed process (performed by the claimed system) is information itself, without being directed to any particular use of that information. See also Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1355 (Fed. Cir. 2016) (“[Merely selecting information, by content or source, for collection, analysis, and display does nothing significant to differentiate a process from ordinary mental processes.”). In summary, while appellant’s particular algorithmic approach may be a particular way to achieve an alternative solution for improving the accuracy of sequence alignment, the claimed invention is, nevertheless, directed to an improved algorithmic analysis. As such, the claims do not integrate the recited judicial exception into a practical application. Notably, there is nothing inventive with regards to the use of a DAG for storing sequence data and the instant claims do not recite any steps for using the information produced by the abstract idea to generate an effect outside of a computer (i.e. a real-world practical application). For at least these reasons, the rejection is maintained.
Conclusion
No claims are 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PABLO S WHALEY whose telephone number is (571)272-4425. The examiner can normally be reached between 1pm-9pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anita Coope can be reached at 571-270-3614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PABLO S WHALEY/Primary Examiner, Art Unit 3619