DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/19/2026 has been entered.
Applicant's amendments and remarks, filed on 03/19/2026, 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 Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn.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 35-54 are presently under examination.
Claims 1-34 are cancelled.
Priority
Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a continuation of and claims benefit to U.S. application no. 15/679,261 filed August 17, 2017, which is a division of U.S. application no. 13/363,717 filed February 1, 2012 (now abandoned), which claims priority to U.S. application no. 61/483,442 filed May 6, 2011, U.S. application no. 61/446,427 filed February 24, 2011, and U.S. application no. 61/438,545 filed February 1, 2011. For reasons of record, priority is only granted to U.S. application no. 61/483,442, filed May 6, 2011. Applicant has not disputed this issue.
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 35-54 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.
Step 1
Regarding claim(s) 34, 44, 53, these claims are representative of the invention and recite performing a series of process steps. As such, the claims fall into one of the four statutory categories.
A. Guidance Step 2A, Prong 1
The Revised Guidance instructs us first to determine whether any judicial exception to patent eligibility is recited in the claim. The Revised Guidance identifies three judicially-excepted groupings identified by the courts as abstract ideas: (1) mathematical concepts, (2) certain methods of organizing human behavior such as fundamental economic practices, and (3) mental processes. Regarding claim(s) 34, 44, 53, the following limitations constitute the abstract idea for the following reasons:
mapping the contiguous portion of the fragment sequence to the reference genome using an approximate string matching method to produce an at least partial match of the contiguous portion to the reference sequence, wherein the approximate string matching method matches the contiguous portion of the fragment sequence to the reference sequence while allowing a limited number of mismatches;
mapping a remaining portion extending from the anchor portion of the fragment sequence to the reference genome using an ungapped local alignment method…;
mapping the same remaining portion extending from the anchor portion of the fragment sequence to the reference genome using a gapped alignment method to produce a gapped alignment of the remaining portion extending from the anchor portion, wherein the gapped alignment method includes calculating a gapped alignment score for a given gapped alignment…;
determining a first quality value for the ungapped alignment by calculating a first posterior probability of the ungapped alignment of the fragment sequence with the reference genome…;
comparing the first quality value and the second quality value to determine a higher quality value;
Mental Processes
Under the BRI, the above italicized steps encompass manipulating and/or organizing data, and analyzing the data by calculating and comparing scores. In addition, the specification describes processes for analyzing sequence data that clearly use algorithms for performing at least some of the above functions [0056]. As such, the specification provides sufficient evidence that the claims are directed to an abstract idea since the specific descriptions provided for accomplishing these tasks include only data reception and analysis, which may be performed in the human mind via normal processes of observation and evaluation. Accordingly, when read in light of the specification, the above steps clearly fall within the mental process groupings of abstract ideas because they cover concepts performed in the human mind, including observation, evaluation, judgment, and opinion. See MPEP 2106.04(a)(2), subsection III. [Step 2A, Prong 1: YES].
Mathematical Concept
In addition, the “mapping” steps additionally require using “string matching method” and “local alignment method” as well as “calculating” scores. With regards to the “string matching method” and “local alignment method”, these limitations are written effectively as a method for mathematically manipulating and/or relating data to ascertain additional data and are in essence a mathematical algorithm, as characterized by the Supreme Court (Federal Register, Vol. 79, No. 241, December 16, 2014 at 74622, column 2). With regards to the “calculating” steps, these involve mathematical operations and thus amount to mathematical calculations by definition. In addition, the grouping of “mathematical concepts” in the 2019 PEG is not limited to formulas or equations, as words used in a claim operating on data to solve a problem can serve the same purpose as a formula. Therefore, when read in light of applicant’s own specification, the claimed steps clearly encompass mathematical calculations and/or mathematical relationships under the Revised Guidance. For these reasons, the claims are directed to a mathematical concept which is a judicial exception. See MPEP 2106.04 and 2106.05(II), and October 2019 Update at Section I.B. For these reasons, the claims are directed to one or more judicial exceptions. [Step 2A, Prong 1: YES].
B. Guidance Step 2A, Prong 2
Having made that determination, under the 2019 Guidance, the examiner next determines whether there are additional elements beyond the recited abstract idea(s) that integrate them into a practical application. Besides the abstract idea, the claim(s) recite the following additional steps/elements:
receiving a plurality of nucleic acid fragment sequences from a next generation sequencing (NGS)…instrument and a reference genome at a processor….;
selecting a contiguous portion of the fragment sequence;
selecting one of the ungapped alignment and the gapped alignment corresponding to the higher quality value to identify a best alignment of the fragment sequence and the reference sequence for a report.
With regards to the above “receiving” step, this limitation broadly encompasses obtaining data for use by the abstract idea (i.e. data collection). 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 above “selecting” steps, these limitations broadly encompass selecting data a particular data source or type of data to be manipulated by the abstract idea. Therefore, these steps amount 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 NGS instrument and array of sensors, these generically recited elements are merely used by the claimed method to obtain data for subsequent use by the abstract idea. As such, these limitations amount to nothing more than an attempt to generally link the use of the judicial exception to a technological environment and performing extra-solution activity. See MPEP 2106.05(g) and MPEP 2106.05(h).
With regards to the recited processor, this is recited at a high level of generality and thus can be viewed as nothing more than an attempt to generally link the use of the judicial exception to a technological environment or a computer. In addition, “generic computer components such as a computer and database do not satisfy the inventive concept requirement.” See MPEP 2106.05(h). Accordingly, the claim as a whole does not integrate the recited judicial exception into a practical application and the claim is directed to the judicial exception. Accordingly, the claim as a whole does not integrate the recited judicial exception into a practical application and the claim is directed to the judicial exception. [Step 2A, Prong 2: NO]
C. Guidance Step 2B:
This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP 2106.05.
As discussed above, the non-abstract steps/elements amount to nothing more than insignificant extra-solution activity. Moreover, applicant’s own specification teaches routine and conventional sequencing technologies (including NGS) for performing the above steps [See at least ¶0004, ¶0005, ¶0019]. Similarly, Li et al. teaches a review of sequence alignment algorithms for next-generation sequencing that include conventional NGS instruments (see rejection under 35 USC 103 below). Therefore, even upon reconsideration, there is nothing unconventional with regards to the above non-abstract elements/steps. See MPEP 2106.05(d)(Part II). In addition, with regards to the claimed processor, as explained with respect to Step 2A Prong Two, 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). Thus, the independent claim(s) as a whole do not amount to significantly more than the exception itself. Therefore, the claim(s) is/are not patent eligible. [Step 2B: NO].
D. Dependent Claims
Dependent claims 36-43, 45-52, 54 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 this case, claims 36-43, 45-52, 54 further limit the specificity of the abstract idea set forth above (i.e. the type of analysis) or further limit the nature of the data being used for analysis (i.e. the type of gap portions, insertion lengths). Therefore, the subject matter of these claims is still part of the abstract idea and is not patent eligible for the reasons discussed above. As such, the claimed subject matter fails to transform the exception into a patent‐eligible application of that exception and fails to integrate the abstract idea into a practical application for reasons discussed above. Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea without significantly more. For additional guidance, applicant is directed generally to the 2019 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on January 7, 2019.
Response to Arguments
Applicant’s arguments, filed 03/19/2026 have been fully considered but are not persuasive for the following reasons.
Applicant generally argues that the amended claims recite an improvement to the technology, namely by providing more accurate mapping using an anchor portion data structure, and citing similarity to Enfish. In response, the MPEP is clear that the word "improvements" in the context of this consideration is limited to improvements to the functioning of a computer or any other technology/technical field, whether in Step 2A Prong Two or in Step 2B. MPEP 2106.04(d)(1). In this case, applicant has not provided any objective evidence to support the assertion that the claimed invention is directed to an improvement to a computer or computer functionality (as in Enfish). The claims also fail to identify any elements that provides for a sequencing technology. That being said, applicant is essentially arguing that the “mapping” steps (i.e. the abstract idea) is providing the improvement. However, Applicant is reminded that the claimed invention’s use of the ineligible concept to which it is directed (i.e. the abstract idea) 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).
In addition, unlike the instant claims, the claims in Ex Parte Desjardins are directed to a method for training a machine learning model, comprise a plurality of different active method steps directed to model training. Therefore, applications arguments are not persuasive because the instant claims are directed to an entirely different fact pattern. Similar to Recentive v. Fox, applicant is reminded that AI and machine learning claims need to demonstrate a genuine technological advancement beyond merely applying generic ML to a new use case or achieving increased speed and efficiency to be considered patent-eligible under Section 101. See also MPEP 2106.04(d)(1) for a list of considerations for evaluating whether additional elements integrate a judicial exception into a practical application. For at least these reasons, the rejection is maintained.
Claim rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(a):
IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 35-54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 35, 44, 53 recite “mapping…to produce an at least partial match…, wherein the approximate string method matches…with a limited number of mismatches to define an anchor portion of the fragment sequence, wherein a length of the anchor portion is not greater than half the length of the fragment sequence.” The above phrase confusingly recites multiple results-based/intended use limitations directed to the purpose of the claimed mapping (e.g. to produce a partial match, to define an anchor portion). Applicant is reminded that no patentable distinction (i.e. no limit on the claim scope) is made by an intended use or result recitation unless some structural difference is imposed by the use or result on the structure or material recited in the claim. In this case, it is unclear what positive process limitations are intended by the intended-use phrase “…to define an anchor portion of the fragment sequence”, as this does not impose any limiting effect on the claimed mapping. Moreover, the claim does not any steps for actually determining a “length” of the anchor portion (such that any conditional judgement can actually be made on this basis as claimed). A review of the specification [0034] teaches that the sequence alignment method can match an anchor portion of the fragment sequence to a portion of the reference sequence. However, this is not what is being claimed and it is improper to import narrowing limitations into the claims. MPEP 2111.01. Clarification is requested via amendment.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 35-54 are rejected under 35 U.S.C. 103(a) as being unpatentable over Li et al. (Briefings in Bioinformatics, Volume 11, Issue 5, September 2010, pp. 473–483) in view of Morgenstern et al. (Algorithms for Molecular Biology 2006, 1:6, pp.1-12) and Cameron et al. (IEEE Transactions On Computational Biology And Bioinformatics, Vol. 1, No. 3, 2004, pp.116-129).
Li teaches a review of sequence alignment algorithms for next-generation sequencing. Regarding claim(s) 35, 44, 53, Li teaches obtaining a reference genome and obtaining/selecting sequence read data (i.e. fragment sequences) from conventional NGS technologies [page 477, col. 2, page 478, entire, Figures 2 and 3] wherein the reads are associated with specific lengths and bases as well as contiguous errors [Fig. 2, 3, 4], which reasonably suggests contiguous portions.
Li teaches mapping specific portions of sequence reads to a reference genome using string-based methods (which broadly reads on a string matching method as claimed) and seed extension methods [page 476, col. 1, and col. 2], and calculating alignment scores [page 478, col. 2, Figure 3] (which reasonably suggests a limited number of mismatches via scoring procedures). Li teaches mapping specific portions of sequence reads to a reference sequence using seed extension methods [page 475, col. 2]. Li additionally teaches mapping specific portions of sequence reads to a reference sequence using gapped and ungapped alignment algorithms [page 477, col. 2, page 478, entire, Figure 2]. In each case, all programs are capable of genome-wide long-read alignment follow the seed-and-extend paradigm, and extending seed matches with the banded Smith–Waterman algorithm [page 479, col. 1]. In each case, Li teaches calculating base quality scores to determine alignment quality [page 478, col. 2, Figure 3].
Li does not specifically teach an approximate string matching method that matches the contiguous portion of the fragment sequence to the reference genome with a limited number of mismatches to define an anchor portion of the fragment sequence, wherein a length of the anchor portion is not greater than half the length of the fragment sequence. However, it is explicitly noted that intended use limitations have no limiting effect on the functionality of the method as claimed. Moreover, even if these features were given patentable weight, Morgenstern teaches an algorithm and software for determining user-defined anchor points by mapping multiple sequence alignments [Abstract and page 2, entire].Therefore, it still would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have modified the teachings of Li by determining (or defining) an anchor point, as claimed, since alignments-based methods for determining user-defined anchor points was routine and conventional in the art, as taught by Morgenstern and since the length of this anchor point is user-definable and would have been considered a mere design consideration that fails to patentably distinguish over the cited prior art references. The motivation would have been to produce alignments that are biologically more meaningful than alignments produced by fully automated procedures.
Li and Morgenstern do not specifically teach determining a first quality value for the ungapped alignment and a second quality value for the gapped alignment by calculating posterior probabilities P(A/r), wherein a posterior probability P(A/r) is based on a probability of an event A that a fragment sequence r aligns with a particular region of the reference genome as claimed.
Li and Morgenstern do not specifically teach comparing the first quality value and the second quality value to determine a higher quality value; selecting one of the ungapped alignment and the gapped alignment corresponding to the higher quality value to identify a best alignment of the fragment sequence and the reference sequence for a report, as claimed.
However, Cameron teaches mapping sequences using both gapped and ungapped algorithms [Section 2.21-2.23, Figure 2, Section 3.1]; identifying high scoring matches; and determining and comparing quality values for each stage by calculating Karlin-Altschul statistics [Section 2.2.2- 2.23, 2.2.5, Section 3.1], which broadly reads on posterior probability values absent any limiting definition to the contrary. Lastly, Cameron teaches determining optimal alignments including selecting sequences that are aligned using both ungapped methods and gapped methods based on specific scoring criteria [Section 2.2.2- 2.23, 2.2.5, Section 3.1].
Therefore, absent any evidence to the contrary, it would have been obvious to one of ordinary skill in the art before the effective filing date to have modified the teachings of Li and Morgenstern by determining posterior probability quality values for any remaining portions of ungapped and gapped alignments, comparing the first quality value and the second quality value to determine a higher quality value, and selecting ungapped and gapped alignments corresponding to the higher quality value to identify a best alignments for a report, as claimed, since Cameron teaches statistical analysis methods for scoring fragments using both gapped and ungapped sequence alignment methods in order to identify optimal alignments, and since one of skill in the art of bioinformatics would recognize that the formula for posterior probability derived from Bayes’ Theorem, P(A|B) = [P(B|A) * P(A)] / P(B), is well known to represent the probability of a specific event (e.g., a read aligning to a specific position in the genome) given the observed data (the sequence read). The motivation would have been to combine the efficiency of ungapped alignment and the accuracy of gapped alignment, allowing BLAST to accurately filter sequences with lower computational cost, as taught by Cameron [Abstract].
Regarding claim(s) dependent claims 36-43, 45-52, 54, all aspects of these claims are taught or suggested by the combination of Li, Morgenstern, and Datta. Regarding claim(s) 36-38, 45-47, 54, these claims further limit the selecting and mapping steps to be iterative. Li and Cameron do not explicitly teach this feature. However, Li teaches the use of alignment algorithms that include BLAST [page 474, col. 1] and Cameron teaches sequence alignment methods that include optimal local alignment, wherein all possible pathways between two sequences are computed with respect to a scoring scheme [page 117]. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to have performed iterative selecting and mapping, as claimed, since Li and Cameron reasonably suggest iterative processes and since one of ordinary skill in the art would have recognized that BLAST requires iterative analysis in order to search an entire query sequence against a database. The motivation would have been combining prior art elements according to known methods to yield predictable results.
Regarding claim(s) 39, 40-42, 48, 49, Li and Cameron both teach gapped alignment algorithms, as set forth above. In addition, Cameron additionally teaches gapped schemes that explore insertions and deletions [Section 2.2.3] and methods for extending gaps [page 120, col. 1]. Li additionally teaches that programs used are capable of genome-wide long-read alignment and follow the seed-and-extend paradigm which allows for partial hits [page 479, col. 1].
Response to Arguments
Applicant’s arguments have been fully considered but are moot in view of the new grounds of rejection (which relies upon the newly cited teachings of Morgenstern to address new claim limitations).
Conclusion
No claims are allowed.
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
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