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 Amendment/Request for Reconsideration-After Non-Final Rejection, filed 6/10/2026, has been entered and fully considered.
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, or 365(c) is acknowledged. Priority of US application 62/405,824 filed 10/07/2016 is acknowledged.
Status of claims
Claims 1-27 and 31 are cancelled;
Claims 28-30 and 32-58 are pending and are examined on the merits.
Claim Objections
Claim 58 is objected to because of the following informalities: claim 58 recites “the method further automatically terminating…”, which does not sound like a grammar correct clause. “Terminating” should be “terminates”. Appropriate correction is required.
Claim Rejections - 35 USC§ 101
This rejection is maintained from a previous Office Action. Modifications are necessitated by claim amendments.
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 28-30 and 32-58 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 28-30, 32-44, 55 and 57-58 are directed to a machine or manufacturer (here a “system”) for calling variants, with structural components like “a sequencing apparatus” and “a processor”.
Claims 45-54 and 56 are directed to a process (here a “computer-implemented method”) for efficient sequencing of polynucleotides, with functional steps like “receiving”, “performing”, “comparing”, and “determining”.
Step 2A Prong One: Identification of Abstract Ideas
Claim 28 recites:
Determining whether the first nucleotide subsequence aligns to a reference sequence at a first plurality of candidate locations beyond a threshold confidence level using a first process.
This step recites the alignment of one subsequence to a reference sequence at a plurality of candidate locations. Under a BRI, the first subsequence can be a short sequence reads and the reference sequence can be a short-sized bacteria genome. Around a few candidate locations, this work can be done by a human with the help of a pen/paper. Therefore, this step is directed to an abstract idea of mental processes.
Comparing the one or more additional nucleotides in the second nucleotide subsequence to the reference sequence to call first variants based in part on the first plurality of candidate locations, if the first nucleotide subsequence is aligned to the reference sequence beyond the threshold confidence level.
This step recites the extended alignment of one or more nucleotides to a reference sequence guided by the mapping location of the existing alignment of the first subsequence. This work can be achieved in the human mind easily. Therefore, this step is directed to an abstract idea of mental processes.
Repeating the first process by aligning the entire second nucleotide subsequence to the reference sequence to call second variants if the first nucleotide subsequence is not aligned to the reference sequence beyond the threshold confidence level.
This step recites the alignment of one subsequence to a reference sequence at a plurality candidate locations. Under a BRI, the first subsequence can be a short sequence reads and the reference sequence can be a short-sized bacteria genome. Around a few candidate locations, this work can be achieved by a human with the help of a pen/paper. Therefore, this step is directed to an abstract idea of mental processes.
Claim 45 recites:
Performing a secondary analysis of the first nucleotide subsequence of the read based on a reference sequence using a first process or a second process,
This step recites “a secondary analysis” in a general way, but involves the sequence reads and the reference sequence. Under a BRI, it reads on data analysis requiring sequence alignment. This step can be achieved by a human with the help of a pen/paper. Therefore, this step is directed to an abstract idea of mental processes.
Wherein the first nucleotide subsequence comprises one or more additional nucleotides compared to a previous iteration, wherein the second process is more computationally efficient than the first process in performing the secondary analysis, wherein the first process aligns the entire first nucleotide subsequence to the reference sequence, wherein the second process aligns the one or more additional nucleotides to the reference sequence based in part on results from the previous iteration, and wherein the secondary analysis comprises:
This step further limit the sequence analysis process, which equates to an abstract idea of mental processes.
Comparing the first nucleotide subsequence to the reference sequence to determine a first subsequence of the reference sequence that has a high degree of similarity to the first nucleotide subsequence;
This step further limit the sequence analysis process, which equates to an abstract idea of mental processes.
As such, under the broadest reasonable interpretation, the claims recite elements that can be practically carried out in the human mind or with pen and paper as claimed, which falls under the “Mental processes”. Although claims recite performing these steps as part of a method executed on a computer, there are no additional imitations to indicate that anything other than a generic computer is required. However, merely requiring that the steps are carried out with a generic computer does not negate the mental nature of these steps and equates rather to merely using a computer as a tool to perform the mental process.
Dependent claims further recite additional limitations to the sequence analysis procedures, or barely mention that the software program is recorded in a non-transitory computer readable medium (claims 55-56). Hence, the claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)).
Step 2A Prong Two: Consideration of Practical Application
The claims result in a process of “providing the first or second variant calls to a user at time intervals depending on the available computing resources “ (claim 28) or “providing results of the secondary analysis to a user at time intervals depending on the available computing resources” (claim 45), which equate to insignificant extra-solution activities of data outputting. The claims do not recite any additional elements that integrate the abstract idea/judicial exception into a practical application.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than
a drafting effort designed to monopolize the exception.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
Claim 28 recites:
A sequencing apparatus configured to determine the nucleotide sequence of a polynucleotide.
This step recites a “sequencing apparatus”, which equates to an additional element.
A processor configured to control the sequencing apparatus and to execute instructions that perform a method comprising.
This step recites a “processor”, which equates to an additional element.
Receiving a first nucleotide subsequence of the polynucleotide.
This step recites a acquiring a data input of “a first nucleotide subsequence of the polynucleotide”, which equates to an additional element of data inputting.
Receiving a second nucleotide subsequence of the polynucleotide from the sequencing apparatus, wherein the second nucleotide subsequence comprises the first nucleotide subsequence plus one or more additional nucleotides.
This step recites a acquiring a data input of “a second nucleotide subsequence of the polynucleotide”, which equates to an additional element of data inputting.
Providing the first or second variant calls to a user at time intervals depending on the available computing resources.
This step recites reporting a variant calls to a user, which equates to an additional element of data outputting.
Claim 45 recites:
Receiving a first nucleotide subsequence of a read from a sequencing apparatus during a sequencing run of the first nucleotide subsequence.
This step equates to an additional element of data gathering.
Providing results of the secondary analysis to a user at time intervals depending on the available computing resources.
This step recites reporting a secondary analytical result to a user, which equates to an additional element of data outputting.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the above additional elements can be divided into three groups: elements directed to (1) acquiring the input sequence data, as well as the apparatus for generating the sequence data; (2) computers (processors, storage medium, and display interface); and 3) output analysis results. The first and the third groups are insignificant extra-solution activities because they are necessary for data-gathering or data outputting. The second group is drawn to nothing more than that of generic computers performing the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
Regarding the three groups: (1) acquiring the input sequence data, as well as apparatus for generating the sequence data; (2) computers (processors, storage medium, and display interface; and 3) output analysis results. MPEP 2106.05(d).II list several activities related to the above identified additional elements as well‐understood, routine, and conventional functions when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Particularly the following activity is highly related to the group 1) additional elements, which comprises sequencing apparatus configured to determine nucleotide sequence of a polynucleotide claimed additional elements:
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546;
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
Although the sequencing apparatus is not explicitly designated as conventional here, generic sequencing apparatus is conventional as they are available in commercial service.
Regarding the group 2) additional elements, the claims as a whole amount to nothing more than generic computer functions merely used to implement an abstract idea. Courts have held computer‐implemented processes as well‐understood, routine, and conventional functions when they are claimed in a merely generic manner. (MPEP 2106.05(d).II).
Regarding the group 3) additional elements, outputting the analytical results is well-known, insignificant and amounts to necessary data gathering and outputting.
Hence all the three groups of additional elements are well-known and conventional.
Therefore, at step 2B, the additional elements failed to provide the something to be significantly more. (see MPEP 2106.05(g)). (Step 2B: No).
For these reasons, the rejection under 35 USC § 101 is maintained.
Response to Applicant’s Argument:
Applicant's arguments filed 10 June 2026 have been fully considered but they are not persuasive. Particularly:
In the Remarks filed 10/06/2026, Applicant argues (page 9, 2nd para) that claims 28 and 45 as amended, “The second process directly compares one or more additional nucleotides in the second nucleotide subsequence to the reference sequence based in part on the first plurality of candidate locations-in such case, the prior results are conditionally reused. Since this selection leads to different amounts of computing resources being used, it would result in different amounts of available computing resources in the system. As recited in the claims, the time intervals at which the variant calling results are provided to the user are adjusted so that the computing resources are allocated efficiently in the system. Therefore, the system and method of claims 28 and 45, respectively, provide a technological improvement to the polynucleotide sequencing technology, and thus integrate the alleged abstract idea into a practical application that satisfies the Step 2A Prong II analysis.”
In response, Applicant’s argument is not persuasive. At the last step of both claims 28 and 45 claims recite insignificant extra-solution activities of data outputting, the sequencer (or any other additional element) never applies, or captures, or reflects the analytical results (leading to the expedited variant calls). The claims do not recite any additional elements that integrate the abstract idea into a practical application. An abstract idea (such as real-time sequence analysis) cannot integrate claims into a practical application at Step 2A/Prong Two.
In the Remarks, Applicant argues (page 9, last para) that claims 28 and 45 “providing improvement in the functioning of a computer”.
In response, Applicant’s argument is not persuasive. The real-time secondary sequence analysis (which reads on abstract ideas) can go on continuously, at a fast pace. However, data analysis steps drawn to an abstract idea performed by a computer is still an abstract idea. Computations on a lot of data performed mentally, or with paper and pencil, would take considerable time and effort, but that is, of course, the singular purpose of computers and computer networks, to perform large numbers of calculations, via algorithms, rapidly, and without error (assuming no error in user input). Although a general purpose computer can perform calculations at a rate and accuracy that can far outstrip the mental performance of a skilled artisan, the nature of the activity is essentially the same, and constitutes an abstract idea. See Bancorp Serves., L.L. C. v. Sun Life Assur. Co. of Canada (U.S.), 687 F.3d 1266,1278 (Fed. Cir. 2012) (holding that “the fact that the required calculations could be performed more efficiently via a computer does not materially alter the patent eligibility of the claimed subject matter”); see also See SiRF Tech., Inc. v. Int’l Trade Comm ’n, 601 F.3d 1319,1333 (Fed. Cir. 2010) (holding that: In order for the addition of a machine to impose a meaningful limit on the scope of a claim, it must play a significant part in permitting the claimed method to be performed, rather than function solely as an obvious mechanism for permitting a solution to be achieved more quickly, i.e., through the utilization of a computer for performing calculations).
In the Remarks, Applicant argues (page 10, 1st para) that claims 28 and 45 “encompasses inventive concepts. The overcall secondary analysis process, as recited in claims 28 and 45, is non-routine and unconventional, being more efficient compared to existing secondary analysis processes due to dynamically selecting between two different variant calling processes depending on prior results of sequence alignment and variant calling, as well as conditionally reusing the prior results”. Applicant’s argument refers to Step 2B in the 101 analysis.
In response, Applicant’s argument is not persuasive. MPEP 2106.05(d).II list several activities related to the above identified additional elements as well‐understood, routine, and conventional functions when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Particularly the following activity is highly related to the group 1) additional elements, which comprises sequencing apparatus configured to determine nucleotide sequence of a polynucleotide claimed additional elements:
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546;
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
Although the sequencing apparatus is not explicitly designated as conventional here, generic sequencing apparatus is conventional as they are available in commercial service.
Hence, the 101 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 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.
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/GL/
Patent Examiner
Art Unit 1686
/Anna Skibinsky/
Primary Examiner, AU 1635
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