DETAILED ACTION
Applicant’s response, filed Dec 22 2025, has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
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 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.
Claim Status
Claims 2-21 are pending.
Claim 1 is canceled.
Claims 2-21 are rejected.
Priority
This application is a CON of 14/811,836 filed Jul 29 2025, which claims priority to PRO 62/188,443, filed Jul 2 2015.
Accordingly, each of claims 2-21 are afforded the effective filing date of Jul 2 2015.
Drawings
The replacement drawing sheets submitted Dec 22 2025 are accepted and the outstanding objections from the previous Office Action are withdrawn.
Specification
The amendments to the specification submitted Dec 22 2025 are accepted and the outstanding objections from the previous Office Action are withdrawn.
Claim Objections
The outstanding objections to the claims are withdrawn in view of the amendments submitted herein.
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.
A. Claim 21 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because they recite a “computer readable storage medium”. The broadest reasonable interpretation (BRI) of "a computer readable medium" may encompass non-statutory transitory forms of signal transmission machine (see MPEP § 2106.03), which is directed to non-statutory subject matter. Therefore the claims read on carrier waves and include transitory propagating signals. (In re Nuijten, Federal Circuit, 2006). In order to advance compact prosecution, claim 21 will continue to be examined under the 35 U.S.C. 101 framework below. The rejection is maintained from the previous Office Action.
B. Claims 2-9 and 19-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more. Claim 21 is additionally examined under the 35 USC 101 framework in the interest of compact examination, as described above. Any newly recited portions are necessitated by claim amendment.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, the claims are directed to a method and a system, i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03]. It is noted that claim 21 is directed to the non-statutory subject matter of a computer readable medium as described above.
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) are as follows:
Independent claims 2, 19, and 21: selecting… a reduced number of cells of a hidden markov model (HMM) matrix structure from the HMM matrix structure using the set of control parameters, the selecting limiting a set of cells of the HMM matrix structure that contribute to a composite probability determination to a subset of cells of the HMM matrix structure, the subset of cells associated with a corresponding set of differing alignments of the read sequence to the haplotype and probabilities of those differing alignments; and
performing… one or more HMM operations using the reduced number of cells of the HMM matrix structure, the one or more HMM operations determining a composite probability of observing the read given the haplotype based on the subset of cells and the probabilities of the differing alignments.
Dependent claim 3: processing… the obtained haplotype sequence and the obtained read sequence through the first processing engine, wherein… generates the set of control parameters based on the processing the obtained haplotype sequence and the obtained read sequence through the first processing engine.
Dependent claim 4: correlating… the obtained haplotype sequence and the obtained read sequence to obtain correlations of the obtained haplotype sequence and the obtained read sequence, wherein… generates the set of control parameters based on the correlations of the obtained haplotype sequence and the obtained read sequence.
Dependent claims 5-9 and 20 recite further steps that limit the judicial exceptions in the claims from which they depend, as described above, and, as such, also are directed to those abstract ideas. For example, claims 5-7 further limit the correlations used to generate the set of control parameters; claims 8-9 and 20 further limit the control parameters.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind and/or by mathematical operation because the method only requires a user to manually perform hidden markov model operations using a reduced matrix. Without further detail as to the methodology involved in “selecting”, “performing”, “processing”, “correlating”, and “generating”, under the BRI, one may simply, for example, use pen and paper to correlate a haplotype sequence and a read sequence, generate a set of control parameters, select a reduced number of cells of a hidden markov model matrix structure, and perform hidden markov model operations using the reduced number of cells of the hidden markov model matrix structure. FIG. 4-7 and 9 demonstrate visually how the process of correlating reads and performing hidden markov model operations could be performed manually, using pen and paper as an aid. Those steps directed to performing hidden markov model operations and performing a Fast Fourier Transform for correlation require mathematical techniques as the only supported embodiments, as is disclosed in the specification at: [00052; 00058-00061; 00092].
Therefore, claims 2, 19, and 21 and those claims dependent therefrom recite an abstract idea [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Independent claim 2: obtaining, by the variant calling module, a haplotype sequence and a read sequence;
providing, by the variant calling module, the obtained haplotype sequence and the obtained read sequence as inputs to a first processing engine; and
obtaining, by the variant calling module and from the first processing engine, a set of control parameters generated by the first processing engine based on the first processing engine processing the obtained haplotype sequence and the obtained read sequence.
The claims also include non-abstract computing elements. For example, independent claim 2 includes a variant calling module that includes a plurality of processing engines; independent claim 19 includes a system comprising one or more processors, and one or more memory device storing instructions that, when executed, cause the one or more processors to perform operations by a variant calling module that includes a plurality of processing engines; and independent claim 21 includes a computer readable storage medium storing instructions that, when executed by one or more processors, cause the one or more processors to perform operations by a variant calling module that includes a plurality of processing engines.
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to data gathering, such as “obtaining” data, and to data outputting, such as “providing” data, perform functions of collecting the data needed to carry out the judicial exceptions. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
Further steps directed to the additional non-abstract computing elements described above do not describe any specific computational steps by which the “computer parts” perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, and therefore the claim does not integrate that judicial exceptions into a practical application. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc.… are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (MPEP 2106.05(f)). Further, the computer system contains the recited variant calling module (i.e., software) that is used for performing the recited judicial exceptions. Thus, the limitations only generically link the use of the judicial exceptions to the technological environment of a computer.
The specification discloses that the most resource extensive operation in variant calling in the pair HMM evaluation, which the invention accelerates with custom hardware at [00040]. However, the specification does not provide a clear explanation for how the additional elements as recited in the claims provide these improvements. Therefore, the additional elements do not clearly improve the functioning of a computer, or comprise an improvement to any other technical field. Further, the additional elements do not clearly affect a particular treatment; they do not clearly require or set forth a particular machine; they do not clearly effect a transformation of matter; nor do they clearly provide a nonconventional or unconventional step (MPEP2106.04(d)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, the prior art review to Benkrid et al. (International Journal of Reconfigurable Computing, 2012, , p. 1-16; NPL #172 on the Apr 8 2024 IDS) discloses that performing parallel processes on different types of computer hardware is a well-understood, routine, conventional activity known to the industry (entire document is relevant). Further, the courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(II)(i)). As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
With respect to claims 2, 19, and 21 and those claims dependent therefrom, the computer-related elements or the general purpose computer do not rise to the level of significantly more than the judicial exception. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (Alice Corp., 573 U.S. at 225-26, 110 USPQ2d at 1984; see MPEP 2106.05(A)). The specification also notes that computer processors and systems, as example, are commercially available or widely used at [00099]. The additional elements are set forth at such a high level of generality that they can be met by a general purpose computer. Therefore, the computer components constitute no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the judicial exceptions (see MPEP 2106.05(b)I-III).
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, claims 2-9 and 19-21 are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
Response to Applicant Arguments
At p. 14-15, par. 2, Applicant submits that claim 21 recites a statutory category because it recites a “computer readable storage medium”, which is not the as a computer readable medium. Applicant submits that The Board of Patent Appeals and Interferences in Ex parte Wei Hu, BPAI Appeal 2010-000151 (2012) found that a computer readable storage medium recites statutory subject matter because it is directed to a tangible storage medium that can be read by a computer.
It is respectfully submitted that this is not persuasive. Ex parte Wei Hu is non-precedential and therefore only applies to the facts of that particular case, which does not match the fact pattern of the instant claims. It is further noted that even though the PTAB determined that a computer readable storage medium recites statutory subject matter, the patent that was ultimately issued from the application was amended to recite “non-transitory”.
At p. 15, par. 3 through p. 17, Applicant submits that now recite an effect of selecting the reduced number of cells of the HMM matrix structure from the HMM matrix structure using the set of control parameters and performing HMM operations using the reduced number of cells of the HMM matrix structure, the one or more HMM operations determining a composite probability of observing the read given the haplotype based on the subset of cells and the probabilities of the differing alignments, which emphasizes the reduced processing and computational resource consumption provided by the variant caller. Applicant submits that limiting the set of cells is enabled by the control parameters, which is part of the “obtaining” limitation which is an additional element. Applicant therefore submits that the additional element therefore imposes a meaningful limitation on the claim and is not merely data gathering.
It is respectfully submitted that this is not persuasive. That limitations indicated by Applicant regarding selecting the reduced number of cells and performing the HMM operations are those which recite judicial exceptions. Judicial exceptions cannot be a practical application of the judicial exception. The courts have made clear that a judicial exception is not eligible subject matter (Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)) if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"); Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016) (eligibility "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself."). For a claim reciting a judicial exception to be eligible, it is the additional elements (if any) in the claim that must "transform the nature of the claim" into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981, either at Prong Two or in Step 2B. If there are no additional elements in the claim, then it cannot be eligible. It is submitted here that the instant claims do not include any additional elements that provide for a practical application.
The claims are not considered to recite an improvement in the functioning of a computer because they merely recite a way to perform fewer operations by the computer. The way that the computer performs those operations are not altered in any way except that they perform fewer. Therefore, the actual performance of the computer is not improved by a claim which merely recites performing fewer operations.
Applicant’s remarks regarding the use of the control parameters as providing a meaningful limitation are not convincing because the control parameters provide the alleged improvement in the steps which recite judicial exceptions, contrary to Applicant’s submission that the “obtaining” step provides the improvement. The “obtaining” step merely provides the data of the control parameters to the computer to perform the judicial exception, and therefore does serve a data gathering function in the claims as a whole at Step 2A, Prong 2.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
A. Claims 2-5, 7-13, and 15-21 are rejected under 35 U.S.C. 103 as being unpatentable over Giraldo et al. (Design, Automation & Test in Europe Conference and Exhibition, 2010, p. 405-410; cited on the Apr 8 2024 IDS) in view of Batista et al. (Journal of Parallel and Distributed Computing, 2008, 68(4):548-561; previously cited). The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 2 discloses a method. Claim 10 discloses an integrated circuit for reduced computation variant calling by a variant calling module that includes a plurality of processing engines, the integrated circuit comprising multiple hardware logic gates that have been physically configured into one or more hardware digital logic circuits that realize functionality of the variant calling module. Claim 19 discloses a system for reduced computation variant calling by a variant calling module that includes a plurality of processing engines, the system comprising: one or more processors; and one or more memory device storing instructions that, when executed, cause the one or more processors to perform operations. Claim 21 discloses a computer readable storage medium storing instructions that, when executed by one or more processors, cause the one or more processors to perform operations for reduced computation variant calling by a variant calling module that includes a plurality of processing engines.
The operations of claims 1, 10, 19, and 21 comprise:
obtaining, by the variant calling module, a haplotype sequence and a read sequence;
providing, by the variant calling module, the obtained haplotype sequence and the obtained read sequence as inputs to a first processing engine;
obtaining, by the variant calling module and from the first processing engine, a set of control parameters generated by the first processing engine based on the first processing engine processing the obtained haplotype sequence and the obtained read sequence;
selecting, by the variant calling module and using a second processing engine, a reduced number of cells of a hidden markov model (HMM) matrix structure from the HMM matrix structure using the set of control parameters, the selecting limiting a set of cells of the HMM matrix structure that contribute to a composite probability determination to a subset of cells of the HMM matrix structure, the subset of cells associated with a corresponding set of differing alignments of the read sequence to the haplotype and probabilities of those differing alignments; and
performing, by the variant calling module, one or more HMM operations using the reduced number of cells of the HMM matrix structure, the one or more HMM operations determining a composite probability of observing the read given the haplotype based on the subset of cells and the probabilities of the differing alignments.
The prior art to Giraldo discloses an algorithm called the Divergence Algorithm (i.e., variant calling module), which not only enables the FPGA accelerator to reduce execution time, but also enables further acceleration of the alignment generation algorithm of the HMMER programs by reducing the number of cells of the Dynamic Programming matrices it has to calculate. (abstract). Giraldo teaches outputting the similarity score between a sequence and the reference (i.e., haplotype sequence) and limits of the area of the Dynamic Programming matrices that contain the optimal alignment (p. 1, col. 2, par. 2; section V, p. 3-4), which reads on the limitations directed to “obtaining” a haplotype and a sequence, “providing” a set of control parameters, and “selecting” a reduced number of cells of a matrix structure as instantly claimed, except for a “read” sequence, which is interpreted as a sequence of nucleotides and not proteins, as taught by Giraldo (p. 1, col. 1, par. 1).
Giraldo teaches that the similarity score indicates the probability that a sequence belongs to the family (p. 2, col. 1, par. 1), where the similarity score is based on the transition and emission probabilities between states for each residue of a sequence with a total length of n (p. 2, col. 1), which reads on set of differing alignments of the read sequence to the haplotype and probabilities of those differing alignments as instantly claimed, where the similarity score reads on a cumulative probability of those alignments. As Giraldo teaches that HMMER first computes the probability that the sequence belongs to the family as a similarity score and then generates the resulting alignment in the case the score is sufficiently good, it is considered that Giraldo fairly teaches the one or more HMM operations determining a composite probability of observing the read given the haplotype based on the subset of cells and the probabilities of the differing alignments as instantly claimed.
Giraldo teaches that the software then calculates only that small area of the Dynamic Programming matrices to return the same alignment as the unaccelerated software (p. 1, col. 2, par. 2; p. section V, p. 3-4). Giraldo teaches that the Dynamic Programming matrices are comprised of HMM nodes (i.e., cells of a HMM matrix) (Figure 3). Giraldo teaches that the divergence algorithm is implemented using HMMER’s programs (i.e., performing HMM operations using the reduced number of cells of the HMM matrix structure) (p. 3, section IV). Giraldo teaches that FPGA-based accelerators (i.e., an integrated circuit as in claim 10) are composed of processing elements connected together to exploit the algorithm parallelism (p. 2, col. 2, par. 2), and for implementation of the Divergence Algorithm, each processing elements of a linear array of processing elements represents one node of the profile HMM and computes the scores for the current sequence element in the current node as well as the alignment limits (section VI, p. 5), which reads on at least first and second processing engines as instantly claimed. Giraldo teaches that the hardware includes RAM memories (i.e., memory device as in claim 19; computer readable storage medium as in claim 21).
Giraldo does not explicitly teach analyzing a “read” sequence, which is interpreted as a sequence of nucleotides, as is supported by the specification as published at least at [0007].
However, the prior art to Batista discloses a parallel exact strategy based on the divergence concept to locally align long biological sequences of DNA using the Smith-Waterman algorithm (abstract; section 2, p. 3-4; section 4, p. 6-7; Figures 6-7).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, Giraldo and Batista because both references disclose algorithms and hardware for accelerating sequence alignment using a divergence algorithm. Batista teaches using the divergence algorithm for Smith-Waterman alignments of DNA sequences, and Giraldo teaches modifying that algorithm for HMM operations of protein sequences (p. 3, col. 1, par. 4). It would have therefore been obvious to one of ordinary skill in the art to use the method of Giraldo to analyze DNA sequence alignment because the substitution of DNA sequences for protein sequences is no more than the simple substitution of one known element for another.
Regarding claims 3-5, 7, 11-13, and 15, Giraldo in view of Batista teaches the method of claim 2 and the integrated circuit of claim 10. Claims 3 and 11 further add processing, by the variant calling module, the obtained haplotype sequence and the obtained read sequence through the first processing engine, wherein the first processing engine generates the set of control parameters based on the processing the obtained haplotype sequence and the obtained read sequence through the first processing engine. Claims 4 and 12 further add that the processing, by the variant calling module, the obtained haplotype sequence and the obtained read sequence through the first processing engine comprises: correlating, using the first processing engine, the obtained haplotype sequence and the obtained read sequence to obtain correlations of the obtained haplotype sequence and the obtained read sequence, wherein the first processing engine generates the set of control parameters based on the correlations of the obtained haplotype sequence and the obtained read sequence. Claims 5 and 13 further add correlating using the first processing engine, the obtained haplotype sequence and the obtained read sequence to obtain a correlation of the obtained haplotype sequence and the obtained read sequence, wherein the first processing engine generates the set of control parameters based on the correlation of the obtained haplotype sequence and the obtained read sequence. Claims 7 and 15 further add correlating, using the first processing engine, uses a sliding match count correlation operation.
Giraldo teaches calculating the alignment limits (i.e., set of control parameters in claims 3 and 11) for each sequence element (section V, p. 3-4, especially section B). Giraldo teaches calculating the scores (i.e., correlating as in claims 4-5 and 12-13) for the simplified algorithm as each element of the sequence passes through the HMM nodes and using those score to calculate the alignment limits (section V, p. 3-4, especially sections A and B). Giraldo teaches that the sequence is compared to the reference using the Dynamic Programming matrix, where the sequence is compared at each HMM node as the sequence passes through and the number of matches, insertions, and deletions are determined to find the maximum operator (p. 4, col. 1, par. 1; Figure 3), which reads on a sliding match count correlation operation as claimed in claims 7 and 15.
Regarding claims 8, 16, and 20, Giraldo in view of Batista teaches the method of claim 2, the integrated circuit of claim 10, and the system of claim 19. Claims 8, 16, and 20 further add that the set of control parameters include a starting center point of a first row of the HMM matrix structure and a width of a first row of the HMM matrix structure.
Giraldo teaches an Alignment Initial Line (i.e., first row) in the Dynamic Programming matrix with an Alignment Inferior and Superior Divergence setting the limits of the width of the alignment region (Figure 3). As Giraldo teaches an alignment region for each line which has a width, it is considered that that line inherently has a center point as instantly claimed.
Regarding claims 9 and 17, Giraldo in view of Batista teaches the method of claim 2 and the integrated circuit of claim 10. Claims 9 and 17 further add that the first row of the matrix structure is a top row of the HMM matrix structure.
Giraldo teaches an Alignment Initial Line in the Dynamic Programming matrix (Figure 3), but does not show that it is the top row of the matrix.
However, Batista shows that the first row of the alignment is the top row of the matrix (Figure 6).
Regarding claim 18, Giraldo in view of Batista teaches the integrated circuit of claims 10 and 16. Claim 18 further adds that the integrated circuit is a field programmable gate array (FPGA).
Giraldo teaches an FPGA (abstract; p. 1, col. 1, par. 2 through col. 2, par. 2; p. 2, col. 2, par. 2 through p. 3, col. 1, par. 3).
B. Claims 6 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Giraldo in view of Batista, as applied to claims 2 and 10 as above, and in further view of Cheever et al. (Bioinformatics, 1991, 7(2), pp.143-154; previously cited). The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding claims 6 and 14, Giraldo in view of Batista teaches the method of claim 1 and the system of claim 10 as described above. Claims 6 and 14 further add correlating, using the first processing engine, uses a Fast Fourier Transform (FFT).
Neither Giraldo nor Batista teach using FFT to correlate sequences.
However, the prior art to Cheever discloses a Fast Fourier transform-based correlation of DNA sequences (title; entire document is relevant).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, Giraldo in view of Batista with Cheever because each reference discloses methods for correlating DNA sequences. The motivation to use FFT to correlate sequences would have been to perform rapid similarity searches on DNA and protein sequence databases, as taught by Cheever (p. 143, col. 1, par. 1). Therefore, the substitution of a correlation of sequences by FFT for a correlation of sequences by the method taught by Giraldo is no more than the simple substitution of one known element for another.
Response to Applicant Arguments
At p. 17-20, Applicant submits that the prior art to Giraldo, Batista, and Cheever cited in the outstanding rejection from the previous Office Action do not using the HMM matrix structure to determine a composite probability, or that the subset of cells is associated with a corresponding set of differing alignments of the read sequence to the haplotype and the probabilities of the differing alignments.
It is respectfully submitted that this is not persuasive. Although Giraldo does teach that bounding the search for an alignment to certain cells in the HMM matrix as submitted by Applicant, it is noted that Giraldo also teaches determining that the similarity score indicates the probability that a sequence belongs to the family (p. 2, col. 1, par. 1), where the similarity score is based on the transition and emission probabilities between states for each residue of a sequence with a total length of n (p. 2, col. 1), which reads on set of differing alignments of the read sequence to the haplotype and probabilities of those differing alignments as instantly claimed, where the similarity score reads on a cumulative probability of those alignments. As Giraldo teaches that HMMER first computes the probability that the sequence belongs to the family as a similarity score and then generates the resulting alignment in the case the score is sufficiently good, it is considered that Giraldo fairly teaches the one or more HMM operations determining a composite probability of observing the read given the haplotype based on the subset of cells and the probabilities of the differing alignments as instantly claimed. Giraldo therefore teaches bounding the cells of the matrix to an alignment region to perform the determination of the similarity score within, as illustrated in Figure 3. It is noted that the instant application also appears to similarly bound the cells of the HMM matrix in FIG. 4-6.
Applicant’s remarks regarding using the final-row cells to arrive at the probabilities are acknowledged, but are not commensurate with the scope of the claims. It is noted that the cited art of record does not appear to disclose this feature. Under the BRI of the claims as submitted, it is not apparent that similarity score calculated by Giraldo for the alignment within the alignment region is patentably distinct from a composite probability score for observing a read given the probabilities of the different alignments, as instantly recited.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 2-8, 10-16, and 19-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 27-28, and 35 of copending Application No. 14/811,836 (reference application; now allowed) in view of Giraldo et al. (Design, Automation & Test in Europe Conference and Exhibition, 2010, p. 405-410; cited on the Apr 8 2024 IDS). Claims 9 and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 27, and 35 of copending Application No. 14/811,836, in view of Giraldo, as applied to claims 2 and 10, and in further view of Batista et al. (Journal of Parallel and Distributed Computing, 2008, 68(4):548-561; newly cited). Claim 18 is provisionally over claims 1, 5, 27, and 35 of copending Application No. 14/811,836, in view of Giraldo as applied to claim 10, and in further view of the features of the reference disclosure. The rejection is newly stated and is necessitated by claim amendment.
Regarding instant claims 2, 10, 19, and 21, reference claims 1, 5, 27, and 35 (the entire claim is relevant) disclose the limitations of claims 2, 10, 19, and 21 except for “the selecting limiting a set of cells of the HMM matrix structure that contribute to a composite probability determination to a subset of cells of the HMM matrix structure, the subset of cells associated with a corresponding set of differing alignments of the read sequence to the haplotype and probabilities of those differing alignments” and “the one or more HMM operations determining a composite probability of observing the read given the haplotype based on the subset of cells and the probabilities of the differing alignments”.
However, the prior art to Giraldo discloses an algorithm called the Divergence Algorithm (i.e., variant calling module), which not only enables the FPGA accelerator to reduce execution time, but also enables further acceleration of the alignment generation algorithm of the HMMER programs by reducing the number of cells of the Dynamic Programming matrices it has to calculate. (abstract). Giraldo teaches outputting the similarity score between a sequence and the reference (i.e., haplotype sequence) and limits of the area of the Dynamic Programming matrices that contain the optimal alignment (p. 1, col. 2, par. 2; section V, p. 3-4), which reads on the limitations directed to “obtaining” a haplotype and a sequence, “providing” a set of control parameters, and “selecting” a reduced number of cells of a matrix structure as instantly claimed, except for a “read” sequence, which is interpreted as a sequence of nucleotides and not proteins, as taught by Giraldo (p. 1, col. 1, par. 1). Giraldo teaches that the similarity score indicates the probability that a sequence belongs to the family (p. 2, col. 1, par. 1), where the similarity score is based on the transition and emission probabilities between states for each residue of a sequence with a total length of n (p. 2, col. 1), which reads on set of differing alignments of the read sequence to the haplotype and probabilities of those differing alignments as instantly claimed, where the similarity score reads on a cumulative probability of those alignments. As Giraldo teaches that HMMER first computes the probability that the sequence belongs to the family as a similarity score and then generates the resulting alignment in the case the score is sufficiently good, it is considered that Giraldo fairly teaches the one or more HMM operations determining a composite probability of observing the read given the haplotype based on the subset of cells and the probabilities of the differing alignments as instantly claimed. Giraldo teaches that the software then calculates only that small area of the Dynamic Programming matrices to return the same alignment as the unaccelerated software (p. 1, col. 2, par. 2; p. section V, p. 3-4). Giraldo teaches that the Dynamic Programming matrices are comprised of HMM nodes (i.e., cells of a HMM matrix) (Figure 3).
Regarding claims 2, 10, 19, and 21, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the reference application and Giraldo because both references disclose methods for comparing sequences using hidden markov algorithms. The motivation to calculate a cumulative probability would have been to find the best alignment, as taught by Giraldo (p. 2, col. 1).
Regarding instant claims 3-5 and 11-13, reference claims 1, 5, 27, and 35 (generating… a correlation) disclose the limitations of claims 3-5 and 11-13.
Regarding claims 6 and 14, reference claims 1, 5, 27, and 35 (generating… a correlation between the haplotype sequence and the read sequence using a Fourier transform) discloses the limitations of claims 6 and 14.
Regarding instant claims 7 and 15, reference claims 1, 5, 27, and 35 (wherein each of the one or more determined values corresponds to at least one of an offset of a max match count value, a ratio of a max match count value to a read length, and a ratio of a max match count value to a second highest match count value) disclose the limitations of claims 7 and 15.
Regarding instant claims 8, 16, and 20, reference claims 2, 5, 28, and 35 (wherein the data describing the portion of the first row and the cell width of the portion comprises a starting center point and a row width on a first row of the HMM matrix structure) disclose the limitations of claims 8, 16, and 20.
Regarding claims 9 and 17, the reference application does not disclose that the first row of the matrix structure is a top row of the HMM matrix structure.
However, the prior art to Batista discloses a parallel exact strategy based on the divergence concept to locally align long biological sequences of DNA using the Smith-Waterman algorithm (abstract; section 2, p. 3-4; section 4, p. 6-7; Figures 6-7). Batista shows that the first row of the alignment is the top row of the matrix (Figure 6).
Regarding claims 9 and 17, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the reference application and Batista because each reference discloses methods for selecting portions of a matrix to perform sequence alignment. The motivation would have been to use a parallel method for distributing sequence alignment tasks, as taught by Batista (p. 3, col. 1, par. 1-2).
Regarding claim 18, the reference application does not claim a field programmable gate array. However, the reference specification discloses FPGA’s as an example of an integrated circuit [0098-0099; 0103].
Regarding claim 18, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify, in the course of routine experimentation and with a reasonable expectation of success, the reference application to limit the integrated circuit to an FPGA because the reference disclosure provides FPGA’s as one of the types of integrated circuits which may be used. In view of the reference disclosure of only an FPGA or an ASIC as types of hardware for use in the method, it would have been obvious to try either type of hardware because the reference disclosure offers only a finite number of choices, and each would have had a predictable solution when used to employ the disclosed method.
Response to Applicant Arguments
At p. 14, Applicant submits that the filing of a Terminal Disclaimer will be considered when obviousness-type double patenting is the only remaining rejection. The rejection is accordingly 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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/J.N.S./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685