DETAILED ACTION
Applicant’s response, filed Sep 28 2026, 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 Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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 1-20 are pending.
Claims 1-20 are rejected.
Priority
This application is a CON of 16/477,923, filed Jul 15 2019 (now USP 11,929,143), which claims priority to PCT/US2018/014714, filed Jan 22 2018, and PRO 62/448,594, filed Jan 20 2017.
Accordingly, each of claims 1-20 are afforded the effective filing date of Jan 20 2017.
Claim Objections
The outstanding objections to the claims are withdrawn in view of the amendments submitted herein.
Claim Rejections- 35 USC § 112
The outstanding 35 USC 112(a) and (b) rejections to the claims are withdrawn in view of the amendments and Applicant’s remarks (p. 13-14) submitted herein.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.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more. 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, a system, and a non-transitory computer readable storage medium, i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03].
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 1, 9, and 15: generating an alignment computer file comprising on-target sequence reads and associated genomic positioning data, wherein generating the alignment computer file comprises aligning the sequence reads to a reference genome and matching the aligned sequence reads to genomic sequences corresponding to probe oligonucleotides of a probe panel to obtain the on- target sequence reads;
generating a probe coverage data file for the sample using the on-target sequence reads and the associated genomic positioning data, wherein generating the probe coverage data file comprises:
determining a position read coverage for each base in each probe oligonucleotide by quantifying the on-target sequence reads that map to each base in the genomic sequences corresponding to each probe oligonucleotide,
determining a probe coverage for each probe oligonucleotide based on the position read coverage for each base in the genomic sequences corresponding to the probe oligonucleotide, and
determining a normalized probe coverage quantification for each probe oligonucleotide based on the probe coverages, wherein the probe coverage data file comprises the normalized probe coverage quantifications;
generating segments and associated probe coverage quantification data for each segment using a segmentation model and the probe coverage data file;
identifying genes overlapping with the segments using a gene identifier model based on the segments and the associated probe coverage quantification data;
generating filtered segments using a segment filter model and based on the identified genes and the associated probe coverage quantification data for each segment; and
determining a presence or absence of a genetic variation in the sample based on the filtered segments.
Dependent claims 5-8, 12-14, and 18-19 recite further steps that limit the judicial exceptions in independent claims 1, 9, and 15 and, as such, also are directed to those abstract ideas. For example, claim 5 further limits the probe panel to covering the genetic variation; claims 6, 12, and 18 further limit generating the segments; and claims 7-8, 13-14, and 19-20 further limit generating the filtered segments.
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 determine a presence or an absence of a genetic variation in a sample. Without further detail as to the methodology involved in “generating”, “determining”, “identifying”, and “normalizing”, under the BRI, one may simply, for example, use pen and paper to generate an alignment file by aligning sequence reads to a reference genome and matching aligned reads to sequences corresponding to probes; generate a probe coverage data file by determining a position read coverage for each base, determining a probe coverage for each probe oligonucleotide, and determining a normalized probe coverage quantification; generate segments and associated probe coverage quantification data using a model which could be a set of rules or a mathematical process; identify genes overlapping with the segments using a model which could be a set of rules or a mathematical process; generate filtered segments using a model which could be a set of rules or a mathematical process; and determine a presence or absence of a genetic variation based on the filtered segments. Such actions encompass observations, evaluations, judgments, which are concepts able to be performed in the human mind. Some of these steps, including determining a position read coverage for each base, determining a probe coverage for each probe, determining a normalized probe coverage quantification, and using a segmentation model (see the specification as published at [0082] which describes suitable segmentation models as including those that examine likelihood ratio statistics), require mathematical techniques as the only supported embodiments, as they express mathematical relationships in words.
Therefore, claims 1, 9, and 15 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 1: ligating nucleic acid molecules with adapters to generate sequence constructs, wherein the nucleic acid molecules are from a biological sample obtained from a subject and each sequence construct comprises an adapter ligated to an end of a nucleic acid molecule; and
sequencing the sequence constructs to obtain sequence reads.
Independent claims 9 and 15: obtaining sequence reads, wherein the sequence reads have been obtained by sequencing sequence constructs, wherein the sequence constructs have been generated by ligating nucleic acid molecules with adapters, and wherein the nucleic acid molecules are from a biological sample obtained from a subject and each sequence construct comprises an adapter ligated to an end of a nucleic acid molecule.
Dependent claim 2: generating, using a first polymerase chain reaction (PCR), library constructs for the sequence constructs;
capturing a subset of the library constructs using the probe oligonucleotides of the probe panel under hybridization conditions to enrich for one or more genomic regions of interest; and
generating, using a second PCR, enriched library constructs for each library construct of the subset of the library constructs, wherein the sequencing sequences the enriched library constructs to obtain the sequence reads.
Dependent claim 3: enriching nucleic acid molecules of a predetermined fragment length.
Dependent claims 4, 11, and 17: quantifying the enriched library constructs using capillary electrophoresis (CaliperGX) or a PCR-based method; and
normalizing the enriched library constructs to a fixed concentration based on the quantification, wherein the sequencing sequences the normalized enriched library constructs to obtain the sequence reads.
Dependent claims 10 and 16 further limit the obtained sequence reads to having been obtained by sequencing enriched library constructs.
The claims also include non-abstract computing elements. For example, independent claim 1 includes a computer-implemented method; independent claim 9 includes a system comprising one or more processors and memory coupled to the one or more processors, the memory encoded with a set of instructions configured to perform a method; and independent claim 15 includes a non-transitory computer readable storage medium storing instructions that, when executed by one or more processors of a computing system, cause the computing system to perform a method.
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 “ligating”, “obtaining” sequence constructs, “generating” library constructs, “capturing” a subset of library constructs using probe oligonucleotides, “enriching” nucleic acid molecules of a predetermined fragment length, “quantifying” constructs, “normalizing” constructs, and “sequencing” in claims 1-4, and “obtaining” sequence reads in claims 9 and 15, 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/elements directed to additional non-abstract computer elements 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)).
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 specification as published discloses that methods for enriching fragments from a select genomic region [0139-0140; 0172], using commercially manufactured enrichment probes and systems [0142; 0386], or size fractionation [0143], for preparing a nucleic acid/sequencing library [0155] (which encompasses ligation and PCR as instantly claimed), and for sequencing [0179], using commercially available sequencing kits and instruments [0191], can be done using methods known in the art. The specification as published also discloses that library quantification can be performed using commercially available equipment such as CALIPER LABCHIP GX or known PCR-based methods [0385]. Further, the prior art review to Ballester et al. (Expert Review of Molecular Diagnostics, 2016, 16(3):357-372; newly cited; Table 1 and Figure 1 in particular; entire document is relevant) and Kozarewa et al. (Current Protocols in Molecular Biology, 2015, 112(1):7-21; newly cited; p. 7, col. 1, par. 1; entire document is relevant) disclose that ligating nucleic acids, capturing nucleic acids with probes under hybridization conditions, performing PCR, size enrichment, and sequencing are well-understood, routine, conventional activities previously known to the industry. Additionally, 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 1, 9, and 15 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 as published also notes that computer processors and systems, as example, are commercially available or widely used at [0347]. 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, the instant claims 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. 15, par. 4, Applicant submits that the claims do not recite a law of nature.
It is agreed that the instant claims do not recite a law of nature and that language has been removed from the above rejection.
At p. 15, par. 5 through p. 17, par. 2, Applicant submits that the recited computer files, models, and steps that act on the files and models in claims 1, 9, and 15 should not be considered to recite judicial exceptions at Step 2A, Prong 1. Applicant submits that a computer file is neither an abstract idea nor a mathematical concept, but rather a data structure stored in computer memory. Applicant submits that the each of the models is recited as a distinct component applied to specified inputs and producing specified outputs, and each is an additional element to be evaluated. Applicant submits that the recited steps act on the computer files and models and are defined by reference to a specific data structure, to a specific recited component, or to the output of a preceding limitation, and characterization as an abstract idea can only be reached by disregarding the file and model on which each operates.
It is respectfully submitted that this is not persuasive. Regarding the computer files, the limitations are directed to “generating” an alignment computer file and a probe coverage data file by performing the recited steps. Each of those steps (aligning sequences, determining a position read coverage, determining a probe coverage, and determining a normalized probe coverage) recite steps which are considered to recite an abstract idea and/or mathematical process, as described in the above rejection. The claims therefore recite generating the computer files by the performance of these abstract ideas rather than by claiming the computer file/data structure as argued by Applicant. Ultimately, the step of “generating” a computer file is considered to encompass the action of recording and storing information on a computer, which also encompasses the mental action of recording data using a computer as a tool. If a claim recites a limitation that can practically be performed in the human mind, with or without the use of a physical aid such as pen and paper, the limitation falls within the mental processes grouping, and the claim recites an abstract idea. See, e.g., Benson, 409 U.S. at 67, 65, 175 USPQ at 674-75, 674 (noting that the claimed "conversion of [binary-coded decimal] numerals to pure binary numerals can be done mentally," i.e., "as a person would do it by head and hand."); Synopsys, 839 F.3d at 1139, 120 USPQ2d at 1474 (holding that claims to the mental process of "translating a functional description of a logic circuit into a hardware component description of the logic circuit" are directed to an abstract idea, because the claims "read on an individual performing the claimed steps mentally or with pencil and paper").
Regarding the models, Applicant’s arguments are not convincing because Applicant has given no reasons why the models should not be considered to recite mental processes. That the models require specific inputs and produce specified outputs does not alter the fact that the actions performed on those inputs to produce the specified outputs could not be performed mentally. At most, each of the recited models merely recite applying the judicial exceptions of generating segments and associated probe coverage quantification data, identifying genes overlapping with the segments, and generating filtered segments to a computer environment. However, without further limiting these models, their interpretation as either mental or mathematical processes is not a broader construction of the recited language, but a reasonable interpretation under the broadest reasonable interpretation of the claims.
Regarding the steps that act on the computer files and models, each of those steps can be performed on the data stored in the computer file or using a model which is considered to recite either a mental action or a mathematical process, as described above. Because each of the limitations pointed to by Applicant are considered to be able to be performed mentally or describe mathematical processes, as described in the above rejection, they are considered to recite abstract ideas. That the action acts on computer files, or specific data structures as alleged by Applicant, using models, does not alter the fact that the claims recite abstract ideas performed on data.
At p. 18, par. 2 through p. 19, Applicant submits that the claims provide an improvement to the functioning of a computer and to the technical field of copy number alteration detection from targeted sequencing data. Applicant submits that the invention provides a solution to the technical problem of using targeted sequencing data to detect CNAs by determining read coverage for each probe. Applicant submits that the probe coverage data file is not a generic repository of results, but rather a data structure organized around the probe oligonucleotides that contains substantially less data than the full set of sequence reads while preserving the information required for copy number analysis. The resulting models operate on the file rather than the underlying data, allowing efficient analysis. Applicant submits that the claimed invention requires a specific construction (coverage determined at each base of each probe oligonucleotide, reduced to a probe coverage for each probe oligonucleotide, normalized, and assembled into the probe coverage data file, as opposed to merely any form of storing coverage data), similarly to Enfish, LLC v. Microsoft Corp., 822 F.3d 1327, 1336-37 (Fed. Cir. 2016). Applicant also points to U.S. Patent No. 11,929,143 which was found patent eligible for the reasons presented by Applicant herein.
It is respectfully submitted that this is not persuasive. The downstream which act on the computer file and the models that provide the supposed improvement (i.e., efficient analysis when detecting CNAs) in the instant claims are steps that are, themselves, the judicial exceptions and cannot therefore be a practical application of the judicial exception, as discussed above. 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. Rather, the “additional element” in the instant claims (see exemplary claim 1) includes only steps directed to data gathering and applying the judicial exceptions to a computer environment, and do not integrate any of the recited judicial exceptions into a practical application, nor do the claims as a whole include any inventive concept beyond well-understood, routine and conventional steps.
Regarding Enfish, it is considered that the claims are not analogous to those at issue in Enfish. Enfish recites a self-referential table that improves existing technology through the way the computer stores and retrieves data in memory in combination with the specific data structure recited in the claims that demonstrated eligibility. The instant claims do not recite a specific data structure that improves the functioning of a computer in downstream tasks, as alleged by Applicant, because the supposed improvement is merely the computer functioning in the same way as always but on compressed, or less, data. The instant method is therefore not analogous to the claims at issue in Enfish, nor does the instant method provide any improvement or change to how the computer functions when determining the presence or absence of a genetic variation in sequencing data.
Regarding US Patent 11,929,143, it is noted that the instant claims and those in the allowed patent are different in scope. Eligibility in the earlier application does not guarantee eligibility in a different claim set, where examination of eligibility is a fact based assessment. As described in the above rejection, it is considered that the instant claims are not patent eligible.
At p. 20, par. 1, Applicant submits that the claims effect a transformation of a particular article toa different state by ligating adapters to nucleic acid molecules, resulting in sequence constructs having a composition different from the starting molecules.
It is respectfully submitted that this is not persuasive. The ligation of adapters to the nucleic acid molecules does not convert the molecules to something other than a nucleic acid. The ligated molecules still have the same nucleic acid composition, even though the sequence of those nucleic acid molecules is altered. It is therefore considered that the ligation step in claim 1 does not transform the nucleic acid molecules to a different state or thing, as is required to demonstrate a particular transformation (see MPEP 2106.05(c)).
At p. 20, par. 2 through p. 21, par. 2, Applicant submits that the alleged exception is applied in a meaningful way because the additional elements of the claims are not recited at a level of generality that would permit the claims to preempt the alleged exception. Applicant further submits that the ligating and sequencing limitations are not merely data gathering limitations, but that they produce the specific data whose per-base, per-probe distribution is the subject of the claimed improvement.
It is respectfully submitted that this is not persuasive. While preemption is the concern underlying the judicial exceptions, it is not a standalone test for determining eligibility (Rapid Litig. Mgmt. v. CellzDirect, Inc., 827 F.3d 1042, 1052, 119 USPQ2d 1370, 1376 (Fed. Cir. 2016)). It is necessary to evaluate eligibility using the Alice/Mayo test, because while a preemptive claim may be ineligible, the absence of complete preemption does not demonstrate that a claim is eligible (Diamond v. Diehr, 450 U.S. 175, 191-92 n.14, 209 USPQ 1, 10-11 n.14 (1981); “We rejected in Flook the argument that because all possible uses of the mathematical formula were not pre-empted, the claim should be eligible for patent protection”; see MPEP 2106.04).
It is considered that each of the limitations in the claims is considered according to the broadest reasonable interpretation. Each of the limitations is discussed in the above rejection to determine whether the limitations recite a judicial exception at Step 2A, Prong 1, or an additional element at Step 2A, Prong 2. Each of the limitations are then considered in relationship to each other, or the claim as a whole, to determine how those additional elements function in the claims. The additional elements in the claims are found to recite either data gathering steps which produce the data required by the judicial exceptions for their performance, or general computer elements which merely apply the judicial exceptions to a computer environment. The limitations are not evaluated at too high a level of generality, but are examined under the BRI.
Additionally, the ligation and sequencing steps are still considered to be data gathering steps because they produce the specific data analyzed in the claims, as submitted by Applicant at p. 21, par. 1. Further, Applicant’s remarks that the ligating and sequencing steps provide the improvement are not convincing as Applicant submitted remarks at p. 18, par. 2, that those steps contributed to the specific technical problem faced by the invention. Any improvement in the claims flows from the performance of the judicial exceptions in analyzing the sequencing data coverage, which, as discussed above, cannot provide a practical application.
At p. 21, par. 3 through p. 22, Applicant submits that the additional elements, alone and as an ordered combination, provide for significantly more at Step 2B because the Office Action has not established that the additional elements of (i)-(vii) as identified on p. 16-17 of Applicant’s remarks are conventional. Further, Applicant submits that the specification describes the conventional state of the art and distinguishes it from the claimed invention, pointing to how analytical methods are inefficient in their application to targeted sequencing data to enable CAN detection.
It is respectfully submitted that this is not persuasive. MPEP 2106.05(d) sets forth that, at Step 2B, it is the additional elements which are examined to determine whether they are well-understood, routine, conventional activities previously known to the industry. The analysis at Step 2A, Prong 2, considers the claims as a whole, i.e., the additional elements in combination with the judicial exceptions (see MPEP 2106.05(a)), although the integration or improvement provided in the claim must flow from the additional elements and not the judicial exceptions to be considered persuasive. However, Step 2B requires examining only the additional elements, either alone or in combination with one another, for conventionality. An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself (Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966)). The limitations (i)-(vii) pointed to be Applicant are considered to recite a judicial exception as described above and are therefore not considered at Step 2B. Likewise, Applicant’s arguments regarding the conventionality of the analysis methods to targeted sequencing data are not convincing because Applicant is arguing that those analytic steps (i.e., the judicial exceptions), are the unconventional components of the claims.
Further, Applicant’s arguments are not completely commensurate with the scope of the claims. The independent claims do not recite determining a copy number, but rather recite “determining a presence or absence of a genetic variation”. However, those claims which do recite “determining a copy number” are also considered to recite judicial exceptions which are not considered at Step 2B.
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 1-2, 5-10, 12-16, and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-9, 15, and 17 of U.S. Patent No. 11,929,143 in view of Boeva et al. (Bioinformatics, 2014, 30(24):3443-3450; cited on the Aug 4 2025 IDS). Any newly recited portions are necessitated by claim amendment.
Claims 3-4, 11, and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-9, 15, and 17 of U.S. Patent No. 11,929,143 in view of Boeva, as applied to claims 1-2, 9-10, and 15-16, and in view of Kozarewa et al. (Current Protocols in Molecular Biology, 2015, 112(1):7-21; newly cited). Any newly recited portions are necessitated by claim amendment.
Reference claims 1, 8-9, 15, and 17 disclose instant claims 1-2, 9-10, and 15-16, except for the limitations directed to “identifying genes overlapping with the segments using a gene identifier model based on the segments and the associated probe coverage quantification data” and “generating filtered segments using a segment filter model and based on the identified genes and the associated probe coverage quantification data for each segment”.
However, the prior art to Boeva discloses a method that includes a multifactor normalization and annotation technique enabling the detection of large copy number changes from amplicon sequencing data (abstract). Boeva teaches normalizing sample read counts and segmenting the resulting profiles (p. 3446, col. 1, par. 3). Boeva teaches a readjustment strategy (i.e., gene identifier model) of segmentation with a gene-aware model by identifying breakpoints that fall within a gene (i.e., genes overlapping with the segments) and examining the amplicons in the genes to determine whether they are correctly annotated (i.e., based on the segments and the associated coverage data) (p. 3446, col. 2, par. 6). Boeva teaches clustering segments based on the mean values of the normalized copy number changes expressed as integers in the segments to cluster segments with the same number of copies together (i.e., segment filter model) (p. 3446, col. 1, par. 4), where all segments with mean values clustered with zero are considered copy neutral (p. 3446, col. 1, par. 6). Boeva teaches filtering candidate copy number aberrations with a P--value above a threshold after performing a test to determine whether the target regions are copy-neutral (p. 3446, col. 2, par. 2-3).
Reference claims 1, 9, and 15 disclose instant claim 5.
Reference claims 1, 8-9, 15, and 17 disclose instant claims 6, 12, and 18.
The reference patent does not disclose instant claims 3-4, 7-8, 11, 13-14, 17, and 19-20.
However, the prior art to Kozarewa discloses an overview of target enrichment strategies for next generation sequencing (title; abstract).
Regarding instant claim 3, Kozarewa teaches PCR target enrichment strategies to produce amplicons with lengths compatible with existing sequencing platforms (i.e., enriching nucleic acid molecules of a predetermined fragment length) (p. 6, col. 2, par. 2).
Regarding instant claims 4, 11, and 17, Kozarewa teaches analyzing the concentrations of PCR products on a gel or with capillary electrophoresis for quantitative and qualitative DNA analysis, where Caliper GX may be used (p. 6, col. 2, par. 2). Kozarewa teaches equimolar pooling of PCR amplicons after quantification (p. 6, col. 2, par. 2).
Regarding instant claims 7-8, 13-14, and 19-20, Boeva teaches clustering segments based on the mean values of the normalized copy number changes expressed as integers in the segments to cluster segments with the same number of copies together (p. 3446, col. 1, par. 4), where all segments with mean values clustered with zero are considered copy neutral (i.e., segment filter model) (p. 3446, col. 1, par. 6). Boeva teaches that the targets are genes (p. 3444, col. 1, par. 3). Boeva teaches filtering candidate copy number aberrations with a P--value above a threshold after performing a test to determine whether the target regions are copy-neutral (p. 3446, col. 2, par. 2-3). As Boeva teaches that “zero” is considered copy neutral (p. 3446, col. 1, par. 6), and as the copy number changes are expressed in integers (p. 3446, col. 1, par. 4), it is considered that Boeva fairly teaches filtering out the copy neutral segments and keeping those that have an integer (i.e., less than 0.9 copy number loss or 1 copy number gain).
Regarding claims 1-2, 5-10, 12-16, and 18-20, 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, the reference patent and Boeva because each reference discloses methods for determining copy number variations in targeted sequencing data. The motivation would have been to use features of a method that would enable the detection of large copy number changes from targeted sequencing data, as taught by Boeva (abstract).
Regarding claims 3-4, 11, and 17, 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, the reference patent in view of Boeva and Kozarewa because each reference discloses methods for generating targeted sequencing data. The motivation would have been use methods known in the art for target enrichment for next-generation sequencing, thereby eliminating genomic regions that are not of interest for a particular experiment, obtain greater depth of DNA sequencing coverage for regions of interest, and increase the sampling numbers of individuals, thereby saving time and cost, as taught by Kozarewa (abstract).
Response to Applicant Arguments
At p. 24, Applicant requests that the double patenting rejection be held in abeyance until the application is otherwise in condition for allowance.
It is respectfully submitted that the non-statutory double patenting rejections cannot be held in abeyance and are accordingly maintained and updated in view of claim amendment.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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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/JANNA NICOLE SCHULTZHAUS/Examiner, Art Unit 1685
