DETAILED ACTION
Applicant’s response, filed Feb 20 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 Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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 1-23, 32-37, and 49 are pending.
Claims 33-37 and 49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, as set forth in the Non-Final Office Action dated Oct 20 2025.
Claims 24-31, 38-48, and 50-90 are canceled.
Claims 4 and 13 are objected to.
Claims 1-23 and 32 are rejected.
Priority
The instant Application claims domestic benefit to US provisional application 62/837,034, filed Apr 22 2019. However, the provisional application does not provide support for a formalin fixed paraffin embedded block, slide, or curl of a test subject as recited in claim 15.
Applicant's claim for the benefit of a prior-filed application, PCT/US2020/029113, filed Apr 21 2020, is acknowledged.
Accordingly, each of claims 1-14, 16-23 and 32 are afforded the effective filing date of Apr 22 2019 and claim 15 is afforded the effective filing date of Apr 21 2020.
Information Disclosure Statement
Applicant’s remarks regarding the filing of a subsequent IDS to address minor errors in the previously filed IDS are acknowledged. All references submitted by Applicant have been considered.
Specification
The amendments to the abstract submitted Feb 20 2026 are accepted and the outstanding objections from the previous Office Action are withdrawn.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The outstanding objections to the claims are withdrawn in view of the amendments submitted herein.
The claims are objected to because of the following informalities. The instant objection is newly stated and is necessitated by claim amendment.
Claim 4 recites “with a third and greater haplotypes” on the 2nd-3rd lines, which is not grammatically correct because “a” signifies a singular noun, but “haplotypes” is plural.
Claim 13 recites “wherein the targeted oligonucleotide panel comprises oligonucleotides capturing a region of a genome correspond to”, which is not grammatically correct. It is recommended to amend the claim to recite “capturing a region of a genome corresponding to” or similar.
Claim Interpretation
The claim interpretation set forth for claims 1 and 3-4 in the previous Office Action is withdrawn in view of the amendments submitted herein.
In claim 7, the limitation “for assessing contamination of a sample” is interpreted under the BRI as an intended use of calibrating cutoff values for the candidate microhaplotypes. See MPEP 2111.04(I), where “for” is considered to recite an example of claim language that suggests or makes optional but does not require steps to be performed. It is noted that claim 10 explicitly recites active steps for assessing contamination of a sample.
Claim Rejections- 35 USC § 112
Unless otherwise noted, the outstanding 35 USC 112(b) and (d) rejections to the claims are withdrawn in view of the amendments submitted herein.
35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 4 and 13 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. The instant rejection is newly stated and is necessitated by claim amendment.
Claim 4 recites “wherein at least three microhaplotypes are determined to be present in the biological sample, with a third and greater microhaplotypes having a total frequency of greater than 1% when compared against data from the plurality of variant sets corresponding to the plurality of reference samples”. First, it is not clear what microhaplotypes are being referenced. Claims 1 and 2, from which claim 4 depends from, previously recite only candidate microhaplotype sets, with claim 2 further recited “determining one or more haplotypes present in the biological sample”. It is not clear claim 4 intends to further limit the candidate microhaplotype sets, the determined haplotypes present in the biological sample, or new at least three microhaplotypes, and, if so, whether the determination of those at least three microhaplotypes is required (see MPEP 2111.04.I). For compact examination, it is assumed that the claim intends to further limit the determined haplotypes. The rejection may be overcome by clarifying the relationship of the terms. Second, the term “greater” in claim 4 is a relative term which renders the claim indefinite. The term “greater” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Further, the claim does not provide any degree of comparison for what the third microhaplotype is greater than. Therefore, the scope of the third microhaplotype is not clear. For compact examination, art reading on the identification of a microhaplotype greater than 1% in comparison to reference samples will be considered relevant.
Claim 13 recites “wherein the targeted oligonucleotide panel comprises oligonucleotides capturing a region of a genome correspond to one or more genomic regions selected from those set forth in Tables 5, 6, or 7”. MPEP 2173.05(s) sets forth that "incorporation by reference to a table is only permitted in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim”. There is no indication that the invention cannot be defined in words nor that it is more concise to incorporate by reference rather than duplicating the table into the claim. Therefore, the incorporation by reference of the candidate microhaplotypes corresponding to one or more genomic regions selected from those set forth in Tables 5, 6, or 7 in the claim is improper. It is further noted that it is not clear whether claim 13 intends to limit the region of interest identified in claim 1, step a), such that only a genomic region set forth in Tables 5, 6, or 7 is selected as a region of interest which is then analyzed to identify the SBSs listed in the tables, or if claim 13 intends to limit the results from the method of claim 1 in an undefined manner, which would raise further clarity issues. For compact examination, it is assumed that the claim intends to limit the identified region of interest from claim 1, and that any whole genome sequencing or analysis experiment would provide data on the genomic regions set forth in the Tables in the specification. The rejection may be overcome by reciting the metes and bounds of the genomic regions and the corresponding candidate microhaplotypes in the claims.
Response to Applicant Arguments
At p. 12, par. 3, Applicant submits that incorporating the entirety of Tables 5-7 into the claim language is impractical and would render the claim unduly lengthy and cumbersome.
It is respectfully submitted that this is not persuasive. MPEP 2173.05(s) sets forth that “Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)”. Applicant has not provided any reasons why the inclusion of the information in the tables would be cumbersome, and the argument that the claims would be unduly lengthy is not convincing. The claims may be as long as are required to clearly convey their scope. The information in Tables 5-7 which Applicant intends to incorporate into the claims is able to be presented in the specification and could therefore also be included in the claims.
Claim Rejections - 35 USC § 101
The outstanding rejections under 35 USC 101 to claims 2, 4, and 14-17 are hereby withdrawn in view of the amendments submitted herein. Claim 2 includes steps that are in addition to the recited judicial exceptions that provide for integration of the recited exceptions into a practical application of those exceptions. Specifically, the steps directed to “sequencing, using the targeted oligonucleotide panel, nucleic acid obtained from a biological sample of a test subject to obtain sequence reads from the region of interest and the bordering region” is an additional element that integrates the judicial exceptions present in the claims into a practical application at Step 2A, Prong 2. The step of sequencing nucleic acid obtained from a biological sample of a test subject uses the targeted oligonucleotide panel designed in claim 1, and therefore goes beyond generally linking the use of the judicial exception to a particular technological environment, but transforms the judicial exception into patent-eligible subject matter by sufficiently limiting the abstract ideas recited in the claims to the design and use of a targeted oligonucleotide panel for sequencing specific genomic regions (see MPEP 2106.05(e)). Claims 4 and 14-17 are dependent from claim 2 and are patent eligible for the same reasons.
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, 3, 5-13, 18-23, and 32 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, 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).
The claims also recite a law of nature or a natural phenomenon. The MPEP at 2106.04(b) further explains that laws of nature and natural phenomena include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature.
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), as well as a law of nature or a natural phenomenon are as follows:
Independent claim 1: a) identifying a region of interest of the genome;
b) determining a bordering region for the region of interest, wherein the bordering region comprises regions flanking the region of interest, and wherein the regions flanking the region of interest comprise less than 200 nucleotide base pairs;
d) detecting single base pair substitutions (SBSs) within the region of interest and the bordering region based on the sequence reads;
e) grouping the detected SBSs into a plurality of variant sets for the region of interest;
f) analyzing each variant set in the plurality of variant sets for linkage disequilibrium to identify candidate microhaplotypes; and
g) designing a targeted oligonucleotide panel for amplification or sequencing of regions comprising the detected SBSs in the candidate microhaplotype sets.
Dependent claim 3: filtering the plurality of variant sets based on a frequency threshold for the detected SBSs, wherein remaining variant sets after the filtering are analyzed for the linkage disequilibrium.
Dependent claim 7: calibrating cutoff values for the candidate microhaplotype sets for assessing contamination of a sample.
Dependent claim 10: determining, for each individual in the plurality of individuals, a number and genotype of variant sets with one and/or two microhaplotypes based on the sequence variant data; and
comparing the number and genotype of the variant sets between each individual.
Dependent claim 11: assessing sample contamination utilizing determined cutoff values for frequency of candidate microhaplotype sets, where each candidate microhaplotype set comprises a set of SBSs that define at least 3 microhaplotypes.
Dependent claim 12: assessing sample contamination utilizing determined cutoff values for frequency of candidate microhaplotype sets, where each candidate microhaplotype set comprises a set of SBSs that define at least 4 or more microhaplotypes.
Dependent claim 32: assessing quality of samples from a particular source or vendor or technician preparing or sequencing samples.
Dependent claims 5-6, 8-9, 13-21, and 23 recite further steps that limit the judicial exceptions in independent claim 1 and, as such, also are directed to those abstract ideas. For example, claims 3-6 and 20-21 further limit the region flanking the region of interest or the region of interest; claims 8-9 and 18 further limit calibrating cutoff values in claim 7; claims 13 and 19 further limits the candidate microhaplotype sets; and claim 23 further limits the genome.
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 identify candidate microhaplotypes in a region of interest of a genome. Without further detail as to the methodology involved in “identifying”, “determining”, “detecting”, “grouping”, “analyzing”, “designing”, “detecting”, and “assessing”, under the BRI, one may simply, for example, use pen and paper to identify a region of interest of a genome, determine bordering regions of a certain size near the region of interest, detect single base pair substitutions in the region of interest and the bordering regions, group the detected variants into sets, analyze variant sets for linkage disequilibrium to identify candidate microhaplotype sets, design a targeted oligonucleotide panel that would amplify or sequence the regions comprising the candidate microhaplotype sets, calibrate cutoff values for the candidate microhaplotypes, and assess sample contamination using the candidate microhaplotypes and their cutoff values. The claims additionally recite the mathematical concept of analyzing variant sets for linkage disequilibrium. The limitation requires the performance of mathematical concepts as its only embodiment, as is supported by Applicant’s argument on p. 13, final paragraph, submitted herein, that sets forth that this step “recites a specific, technical analytical process that objectively identifies microhaplotype sets using linkage disequilibrium, which inherently relies on complex computational algorithms and the underlining population”.
The specification as published discloses that microhaplotypes are short segments of DNA characterized by the presence of two or more closely linked SNPs that present three or more allelic combinations (i.e., “haplotypes”) within a population, where the short distance between SNPs implies an extremely low recombination rate among them [0029]. Therefore the claims also recite the natural relationship between variants and their relationship in a genome used to identify the SBSs as microhaplotypes.
Therefore, claim 1 and those claims dependent therefrom recite an abstract idea and a law of nature/natural phenomenon [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: c) obtaining sequence reads corresponding to a plurality of reference samples, wherein the sequence reads cover the region of interest and the bordering region.
Dependent claim 10: obtaining sequence variant data corresponding to a plurality of individuals.
Dependent claim 22: isolating DNA comprising the candidate microhaplotype sets.
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” sequence reads in claim 1 and sequence variant data in claim 10, 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)). It is noted that obtaining sequencing reads and sequence variant data as recited reads merely on a computer or a person obtaining the data of the reads and does not require any physical steps.
The step in claim 22 directed to isolating DNA comprising the candidate microhaplotype is a mere instruction to apply an exception (see MPEP 2106.05(f)) and is insignificant extra-solution activity (see MPEP 2106.05(g)). Isolating DNA from a sample would inherently isolate DNA with the candidate microhaplotypes because all the DNA from the sample is isolated during such an action. The claim therefore merely recites the idea of using the results from the judicial exception without any reason for performing such an action. Isolating the DNA comprising the candidate microhaplotypes is also an activity which is incidental to the primary process of the claim and is therefore merely a nominal or tangential addition to the claim.
The specification discloses that the invention provides a detection method that is independent of Minor Allele Frequencies at [0006], but does not provide a clear explanation for how the additional elements 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 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)). Further, the courts have found analyzing, and therefore isolating, DNA is a well-understood, routine, and conventional activity in the life science arts when claimed in a merely generic manner (Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017); Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015); Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017); Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546; University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); see MPEP 2106.05(d)). 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 “apply it” step as recited in the instant claims constitutes 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)).
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. 13, par. 4 through p. 14, par. 2, Applicant submits that at least steps c), f), and g) of claim 1 recite additional elements and not judicial exceptions. Applicant submits that “c) obtaining sequence reads” cannot be performed by the human mind. Applicant submits that “f) analyzing each variant set… for linkage disequilibrium” recites a specific, technical analytical process that objectively identifies microhaplotype sets using linkage disequilibrium, which inherently relies on complex computational algorithms and the underlining population data and which cannot be practically performed in the mind. Applicant submits that “g) designing a targeted oligonucleotide panel” directly links the computational analysis to a real world, physical outcome by requiring the design of laboratory reagents tailored to the results of the analysis, which is a tangible step that cannot be performed by the human mind.
It is respectfully submitted that this is not persuasive. While it is agreed that step c) recites an additional element rather than a judicial exceptions, steps f) and g) both recite judicial exceptions.
Analyzing variant sets for linkage disequilibrium recites a step of data analysis only, and Applicant has provided no reasoning as to why such an action could not be performed mentally besides that the process relies on complex computational algorithms. Applicant’s remarks therefore lack factual support and are not evidentiary. The claims are not limited in any way that indicates too much data would be required to be examined, as the claims require only detecting groups of SBSs within a region of a genome in a plurality of reference samples, without any limit to the number of groups of SBSs or reference samples being examined. Even if the claims were to require that a large number of groups of SBSs and reference samples were to be analyzed, such an argument would not be convincing without evidence that such analysis could not be performed mentally. Further, Applicant’s remarks indicate that such linkage disequilibrium analysis is in fact a mathematical process, which is not altered by the complexity of the mathematical concept being performed.
Designing a targeted oligonucleotide panel recites a judicial exception because “designing” indicates only the conceptual planning of the panel is required, but not the actual manufacture of the tangible panel itself. Therefore, the limitation merely recites the mental process of planning a targeted oligonucleotide panel that could be used for amplification or sequencing processes.
At p. 14, par. 3 through p. 15, par. 2, Applicant submits that at Step 2A, Prong 2, the additional elements and claim 1 as a whole integrate the judicial exception into a practical application because they provide an improvement to a technical field and integration with a particular machine or manufacture.
It is respectfully submitted that this is not persuasive. Applicant alleges that identifying informative microhaplotype sets and designing targeted oligonucleotide panels represents an improvement to targeted sequencing or amplification However, steps directed to identifying informative microhaplotype sets and designing targeted oligonucleotide panels represents that provide the supposed improvement in the instant claims are steps that are, themselves, the judicial exceptions and cannot therefore 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. Rather, the “additional element” in the instant claims (see exemplary claim 1) includes only the step of “obtaining sequence reads”. As set forth above, said steps operate in the claim as data gathering steps 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. It is noted that claim 2 actually recites the use of the targeted oligonucleotide panel for sequencing, which is a physical process and therefore also limits the panel to the physical world as well. Claim 2 is accordingly not rejected under 35 USC 101. For the targeted oligonucleotide panel to integrate the recited judicial exceptions into a practical application that improves sequencing, both the tangible panel and the sequencing must be actively recited.
Applicant’s remarks regarding a particular machine or manufacture are not convincing because, while MPEP 2106.05(b) does set forth that the application of a judicial exception with, or by use of, a particular machine may integrate a judicial exception into a practical application in Step 2A Prong 2or recite significantly more than a judicial exception in Step 2B, this requires that the particular machine apply the judicial exception. In the instant claims, there is no particular machine recites which applies the judicial exception. MPEP 2106.05(b)(III) sets forth that if the use of a machine contributes only nominally or insignificantly to the execution of the claimed method (e.g., in a data gathering step), it would not integrate a judicial exception or provide significantly more. The only additional element in claim 1 recites “obtaining sequence reads”, which could merely be performed by receiving data on a computer. Further, the claims do not recite the specialized laboratory equipment and reagents as argued by Applicant. Applicant’s remarks are therefore not commensurate with the scope of the claims.
At p. 15, par. 3 through p. 16, par. 3, Applicant submits that the specific laboratory and computational steps of c), f), and g) provide a workflow and custom panel which is not conventional at Step 2B.
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 pointed to be Applicant in steps f) and g), i.e., the “workflow” as submitted by Applicant, are considered to recite a judicial exception as described above and are therefore not considered at Step 2B. The step of “obtaining” data recited in c) is merely the conventional functioning of a computer.
Claim Rejections - 35 USC § 102
The outstanding rejections from the previous Office Action are withdrawn in view of the amendments submitted herein. Specifically, Kidd et al. (Investigative Genetics, 2015, 6(1):1-10; cited on the Oct 19 2021 IDS) does not specifically disclose at least the second claimed step of determining and analyzing additional flanking regions for further SBSs, as argued by Applicant at p. 16, par. 4 in the remarks submitted herein.
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 1-8, 10-14, 16-20, 22-23, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Kidd et al. (Investigative Genetics, 2015, 6(1):1-10; cited on the Oct 19 2021 IDS) in view of Oldoni et al. (Forensic Science International: Genetics, Oct 1 2018; 38:54-69; newly cited). The instant rejection is newly stated and is necessitated by claim amendment.
The prior art to Kidd discloses criteria for selecting microhaplotypes for mixture detection (title). Kidd teaches the instant features as follows. Instantly claimed elements which are considered to be equivalent to the prior art teachings are described in bold for all claims.
Claim 1 discloses method of identifying microhaplotypes in a genome comprising:
a) identifying a region of interest of the genome;
b) determining a bordering region for the region of interest, wherein the bordering region comprises regions flanking the region of interest, and wherein the regions flanking the region of interest comprise less than 200 nucleotide base pairs;
c) obtaining sequence reads corresponding to a plurality of reference samples, wherein the sequence reads cover the region of interest and the bordering region;
d) detecting single base pair substitutions (SBSs) within the region of interest and the bordering region based on the sequence reads;
e) grouping the detected SBSs into a plurality of variant sets for the region of interest;
f) analyzing each variant set in the plurality of variant sets for linkage disequilibrium to identify candidate microhaplotypes; and
g) designing a targeted oligonucleotide panel for amplification or sequencing of regions comprising the detected SBSs in the candidate microhaplotype sets.
Kidd teaches selecting loci (i.e., a) regions of interest of the genome) (p. 2, col. 1, par. 3 through p. 3, col. 2, par. 3) and examining the alleles and single nucleotide polymorphisms (SNPs) of the loci to identify microhaplotypes in large public data sets based on massive parallel sequencing (MPS) (i.e., c) obtaining sequence reads corresponding to a plurality of reference samples; and d) detecting SBSs… based on the sequence reads) (abstract; p. 2, co1. 1, par. 2 through col. 2, par. 1; p. 3, col. 2, par. 4 through p. 4, col. 1, par. 1; p. 5, col. 2, par. 2; entire document is relevant). The SNPs taught by Kidd are considered to fairly teach SBSs as instantly claimed because a single base pair substitution is a type of SNP, as is supported by the instant specification as published at [0028]. Kidd teaches that the microhaps are defined as loci of two or more SNPs within the span of a single sequence run (i.e., also reads on a region of interest; e) grouping detected SBSs into a plurality of variant sets) (p. 2, col. 1, par. 1). Kidd teaches that certain microhaplotypes have additional documented SNPs/variants within 200 bp (i.e., step b and d) (p. 9, col. 1, par. 1; Table 4). Kidd teaches determining the linkage disequilibrium of the SNPs (i.e., step f) (p. 2, col. 1, par. 2). Kidd teaches evaluating candidate microhaplotypes using TaqMan assays to detect the individual SNPs (p. 5, col. 2, par. 3), which is considered to inherently recite the design of a targeted oligonucleotide panel for amplification of the SNPs using the TaqMan assay; Kidd is therefore considered to teach step g) as instantly claimed. Kidd also teaches the identification of specific microhaplotypes (Table 3), which also reads on a microhaplotype panel as instantly claimed. Although Kidd teaches that additional SNPs are present in the regions around specific microhaplotypes (i.e., region of interest) (p. 9, col. 1, par. 1; Table 4), which reads on bordering regions as instantly claimed, Kidd does not teach limitation b) regarding determining a bordering region of less than 200 nucleotide base pairs, d) detecting SBSs within the region of interest and the bordering region, and e) grouping the detected SBSs into a plurality of variant sets as instantly claimed.
However, Oldoni discloses a review on microhaplotype loci (abstract). Oldoni teaches that a criterion of selecting microhaplotype loci includes detection of at least three SNPs within a 200 bp single sequence that is currently a routine read length for MPS platforms, but that the read length can be expanded to approximately 300 bp for certain loci to include more SNPs within the amplicon that increase the number of potential alleles (p. 57, section 2.7). Expanding a 200 bp region (i.e., a region of interest) to 300 bp reads on determining a border region flanking the region of interest by 100 bp, which is an example that anticipates the instantly claimed range of less than 200 nucleotide base pairs. Oldoni additionally discloses panels of microhaplotype loci (Table 1; p. 59, col. 1, par. 1 through p. 65, col. 1, par. 4; see specifically p. 64, col. 2, par. 3 and section 3.4), which teaches step g).
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, Kidd and Oldoni because both references disclose methods for identifying microhaplotype loci. The motivation to expand the examined region beyond the 200 bp taught by Kidd to 300 bp as taught by Oldoni would have been to include more SNPs within certain loci to increase the number of potential alleles, as taught by Oldoni (p. 57, col. 2, par. 3).
Regarding claim 2, Kidd in view of Oldoni teaches the method of claim 1 as described above. Claim 2 further adds sequencing, using the targeted oligonucleotide panel, nucleic acid obtained from a biological sample of a test subject to obtain sequence reads from the region of interest and the bordering region; detecting candidate SBSs within the region of interest and the bordering region, wherein each candidate SBS is a member of at least one of the candidate microhaplotype sets; and determining one or more haplotypes present in the biological sample based on the candidate SBSs.
Kidd does not teach these limitations.
However, Oldoni teaches multiple MPS microhaplotype panels that have been developed and used to amplify and sequence test samples (Table 1; p. 59, col. 1, par. 1 through p. 65, col. 1, par. 4; see specifically p. 64, col. 2, par. 3 and section 3.4).
Regarding claim 3, Kidd in view of Oldoni teaches the method of claim 1 as described above. Claim 3 further adds filtering the plurality of variant sets based on a frequency threshold for the detected SBSs, wherein remaining variant sets after the filtering are analyzed for the linkage disequilibrium.
Kidd teaches focusing on loci that have alleles at greater than 5% (i.e., a frequency threshold) (p. 2, col. 1, par. 1).
Regarding claim 4, Kidd in view of Oldoni teaches the method of claims 1-2 as described above. Claim 4 further adds that at least three microhaplotypes are determined to be present in the biological sample, with a third and greater microhaplotypes having a total frequency of greater than 1% when compared against data from the plurality of variant sets corresponding to the plurality of reference samples.
Kidd teaches using microhaplotypes with 3-5 alleles and at 2-5 loci to determine mixtures (Tables 1-2). As it is not clear what the microhaplotypes in the claim are intended to refer to (see the above 35 USC 112(b) rejection), it is considered that both the number of microhaplotypes at different loci and the number of microhaplotypes with different alleles read on the microhaplotypes determined in a sample as instantly claimed. Kidd therefore teaches an overlapping range which anticipates or alternatively makes obvious the instantly claimed range of at least 3 microhaplotypes. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). Also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05.
Kidd teaches focusing on loci that have alleles at greater than 5% in the large datasets (i.e., a total frequency in a plurality of reference samples) (p. 2, col. 1, par. 1). Kidd therefore teaches an overlapping range which anticipates or alternatively makes obvious the instantly claimed range of greater than 1%. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). Also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05.
Regarding claims 5-6, Kidd in view of Oldoni teaches the method of claim 1 as described above. Claim 5 further adds that the region of interest of a) has SBSs at a frequency of between 10-90%. Claim 6 further adds that the regions flanking the region of interest have SBSs at a frequency of between 5-95%.
Kidd teaches focusing on loci that have alleles at greater than 5% (p. 2, col. 1, par. 1). Kidd therefore teaches an overlapping range which anticipates or alternatively makes obvious the instantly claimed range of 10-90% in claim 5 and 5-95% in claim 6. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). Also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05.
Regarding claim 7, Kidd in view of Oldoni teaches the method of claim 1 as described above. Claim 7 further adds calibrating cutoff values for the candidate microhaplotype sets for assessing contamination of a sample.
Kidd teaches developing empiric threshold (i.e., cutoff value) based on the frequency distributions of microhaplotypes (i.e., calibrating) (p. 4, col. 1, par. 1). Kidd teaches that their method is developed to detect and resolve mixtures of DNA from two or more individuals in a sample (p. 1, col. 2, par. 1; p. 2, col. 1, par. 3 through col. 2, par. 2), which fairly reads on assessing contamination as instantly claimed.
Regarding claim 8, Kidd in view of Oldoni teaches the methods of claims 1 and 7 as described above. Claim 8 further adds that the calibrating cutoff values for the candidate microhaplotype sets comprises calculating thresholds for contamination detection and degree of contamination using only DNA sequence reads overlapping the candidate microhaplotype sets.
As Kidd teaches using SNP frequency data to determine microhaplotype frequency distributions and develop empiric thresholds for mixture detection (i.e., sample contamination) (p. 3, col. 2, par. 2-3p. 4, col. 1, par. 1; Table 1), it is considered that Kidd would have had to use only DNA sequence reads that overlap the microhaplotypes as instantly claimed.
Regarding claim 10, Kidd in view of Oldoni teaches the methods of claims 1 and 7-8 as described above. Claim 10 further adds obtaining sequence variant data corresponding to a plurality of individuals; determining, for each individual in the plurality of individuals, a number and genotype of variant sets with one and/or two microhaplotypes based on the sequence variant data; and comparing the number and genotype of the variant sets between each individual to asses identity or contamination.
Kidd teaches using SNP frequency data from a large data set of MPS (i.e., sequence variant data) to determine microhaplotype frequency distributions and develop empiric thresholds for mixture detection (p. 3, col. 2, par. 2-3p. 4, col. 1, par. 1; Tables 1-2; Figure 1). Kidd teaches mixtures of DNA from two or more individuals in a single sample (i.e., contamination) (p. 1, col. 2, par. 1).
Regarding claims 11-12, Kidd in view of Oldoni teaches the methods of claims 1 and 7 as described above. Claim 11 further adds assessing sample contamination utilizing determined cutoff values for frequency of candidate microhaplotype sets, wherein each candidate microhaplotype set comprises a set of SBSs that define at least 3 microhaplotypes. Claim 12 further adds assessing sample contamination utilizing determined cutoff values for frequency of candidate microhaplotype sets, wherein each candidate microhaplotype set comprises a set of SBSs that define at least 4 or more microhaplotypes.
Kidd teaches using microhaplotypes with 3-5 alleles and at 2-5 loci to determine mixtures (Tables 1-2). Kidd teaches an overlapping range which anticipates or alternatively makes obvious the instantly claimed range of at least 3 or 4 microhaplotypes. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). Also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05.
Regarding claim 13, Kidd in view of Oldoni teaches the methods of claim 1 as described above. Claim 13 further adds that the targeted oligonucleotide panel comprises oligonucleotides capturing a region of a genome correspond to one or more genomic regions selected from those set forth in Tables 5, 6, or 7.
Kidd teaches examining large datasets generated from either chip-based genotyping or whole-genome massive parallel sequencing (p. 2, col. 1, par. 2 through col. 2, par. 1). It is therefore considered that these data would provide information about the genomic regions in Tables 5, 6, or 7 because they provide information about the entire genome (see the above 35 USC 112(b) rejection), and as Kidd in view of Oldoni teaches the method steps of claim 1, it would have been obvious to identify at least one of the genomic regions set forth in Tables 5, 6, or 7 using whole-genome sequencing data.
Regarding claims 14 and 16-17, Kidd in view of Oldoni teaches the methods of claims 1-2 as described above. Claim 14 further adds that the biological sample comprises DNA from a tumor or a liquid biopsy of the test subject. Claim 16 further adds that the liquid biopsy is from amniotic fluid, aqueous humour, vitreous humour, blood, whole blood, fractionated blood, plasma, serum, breast milk, cerebrospinal fluid (CSF), cerumen, chyle, chime, endolymph, perilymph, feces, breath, gastric acid, gastric juice, lymph, mucus, pericardial fluid, peritoneal fluid, pleural fluid, pus, rheum, saliva, exhaled breath condensates, sebum, semen, sputum, sweat, synovial fluid, tears, vomit, prostatic fluid, nipple aspirate fluid, lachrymal fluid, perspiration, cheek swabs, cell lysate, gastrointestinal fluid, biopsy tissue, or urine. Claim 17 further adds that the biological sample is from a circulating tumor cell of the test subject.
Kidd teaches analyzing mixtures of DNA samples for forensic purposes (see at least the abstract). Kidd does not teach specific sample types claimed.
However, Oldoni teaches examining samples from cancer patient blood (i.e., a tumor in claim 14; a circulating tumor cell of the test subject in claim 17) and of maternal blood (i.e., a liquid biopsy in claim 14; blood in claim 16) for fetal DNA microhaplotypes (p. 64-65, section 3.7).
Regarding claim 18, Kidd in view of Oldoni teaches the methods of claims 1 and 7 as described above. Claim 18 further adds that calibrating comprises analysis of the candidate microhaplotype sets in multiple samples obtained from humans of different ethnicities.
Kidd teaches examining population-specific allele frequencies for six microhaplotypes (i.e., different ethnicities) (p. 4, col. 2, par. 2; Figure 3-5) and refers to the samples as being from a three person mixture (p. 3, col. 2, par. 3), which reads on humans as instantly claimed.
Regarding claim 19, Kidd in view of Oldoni teaches the method of claim 1 as described above. Claim 19 further adds that the candidate microhaplotype sets comprise a set of the detected SBSs that define at least 3, 4 or more microhaplotypes.
Kidd teaches using microhaplotypes with 3-5 alleles (i.e., SBSs) and at 2-5 loci to determine mixtures (Tables 1-2). As Kidd teaches a range of 3-5 alleles, it is considered that this range anticipates the instantly claimed range of 3, 4 or more sets of SNP sequence variants.
Regarding claim 20, Kidd in view of Oldoni teaches the method of claim 1 as described above. Claim 20 further adds that the region of interest is within a gene, an intron and/or an exon or between genes.
Kidd teaches examining large datasets generated from either chip-based genotyping or whole-genome massive parallel sequencing (p. 2, col. 1, par. 2 through col. 2, par. 1). Such data would inherently provide information about genetic sequences which are within a gene, an intron and/or an exon or between genes, as instantly claimed. Therefore Kidd is considered to teach the instant limitation.
Regarding claim 22, Kidd in view of Oldoni teaches the method of claim 1 as described above. Claim 22 further adds isolating the DNA comprising the candidate microhaplotypes.
As Kidd teaches analyzing a set of DNA samples for microhaplotypes (p. 3, col. 2, par. 4), it is considered that Kidd would have inherently had to have isolated the DNA from those samples in order to analyze them.
Regarding claim 23, Kidd in view of Oldoni teaches the method of claim 1 as described above. Claim 23 further adds that the genome is from a human.
Kidd teaches examining population-specific allele frequencies for six microhaplotypes (p. 4, col. 2, par. 2; Figure 3-5) and refers to the samples as being from a three person mixture (p. 3, col. 2, par. 3), which reads on human genome samples being analyzed.
Regarding claim 32, Kidd in view of Oldoni teaches the method of claim 1 as described above. Claim 32 further adds assessing quality of samples from a particular source or vendor or technician preparing or sequencing samples.
Kidd teaches examining samples to detect mixtures using identified microhaplotypes (see the Methods and Results and discussion on p. 2-9). The presence of mixed samples reads on sample quality from a particular source as instantly claimed.
B. Claims 9 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Kidd in view of Oldoni, as applied to claims 1 and 7-8 as described, and in view of Ricke et al. (US 2021/0017592; priority to Jul 7 2018; previously cited; corresponds to WO 2019/010410 cited on the Oct 19 2021 IDS). The instant rejection is newly stated and is necessitated by claim amendment.
Regarding claim 9, Kidd in view of Oldoni teaches the methods of claims 1 and 7-8 as described above. Claim 9 further adds that the DNA sequence reads being used to calibrate the thresholds for the contamination detection and the degree of contamination are mixed pairwise in silico, alternately using each DNA sequence as primary sample and contaminant.
Kidd does not teach this claim.
However, the prior art to Ricke discloses systems and methods for identifying individuals from one or more samples (abstract). Ricke teaches performing in silico mixtures of individuals to enhance accuracy in predicting the number of contributors in mixtures of samples [0234; 0288-0291; 0786-0810].
Regarding claim 21, Kidd in view of Oldoni teaches the method of claim 1 as described above. Claim 7 further adds the region of interest is within an exome.
Kidd does not explicitly teach analyzing exome data.
However, Ricke teaches identifying multiple sequence variants in a single DNA sequence read that represent the variants from one source chromosome (from an individual) representing a phased microhaplotype [0097-0107] using high throughput sequencing data [0532], which includes high throughput exome sequencing [0516].
Regarding claims 9 and 21, 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, Kidd in view of Oldoni and Ricke because both references disclose methods for analyzing microhaplotypes to detect mixtures in samples. Regarding claim 9, the motivation to perform an in silico analysis would have been to enhance accuracy in predicting the numbers of contributors, as taught by Ricke [0234]. Regarding claim 21, the motivation to examine exome data would have been to examine the impact of gene, promoter, splicing, and coding sequence variants on gene expression, splicing, or function, as taught by Ricke [0516].
C. Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Kidd in view of Oldoni, as applied to claims 1-2 as described above, and in view of Douville et al. et al. (Proceedings of the National Academy of Sciences, 2018, 115(8):1871-1876; previously cited). The instant rejection is newly stated and is necessitated by claim amendment.
Regarding claims 15, Kidd in view of Oldoni teaches the methods of claims 1-2 as described above. Claim 15 further adds that the biological sample comprises DNA extracted from a formalin fixed paraffin embedded block, slide, or curl of the test subject, which Kidd does not teach.
However, the prior art to Douville discloses methods for detecting aneuploidy in cancer cells using sequencing methods (abstract). Douville teaches that tumors were formalin-fixed and paraffin-embedded, followed by DNA purification and analysis for mutation (p. 1876, col. 2, par. 2).
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, Kidd in view of Oldoni and Douville because each reference discloses methods for analyzing DNA via sequencing from tissue samples. The simple substitution of one known sample processing type as taught by Douville, which is capable of having DNA extracted and sequenced for mutation analysis, for the sample type taught by Kidd thus is no more than the simple substitution of one known element for another, which would have produced the predictable result of producing sequencing data capable of being analyzed using the method of Kidd in view of Oldoni.
Response to Applicant Arguments
With respect to Applicant’s arguments under 35 USC 102, the arguments have been fully considered but are moot in view of the new grounds of rejection set forth above as necessitated by claim amendment herein.
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