DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant Response
Applicant's response, filed 02/12/2026, 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 Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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.
Claim Status
Claims 1-12, 14-17, 19, 20-26 and 35 are canceled.
Claims 13, 18, 27-34, and 36 are pending and are under examination herein.
Claims 13, 18, 27-34, and 36, and 36 are rejected.
Priority
The instant application is a Continuation of 15/917286 filed 03/09/2018 ,now U.S. Patent # 11515006, which is a Continuation of PCT/US2016/052912 filed 09/21/2016, which claims priority from Provisional Application 62/221574 filed 09/21/2015. As such, the effective filing date assigned to each of claims 13, 18, 27-34, and 36, and 36 is 09/21/2015.
Drawings
The drawings were accepted in the office action mailed 05/16/2024.
Claim Rejections - 35 USC § 112
The rejections of claims 14 and 20 under 35 U.S.C. 112(d) are withdrawn in view of cancelation of the claims in the claim amendments filed 02/12/2026.
Claim Rejections - 35 USC § 101
The rejection of claims 14 and 20 under 35 USC § 101 is withdrawn in view of cancellation of the claims in the claim amendments filed02/12/2026.
MAINTAINED REJECTION:
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 13, 18, 27-34, and 36 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea/law of nature/natural phenomenon without significantly more. Newly recited portions are necessitated by claim amendments.
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claim 13 recites for (d) each matching reference genome of the one or more matching reference genomes: determining a first amount of the first plurality of sequence reads that aligns to the matching reference genome; determining a second amount of the second plurality of sequence reads from a negative control sample that align to the matching reference genome; determining a reads per million (RPM) ratio of the first amount and the second amount; comparing the ratio to a threshold value of 10; and (e) based least in part on the comparing one or more RPM ratios to the threshold value in (iv), increasing discrimination in the first plurality of sequence reads from a background signal, thereby providing an output as indicative of a presence of potential pathogens when one or more RPM ratios meet or exceed the threshold value or an absence of potential pathogens in the test sample when one or more RPM ratios are below the threshold value.
Claim 18 recites assigning each of the first or the second plurality of sequence reads aligned to the one or more matching reference genomes to a single classification level in a taxonomy, wherein the first amount of sequence reads and the second amount of sequence reads are determined for one or more classification levels of the one or more matching reference genome.
Claim 31 recites further comprising determining a normalized first plurality of sequence reads by applying a first normalization to the first plurality of sequence reads based on a total number of sequence reads in the first plurality of sequence reads..
Claim 32 recites wherein the first normalization is a number of sequence reads per million sequence reads.
Claim 33 recites further comprising determining a normalized second plurality of sequence reads by applying a second normalization to the second plurality of sequence reads, wherein the second normalization is based on a number of sequence reads in the second plurality of sequence reads.
Claim 34 recites wherein the determining the RPM ratio in (iii) comprises the normalized first plurality of sequence reads and the normalized second plurality of sequence reads.
Claim 36 recites wherein the second normalization is a number of sequence reads per million sequence reads.
These recitations equate to steps of collecting information, analyzing data and making observations, evaluations and judgements that can be carried out in the human mind. Specifically, determining a first and second plurality of sequence reads that aligns to one or more matching reference genome, determining RPM ratio between the first and second amount, comparing the RPM ratios to a threshold value of 10, increasing the discrimination of the first plurality of sequence reads from a background signal to provide an output of the presence of a potential pathogen when the RPM ratios meet or exceed the threshold value or absence of a potential pathogen when the ratio is below the threshold value, assigning classification levels to aligned reads, and normalizing the reads can be practically performing the human mind as claimed and are similar to the concepts of collecting and comparing known information in Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1067, 100 USPQ2d 1492, 1500 (Fed. Cir. 2011) and collecting information, analyzing it, and reporting certain results of the collection and analysis in Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016) that the courts have identified as concepts that can be practically performed in the human mind. Therefore, each of the above recited limitations fall under the “Mental Processes” grouping of abstract ideas. As discussed in the MPEP 2106.04(a)(2)(II)(C), the courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. The claims are still considered to recite a mental process even if the claims use a computer as a tool to perform the concept. Furthermore, the steps as claimed for determining RPM ratios between the first and second amount and normalizing the reads equate to organizing information and manipulating information through mathematical correlations and reciting a mathematical equation, similar to the concepts of taking existing information, manipulating the data using mathematical functions, and organizing this information into a new form in Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344, 1350, 111 USPQ2d 1717, 1721 (Fed. Cir. 2014). Therefore, these limitations fall under the “Mathematical Concepts” grouping of abstract ideas. Claims 32, 34 and 36 further qualify the recited judicial exceptions As such, claims 13, 18, 27-34, and 36 recite an abstract idea (Step 2A, Prong 1: YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception to affect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere data-gathering and insignificant extra-solution activity:
Claim 13 recites preparing the test sample from a polymerase chain reaction (PCR) buffer, wherein preparing the test sample comprises adding nucleic acid molecules from the biological material to the PCR buffer, preparing a negative control sample from the PCR buffer, wherein preparing the negative control sample does not comprise adding nucleic acid molecules from the biological material to the PCR buffer; sequencing nucleic acids from the test sample and the negative control sample, and (a) receiving a first plurality of sequence reads from the test sample; (b) receiving a second plurality of sequence reads from the negative control sample; a computer; (c) preparing both a computer global nucleotide alignment technique and a computer local nucleotide alignment technique to successively align both the first plurality of sequence reads and the second plurality of sequence reads to a plurality of classified reference genomes in a reference database, thereby obtaining alignment results that include, for each of at least a portion of the first plurality of sequence reads and the second plurality of sequence reads, one or more matching reference genomes to which the sequence read aligns, wherein the plurality of classified reference genomes comprises a human reference genome and a reference genome of the microbial organism.
Claim 27 recites wherein the nucleic acid molecules comprise DNA.
Claim 28 recites wherein the nucleic acid molecules comprise RNA.
Claim 29 recites wherein the nucleic acid molecules comprise DNA and RNA.
Claim 30 wherein the nucleic acid molecules comprise cDNA.
Claims 18, 31-34 and 36 do not recite elements in addition to the recited judicial exceptions. Claims 13-14 recite limitations for gathering data, and claims 20 and 27-30 recite further limitations for the types of data gathered. These limitations equate to mere data gathering and selecting a particular data source or type of data to be manipulated, and data outputting, which the courts have found to be insignificant extra-solution activity (see MPEP 2106.05(g)). The limitations for receiving information, storing data and sending data also equate to steps of data gathering that the courts have identified as insignificant extra-solution activity in Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015). As discussed in the MPEP, the courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. The claims are still considered to recite a mental process even if the claims use a computer as a tool to perform the concept. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. There is no indication that any of these additional elements provide a practical application of the recited judicial exception outside of the judicial exception itself. As such, claims 13, 18, 27-34, and 36 are directed to an abstract idea (Step 2A, Prong 2: NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). Further analyzing the additional elements under step 2B, the additional elements as described above do not rise to the level of significantly more than the judicial exception. As set forth in the MPEP, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either 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 under the 2B analysis, performing sequencing on nucleic acids and receiving sequence data are laboratory techniques that the courts have recognized as well-understood, routine, conventional activity in the life science arts, as they are similar to using polymerase chain reaction to amplify and detect DNA (Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016) and Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015)), amplifying and sequencing nucleic acid sequences (University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)) and analyzing DNA to provide sequence information or detect allelic variants (Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546. (See MPEP2106.05(d)).
The prior art to Muhl et al. (Diagnostic Microbiology and Infectious Diseases vol. 66, pages 41-49 (2010); previously cited; hereafter referred to as Muhl) shows use of no copy controls (termed NEC) when performing PCR amplifications of a sample (fig 1A; fig 3-5). Muhl also discloses sequencing of amplicons in negative controls (p 44-45; table 2). Furthermore, Salter et al. (BMC Biol 2014, 12, 87; previously cited) also discloses concurrently sequencing negative controls and test samples to detect contamination ( p 4, col 1,para 2; p 8, col 1, para 3-p 9, col 1, para 1). Furthermore, the prior art to Thompson et al. (Bioinformatics, Volume 19, Issue 9, June 2003, Pages 1155–1161; newly cited) discloses a program for two-step refinement process by determining and aligning global and then local core blocks, in which well aligned regions can be differentiated and alignment correction is then restricted to the less reliable regions and the error correction stage involves a hierarchical, progressive realignment of the local regions defined in the initial analysis stage (abstract; p 1156, col 2, para 3- p 157, col 2, para 6). The prior art to Homer et al. (BMC Bioinformatics 2009, 10, 175, pages 1-11; newly cited) also discloses local sequence alignment is typically a final finishing step in a two-stage search process found in many current sequence alignment tools that support alignment of a short sequence to an entire genome (p 2, col 1, para 2). Chaisson and Tesler ( BMC Bioinformatics 2012, 13, 238; newly cited) also discloses aligning SMS reads with high indel rates to genomes as follows: first, find clusters of short exact matches between the read and the genome using either a suffix array or BWT-FM index, and then, perform a more detailed alignment of the regions where reads are matched to assign the alignment (p 2, col 1, para 4-p 3, col 1, para 1; fig 9). Schneeberger et al. (Genome Biol 2009, 10, R98; p 1-12; newly cited), discloses a publicly available software tool, GenomeMapper, which supports simultaneous mapping of short reads against multiple genomes and performs both accurate global and local alignments, and that with the first step of the alignment procedure, GenomeMapper scans the hash index for k-mers identical between read and genome graph to detect quickly all genomes and locations with nearly identical alignments, in the second step, GenomeMapper determines the location and sequence of nearly identical maximal substrings (NIMS) between read and genome graph, and finally, GenomeMapper will perform a k-banded alignment by applying dynamic programming to ensure a consistent gap placement (abstract; fig 1; p 2, col 2, para 1-2; p 5, col 1, para 4-p 6, col 1, para 3; fig 1-2; p 11, col 1, para 2). The prior at to Swei et al. (PloS one, 8(4), p.e62083, p 1-9; newly cited) also discloses extracting cNDA and using SNAP and then BLASTn to perform both global and local alignments for a plurality of reference genomes, including human and bacterial databases, after preprocessing and removal of sequences corresponding to host background and/or laboratory contamination (p 2, col 1, para 2-p 3, col 2, para 1; p 5, col 1, para 2-col 2, para 2; table 1).
As such, activities such as data gathering do not provide a non-conventional or unconventional step. Rather, the data gathering and outputting 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)).
Therefore, the additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception, and the claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claims 13, 18, 27-34, and 36 are not patent eligible.
Response to applicant’s arguments
Applicant states claim 13 is patent-eligible because it provides a specific inventive concept, because it recites additional elements, when considered as an ordered combination, are not well-understood, routine or conventional, and are not disclosed by the cited art, and further that Naccache and Huson both fail to discloses performing both a global and local alignment technique to successively aligning the sequence reads, and requests withdrawal of the rejection (Applicant Arguments, p 6, para 2 –p 7, para 6).
It is respectfully submitted that this is not persuasive. New art has been cited to show the combination of the recited additional elements are well-understood, routine and conventional in the art, as discussed above. Therefore, the additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception, and the claims do not amount to significantly more than the judicial exception itself, and the rejection is maintained.
Claim Rejections - 35 USC § 103
The rejections of claims 13, 18, 27-34 and 36 under 35 U.S.C. 103 as being unpatentable over Naccache et al. (IDS 1/29/2020, ref 4; previously cited; hereafter referred to as Naccache), and further in view of Muhl et al. (Diagnostic Microbiology and Infectious Diseases vol. 66, pages 41-49 (2010); previously cited; hereafter referred to as Muhl) were withdrawn in the office action mailed 09/24/2024, as neither Naccache nor Muhl not appeared to disclose or suggest successively aligning the reads with a global and local alignment technique or providing an output indicative of a presence of potential pathogens when the ratio of the first amount of the first plurality of sequence reads that aligns to the matching reference genome and second amount of the second plurality of sequence reads that aligns to the matching reference genome meets or exceeds the threshold value of 10, or an absence of potential pathogens in the test sample when the ratio of the first amount of the first plurality of sequence reads that aligns to the matching reference genome and second amount of the second plurality of sequence reads that aligns to the matching reference genome is below the threshold value of 10.
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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/N.D./ Examiner, Art Unit 1686
/Karlheinz R. Skowronek/ Supervisory Patent Examiner, Art Unit 1687