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 .
Claim Status
Claims 1-13 are pending.
Priority
This application is a 371 of PCT/EP2021/056008, filed 03/10/2021, which claims benefits under U.S.C 119 to application no. 20162646.2, filed 03/12/2020 by the European Patent Office. The instant application has the effective filing date of 12 March 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/27/2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Drawings
The drawings, submitted on 09/12/2022, are objected to by the examiner for the nucleotide sequence listing deficiencies, explained below.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency 1- Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specific deficiency 2-This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that the sequence found in Figure 17 of the drawings (09/12/2022) does not match the sequence within the XML listing.
Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and a statement that the substitute specification contains no new matter.
Specification
The specification is objected to because it contains an embedded hyperlink and/or other form of browser-executable code.
Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Browser-executable code is found in the following locations:
Page 12, Line 37
Page 13, Line 29
Page 14, Line 34
Page 30, Line 15
Page 30, Line 29
Page 33, Line 16
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 1-13 are rejected under U.S.C 101 because the claimed invention is directed to abstract ideas without significantly more, as detailed in the analysis below.
Eligibility Step 1: Subject matter eligibility evaluation in accordance with MPEP § 2106:
Claims 1-11 are directed to a statutory category (method).
Claim 13 is directed to a statutory category (system).
Claim 12 is NOT directed to a statutory category (computer program product).
Claims 12 is non-statutory as it recites “a computer program product”. The claims asinstantly recited read on carrier waves, which are transitory propagating signals and therefore are not proper patentable subject matter because they do not fit within any of the four statutory categories of invention (In re Nuijten, Federal Circuit, 2007). It is noted that the recitation of a "non-transitory computer readable medium" would overcome the rejection with respect to claim 12 reading on signals. However, the amendment to only "non-transitory computer readable medium" would notovercome the rejection under 35 U.S.C. 101 since the claims would still be directed to a judicial exception without significantly more (see below).
Though claim 12 does not recite a statutory category of invention, in the interest of compact prosecution, the remaining steps of the subject matter eligibility analysis continues below on all claims.
Claims 1-11 and 13 [Eligibility Step 1: YES]
Claim 12 [Eligibility Step 1: NO]
Eligibility Step 2A: This step determines whether a claim is directed to a judicial exception in accordance with MPEP § 2106.
Eligibility Step 2A -- Prong One: Limitations are analyzed to determine if the claims recite any concepts that could equate to a judicial exception (i.e. abstract idea, law of nature, or natural phenomenon). Possible judicial exceptions are explored below.
Recitations of Judicial Exceptions:
Claim 1: A computer-assisted process for detecting a genome sequence in digital form in a genome of a microorganism in digital form, the process involving:
for each k-mer, determining its absence or presence in the genome; (mental process)
determining that the genome sequence is present in the genome if the percentage of k-mers detected as being present in the genome is above a predetermined threshold. (mental process)
Claim 2: The process as claimed in claim 1, in which the determination of the presence or absence of a k-mer in the genome is obtained by detecting at least one identical copy of the k-mer in the genome (mental process)
Claim 3: The process as claimed in claim 2, in which the digital genome consists of a set of genome sequences produced by a sequencing platform, or "reads",
and according to which the determination of the presence or absence of a k-mer in the genome is obtained by detecting Ncov, identical copies of the k-mer in the genome, where the integer Ncov is equal to:
N
c
o
n
v
=
τ
×
N
r
N
g
where: Nr is the total number of bases included in the digital genome, Ng is the total number of bases of a reference genome of the species to which the microorganism, and
τ
is a percentage between 5% and 15%. (mathematical concept, mental process)
Claim 4: The process as claimed in claim 2, in which the genome of the microorganism is included in a set of genomes derived from the direct sequencing of a sample, each digital genome consisting of a set of genome sequences produced by a sequencing platform, or "reads",
and according to which the determination of the presence or absence in the genome is obtained by detecting NCoV identical copies of the k-mer in the genome, where the integer NCoV is equal to:
N
c
o
n
v
=
τ
×
ρ
N
r
N
g
where: Nr is the total number of bases included in the digit al genome, Ng is the mean total number of bases of a genome of the species to which the microorganism belongs, p is the relative proportion of the microorganism in the sample, is the percentage and
τ
is a percentage between 5% and 15. (mathematical concept, mental process)
Claim 7: The process as claimed in claim 6, in which the space of the genome sequence lengths is divided into three intervals, and according to which the predetermined threshold takes a single value per interval. (mental process)
Claim 8: The process as claimed in claim 7, according to which k is between 15 and 50, and according to which if L ≤ 61 then
s
u
n
i
= 90%, if 61< L ≤ 100 then
s
u
n
i
= 80% and if 100 < L then
s
u
n
i
= 70%, in which L is the length of the genome sequence and
s
u
n
i
is the predetermined threshold value. (mental process)
Claim 9: The process as claimed in claim 1, comprising the detection of a group of genome sequences, the detection involving:
detecting each genome sequence of the group in accordance with the process of claim 1; (mental process, additional element)
determining that the group of genome sequences is present in the genome: (mental process)
if at least one genome sequence of the group is detected:
if all the genome sequences of the group are detected:
if the percentage of genome sequences of the group that are detected is above a second predetermined threshold:
or with a probability equal to the percentage of genome sequences of the group that are detected as being present.
Finding identical subsequences from a larger sequence and organizing information via separating and designating values can be accomplished through mere mental observations of data. As such, the noted limitations fall within the mental process grouping of abstract ideas.
Furthermore, limitations that recite mathematical formulas and calculations require both mental observations of data and mathematical analysis techniques that can be fully executed with use of a pen and paper. As such, limitations that involve activities of this manner fall into the mental process and/or mathematical concept grouping of abstract ideas.
As such claims 1-4 and 7-9 appear to recite judicial exceptions (abstract ideas).
Eligibility Step 2A – Prong Two: A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. If the claim contains no additional claim elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d)).
Eligibility Step 2B: Claim elements are probed for inventive concept equating to significantly more than the judicial exception (MPEP 2106.04(II)).
Additional Elements within the claimed invention include:
Claim 1: A computer-assisted process for detecting a genome sequence in digital form in a genome of a microorganism in digital form, the process involving:
storing in a computer memory a set of digital genome sequences of constant length k, or "k-mers", the set being obtained by sliding, with a constant step, a window of length k over the genome sequence;
This limitation completes necessary data gathering activities for the claimed invention and does not place necessary limits on or integrate the abstract ideas into practical application.
[Eligibility Step 2A – Prong Two: YES]
Such data gathering activities that store and retrieve information in memory are considered well-understood, routine, and conventional per Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93;
[Eligibility Step 2B: NO]
Additional Elements that may be categorized differently include:
Claim 5: The process as claimed in claim 1, in which the predetermined threshold is dependent on the length of the genome sequence.
Claim 6: The process as claimed in claim 5, in which the predetermined threshold value decreases with the value of the length of the genome sequence.
Claim 10: The process as claimed in claim 9, in which the second threshold is greater than or equal to 20%.
The limitations above specify the relationships and length of the data used in downstream analysis. Selecting a particular type of data to be manipulated is also as an insignificant extra-solution activity and does not integrate the judicial exceptions of the claimed invention as a whole into practical application per MPEP 2106.05(g).
[Eligibility Step 2A – Prong Two: YES]
Considering the types of data (genome sequences of different lengths) are also well-understood, routine, and conventional in the art, the elements further lack inventive concept per Intellectual Ventures I LLC v. Erie Indem. Co., 850 F.3d at 1328-29, 121 USPQ2d at 1937.
[Eligibility Step 2B: NO]
Additional Elements that may be categorized differently include:
Claim 11: The process as claimed in claim 1, also comprising the total or partial sequencing of the genome of the bacterial strain so as to produce the genome in digital form.
Claim 12: A computer program product storing computer-executable instructions for performing a process as claimed in claim 1.
Claim 13: A system for detecting a genome sequence in a genome of a microorganism, comprising:
a sequencing platform for the partial or total sequencing of the genome of the strain;
a computer unit configured to apply a detection process as claimed in claim 1.
These limitations represent generic computer or sequencing components and processes that generate, transmit, and/or receive data necessary to complete the steps of the claimed invention. As such, the components when viewed separately or in the context of the whole, merely act as tools to execute the judicial exceptions, but do not integrate them into practical application, per Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016).
[Eligibility Step 2A – Prong Two: YES]
The techniques, as claimed, were further established as well-understood, routine, and conventional by the courts, in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), which recognized nucleic acid sequencing; and Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546, which recognized the analysis of DNA to provide sequence information.
[Eligibility Step 2B: NO]
As such, claims 1-13 are directed to judicial exceptions without significantly more and are rejected under 35 U.S.C 101.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7-9 and 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention for the following reasons.
Claim 7 recites dividing “the space of the genome sequence lengths” in which “the space” lacks antecedent basis and does not clearly point out what is being divided. Please clarify and provide antecedent basis for the term.
Claim 8 recites “the length of the genome sequence,” wherein it is unclear whether the “genome sequence” is referencing genome sequences of constant length, defined as “k-mers” in claim 1, the entire genome, or a portion of a genomic sequence, which the limitation is instantly interpreted as.
Claim 9 recites “determining that the group of genome sequences is present in the genome”… “with a probability equal to the percentage of genome sequences in the group that are detected as being present”, wherein it is unclear what probability is determined. Clarification is required.
Instantly the limitation is interpreted as determining that a group of genomic sequences is present… if a percentage, equal to if the percentage of each genomic sequence within the group determined to be present according to the technique in claim one, are detected.
Claim 13 recites “…sequencing of the genome of the strain” wherein, “the strain” lacks antecedent basis. To overcome this rejection, please amend to “a strain” or provide antecedent basis for the term in claim 1, which it depends.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 9, 10, and 12 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Fisher (2017/0364666).
Claims 1 and 12 are directed to computer-implemented methods and products that store sets of genome sequences with a constant length (k-mers) in memory; and determine whether a k-mer is present within a microbial genome if each unique k-mer is detected above a predetermined threshold percentage.
Fisher describes computer implemented methods and systems of strain typing microbial samples via k-mer analysis.
Regarding claims 1 and 12, Fisher teaches a system that may include one or more processors, and one or more hardware storage devices with stored computer-executable instructions wherein the instructions may cause the computer system to receive a set of nucleotide sequence data [abstract] and generate k-mer profiles which may be stored in the k-mer profile library [0022].
Fisher further teaches that each k-mer is a short nucleotide sequence length of “k” bases derived from the respective strain's sequence data [0013] and that each k-mer is generated by moving one base pair at a time [0022].
Fisher further teaches that the illustrated cutoff filter is operable to filter/exclude those k-mers having counts that fall below a cutoff threshold [0024], which in some embodiments is a percentage [0028].
Regarding claim 2, Fisher teaches that mean k-mer identity for pulsed-field gel electrophoresis (PFGE) categories of identical, closely/possibly related, different k-mer profiles were 99.2%, 94.6%, and 58.3%, respectively [0051] and therefore detects more than one identical k-mer copy.
Claim 9 is directed to detecting a group of genomic sequences and determining if the group is present if one of the following conditions are satisfied:
At least one genomic sequence of a group is detected
All genomic sequences of a group are detected
A percentage of genomic sequences of a group are detected
A percentage, equal to if the percentage of each genomic sequence within the group determined to be present according to the technique in claim one, are detected.
Claim 10 is directed to determining whether a group is present if at least 20% of genomic sequences within a group are detected. This claim is contingent on a non-required condition (limitation (c)) of claim 9 to be met (see MPEP 2111.04 II).
Regarding claims 9 and 10, Fisher teaches detecting MLST type via downloading MLST data for each MLST gene and a text profile file containing the strain type (ST) and corresponding sequence identifier for each of the genes in the profile from pubmlst [0050]; then determining and storing the k-mer content for each sequence as a resource file [0050].
Fisher further teaches comparing the strains and determining a strain type match if a MLST gene shared 100% kID with a queried strain [0050].
Therefore, Fisher teaches determining if a group indicating a particular strain type is present if more than 20% of the sequences corresponding to the known group of sequences within that strain type are detected in the sample.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claims 3, 4, 11, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Fisher (2017/0364666), as applied to claims 1, 2, 9, 10, and 12 above, in view of Ranjan et al. (Biochem Biophys Res Commun; 2016).
Fisher teaches computer implemented methods and systems of identifying k-mers present within a microbial genome, as consistent with claims 1, 2, 9, 10, and 12, detailed above.
Claim 3 is directed to calculating the sequencing depth of coverage via dividing the number of bases in the reads by the total number of bases in a reference genome of a bacterial strand. The claim also multiplies the calculated coverage by an estimated sequencing error rate (τ), within the range of 5-15% (0.05-0.15), in order to derive a metric of identical k-mers within the genome.
Claim 4 is directed multiplying the result of the previous equation with a relative proportion of microorganism within the sample.
Regarding claim 3 and 4, Fisher teaches that multiplying the estimated coverage by a cutoff multiplier of about 0.2 (e.g., 0.05 to 0.40 or 0.1 to 0.3) provides a suitable cutoff threshold to remove sufficient proportion of error k-mers [0024] and can be adjusted accordingly to account for higher or lower sequencing error rates [0024]. Therefore, Fisher teaches multiplying the sequencing depth of coverage by a percentage (τ) that can fall within the range of .05-.40 or .10-.30, which both overlap within the range of τ (0.05-0.15) for the claimed invention.
Fisher does not teach calculating sequencing depth of coverage in the same manner as the claimed invention (claims 3 and 4); accounting for the proportion of microorganism in the sample (claims 4); or explicitly including a sequencing platform (claim 13) for the total or partial sequencing of the bacterial genome strain within its system (claim 11).
Ranjan et al. describes microbiome analysis via various sequencing techniques.
Regarding claim 3, Ranjan et al. teaches that the percentage of genome coverage was calculated using the formula [total number of bases aligned/genome size (bases) × 100] (page 5, column 1). Regarding claim 4, Ranjan et al. further teaches taking the percentage of relative abundance of the species into account within the calculation (page 5, column 1).
Regarding claims 11 and 13, Ranjan et al. teaches comparing the 16S rRNA amplicon versus the Whole Genome Sequencing (WGS) method and the Illumina HiSeq versus MiSeq platforms (page 3, column 1) in order to rigorously determine the optimal methods for microbiome analysis (page 6, column 1).
Therefore, Fisher teaches a framework of microbial data analysis that includes determining an appropriate amount of k-mers, as it relates to depth of coverage and sequencing errors rates. Ranjan et al. provides sufficient motivation to one of ordinary skill in the art to further include sequencing platform analysis and a known of coverage calculation technique to result in an expected improvement to the overall system.
Claims 5, 6, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Fisher (2017/0364666), as applied to claims 1, 2, 9, 10, and 12 previously, in view of Zhao (2015/0347676) and in further view of Huang et al. (Synthetic and Systems Biotechnology; vol. 4; 2019)
Fisher teaches computer implemented methods and systems of identifying k-mers present within a microbial genome as consistent with claims 1, 2, 9, 10, and 12, and detailed previously.
Fisher does not teach that the threshold for selecting k-mers is dependent (claim 5), or proportional (claim 6) to the value of k; nor does Fisher teach exemplifying this relationship by determining different threshold minimums for three different k-mer lengths (claim 7).
Zhao describes a method of diagnostic testing using k-mer sequence data.
Zhao teaches grouping together mapped sequence reads according to various parameters and assigning them to particular portions and that can be used to identify a portion (e.g., the presence, absence) present in a sample [0157].
Zhao further teaches that in some embodiments, a portion, is defined based on partitioning of a particular size, coverage [0157], or length of genomic sequence and can be selected, filtered and/or removed from consideration using any suitable criteria know in the art [0158].
Zhao does not teach assigning filtering thresholds to sequences of varying lengths (intervals).
Huang et al. describes the statistical power of k-mer based aggregative statistics for the alignment free detection of horizontal gene transfers.
Huang et al. teaches comparing and identifying the optimal k when the statistical power is the highest and that if the k is too small, the statistics power is low (page 155, column 1). Huang et al. further teaches when k = 4, the highest statistical power is <70% (page 15, column 1) and when the k is larger than 5, the statistical power is generally better than 80% (page 155, column 1); therefore, the optimal k depends on coverage rate and the underlying sequence relatedness as represented by the length of the motif, L (page 155, column 1).
Though Huang et al. only provides threshold suggestions for two different intervals (k =4 and k >5), Fig. 4 shows the statistical power of k at five different intervals (page 154, fig. 4). Highlighting different interval quantities is the result of a design choice that would be obvious to one of ordinary skill in the art in modify in order to convey the statistical relationship of the variables, wherein k and L can have any value.
As such, Zhao et al. suggests a base technique of grouping and filtering genomic sequences according to analogous parameters of the claimed invention and Huang et al. teaches that k-mer based alignment-free sequence comparison is effective at comparing multiple sequences and identifying genetic variations that play a key role in the evolution of species and microbial genome diversity, without incurring significant computational cost (page 156, column 1). This provides sufficient motivation for one of ordinary skill in the art to select k values and significance threshold percentages as filtering criteria, from the options set forth by Zhao, in order to improve the microbial k-mer based sequence analysis system.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Fisher (2017/0364666) in view of Zhao (2015/0347676) and Huang et al. (Synthetic and Systems Biotechnology; Vol. 4; 2019), as applied to claims 1, 2, 5-7, 9, 10, and 12 above, and in further view of Mahé et al. (BMC Bioinformatics; Vol. 19 (383); 2018).
Fisher, in view of Zhao and Huang et al., teach assigning k-mer filter thresholds to intervals of varying sequence lengths (claim 7). Fisher further teaches that k-mers, analyzed for microbial strain typing and antibiotic resistance identification [0021] are more preferably within the range of about 21-31 base pairs [0022].
The references do not teach that for a k-value between 15 and 50, the minimum presence required to determine if a k-mer is present within sequencing data is 70%, 80%, or 90%, depending on if the sequencing data length is respectively less than 61 genomic units, between 61 and 100 genomic units, or over 100 genomic units (claim 8).
Mahé et al. describes a method of bacterial resistance prediction using k-mer analysis.
Mahé et al. teaches that for each set of equivalent k-mers which corresponded to a single unitig whose length ranged from 31 (the size of the individual k-mers) to 61 nucleotides (page 6, column 1), the unitigs were highly conserved, with a minimum percent identify equal to 96.7% (page 6, column 1). Therefore, Mahé et al. teaches that if the length of a genomic sequence is less than or equal to 61 nucleotides, the threshold of 31-mers filtered is above a minimum 90% threshold.
Fisher, in view of Zhao and Huang et al., support the proportional relationship between the length of a genomic sequence and the threshold value required to filter non-significant k-mers from microbial sequence data. Fisher further provides sufficient motivation for one of ordinary skill in the art to utilize k-mers within the claimed range (10-50). Therefore, determining the minimum percent identity for a 31-mer to be greater than 90% is an obvious implement to one of ordinary skill in the art, based on the referenced prior art teachings applied to a known framework with a reasonable expectation of success.
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).
Claims 1 and 11-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent Application no. 18/853,496 (reference) in view of Jaillard et al (IDS reference, filed 12/27/2022; Non-Patent Literature; cite no. 5; 2018).
The reference claim is directed to a method of sequencing a microbial organism genome, calculating sequencing depth of coverage, and detecting target genomic sequences as present, based on the calculated amount of identical copies being greater than a predetermined fraction of the sequencing depth.
Therefore, the instant claims and reference claims have the same effect and function. They differ slightly in scope as the reference claim also generates multiple sets of genomic subsequences (k-mers), based the location of the neighboring position of the target sequences. Generating subsequences of this nature is a modification of obvious to one of ordinary skill of the art to apply to the instant claims in view of Jaillard et al. which teaches that exploiting the genetic environment of the significant k-mers through their neighborhood sequences provides a valuable interpretation framework and reduces the amount data and computation time needed to perform other k-mer based approaches (page 12, column 1).
Although the claims at issue are not identical, they are not patentably distinct from each other. As such, claims 1 and 11-13 are provisionally rejected. The rejection is provisional as the co-pending claims have not yet been patented.
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.
Conclusion
No claims are currently allowed.
Correspondence
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/M.K.T./Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687