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 .
Status of Claims
Claims 1-4, 6-11, and 13-15 pending and examined on the merits.
Claims 5 and 12 cancelled.
Priority
The instant application filed on 5/25/2022 is a 371 national stage entry of PCT/EP2020/084403 having an international filing date of 12/3/2020, and claims the benefit of priority to provisional U.S. Application No. 62/947,023 filed on 12/12/2019. Thus, the effective filing date of the claims is 12/12/2019.
The applicant is reminded that amendments to the claims and specification must comply with 35 U.S.C. § 120 and 37 C.F.R. § 1.121 to maintain priority to an earlier-filed application. Claim amendments may impact the effective filing date if new subject matter is introduced that lacks support in the originally filed disclosure. If an amendment adds limitations that were not adequately described in the parent application, the claim may no longer be entitled to the priority date of the earlier filing.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 5/25/2022 has been entered and considered. A signed copy of the corresponding 1449 form has been included with this Office action.
Specification
The disclosure is objected to because of the following informalities: The abstract contains references to identifiers in the drawing. These identifiers belong only in the specification and drawings of the disclosure per MPEP 608.01(f).
Appropriate correction is required.
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 1-4, 6-11, and 13-15 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.
Claims 1 and 9 recite "determining, using the received ploidy range and/or received contamination rate range, adjusted segmentation values for the plurality of CNV calls". It is not clear what "segmentation values" are meant to represent in the claims, and the instant specification does not illuminate the matter. To further prosecution, the term "segmentation values" are interpreted as values derived from mapping sequence reads to a reference genome, then calculating a mapped read depth (e.g. an average read depth) over some predetermined window size, along the entire reference sequence. This value (per window) may then be adjusted or normalized as described in the claim.
Additionally, Claims 1 and 9 recite "for the copy number variation profile of the tumor cells of the tumor" in lines 18-19 and 14-15, respectively. There is insufficient antecedent basis for “the tumor cells of the tumor”. To further prosecution, the limitation is interpreted as “for the copy number variation profile of the target cells".
Claim 2 recites "The method of claim 1, further comprising the step of identifying" in lines 1-2. There is insufficient antecedent basis for “the step of identifying”. To further prosecution, the limitation is interpreted as “a step of identifying".
All remaining claims rejected due to dependency on claim 1 or 9.
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 1-4, 6-11, and 13-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of a mental process, a mathematical concept, organizing human activity, or a law of nature or natural phenomenon without significantly more. 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:
Claims 1 and 9: “determining, from the received sparse genome data, an unadjusted CNV profile comprising a plurality of CNV calls for a plurality of chromosomes” provides an evaluation (determining a CNV profile involves an evaluation of the sequencing data) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“normalizing the unadjusted CNV profile” provides a mathematical calculation (normalizing data requires mathematical calculations) that is considered a mathematical concept, which is an abstract idea.
“determining, using the received ploidy range and/or received contamination rate range, adjusted segmentation values for the plurality of CNV calls; determining a plurality of adjustment scores comprising a distance between adjusted segmentation values and closest whole integers for a CNV call” and “determining adjusted segmentation values for the plurality of CNV calls comprises determining an adjusted segmentation value for each CNV segment using a sampling rate for the ploidy range and/or for the contamination rate; and wherein the adjusted segmentation values are calculated using the equation: Sadj = P(S - C)/(1 - C)” provides a mathematical calculation (determining segmentation values requires mathematical calculations, e.g. the claimed mathematical function) that is considered a mathematical concept, which is an abstract idea.
“comparing the determined plurality of adjustment scores to one or more predetermined factors for selecting a CNV profile best fit” provides a comparison (comparing scores for best fit) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“selecting, based at least in part on the comparison, one of the plurality of adjustment scores as a best fit” provides an evaluation (selecting involves an evaluation of available options) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
Claim 2: “identifying, using the CNV profile report, one or more causal CNVs” provides an evaluation (identifying causal CNVs) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
These recitations are similar to the concepts of collecting information, analyzing it, and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or are mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. Additionally, while claims 9-11, and 13-15 recite performing some aspects of the analysis on “A system for determining a copy number variation (CNV) profile of target cells from a sample, comprising: [] a processor configured to..”, there are no additional limitations that indicate that this requires anything other than carrying out the recited mental processes or mathematical concepts in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then it falls within the “Mental processes” grouping of abstract ideas. As such, claims 1-4, 6-11, and 13-15 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). The judicial exceptions listed above are not integrated into a practical application because the claims do not recite an additional element or elements that reflects an improvement to technology. Specifically, the claims recite the following additional elements:
Claims 1 and 9: “receiving sparse genome sequencing data” and “receiving a range for possible ploidy for the CNV profile, and/or receiving a range for a possible contamination rate for the CNV profile” provides insignificant extra-solution activities (receiving data is a pre-solution activity involving data gathering steps) that do not serve to integrate the judicial exceptions into a practical application.
“generating, using the selected a best fit adjustment score, an adjusted CNV profile report; and reporting the generated adjusted CNV profile report” provides insignificant extra-solution activities (generating a report and reporting data are a post-solution activities involving data gathering and manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
Claim 2: “providing an intervention based on the identified one or more causal CNVs” restricts use to a particular environment or application without adding significant innovation that does not serve to integrate the judicial exceptions into a practical application because they are post-solution activities involving a mere field of use.
Claims 4 and 10: “the range for possible ploidy for the CNV profile and the range for a possible contamination rate for the CNV profile is received from a user of the CNV profiling system” provides insignificant extra-solution activities (receiving data is a pre-solution activity involving data gathering steps) that do not serve to integrate the judicial exceptions into a practical application.
The steps for receiving and outputting data are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application because they are pre- and post-solution activities involving data gathering and manipulation. Additionally, the steps for providing and intervention restricts use to a particular environment or application without adding significant innovation that does not serve to integrate the judicial exceptions into a practical application because they are post-solution activities involving a mere field of use (see MPEP 2106.04(d)(2) - Integration of a Judicial Exception Into A Practical Application; MPEP 2106.05(g) - Insignificant Extra-Solution Activity; and MPEP 2106.05(h) - Field of Use and Technological Environment). Furthermore, the limitations regarding implementing program instructions do not indicate that they require anything other than mere instructions to implement the abstract idea in a generic way or in a generic computing environment. As such, this limitation equates 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. Therefore, claims 1-4, 6-11, and 13-15 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). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application, or equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment.
As discussed above, there are no additional elements to indicate that the claimed “system for determining a copy number variation (CNV) profile of target cells from a sample, comprising: [] a processor configured to..” requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims. Additionally, the limitations for receiving and outputting data are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application. Furthermore, no inventive concept is claimed by these limitations as they are well-understood, routine, and conventional.
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. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 1-4, 6-11, and 13-15 are not patent eligible.
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.
Claims 1-4, 6-11, and 13-15 rejected under 35 U.S.C. 103 as being unpatentable over Wigler et al. (US-20190325113) in view of Azab et al. (US-20190371429) and Prandi et al (Prandi et al. "Ploidy‐and purity‐adjusted allele‐specific DNA analysis using CLONETv2." Current protocols in bioinformatics 67.1 (2019): e81).
Regarding claims 1, 3-4, 8-11, and 15, Wigler teaches a method determining a copy number variation (CNV) profile of target cells from a sample, using a CNV profiling system (claims 1 and 9) and the target cells are tumor cells (claims 8 and 15) (Para.0015 "the method includes obtaining a segmented genomic profile [GP], of DNA extracted from one or more affected or diseased cells, e.g., tumor cells, from a first individual patient, said [GP] comprising information on the copy number of a plurality of discrete segments of the genome, or one or more portions of the genome; wherein, when relative copy number as a function of genomic position is plotted for a plurality of genomic segments within said [GP]").
Wigler also teaches receiving sparse genome sequencing data comprising sequencing from both target and non-target cells from the sample (Para.0112 "In certain embodiments of the present invention, the whole genome is profiled globally. In alternative embodiments, one or more portions (e.g., regions or loci) of the genome known to be susceptible to chromosomal rearrangements are profiled").
Wigler also teaches determining, from the received sparse genome data, an unadjusted CNV profile comprising a plurality of CNV calls for a plurality of chromosomes (Para.0026 show copy number profiles of 22 chromosomes).
Wigler also teaches comparing the determined plurality of adjustment scores to one or more predetermined factors for selecting a CNV profile best fit (Para.0114 "It will be recognized that response of other diseased tissues or cells of a patient characterized by genomic rearrangements may similarly be measured, the data annotated and stored in databases for comparisons that enable similarities to be evaluated and used to assign a probabilistic measure of an outcome or a set of outcomes relating to the disease and/or the patient in other, non-cancer related disorders, conditions and diseases").
Wigler also teaches selecting, based at least in part on the comparison, one of the plurality of adjustment scores as a best fit for the copy number variation profile of the [target cells] (Para.0114 implies ranking probabilities from a comparison).
Wigler also teaches generating, using the selected a best fit adjustment score, an adjusted CNV profile report (Para.0050 Figure 19 illustrates a ranked output table of outcomes for an individual).
Wigler does not explicitly teach: normalizing the unadjusted CNV profile; receiving a range for possible ploidy for the CNV profile, and/or receiving a range for a possible contamination rate for the CNV profile, the contamination rate corresponding to contamination of the CNV profile by non-target cells; determining, using the received ploidy range and/or received contamination rate range, adjusted segmentation values for the plurality of CNV calls; determining a plurality of adjustment scores comprising a distance between adjusted segmentation values and closest whole integers for a CNV call; nor reporting the generated adjusted CNV profile report, wherein determining adjusted segmentation values for the plurality of CNV calls comprises determining an adjusted segmentation value for each CNV segment using a sampling rate for the ploidy range and/or for the contamination rate; and wherein the adjusted segmentation values are calculated using the equation: Sadj = P(S - C)/(1 - C), where Sadj, is an adjusted segmentation value for a CNV segment, P is a ploidy value from the range for possible ploidy, C is a contamination rate value from the range for possible contamination rate, and S is a segmentation value before adjustment.
However, Azab teaches normalizing the unadjusted CNV profile; and determining, using the received ploidy range and/or received contamination rate range, adjusted segmentation values for the plurality of CNV calls (claims 1 and 9), and the unadjusted CNV profile is normalized to a mean value of one (claims 3 and 11) (Para.0241 "normalization comprises a sophisticated mathematical adjustment to bring probability distributions of adjusted values into alignment. In some embodiments normalization comprises aligning distributions to a normal distribution. In certain embodiments normalization comprises mathematical adjustments that allow comparison of corresponding normalized values for different datasets in a way that eliminates the effects of certain gross influences (e.g., error and anomalies [etc]").
Azab also teaches receiving a range for possible ploidy for the CNV profile, and/or receiving a range for a possible contamination rate for the CNV profile, the contamination rate corresponding to contamination of the CNV profile by non-target cells (claims 1 and 9) and the range for possible ploidy for the CNV profile and the range for a possible contamination rate for the CNV profile is received from a user of the CNV profiling system (claims 4 and 10) (Para.0351 "Non-limiting examples of data and/or information include [] providing or determining expected levels and expected ranges (e.g., expected level ranges, threshold ranges and threshold levels), [] providing identification (e.g., identifying a copy number alteration, genetic variation/genetic alteration or aneuploidy)").
Azab also teaches determining a plurality of adjustment scores comprising a distance between adjusted segmentation values and closest whole integers for a CNV call (Para.0636 "for each variant (one sample data point in the DP and AF classification plane specific to the position), its mahalanobis distance from the distribution center is computed. The p value for the mahalanobis distance is then calculated as the tail probability of a chi square distribution with degree of freedom equal to 2").
However, Prandi teaches utilizing purity and ploidy for adjusting allele copy number estimates (Page 2 paragraph 2 "Many computational methods identify somatic copy-number aberrations from the relative amounts of DNA in a tumor and its matched normal sample, but accurate estimation of the integer number of copies of each allele requires purity and ploidy adjustments (Bao, Pu, & Messer, 2014)").
Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to modify the methods of Wigler as taught by Azab in order to identify genetic variances that can lead to diagnosis of a medical condition (para.0005 "Identifying one or more genetic variations and/or genetic alterations (e.g., copy number alterations, copy number variations, single nucleotide alterations, single nucleotide variations, chromosome alterations, translocations, deletions, insertions, and the like) or variances can lead to diagnosis of, or determining predisposition to, a particular medical condition"). One skilled in the art would have a reasonable expectation of success because both methods are concerned with identifying causal CNVs using genomic data.
Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to modify the methods of Wigler as taught by Prandi in order to accurately estimate allele copy numbers (Page 2 paragraph 2 "Many computational methods identify somatic copy-number aberrations from the relative amounts of DNA in a tumor and its matched normal sample, but accurate estimation of the integer number of copies of each allele requires purity and ploidy adjustments (Bao, Pu, & Messer, 2014)"). One skilled in the art would have a reasonable expectation of success because both methods are concerned with estimating copy number variations for cancer detection and/or diagnosis.
Regarding claim 2, Wigler in view of Azab and Prandi teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Wigler also teaches identifying, using the CNV profile report, one or more causal CNVs and providing an intervention based on the identified one or more causal CNVs (Para.0067 "FIG. 34 illustrates that the presence of a causal genetic variant detected by ROMA correlates with familial inheritance of a disease").
Regarding claims 6 and 13, Wigler in view of Azab and Prandi teach the methods of Claims 1 and 9 on which this claim depends/these claims depend, respectively. Azab also teaches determining a plurality of adjustment scores using various methods including distance measures (Para.0241 "normalization comprises a sophisticated mathematical adjustment to bring probability distributions of adjusted values into alignment. In some embodiments normalization comprises aligning distributions to a normal distribution. In certain embodiments normalization comprises mathematical adjustments that allow comparison of corresponding normalized values for different datasets in a way that eliminates the effects of certain gross influences (e.g., error and anomalies [etc]" and Para.0636 "for each variant (one sample data point in the DP and AF classification plane specific to the position), its mahalanobis distance from the distribution center is computed. The p value for the mahalanobis distance is then calculated as the tail probability of a chi square distribution with degree of freedom equal to 2").
Regarding claims 7 and 14, Wigler in view of Azab and Prandi teach the methods of Claims 1 and 9 on which this claim depends/these claims depend, respectively. Wigler also teaches one of the one or more predetermined factors for selecting a CNV profile best fit is a CNV profile, a ploidy value or range, and/or a contamination value or range previously observed and determined to be meaningful (Table 8 contains a list of genomic loci that are involved in breast cancer diagnosis or susceptibility).
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Kim et al. "Comparison of Normalization Methods for Defining Copy Number Variation Using Whole-genome SNP Genotyping Data." Genomics & informatics 6.4 (2008): 231-234
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert A. Player whose telephone number is 571-272-6350. The examiner can normally be reached Mon-Fri, 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D. Riggs can be reached at 571-270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/R.A.P./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686