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 .
Applicants Amendment
Applicants’ preliminary amendment filed 7/29/2022 has been received and entered. Claims 1-20 have been cancelled, claims 21-40 have been added.
Claims 21-40 are pending.
Priority
This application filed 12/16/2021 is a continuation of 16/737819 filed 1/8/2020, now US Patent 11,242569, which is a continuation of 15/442993 filed 2/27/2017, now Abandoned, which is a continuation of PCT/US2016/0673556 filed 12/16/2016, which claims benefit to US provisional application 62/269051 filed 12/17/2015.
Information Disclosure Statement
The six information disclosure statements (IDS) submitted on 7/29/2022 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
It is noted that the IDS contain office actions related to foreign applications, but do not provide a context or specific claims or references that are discussed in the actions (see for example #34 and #35 Singapore written opinions dated 1/5/2021, 1/17/2020 for the same application). These have been reviewed for what is provided within them, but the relevant application material such as specification, claims and cited references have not been used for the review.
Additionally, the listing of references in the specification is not a proper information disclosure statement. For example, the specification notes citations and makes reference to methods used and contemplated (see [0051], [0070]-[0075], [0087] for example). 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 21-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11,242569 (parent application 16/737819 filed 1/8/2020). Although the claims at issue are not identical, they are not patentably distinct from each other because the present continuation, while being directed to a method, provides for the instructions implemented on the system set forth in the patent. Each provide steps of receiving and aligning sequence read data and making adjustments to transform the data into an accurate analysis of copy number for a particular genetic loci.
A copy of independent claim 1 of ‘569 is provided for comparison and completeness of the record.
A system for determining a copy number of one or more genetic loci, comprising a controller comprising, or capable of accessing, non-transitory computer- readable media comprising computer-executable instructions which, when executed by one or more electronic processors, perform at least:
(a) obtaining sequencing reads of deoxyribonucleic acid (DNA) molecules of a cell-free bodily fluid sample of a subject, wherein the DNA molecules of the cell-free bodily fluid sample are enriched for a plurality of genetic loci using one or more oligonucleotide probes that are complementary to at least a portion of one or more genetic loci from the plurality of genetic loci;
(b) generating from the sequencing reads a first data set of baselining genetic loci comprising, for one or more genetic loci of the plurality of genetic loci, a quantitative measure related to sequencing read of the one or more genetic loci;
(c) transforming the first data set of baselining genetic loci into a saturation equilibrium- corrected data set by:
(i) generating a quantitative measure related to guanine-cytosine (GC) content of the one or more genetic loci;
(ii) generating a quantitative measure related to a probability that a strand of DNA molecule derived from the one or more genetic loci of the cell-free bodily fluid sample is represented within the sequence reads;
(iii) generating a first transformation by relating the sequencing read coverage in the first data set to both the quantitative measure related to GC content of the one or more genetic loci and the quantitative measure related to a probability that a strand of DNA molecule derived from the one or more genetic loci of the cell-free bodily fluid sample is represented within the sequence reads, and
(iv) applying the first transformation to the sequencing read coverage of the one or more genetic loci of the first data set to generate the saturation equilibrium-corrected data set, wherein the saturation equilibrium-corrected data set comprises a first set of transformed sequencing read coverages of the first data set of genetic loci;
(d) transforming the saturation equilibrium-corrected data set into a probe efficiency- corrected data set by:
(i) removing from the saturation-corrected data set genetic loci that are high-variance genetic loci with respect to the first set of transformed sequencing read coverages, thereby providing a second data set of baselining genetic loci;
(ii) obtaining a second transformation that has been generated from a reference data set from sequencing reads from the one or more genetic loci of the plurality of genetic loci of one or more reference samples, wherein the second transformation has been generated by:
(a) generating a quantitative measure related to guanine- cytosine (GC) content of the one or more genetic loci of the one or more reference samples:
(b) generating a quantitative measure related to a probability that a strand of DNA molecule derived from the one or more genetic loci of the one or more reference samples is represented within the sequence reads of the one or more reference samples:
(c) generating a reference transformation by relating the sequencing read coverage in the reference data set to both the quantitative measure related to guanine-cytosine (GC) content of the one or more genetic loci GC content of the one or more reference samples and the quantitative measure related to a probability that a strand of DNA molecule derived from the one or more genetic loci of the one or more reference samples is represented within the sequence reads; and (d) applying the reference transformation to the sequencing read coverage of the one or more genetic loci of the first data set to generate a second transformation; and (iii) applying the second transformation to the second data set of baselining genetic loci to generate the probe efficiency-corrected data set, wherein the probe efficiency-corrected data set comprises a second set of transformed sequencing read coverages of the first data set of genetic loci:
(e) obtaining determining a baseline sequencing read coverage for the first data set, wherein the baseline sequencing read coverage comprises an expected sequencing read coverage for the first data set based on saturation equilibrium and probe efficiency of the one or more oligonucleotide probes that are complementary to the at least the portion of the one or more genetic loci from the plurality of genetic loci; and
(f) applying the baseline sequencing read coverage for the first data set to the probe efficiency-corrected data set to determine a copy number for at least one genetic locus of the one or more genetic loci relative to the baseline sequencing read coverage.
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 21-41 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 pre-AIA the applicant regards as the invention. Specifically, the metes and bounds of claim 21 step (d) which recites and requires correcting the data set by performing ‘saturation equilibrium correction’ and ‘probe efficiency correction’ are vague and appear undefined. In review of the present specification, literal support for the terms are identified, however there is no specific guidance or description on what is performed to obtain a ‘saturation equilibrium correction’ or a ‘probe efficiency correction’. Step (a) generically provides for receiving data that is enriched, but fails to provide adequate means such that there could be a correlation to the analysis that follows. For example, any form of sequence data from a loci can be obtained, even in silico, and it is unclear how these are specifically supposed to be used to correct the data set obtained in step (a) where sequence reads are simply received from any source and is not clearly indicated to provide. Additionally, step (d) for ‘determining a baseline’ using the ‘saturation equilibrium’ and ‘probe efficiency’ is also not specifically defined, and it is unclear how such values are obtained from read data, and how they are specifically used to provide a baseline as required of the claims.
More clearly setting forth how steps (c) and (d) are to be performed would address the basis of the rejection.
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 21-40 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claim analysis
Claim 21 is generally directed to a computer implemented method which generates a copy number state of a genetic locus through the analysis of sequence reads. More specifically, the claims are directed to a steps in which reads derived for any DNA from a subject representing a locus are obtained/enriched, quantitating the reads at each locus as a first baseline data set, correcting the first data set by correction through saturation equilibrium and probe efficiency to determine/provide a baseline coverage of the first data set, and then determining he copy number for each locus represented in the data set.
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category process.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps a)-g) for using sequence read data to assess and quantitate the number of reads to correlate it the read number to copy number. In view of the guidance of the specification, the first step a) encompasses obtaining the sequence reads from a database for the subsequent analysis and would be included as part of the judicial exception. Alternatively, it is noted that the specification also provides for physical steps for obtaining reads, and that step a) could be interpreted not to be part of the judicial exception (see also claims 29-32 which provide for the use of UMC type adapters in obtaining reads from the sample). In view of the specification and art of record, the step of evaluating ‘read coverage’ is drawn to aligning and comparing sequence to arrive at the identification of aligned sequences to a reference locus and are considered instructional steps, as are the following steps c)-e) which corrects the data set based on further analysis and possible consideration factors such that the final copy number of the locus can be determined. The judicial exception is a set of instructions for analysis of sequence read data, and appears to fall into the category of Mathematical Concepts, that is for steps of providing quantitative measures, correcting and determining steps that appear to require mathematical calculations based on the presences of reads that are being analyzed (see for example the requirement of ‘normalization’ claim 32); and also into the category of Mental Processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion) since the claims and analysis set forth the limitation of enriched read data for a loci and that only one or more loci is required to be assessed indicating that the data encompassed is not complicated or large such that it could be examined in one’s mind or through the use of paper.
Recent guidance from the office requires that the judicial exception be evaluated under a second prong to determine whether the judicial exception is practically applied. In the instant case, the claims do not have an additional element to which the analysis steps a)-e) are applied This judicial exception requires data analysis steps recited at high level of generality and as a claimed system appear only to be stored on a non-transitory medium or implemented by a general purpose computer, which is not found to be a practical application of the judicial exception as broadly set forth.
For step 2B of the 101 analysis, to the extent that obtaining data can be a physical step each of the independent claims recites additional elements and are found to be the steps of obtaining sequence read data. As such, the claims do not provide for any additional element to consider under step 2B that appear to significantly more than a means to provide data for further analysis. The fact pattern here is similar to the Alice framework, where the Court wrote that "[i]n cases involving software innovations, [the step one] inquiry often turns on whether the claims focus on the specific asserted improvement in computer capabilities or, instead, on a process that qualifies as an abstract idea for which computers are invoked merely as a tool." The Court further noted that "[s]ince Alice, we have found software inventions to be patent-eligible where they have made non-abstract improvements to existing technological processes and computer technology." Moreover, these improvements must be specific -- "[a]n improved result, without more stated in the claim, is not enough to confer eligibility to an otherwise abstract idea . . . [t]o be patent-eligible, the claims must recite a specific means or method that solves a problem in an existing technological process." Here, the steps set forth in the judicial exception appear to be abstract instructional steps for analyzing read data and correlating the number of reads with the possible quantification or determination of a state of a specific loci.
As indicated in the summary of the judicial exception above and in view of the teachings of the specification, the steps are drawn to analysis of sequence read data. While the instruction can be stored on a medium and could be implemented on a computer, together the steps do not appear to result in significantly more than a means to analyze enriched sequences. The judicial exception of the method as claimed can be performed by hand and in light of the previous claims to a computer medium and in light of the teaching of the specification on a computer. In review of the instant specification the methods do not appear to require a special type of processor and can be performed on a general purpose computer. Dependent claims set forth additional steps which are more specifically define the source or aspects of the data, specific considerations and steps of calculating, and comparing, but do not add additional elements which result in significantly more to the claimed method for the analysis. It is noted that while the claims set forth or imply information about the sequences being analyzed (that they are from a loci), this is only description of the data being analyzed and context and user defined. As such, the instant claims set forth an inventive concept that are drawn only to an abstract process that only manipulates data and, therefore, are not directed to statutory subject matter. No additional steps are recited in the instantly claimed invention that would amount to significantly more than the judicial exception. Without additional limitations, a process that employs mathematical algorithms (aligning sequences) to manipulate existing information (quantify the number of reads at a given loci) to generate additional information is not patent eligible. Furthermore, if a claim is directed essentially to a method of calculating, using a mathematical formula, even if the solution is for a specific purpose, the claimed method is non-statutory. In other words, patenting abstract idea (quantitating read data) cannot be circumvented by attempting to limit the use to a particular technological environment or purpose and desired result.
One way to overcome a rejection for non-patent-eligible subject matter is to persuasively argue that the claimed subject matter is not directed to a judicial exception. Another way for the applicants to overcome the rejection is to persuasively argue that the claims contain elements in addition to the judicial exception that either individually or as an ordered combination are not well understood, routine, or conventional. Another way for the applicants to overcome the rejection is to persuasively argue that the claims as a whole result in an improvement to a technology. Persuasive evidence for an improvement to a technology could be a comparison of results of the claimed subject matter with results of the prior art, or arguments based on scientific reasoning that the claimed subject matter inherently results an improvement over the prior art. The applicants should show why the claims require the improvement in all embodiments.
Conclusion.
No claim is allowed.
In view of preferred embodiments for the nucleic acid analyzed in the method, at the time of filing the existence of cfDNA and the analysis of the read data present in a sample (from an individual, from a pregnant female, for increased cfDNA in cancer analysis) was an active area of research. Multiple methods of obtaining read data were known, and analysis of the read data were performed by a number of analytical and statistical methods, however the art of record fails to provide the use of ‘saturation equilibrium correction and probe efficiency correction’ for the use of ‘determining a baseline read coverage’ for a dataset as required of the claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Joseph T Woitach whose telephone number is (571)272-0739. The examiner can normally be reached Mon-Fri; 8:00-4:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz R Skowronek can be reached at 571 272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Joseph Woitach/Primary Examiner, Art Unit 1687
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