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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after appeal to the Patent Trial and Appeal Board, but prior to a decision on the appeal. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 2/19/2025 has been entered.
Applicant’s amendment
Applicant’s amendments filed 2/19/2025 been received and entered. Claim 31 has been amended.
Claims 31-47 are pending.
Priority
This application filed 1/22/2020 is a continuation of 15/325046, filed 1/9/2017 now US Patent 10640819, which is a 371 National stage filing of PCT/GB2015/052086 filed 7/17/2015 and claims benefit to foreign application GB14128342 filed 7/18/2014 in Great Britain.
No comment regarding the summary of priority has been made in Applicant’s response.
Receipt was acknowledged of certified copies of papers required by 37 CFR 1.55 in the parent application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/4/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 31-47 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 31 has been amended and still is generally directed to identifying genetic variants present in cfDNA of a sample. More specifically, the claim 31 has been amended that the sample be partitioned into at least two different replicate reactions which are processed by amplification, sequencing and then analyzing the sequence reads to determine read counts, then integrating the result count to determine the presence or absence of ctDNA present in total cfDNA. In view of the guidance of the specification, the number of reads would be determined for any given platform, sequencing process and any depth of sequencing. Once the reads are provided by any of known method or platform, the analysis steps are used on the read distribution to provide a threshold and establish, where it would be possible to partition a sample into an amount or into multiple samples containing possible templates (noting the claims as amended set forth presence or absence of ctDNA) that could/would be amplified so that it is informative, performing amplification and sequencing, and interpreting the presence or absence of the variant in each reaction set, and that the variant that is determined would be correlated to a disease or cfDNA from a tumor.
Response to Applicant’s arguments
Applicant argue that step b) of claim 31 has not been addressed and represents one step that is not well-understood, routine and conventional. Providing an overview of MPEP 2106.07(a) Applicant argues that there is no evidence of record that the steps are known or routine previously also noting that partitioning a sample into replicates increases the probability that the analysis will detect circulating tumor DNA.
In response, steps a)-d) were found to be steps of amplifying a ctDNA sample and sequencing to provide read data, and are methods well known in the art as evidence by the cited references and acknowledgement of the specification (see for example pages 2-3 for use of methodology known in the art). The steps set forth in a)-d) are considered well known and conventional. A review of the references of record demonstrates that Narayan et al. (2012), the method section details that tumor DNA was analyzed by taking blood, extracting the DNA, amplifying the samples in triplicate, and analyzing the sequence reads that were obtained. The disclosure indicating that known methods can be used and teachings such as Narayan et al showing that samples were separated into duplicate, triplicate as common controls were know and used appears to support evidence that these additional elements were known and conventional.
What is left is the analysis of the data that is obtained and considered the judicial exception which assesses the read counts and associates it with presence of ctDNA. The claims broadly provide for obtaining sequence read data from a sample and analyzing the number of times a specific read appears relative to others. It would be well understood that based on potential errors introduced by the process of amplification and sequencing that certain percentage of reads might contain a difference from expected. Analyzing and integrating the results to come to this conclusion is considered instructions, and not a technical improvement to the art.
Accordingly, for the reasons above and of record, the rejection is maintained.
Rejection of Record
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a process.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of establishing a threshold based on the technology being used and expected presence of a target in a sample, and accessing sequence read data for presence or absence of the target sequence. The judicial exception is a set of instructions for setting up the experiment protocol and the analysis of sequence data, and appears to fit into the category of Mathematical Concepts which are the mathematical and statistical calculations used to establish how a sample is aliquotted for amplification and to Mental Processes, which are concepts performed in the human mind (including an observation, evaluation, judgment, opinion). In this case, there is a presumption of knowledge for the sample being analyzed, and the mental process is the analysis and observation for the presence of a variant sequence that informs the presence or absence of the sequence of interest. It is noted that none of the claims recite and in light of the teachings of the specification require the use of a computer for determining a threshold value or assessing the reads that provided in the sequencing reaction.
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 have an additional element for amplification and sequencing, however appear to provide for steps of obtaining sequence information for further analysis and do not appear to be an integrated practical application of the judicial exception. Further, the indicated judicial exception requires steps recited at high level of generality, and is not found to be a practical application of the judicial exception as broadly set forth.
For step 2B of the 101 analysis, each of the independent claims recites additional elements and are found to be the steps of obtaining sequence data. In view of the evidence of record and breadth of the claims, it does not appear that the claims provide for any additional element to consider under step 2B that provides for significantly more than sequence information in each reaction.
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 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 for the presence or absence of possible variant sequences in a sample. The judicial exception of the method as claimed can be performed by hand and in light of the claims do not require a computer or any advanced form of computing power to arrive at the steps as broadly set forth. In review of the instant specification the methods do not appear to require a special type of processor and could be performed on a general purpose computer.
Based upon an analysis with respect to the claim as a whole, claims 31-47 do not recite something significantly different than a judicial exception. Claims 31-47 are directed towards a method of receiving sequence data and comparing the data to identify variant sequences. Dependent claims set forth additional steps which are more specifically define the considerations and steps of calculating, and comparing, and do not add additional elements which result in significantly more to the claimed method for the analysis.
Again, under Step 2B of the two step analysis is to determine whether any element or combination of elements, in the claim is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception. No additional steps are recited in the instantly claimed invention that would amount to significantly more than the judicial exception except to obtain a sample and provide sequencing reads. In addition, the references and teachings of record demonstrates that Narayan et al. (2012), the method section details that tumor DNA was analyzed by taking blood, extracting the DNA, amplifying the samples in triplicate, and analyzing the sequence reads that were obtained. Without additional limitations, a process that employs mathematical algorithms (aligning sequences) to manipulate existing information (identify a probe that starts at a deletion or insertion) 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 (designing probes to a target sequence) 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.
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/Joseph Woitach/Primary Examiner, Art Unit 1687