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, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/31/2025 has been entered.
Applicants Amendment
Applicant’s amendment filed 3/31/2025 has been received and entered. Claims 1 and 23 have been amended, claims 3, 8, 11-16, 24, 25 have been cancelled.
Claims 1, 2, 4-7, 9, 10, 17-23, 26 are pending.
Election/Restriction
Applicant’s election without traverse of Group I, and the specific species in the reply filed on 10/25/2021 was acknowledged. In prosecution the restriction requirement between Groups I and II was withdrawn because the processing of cumulating and amending are similar and do not appear to be a burden to examine together, and the species was withdrawn as it did not appear to be dependent on the means of obtaining the data and the sample itself and do not appear to be a burden to examine the genus.
Claims 1, 2, 4-7, 9, 10, 17-23, 26 are pending. Claims 17-22, 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/25/2021.
Claims 1, 2, 4-7, 9, 10, 23, drawn to a method for detecting an analyte in a sample from a data set comprising a plurality of cycle data points and a medium with the instructions to implement the method are currently under examination.
Priority
This application filed 11/30/2018 is a 371 national stage filing of PCT/KR2017/005790 filed 6/2/2017 and claims benefit to foreign application KR10-2016-0068932 filed 6/2/2016 in Republic of Korea.
In prosecution, receipt was acknowledged of certified copies (entered 11/30/2018) of papers required by 37 CFR 1.55.
No additional comment has been made by Applicants regarding the priority summary.
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, 2, 4-7, 9, 10, 23 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. Specifically, for claims 1 and 23 the amendment to add steps c1 of ‘more than a threshold’ and c2 for the limitation of a ‘predetermined threshold’ appear to be unclear and relative to user choice or design. Review of the specification appears to provide literal support for the limitations, however there is no indication or definition as to what or how a ‘value’ must be defined or determined to define the metes and bounds of the claim embodiments. While broadly one could indicate generically that it is any value, the claim requires specific considerations and ability to practice the claim for reconstructing a data set and ultimately detect a target analyte as set forth in analysis steps of d-e which is not defined in the specification nor the claims such that the metes and bounds are clearly defined as to what and how the values are obtained. In review of the specification, there is an indication that predetermined values can be obtained by predetermined algorithms (see page 41 for example) however there is not specific algorithm provided such that it uniquely identifies noise from real signals. For example, step c2 completely relies on how the user defines the predetermined threshold, and thus for one user the half width may be considered abnormal based on some user defined value, but for another user providing a different threshold would provide for a normal signal and demonstrates the relative nature to the generic and undefined limitations of the claims. Additionally, step c3 it is unclear how an average value is to be obtained as the step only provides for ‘designating’ without any guidance on how or exactly what the average value represents and which signal/peaks are used and how multiple values of multiple signals would be evaluated. Dependent claims do not define nor clarify the issue, and since they rely on successfully practicing the steps of claim 1 are included in the basis of the rejection.
More clearly setting forth how values used in the method are obtained, and how they provide for the ultimate interpretation and analysis of the data to correctly identify an analyte 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 1, 2, 4-7, 9, 10, 23 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
Claims 1 and 23 have been amended and still are directed to a method of detecting an analyte during PCR. More specifically, the claims now require ‘using a real-time PCR machine’ to collect signals during amplification cycles; and a new step c) is inserted for ‘providing an amended signal change-amount data set’ which is further described in a wherein clause setting forth steps c1-c3 which analyze the peaks, determine if any or all abnormal based on predetermined thresholds and providing an average value of the change amounts for the normal cycle peaks over the course of the cycles. In review of the specification, the claims provide collecting real time PCR signals, and providing a graph of the changes or increase in signal over each of the cycles (versus providing a total cumulative amount). Analyzing the signal data this way may identify signal changes between each of the cycles and based on predetermined thresholds and identification of abnormal signals can be used to remove or to ‘smooth’ the data set such that the data set can be interpreted to provide increasing signal and correlated to the presence of a target analyte (which in view of the specification and evidence of record the target analyte would be a nucleic acid which is capable of providing a signal using real time PCR machines). Overall, the claims encompass steps of using real time PCR after which the data obtained is analyzed with a method that comprise the steps of providing data that has a plurality of points related to cycle and signal value, where the change in signal over time is ‘reconstructed’ by providing cumulated values, and dependent claims provide that the value is cumulated through a series of mathematical steps. The claims require performing PCR and at each cycle obtaining the signal strength, calculating the difference in strength as compared to the previous cycle to obtain a ‘change-amount’ and using the change amount value as an indication that the target analyte is present or not present in a sample. As amended, step c provides for identifying any ‘abnormal peak’ and effectively discarding them and evaluating the value as the average of the normal signals before and after the abnormal peak.
In analysis of the requirements of the claim in view of the specification, the step of performing a signal generating process of real time PCR applies to providing signal data which is subsequently analyzed, and broadly the signals produced during the PCR process encompasses the use of any starting compositions, conditions and any possible target analyte from which data is generated, and provided for signal data that is only relevant to many factors in producing the data that is analyzed. As noted throughout the prosecution, consistent with the review of the specification, one interpretation of the steps appears to be to provide a value at each cycle and provide the change during each cycle as would be done in quantitative PCR where each cycle provides an accumulation of cycle values over time. Further, the steps of obtaining the data do not change nor are they affected by post signal analysis, rather only the data obtained is analyzed and assessed. See for example 6A where the data with different baselines is provided, but in providing only the change in signal a new graph form of the data can be provided illustrating the increase in signal at each cycle.
For step 1 of the 101 analysis, the claims as amended are found to be directed to a statutory category of a process and product.
The amended claims now provide a step for generating a signal by real time PCR, and that the instructions to analyze the data are on a processor.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of accessing cycle and signal data during real time PCR, and in an analysis providing the differences between each cycle in change of signal strength, for the determination of a possible accumulation of product being produced. The judicial exception is a set of instructions for analysis of signal data and appears to fall into the category of Mathematical Concepts, as it relates to mathematical calculations that accumulate or amend the data over time (i.e. add values at each cycle to each other) and to Mental Processes which are concepts performed in the human mind (including an observation, evaluation, judgment, opinion) for the ease in manipulating a change in signal data over each cycle represented in the data over time.
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 and only provide instructions to analyze signal and cycle information. The claims as amended require real time PCR, however the data once generated is simply analyzed, where an increase in signal over the cycles indicate increasing amounts of product being formed. This judicial exception for the analysis of the resulting signal data requires steps recited at high level of generality and given that the method could be performed using a computer would be instructions only stored on a non-transitory media, and is not found to be a practical application of the judicial exception as broadly set forth for the product.
For step 2B of the 101 analysis, each of the independent claims fail to recite any additional elements beyond the apparatus used to obtain PCR signal data, and as such do not provide for any additional element to consider under step 2B which appear to provide for significantly more, nor an improvement to a technical field (here affecting the machine for PCR, nor the computer which can be used to analyze the data). Fr the use of a computer to analyze the simple signal to cycle date produced, in explaining the Alice framework, 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 simple numbers provided by the PCR machine can easily be analyzed with simple math, and it appears that the use of a computer is simply a tool.
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 signal data. While the instruction could 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 signal data. The judicial exception of the method as claimed can be performed by hand. 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.
Response to Applicants arguments
Applicant argue thar the claims as a whole provide an improvement to the technology noting the lcaims represent an ordered combination that is not well understood, routine or vonventional. Applicants argue that process is an improvement to real time PCR which assesses and removes abnormal signal peaks and that the assessment allows for better analyte detection using real time PCR amplification and that datasets can contain noise, distortion or fluctuations of the baseline due to contamination problems.
In response, the amendment to the step a) to be directed to real-time PCR has been acknowledged, however provided generically fails to support any specific data type that is derived nor the problems which applicants assert and appear to indicate the data is signal data over cycle time. Further, the data obtained is broadly any of a plurality of cycles and signal values from any portion of an amplification process. Importantly, whatever data set is provided the claims after it is obtained provide a simple analysis of the data in steps b) and c) and in step d) instruction to identify the analyte (if present) using the data which has been indicated to be the judicial exception of the claims. An improvement to the analysis of data is not considered to make the judicial exception patent eligible. Further, as indicated above and prosecution the problems that Applicants indicate are not a necessary property of the data set as generically provided, and having only a plurality of cycle points does not provide an improvement consistent with any of the issues noted by Applicants.
Applicants provide several examples from the figures and analyze the guidance of the specification as applied to the specific examples and argue that the analysis method does not require establishing a base line region, addresses abnormal peaks and data, and state that the analysis method could be applied as a means to establish or determine the presence or absence of a target analyte in a sample result in an improvement over the prior art.
In reply, the claims require providing or transforming the raw data of signal each cycle into an accumulation of the rate of change in the data during PCR. This does not appear to be an improvement, rather another means of evaluating signal data. The various forms of PCR data as exemplified are noted, however this further supports that the methods are directed to the analysis of the data, and not the PCR process itself. While it is argued the clams provide an improvement, it appears that any improvement or difference to that in the art of record is only tied to the judicial exception and the abstract instructional steps of data analysis and not integrated into any specific process. While the data is obtained by a physical process, the analysis steps that follow obtaining the data are simply a method of analyzing any data from a signal generating PCR process as amended. Further, arguments that the analysis provides a better analysis or improved analysis is not sufficient to make a judicial exception patent eligible. Additionally, it is noted that the instant methods do not require any specific machine or special or different data collection, and the judicial exception of the claims which are directed to the analysis of the signal data, a fluorescent value for each cycle, is the basis of the analysis. It is acknowledged that the data analysis steps are not in the prior art as evidenced by the lack of an art rejection, however for the 101 rejection the absence of art for a judicial exception is not the basis of patent eligibility.
Therefore, for the reasons above and of record, the rejection is maintained.
As noted previously, 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 claims allowed.
Lievens et al. (Nucleic Acids Research, published 2011) has been cited as relevant art as it provides that current methodology in real-time Polymerase chain reaction (PCR) analysis performs well provided PCR efficiency remains constant over reactions, but that the data produced where small changes in efficiency occur can lead to large quantification errors. Similarly, Woo et al. it does provide for evidence that real-time PCR and the data obtained was known and machines to gather the data are conventional.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Joseph Woitach/Primary Examiner, Art Unit 1687