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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 3/12/2025 has been entered.
Applicants Amendment
Applicant’s amendment filed 3/12/2025 has been received and entered. Claims 1, 3, 4, 7, 10, 13, 14, 16, 17, 19, 22, 23 have been amended.
Claims 1-27 are pending.
Election/Restriction
Applicant’s election of Group I, claims 1-12 in the reply filed on 2/27/2024 was acknowledged. In prosecution the methods encompassed by the methods of Groups II-III were found to be comprised in the method of elected Group I and the restriction requirement between groups I-III was withdrawn.
Claims 1-27 are pending.
Claims 1-22 have been amended and are consistent with the examined invention.
Claims 23-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/2/2024.
Claims 1-22 drawn to a method for estimating a diagnostic score of a test sample with a mammalian host reference sequence, to a method of estimating a diagnostic score of a test sample with an expected concentration of a reference sequence, and to a method for estimating a diagnostic score of a test sample using standard curves.
Priority
This application filed 3/5/2021 is a Nationals stage filing of PCT/US2019/051765 filed 9/18/2019 which claims benefit to US provisional 62/733517 filed 9/19/2018.
No comments were provided regarding the summary of priority in Applicants instant response.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Specifically, independent claims 1, 13 and 19 have been amended (as well as dependent claims consistently) to recite that the analysis steps end in ‘estimating the quantitative diagnostic score’. A review of the specification fails to provide this specific combination of terms, and it does not provide for any specific algorithm for a score or a quantitative score which would provide with a ‘quantitative’ score. The amendment appears to intend to limit the type of diagnostic score previously pending, but what the scope of this combination of terms encompasses is not defined in the specification, nor clearly provided for in the guidance of the specification. More generally, even if active ‘measuring’ steps result in a meaningful values which can be correlated to a ‘quantity’, it is unclear what algorithm is used or needed to provide for a quantitative score or any particular score. It is unclear if there is any difference between a ‘diagnostic score’ and a ‘quantitative diagnostic score’ as amended, and how this amendment to make it an estimated quantitative score lacking any specific or clear support of the specification for the amendment. The metes and bounds of how the term ‘quantitative’ is intended to limit the claim are not clear given the guidance of the specification and appears that it is a new scope not supported by the specification.
Response to Applicants Arguments
In light of the issue raised in advisory action, Applicants note that terms are not required in haec verba and that the term is clearly supported by the specification even though it is not present verbatim. Applicants note the support in [0051] teaching the estimated diagnostic score combines levels of expression of several biomarkers using a certain algorithm into a single score.
In response, the guidance of the specification is acknowledged and specifically that quantitative method or means can be used, however it is noted that the present claims do not even require ‘quantitative’ methods and simply require ‘measuring an intensity’ and still provides for analysis of ‘estimating’ and no specific limitations that appear to be consistent with ‘quantitative’ as amended. The term ‘quantitative diagnostic score’ appears to be directed to a subgenus of any diagnostic score, and a new scope not supported by the specification.
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 1-22 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, the limitation of ‘quantitative diagnostic score’ is unclear and appears to be undefined. While the specification teaches that quantitative isothermal amplification can be used (see for example [0002]) to obtain fluorescence values to evaluate abundance, and generally for estimating broadly for a ‘score’, there does not appear to be any guidance to how a score is estimated and how the term ‘quantitative’ is intended to limit how the estimation is to be performed or if there are any required limitations or considerations necessary in acquiring values used to make the estimation to provide for a score that is quantitative.
Response to Applicants Arguments
Applicants note that terms are not required literal support and that the term is clearly supported by the specification even though it is not present verbatim. Applicants note the support in [0051] teaching the estimated diagnostic score combines levels of expression of several biomarkers using a certain algorithm into a single score.
In response, the guidance of the specification is acknowledged and specifically that quantitative method or means can be used, however it is noted that the present claims do not even require ‘quantitative’ methods and simply require ‘measuring an intensity’ and still provides for analysis of ‘estimating’ and no specific limitations that appear to be consistent with ‘quantitative’ as amended. More generally, even when active ‘measuring’ steps result in a meaningly which can be correlated to a quantity, it is unclear what algorithm is used or needed to provide for a quantitative score as amended, or more general how the step of estimating is correlated to any quantitative score or value given the general nature of the guidance of the specification. The metes and bounds of how the term ‘quantitative’ is intended to limit the claim are not clear given the guidance of the specification.
More clearly providing steps which inherently result in a quantitative score, or amending the claims to be consistent with the disclosure will 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 1-22 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 1 has been amended and still is generally directed to providing a diagnostic score. A sample is analyzed for two target nucleic acids in two vessels using isothermal amplification (more specifically LAMP- claim 11) and ‘measuring an intensity of a flurescence’ of two targets is a sample where the diagnostic score is based on the abundance of the two targets. More specifically, the claims have been amended in the pre-amble to indicate the method provides a quantitative diagnostic score, and the steps of providing a threshold have been amended from measuring. Dependent claims have been amended to address antecedent basis, and still set forth a viral or bacterial infection is detected and specific target nucleic acids, and different means and models generically to calculate diagnostic score (claim 10 for example) are provided based on the observation and correlation of gene expression changes. The claims do not provide any specific conditions for assessment nor any specific sample from which the data is derived except broadly it is from any mammal and any form of infection and assessed/correlated to a plurality of genes of interest or targets (see claim 9 for a listing of seven genes), and dependent claims provide to use LAMP and general machine learning models for derivation of a score from the data
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a method.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of assessing expression data between two samples to derive a score based on a correlation of an observed expression pattern. The claim requires computing a ‘diagnostic score’ without any specific guidance nor equation and not specific requirement of what target sequences are to be used for the breadth of any mammal as a subject, and dependent claims set forth generically well known models for statistical analysis of data but no specific indication of how they are applied. In review of the breadth of the claims and the guidance of the specification, the judicial exception is a set of instructions for analysis of expression data and appear to fall into the category of Mathematical Concepts, as taking the two threshold values and calculating amounts are mathematical formulas or equations or appear to use mathematical calculations, and also in the category of Mental Processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion) as the requirement of ‘estimating’ the ‘diagnostic score’ is only generically required for only a plurality of target gene expression changes.
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 judicial exception is applied and provides a score after the analysis of quantitative PCR threshold values. The additional elements of the claims provide values of two target sequences generically which are then used to provide a score. This 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 for ‘measuring’ and are found to be the steps of obtaining amplification data. Isothermal amplification was generally known, as well as LAMP as a general technique. Review of the specification does not provide for any new or novel means nor targets from which novel information is derived, or any specific application of the techniques beyond that which is known in the art. To the extent that the models of claim 10 are commonly implemented using a computer it is noted that 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."
Response to Applicants Arguments
Applicants argue the claims do not recite a judicial exception.
In response, as analyzed above and prosecution, the claims comprise two parts first obtaining fluorescent data using a well known method such as LAMP and second processing that data into a value which dependent on the targets, sample, processing,… may result in a diagnostic value. The second part encompassed by the claim is the judicial exception. As acknowledged in the response, the generic recitation of estimation and undefined diagnostic score are considered instructional steps which can be practiced in ones mind or with the aid of paper.
Applicants review the fact pattern of Alice and the 2019 revised guidance of the USPTO and argue the steps of analyzing the fluorescence intensities as a function of time are not mental processes or mathematical concepts.
In response, the guidance of Alice and USPTO guidance has been considered, and given the claims there is no real time considerations or steps as generically required of the amended claims which appear beyond the ability of the artisan to observe and use for estimation of a score as required of claims broadly. It is noted that given the breadth of the claims, even though the claims set forth a diagnostic score, there is no requirement that any correlation that is estimated or calculated is actually correlative or indicative of any specific condition, and only require that the steps be performed and broadly provide for a score.
For Prong 2, Applicants argue that any judicial exception that might be present in the claims is integrated as a whole and improves the functioning of a computer or another technology field. Noting the examples and guidance of the specification, Applicants argue the claimed invention are different from isothermal amplification/LAMP.
In response, the claims as provided clearly encompass the use of LAMP in the recitation of the independent claims of isothermal amplification of the desired targets, and Applicants arguments related to the additional elements appear inconsistent with the claims as amended. As provided in the analysis, the additional element of obtaining the fluorescent data and then the analysis of the data are separate steps which are not integrated, and as noted in the analysis the final step is simply a score which may or may not be diagnostic of anything and appears completely relative to the targets chosen. Again, the method of obtaining the fluorescent data appears to rely on known methods as there are no specific steps in the claims or required/defined by the specification, thus providing data by known means then analyzing it appears to provide that the claims are directed to the judicial exception of computation for the estimate or abstract as simple calculations can be performed in one’s mind.
For prong 2B, Applicant argue that the steps are not well known, and citing the fact pattern of Alice argue the claims provide meaningful limitations that integrate the building blocks into something more when combined with the steps of estimation set forth in the claims.
In response, combining known methods of obtaining data with instructional steps for the analysis of the data obtained are not the basis of finding the two are integrated or unconventional under 2B. As analyzed in prosecution, there are no definitions in the art nor the specification of quantitative diagnostic score, and any possible correlation to a diagnostic is not provided in the instant specification and for the breadth of the claims could provide for a score which is 0 or 1 as quantity but representing the a yes or no answer of the analysis. The specification does not provide any specific means of estimation, nor does it provide guidance to what the targets are, or any clear indication of what a value or score obtained would necessarily represent to consider these broad analysis steps as meaningful limitations of the claim that improve a technical field since any possible correlation for the presence, absence, increase or decrease of an informative target appears to rely on the art.
With respect to prong 2B and the additional elements encompassed by the claims, it has been acknowledged that the use of LAMP has been acknowledged as part of the scope of the claims, and as indicated in the analysis and the specification the method relied upon to practice these steps are known in the art. Further it is noted that the claims generically set forth any target for any mammal and no specific guidance beyond the generic guidance that is known in the art. Setting forth that the analysis requires assessing a ‘threshold’ when obtaining data does not affect how the steps are performed as the use of LAMP for detection already considered the ability to determine the presence, absence or amount based on what could be detected for any given specific LAMP analysis. The claims do not require any unconventional steps recited in the claims nor required of the specification, only that whatever data is obtained is analyzed and used to provide a diagnostic score.
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.
Claim Rejections - 35 USC § 103
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 1-22 rejected under 35 U.S.C. 103 as being unpatentable over Tran et al. (Scientific Reports 6:3129), Gill et al. (NAR (2008)), in instant IDS) and Saharan et al. (2014) is withdrawn.
While analysis of informative nucleic acid targets using LAMP was known which could be generally correlated to a condition in a subject, and that quantitation can be broadly interpreted as a detectable amount or not, it is agreed the art of record fails to provide for quantitative diagnostic scores using time to threshold values of two separate reactions measuring fluorescence to arrive at a time to threshold value and using such values together for estimations as required of the claim as amended.
Conclusion
No claim is allowed.
In prosecution, methods for amplification and quantification of target nucleic acids were demonstrated to be well known and are generally acknowledged in the present specification citing Nixon et al (2014) in [0003] for example. Saharan et al was cited for the teaching of Loop-mediated isothermal amplification (LAMP) based detection of a target nucleic acid. This method amplifies very few copies of target DNA with high specificity, efficiency and rapidity under isothermal conditions by using a set of four specially designed primers and a DNA polymerase with strand displacement activity. More generally, informative targets were known and analyzed as evidenced by Tran et al. provide evidence that there is transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria.
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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/Joseph Woitach/ Primary Examiner, Art Unit 1687