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
Applicant’s amendment filed 4/15/2026 has been received and entered. Claims 1-4, 9, 10, 13, 14, 16, 17, 19 and 22 have been amended, claims 7-8, 23-27 have been cancelled and claims 28-29 have been added.
Claims 1-6, 9-22, 28 and 29 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were found to be comprised in the method of elected Group I and the restriction requirement between groups I-III was withdrawn.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 1-6, 9-22, 28 and 29 are pending.
Newly added claims 28 and 29 are dependent on claims 13 and 19 respectively and are consistent with the examined invention.
Claims 1-6, 9-22, 28 and 29 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 1-6, 9-22 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 is withdrawn.
The amendment to delete the term ‘quantitative’ has addressed the basis of the rejection. In review of the specification, providing a general estimated score is 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 1-6, 9-22 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 is withdrawn.
The amendment to address the limitation of ‘quantitative diagnostic score’ has addressed 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 1-6, 10-22 stand 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.
Examiner comment: newly added claims 28 and 29 have been analyzed and are not included in the basis of the rejection because under Step 2B they provide a unique combination of target nucleic acids to base a diagnostic score upon which is not known nor convention based on the art of record. Similarly, claim 9 has been removed from the basis of the rejection because as amended to be dependent on independent claim 1, is consistent with claims 28 and 29 for providing a unique combination of target nucleic acids to base a diagnostic score upon which is not known nor conventional based on the art of record. When viewed as a whole, the analysis of these specific panels of targets can be used to uniquely distinguish between a viral and bacterial infection, and can be applied and provide the basis of standard of care for a subject.
Claim analysis
Claim 1 has been amended and still is generally directed to providing an estimated diagnostic score. The first two steps have been amended to more specifically require receiving a sample with a wherein clause describing possible difference based on gene expression that might be present and a quantitative amplification of a generic first and second target nucleic acid that might be present in the sample, and a final new wherein clause indicating that difference between target expression observed represent a score indicative of bacterial or viral infection. The claim provides no specific target that is evaluated, nor that the sample necessarily represents a viral or bacterial infection for observing any changes. The two other independent claims have been amended consistently, and provide for a sample which is analyzed for two target nucleic acids in two vessels using isothermal amplification (more specifically LAMP- claim 11) and ‘measuring an intensity of a fluorescence’ of two targets is a sample where the diagnostic score is based on the abundance of the two targets. More specifically, the amendments set forth the sample being tested contains genes that are expressed more highly when there is a viral or bacterial infection, evaluating differences in expression levels and based on the expression levels generate a diagnostic score which ‘indicates whether a patient has a bacterial infection or a viral infection’. 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.
Response to Applicants arguments
Applicants provide an overview of the claim amendments and a summary of the invention as it is related to observable changes in different sets of genes which correlate to either bacterial or viral infection. Noting MPEP 2106.04d1, Applicants argue the claims provide an improvement to existing technology and are not conventional.
In response, given the breadth of the claims where no specific targets are required, there does not appear to be an improvement or even a clear correlation with viral or bacterial infection. The art of record demonstrates that research in infectious diseases was conventional, and provided the basis for changes in gene expression upon infection, for example broadly an increase in genes associated with an immune response or genes directly related to antigen presentation as a consequence of infection. Broadly, the art of record demonstrates that changes in observable gene expression was known and appears conventional. Further, as analyzed in 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. The generic recitation of estimation and undefined diagnostic score are considered instructional steps which can be practiced in one’s mind or with the aid of paper.
Applicants argue that it was not conventional to provide a score which is indicative of viral or bacterial infection, and more specifically for specific sets of targets.
In response, it is agreed that specific targets present in claims 28, 29 and 9 were not associated with infection and as a group were not correlated to either viral or bacterial infection, and have been found patent eligible limitations. With respect to the broader generic claims, it is maintained that changes in gene expression and even specific target genes know to be associated with infection were known and are considered conventional given the breadth of the claims subject to the instant rejection. The guidance of Alice and MPEP 2106 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.
Finally for prong 2B, 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. 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.
Given the evaluation of the amendments and analysis to arguments above, 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.
For clarity of the record, a complete analysis of the claims under 101 is provided.
101 Analysis
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 mathematical 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."
Conclusion
No claim is allowed.
Claims 9, 28 and 29 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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
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