DETAILED ACTION
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 .
Election/Restrictions
Claims 165-169 and 177-182 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species/inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 13 August 2026.
Status of the Claims
Claims 163-182 are pending.
Claims 165-169 and 177-182 are withdrawn following the election filed 13 August 2026.
Claims 163-164 and 170-176 are examined herein.
Claims 1-162 are canceled.
Priority
As detailed on the 06 September 2022 filing receipt, the application claims priority as early as 04 May 2021. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Information Disclosure Statement
Information disclosure statements (IDS) were filed on 07 June 022, 04 January 2023, 14 October 2023, 30 October 2023, 27 March 2024, and 15 July 2026. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the references are being considered by the examiner.
Drawings
The drawings filed 24 June 2022 are accepted.
Claim Rejections - 35 USC § 112(b)
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 163-164 and 170-176 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.
Claim 163 refers to Table 8 in the specification (pgs. 128-148). Because the tables and/or relevant content within the tables is not recited in its entirety in the claim, it is unclear what table contents the claim is intended to include. MPEP § 2173.05(s) explains that where possible, claims are to be complete in themselves. Incorporation by reference to a specific table "'...is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.' Ex parte Fressola... (citations omitted)" (MPEP § 2173.05(s)). It is not clear that the instant claim recitation(s) constitute "exceptional circumstances." As one option to overcome this rejection, the relevant table contents may be individually recited in the claim, for example as a text list. Alternatively, an entire table may be copied into the claim. Any effective citation to the specification, e.g. recitation of "table," must be deleted. Claims 170-176 are dependent on the aforementioned claims and are rejected on similar grounds. It is noted that claim 164 is not rejected because specific genes from Table 8 are specified: LYE6, IRF9, ITGAM, and PSTPIP2.
Claim 163 recites “the expression levels” but expression levels are not previously instantiated, rendering the term’s antecedence unclear. Claims 164 and 170-176 are dependent on the aforementioned claims and are rejected on similar grounds.
Claim 163 recites receiving a biological sample from the subject, measuring expression levels of two genes, and determining whether the subject has an infection based on the expression levels. However, the measuring of expression levels of the genes is not recited as being based on the biological sample of the subject and so the steps are unclear. Claims 164 and 170-174 are dependent on the aforementioned claims and are rejected on similar grounds. Claims 175 and 176 are not rejected on similar grounds because claim 175 requires amplification of nucleic acids in the subject to obtain the expression levels. For compact examination, it is assumed claim will be amended to require the expression measurements are based on the biological sample obtained from the subject as in claim 175.
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 163-164 and 170-176 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than the abstract idea of diagnosing a subject with an infection.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of
nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to methods, which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in claim 163 include using a classification model and details of the receiver operating characteristic. The model, interpreted given its broadest reasonable interpretation in light of the specification, is considered to be a mathematical concept given applicability of the ROC. The classification model is disclosed as a parameterized model outputting a probability (pg. 36, paragraphs [105-106]) including logistic regressions (pg. 179, paragraph [689]), and thus the claim element is interpreted as describing a mathematical concept. A mathematical relationship may be expressed in words and there is no particular word or set of words that indicates a claim recites a mathematical calculation (MPEP 2106.04(a)(2)).
Mental processes, defined as concepts practically performed in the human mind such as steps of observing, evaluating, or judging information, recited in claim 163 include determining whether the subject has an infection, where such a determination is interpreted as data evaluation or judgment and thus a step the human mind is practically equipped to perform.
Claims 170-173 recite additional information about the ROC curve, which is interpreted as part of the mathematical model.
Hence, the claims explicitly recite numerous elements that, individually and in combination,
constitute abstract ideas. The claims must therefore be examined further to determine whether they
integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Because the claims recite judicial exceptions, direction under Step 2A Prong Two provides that the claims must be examined further to determine whether they recite elements in addition to the abstract ideas which integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d)(I); MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d)(III)).
Claims 163 recites receiving a biological sample and measuring the expression levels of two genes. Claims 164 recites specific loci for which expression levels are to be measured. Claims 173-174 recite additional information about the biological sample collection. Claims 175-176 recite additional details of the expression level determination.
Receiving a sample, the type of sample, and steps for determining expression levels of the sample are all related to data gathering to perform the classification which determines whether the individual has an infection. These data gathering steps are considered to be insignificant extra-solution activity and thus do not integrate the abstract ideas into a practical application (MPEP 2106.05(g)).
Thus, the claims recite elements in addition to the abstract ideas which do not integrate the abstract ideas into a practical application, and must be examined further to determine whether elements in addition to the abstract ideas provide significantly more (MPEP 2106.05). [Step 2A Prong Two: Yes]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself. Step 2B of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
Claims 163 recites receiving a biological sample and measuring the expression levels of two genes. Claims 164 recites specific loci for which expression levels are to be measured. Claims 173-174 recite additional information about the biological sample collection, such as being derived from blood. Claims 175-176 recite RT-PCR and LAMP for expression level determination.
The courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93 (storing and retrieving information in memory), as discussed in MPEP 2106.05(d)(II)(i)).
Zhu (BioTechniques 69(4): 317-325, 2020; newly cited) teaches in a review of PCR the techniques of RT-PCR (pg. 319, fourth paragraph), qRT-PCR (pg. 319, fourth paragraph), and LAMP (pg. 321, third paragraph) and their application to gene expression analysis (Fig. 3 caption). It is also considered a conventional laboratory technique to determine the level of a biomarker in blood (MPEP 2106.05(d)(II)).
Therefore, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 163 and 170-175 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Khatri (WO 2017214061 A1; newly cited).
Claim 163 recites a method for diagnosing a subject suspected of having a bacterial or viral
infection, the method comprising receiving a biological sample obtained from the subject; measuring the expression levels of at least two genes selected from Table 8; determining whether the subject has a bacterial infection or viral infection using the expression levels in a classification model which has been validated in multiple independent cohorts, wherein the classification model has an area under the receiver operating characteristic (ROC) curve of at least 0.65 in at least one validation cohort.
Khatri teaches diagnosing a viral infection (abstract) by determining expression levels of two biomarkers found in Table 8 – LY6E, TSPO, NINJ2, ACPP, TBXAS1, PGD, and others (claim 1) – and discrimination against multiple independent cohorts (pg. 67, second paragraph). Khatri teaches determining the presence of an infection when the ROC is at least 0.80 (claim 3), which falls within the range of being at least 0.65.
Claim 170 recites the classification model has an ROC curve of at least 0.7 in at least one validation cohort.
Khatri teaches an elevated threshold for the AUC of 0.80, which falls within the range of being at least 0.7.
Claim 171 recites the classification model has an ROC curve of at least 0.75 in at least one validation cohort.
Khatri teaches an elevated threshold for the AUC of 0.80, which falls within the range of being at least 075.
Claim 172 recites the classification model has an ROC curve of at least 0.8 in at least one validation cohort.
Khatri teaches determining the presence of an infection when the ROC is at least 0.80 (claim 3).
Claim 173 recites the biological sample is a blood sample of the subject.
Khatri teaches whole blood or peripheral blood (claim 5).
Claim 174 recites the biological sample comprises blood, whole blood, plasma, serum, urine, cerebrospinal fluid, fecal, saliva, sweat, tears, pleural fluid, pericardial fluid, peritoneal fluid, nasal swabs, nasopharyngeal swabs, or oropharyngeal swabs of the test subject.
Khatri teaches blood, plasma, serum, blood cells (e.g., peripheral blood mononucleated cells (PBMCS)), fecal matter, urine, spinal fluid, secretions of the skin, respiratory, intestinal, and genitourinary tracts, tears, and saliva (pg. 30, third paragraph).
Claim 175 recites the expression levels are obtained using real-time polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR), or real-time quantitative isothermal amplification on one or more nucleic acid molecules in the biological sample of the subject.
Khatri teaches RT-PCR and quantitative RT-PCR (pg. 52, second paragraph).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 164 is rejected under 35 U.S.C. 103 as being unpatentable over Khatri as applied to claims 163 and 17-175 rejected under 35 USC 102 above and further in view of Tsalik (US 20180245154 A1; previously cited on the 04 January 2023 IDS form).
Claim 164 recites the at least two genes are selected from LY6E, IRF9, ITGAM, and PSTPIP2.
Khatri teaches expression of LY6E among other markers (claim 1) but not IRF9, ITGAM, and PSTPIP2.
Tsalik teaches the combination if LY6E and IRF9 (Table 1).
Combining Khatri and Tsalik
Like Khatri, Tsalik teaches using expression levels to diagnose an infection based on pre-defined thresholds, cut-offs, or ranges (paragraph [13]) in reference to five independently derived dataset for validation of clinical phenotypes (paragraph [163]). Like Khatri, Tsalik teaches panels of multiple genes for which the expression levels are determined to diagnose an infection. Khatri teaches LY6E in combination with markers other than IRF9, but Tsalik teaches them together (Table 1) as both have explanatory power for viral infection. Swapping one marker for expression analysis for another is considered a simple substitution and one obvious to try given the finite list of explanatory markers taught by Tsalik. MPEP 2143 pertains. Therefore, the invention is prima facie obvious.
Claim 176 is rejected under 35 U.S.C. 103 as being unpatentable over Khatri as applied to claims 163 and 17-175 rejected under 35 USC 102 above and further in view of Storch (WO 2019236768 A1; newly cited).
Claim 176 recites the real-time quantitative isothermal amplification is real-time quantitative loop-mediated isothermal amplification (LAMP).
Storch teaches loop-mediated isothermal amplification (paragraph [45]).
Combining Khatri and Storch
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the LAMP technique of Storch with the viral or bacterial infection diagnosis of Khatri because Storch teaches viral infection diagnosis based on expression levels and AUC-based discrimination, wherein loop-mediated isothermal amplification are disclosed as a technique known for amplifying nucleic acids (paragraph [45]). As both Khatri and Storch are directed to the shared field of endeavor of expression-based viral infection diagnosis, their combination would be expected to succeed and be prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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/Robert J. Kallal/Examiner, Art Unit 1685
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