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 .
Claim Objections
Claims 1, 3, 9 and 11 claim objections for informalities have been resolved, and is these rejections are thus withdrawn.
Response to Arguments
Applicant's arguments filed 06/15/2026 have been fully considered but they are not persuasive.
Regarding the 101 rejections on subject matter, the applicant states that for claim 1, the in vitro diagnostic method comprising determining kynurenine levels in saliva and comparing those values with defined reference levels for specific disease states (of COVID), thereby detecting or monitoring inflammation is patent-eligible subject matter.
However, the previous rejection for 101 is directed to the abstract idea (a different category from law of nature or natural phenomenon) of evaluating a level of kynurenine with a control level of kynurenine to be indicative of acute COVID 19 infection, long COVID and/or pediatric inflammatory multisystem syndrome (PIMS), which is defined to be a mental process, where determination whether a patient has COVID is evaluated based on one’s observation, evaluation, judgment and opinion using data as comparison (see MPEP 2106.04(a)). As the subject matter issue has not been resolved, nor does the new dependent claims add anything significantly more than the abstract idea, the 101 rejections for claims 1-3, 6-10, 13-14 and 16-19 are maintained.
Claims 13-14 are not independent as they are dependent on using the method of claim 1. These claims merely add extra solution activity and are still rejected under 101.
Regarding the 102 claim rejections, the applicant states that Fraser et al. (WO 2021207858 A1) depicts kynurenine as a ratio of arginine (Arg) to kynurenine (Kyn), not kynurenine as itself, when measuring values in COVID-19 patients.
However, Fraser et al. states within the description of the application that the metabolites that are required for COVID-19 diagnosis can consist of either arginine, kynurenine, and/or arginine/kynurenine ratio (see col. 55/lines 14-20). While kynurenine is not a primary focus in the figures and most tables, it is stated that in other embodiments, kynurenine by itself, not as a ratio, is a leading metabolite for differentiating between COVID positive and COVID negative patients, where kynurenine is stated to have an increase of 5.1-fold in positive patients, relative to healthy control patients (see col. 25-26/lines 26-13, col. 53-54/lines 23-18). Saliva is additionally an option as a biological sample from a patient for measuring metabolites (see col. 19/lines 6-10). Furthermore, kynurenine is used in determination of COVID-19 disease severity for a COVID-19, and where the severity of COVID-19 further correlates to an increase in inflammatory cytokine levels “cytokine storm” which is the excessive or uncontrolled release of cytokines in response to a pathologic event, such as viral infections (see col. 1/lines 17-21, col. 3/lines 14-22). Even if it doesn’t specify specific values of kynurenine, under broadest reasonable interpretation given the broad elements of claim 1, Fraser et al. continues to define over claim 1 and thus does not make it novel or allowable.
Regarding claim 12, an OCR error mistaken μM to be pM. However, it can still be rejected under routine optimization of ranges to encompass 1 μM as the cutoff of 3.1 is close enough to 1 μM.
Regarding the other 103 rejections, the examiner agrees that Lawler is silent to utilizing saliva, and the rejections for claim 2-3 are withdrawn, but objected to for being dependent on rejected claim 1.
Claim 13-14 cannot be independently allowable, as they are dependent on claim 1’s method which is rejected by Fraser et al. Claim 13 is additionally rejected by Fraser et al., but claim 14 is found to be potentially allowable subject matter.
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 1-3, 6-10, 13-14 and 16-19 are rejected under 35 U.S.C. 101 because it constitutes abstract ideas.
Regarding independent claim 1, a two-step analysis is performed:
Step 1: Does the claim fall within a statutory category?
Yes, it is a method/process.
Step 2A, Prong 1: Identify the law of nature/natural phenomenon/abstract ideas.
An in vitro method for the detection of inflammation caused by an acute COVID 19 infection, long COVID and/or pediatric inflammatory multisystem syndrome (PIMS), wherein a level of kynurenine in saliva is determined and wherein the value of kynurenine measured in the patient to be diagnosed is compared with the average value of kynurenine obtained from a comparable cohort of persons who do not suffer from said diseases, thereby detecting or monitoring the inflammation.
Evaluating a level of kynurenine with a control level of kynurenine to be indicative of acute COVID 19 infection, long COVID and/or pediatric inflammatory multisystem syndrome (PIMS) is considered a mental process, where it is evaluated based on one’s observation, evaluation, judgment and opinion using data as comparison, making this an abstract idea.
Step 2A Prong 2: Has the abstract idea been integrated into a particular practical application?
The claim as a whole does not integrate the abstract idea into a practical application. Other than the abstract idea, claim 1 recites the additional elements: The measured level of kynurenine in saliva. With respect to mentioned additional elements, they represent insignificant extra solution activity (e.g., mere data gathering). Thus, there is no application of the abstract idea, much less a particular practical application.
Step 2B: Does the claim recite any elements which are significantly more than the abstract idea?
Claim 1 does not provide an inventive concept (significantly more than the abstract idea). The measured level of kynurenine in saliva is considered insignificant extra solution activity (e.g., mere data gathering). Furthermore, the additional elements above, alone and in combination within claim 1 as a whole, are well understood, routine, and conventional activities within the prior art (see 35 U.S.C. 102 and 103 rejections).
Dependent claims 2-3, 6-10, 13-14 and 16-19 do not resolve any of the issues discussed above because they involve limitations with more insignificant extra-solution activity (e.g., determining kynurenine levels using an ELISA test), is recited at a high level of generality and/or abstract ideas in the form of mental process. With specific case to new claims 16-19, the application of administering at least one treatment for decreasing inflammation and lowering kynurenine, and monitoring the inflammation of a patient is recited at a high level of generality which is not a particular practical application. Determining if the patient has inflammation is an abstract idea from evaluating based on observations using data as comparison. Where the level of kynurenine in saliva is utilized alone is simply more insignificant extra-solution activities.
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.
Claims 1, 6-7, 10-11, 13 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fraser et al. (WO 2021207858 A1).
Regarding claim 1, Fraser et al. teaches an in vitro method for the detection of inflammation caused by an acute COVID 19 infection, long COVID and/or pediatric inflammatory multisystem syndrome (PIMS) (see Abstract, disclosing methods of diagnosing COVID-19 infections in a subject), wherein the level of kynurenine in saliva is determined (see col. 26/lines 2-6, disclosing the method of diagnosing COVID-19 in a subject comprises (a): measuring an amount of one or more metabolites in a sample from the subject, (b): determining a parameter from the amount of each of the one or more metabolites, (c): comparing the parameter to one or more cutoff values, and based on the comparison, determining whether the subject is COVID-19 positive. See also col. 6/lines 5-7, col. 19/lines 6-10, further disclosing for COVID-19 diagnosis, one of the metabolites of interest is kynurenine, and that test samples includes biological specimens and fluids, such as saliva.) and wherein a value of kynurenine measured in the patient to be diagnosed is compared with the average value of kynurenine obtained from a comparable cohort of persons who do not suffer from said diseases, thereby detecting or monitoring the inflammation (see col. 6/lines 5-7, disclosing that for a COVID-19 diagnostic apparatus, the one or more metabolite is kynurenine (i.e., a diagnostic biomarker), and wherein the diagnosis of COVID-19 positive is indicated when the levels of kynurenine in the sample is statistically elevated from the known normal levels of kynurenine. See also col. 1/lines 17-21, col. 3/lines 14-22, disclosing that kynurenine is used in determination of COVID-19 disease severity for a COVID-19, and where the severity of COVID-19 further correlates to an increase in inflammatory cytokine levels “cytokine storm” which is the excessive or uncontrolled release of cytokines in response to a pathologic event, such as viral infections.).
Regarding claim 6, Fraser et al. teaches the in vitro method according to claim 1, wherein the level of kynurenine is at least two times higher in a patient than in the control group (see Fig. 1A, col. 53-54/lines 27-10., disclosing that in the COVID-19+ cohort, relative to the healthy control subjects, kynurenine increased 5.1-fold.).
Regarding claim 7, Fraser et al. teaches the in vitro method according to claim 1, wherein acute COVID-19 infection is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (see col. 1/lines 9-16, disclosing Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the virus that causes COVID-19 (or COVID 19). COVID-19 primarily affects lungs, and in the most severe cases results in acute respiratory distress syndrome (ARDS) associated with or without multiorgan dysfunction.).
Regarding claim 10, Fraser et al. teaches the in vitro method according to claim 1, wherein it is an ELISA test, or a lateral flow immunochromatographic assay, or a microfluidic test, or a colorimetric test, or an immunoblot (see col. 55, lines 14-20, disclosing point-of-care analyses for these metabolites (arginine, kynurenine, and/or arginine/kynurenine ratio) could be rapidly developed, such as a lateral flow immunochromatographic assay.).
Regarding claim 11, Fraser et al. teaches a use of kynurenine as a biomarker in the in vitro detection of inflammation caused by an acute COVID-19 infection, long COVID and/or PIMS (see col. 26/lines 14-25, disclosing diagnostic biomarkers for COVID-19, where one of the biomarkers includes the metabolite kynurenine. See also col. 55/lines 14-20, disclosing that COVID-19 diagnosis can consist of either arginine, kynurenine, and/or arginine/kynurenine ratio.).
Regarding claim 13, Fraser et al. teaches a test kit with which the level of kynurenine in a body fluid is determined by using the method according to claim 1 (see col. 6/lines 15-20, disclosing a kit for a COVID-19 diagnostic or quantitation assay, the kit comprising one or more internal standards suitable for mass spectrometry, packaging material, and instructions, and where one or more internal standards include one or a combination of kynurenine, arginine, lysophospholipds and creatinine.).
Regarding claim 19, Fraser et al. teaches the in vitro method according to claim 1, wherein the level of kynurenine in saliva is utilized alone and not in a ratio (see col. 19/lines 6-10, col. 55/lines 14-20, disclosing that COVID-19 diagnosis can consist of either arginine, kynurenine, and/or arginine/kynurenine ratio, and that test samples includes biological specimens and fluids, such as saliva.).
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.
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.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Fraser et al. as applied to claim 1 above, and further in view of Anusuya et al. (AU 2021100927 A4).
Regarding claim 8, Fraser et al. teaches methods of diagnosing acute COVID-19 infections in a subject using diagnostic biomarker metabolite kynurenine (see Fraser et al., Abstract, col. 18/lines 3-9, col. 26/lines 14-25).
Fraser et al. fails to teach wherein long COVID is a condition characterized by long-term consequences persisting or appearing after the typical convalescence period of COVID-19.
However, in the analogous art of a process for successful management of COVID-19 positive patients, Anusuya et al. teaches methods for treating COVID-19 patients with mild to moderate symptoms. The methods relate to extreme acute coronavirus 2 respiratory syndrome, and further discusses concerns on patients who recovered from the acute phase of the diseases but continues to experience long term symptoms for months after, known as long COVID (see Anusuya et al., Abstract, col. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the diagnostic methods for COVID-19 of Fraser et al. to incorporate long COVID (as taught by Anusuya et al.), for the benefit of being able to obtain a prognosis and assess recovery and treatment for long COVID patients by detecting inflammation.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Fraser et al. as applied to claim 1 above, and further in view of Chang et al. (WO 2021243007 A2).
Regarding claim 9, Fraser et al. teaches methods of diagnosing acute COVID-19 infections in a subject using diagnostic biomarker metabolite kynurenine (see Fraser et al., Abstract, col. 18/lines 3-9, col. 26/lines 14-25).
Fraser et al. fails to teach wherein PIMS is a systemic paediatric illness involving persistent fever and extreme inflammation following exposure to SARS-CoV-2.
However, in the analogous art of compositions and methods for treating acute respiratory distress syndrome (ARDS) and inflammatory disorders caused by coronaviruses, Chang et al. teaches using compositions for treatment and prevention of sudden acute respiratory syndromes coronavirus infections. A hyperinflammatory condition identified in a small subset of children infected with COVID-19, known as Pediatric Inflammatory Multisystem Syndrome (PIMS), where it is found to be an aberrant immune response to SARS-CoV-2 infections, causing Kawasaki-like disease in genetically predisposed pediatric patients (see Chang et al., Abstract, col. 3-4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the diagnostic methods for COVID-19 of Fraser et al. to incorporate Pediatric Inflammatory Multisystem Syndrome (as taught by Chang et al.), for the benefit of being able determine early diagnosis of PIMS to improve effectiveness of administered treatment to counter disease escalation (see Chang et al., col. 35).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Fraser et al.
Regarding claim 12, Fraser et al. teaches classification between patient cohorts for COVID-19+ metabolomes. The least number of metabolites that were required to maintain a 100% classification accuracy between cohorts was determined with kynurenine to be cutoff ≥ 3.1 μM, and where this metabolite can be found in biological specimens or fluids such as saliva (see Fraser et al. Fig. 1A, col. 18/lines 3-9, col. 53-54/lines 27-10).
While Fraser et al. doesn't explicitly teach the levels of kynurenine to be at least 1μM in saliva, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the range given by Fraser to be ≥ 1 μM of kynurenine for COVID-19 positive patients (see Fig. 1A, col. 18/lines 3-9, col. 53-54/lines 27-10), for the benefit of earlier detection period for diagnosing COVID. The ranges are modified through routine optimization (see MPEP §§ 2144.05.II.A., Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”).
Allowable Subject Matter
Claims 2-3, 14, and 16-18 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.
The following is a statement of reasons for the indication of allowable subject matter: The closest prior art, Fraser et al., disclosing methods of diagnosing COVID-19 infections in a subject. The method of diagnosing COVID-19 in a subject comprises (a): measuring an amount of one or more metabolites in a sample from the subject, (b): determining a parameter from the amount of each of the one or more metabolites, (c): comparing the parameter to one or more cutoff values, and based on the comparison, determining whether the subject is COVID-19 positive. See also further disclosing for COVID-19 diagnosis, one of the metabolites of interest is kynurenine, and that test samples includes biological specimens and fluids, such as saliva (see Fraser et al., Abstract, col. 6/lines 5-7, col. 19/lines 6-10, col. 26/lines 2-6) disclosing that for a COVID-19 diagnostic apparatus, the one or more metabolite is kynurenine (i.e., a diagnostic biomarker), and wherein the diagnosis of COVID-19 positive is indicated when the levels of kynurenine in the sample is statistically elevated from the known normal levels of kynurenine (see Fraser et al., col. 6/lines 5-7). Kynurenine is also used in determination of COVID-19 disease severity for a COVID-19, and where the severity of COVID-19 further correlates to an increase in inflammatory cytokine levels “cytokine storm” which is the excessive or uncontrolled release of cytokines in response to a pathologic event, such as viral infections (col. 1/lines 17-21, col. 3/lines 14-22).
However, Fraser does not disclose or suggest using the determination of kynurenine in saliva as therapy control (as required by claim 2), for monitoring COVID-19 and variants or the recovery of a patient (as required by claim 3). Fraser additionally doesn’t teach a test kit for determining kynurenine in a body fluid that further includes being a ELISA test kit, or a lateral flow immunochromatographic assay test kit, or a microfluidic test kit, or a colorimetric test kit, or an immunoblot test kit (as required by claim 14). Furthermore, Fraser et al. does not disclose or suggest administering a treatment to decrease the inflammation in the patient thereby reducing kynurenine levels in the patient (as required by claim 16), determining that the patient has inflammation based on the value of kynurenine in the patient being at least 1 μM to monitor the inflammation and therapy of the patient (as required by claim 17 and 18).
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tracy C Colena whose telephone number is (571)272-1625. The examiner can normally be reached Mon-Thus 8:00am-5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TRACY CHING-TIAN COLENA/ Examiner, Art Unit 1797
/JENNIFER WECKER/ Primary Examiner, Art Unit 1797
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