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 .
Response to Arguments
Applicant’s arguments, see page 5-11 of remarks, filed 01/23/2026, with respect to the rejection(s) of claim(s) 1-3 and 6-14 under 35 U.S.C. 102 and 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Fraser et al. (WO 2021207858 A1) for claims 1-3 and 6-14 under 35 U.S.C. 102 and 103.
Claim Objections
Claims 1, 3, 9 and 11 objected to because of the following informalities:
PIMS (Paediatric Inflammatory Multisystem Syndrome) abbreviation is not expanded at least once in the claims and should appear once to define it. Appropriate correction is required.
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 and 13-14 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 PIMS, wherein the 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 obtained from a comparable cohort of persons who do not suffer from said diseases, whereby the value of kynurenine in patients is increased.
Measuring the level of kynurenine in saliva to compare with an average control to detect inflammation caused by acute COVID 19 infection, long COVID and/or 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 and 13-14 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) and/or abstract ideas in the form of mental process.
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 and 13 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 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 the value of kynurenine measured in the patient to be diagnosed is compared with the average value obtained from a comparable cohort of persons who do not suffer from said diseases, whereby the value of kynurenine in patients is increased (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.).
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.).
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.).
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.
Claims 2-3 are 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 Lawler et al. (“Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV‑2 Infection and Inflammatory Cytokine Responses”, as cited in the IDS and previous office action).
Regarding claim 2, Fraser et al. teaches a disease severity biomarker (notably not the same as a diagnostic biomarker of which kynurenine is defined as) which is obtained from a subject and analyzed during a subject’s recovery for COVID-19 (i.e. during the subject's rehabilitation therapy), wherein decrease in the levels of the biomarker in the recovery sample relative to the levels obtained in the test sample is indicative of a normalization of the subject (see Fraser et al., col. 11/lines 11-15).
Fraser et al. fails to teach wherein the determination of kynurenine in the saliva is used for therapy control.
However, in the analogous art of "Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV‑2 Infection and Inflammatory Cytokine Responses", Lawler et al. teaches associating SARS-CoV-2 positivity with elevated metabolites in plasma, including kynurenine. Lawler additionally teaches that understanding sequential mechanisms of SARS-CoV-2 from metabolic interactions is critical to developing actionable therapeutic interventions to mitigate adverse outcomes following infections (see Lawler et al., Abstract, Introduction, pg. 2796).
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 diagnosis of COVID-19 using kynurenine from saliva of Fraser et al. to incorporate using the kynurenine measure for developing actionable therapeutic interventions (as taught by Lawler et al.), for the benefit of increasing the potential for personalized treatments and improved recovery rates across the population (see Lawler et al., Introduction, pg. 2796).
Regarding claim 3, Fraser et al. teaches a disease severity biomarker (notably not the same as a diagnostic biomarker of which kynurenine is defined as) which is obtained from a subject and analyzed during a subject’s recovery for COVID-19 (i.e. during the subject's rehabilitation therapy), wherein decrease in the levels of the biomarker in the recovery sample relative to the levels obtained in the test sample is indicative of a normalization of the subject (see Fraser et al., col. 11/lines 11-15).
Fraser et al. fails to teach wherein the determination of kynurenine in a body fluid is used for monitoring acute COVID-19 infection, long COVID and/or PIMS and / or the recovery of a patient.
However, Lawler et al. teaches that detection of systemic metabolic biomarkers (i.e., kynurenine) related to multiple systems gives the potential for measuring systemic recovery in the population as well as measuring acute illness (see Lawler et al., Introduction, pg. 2796).
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 diagnosis of COVID-19 using kynurenine from saliva of Fraser et al. to incorporate using the kynurenine measure for monitoring acute illness of SARS-CoV-2 and recovery in a patient (as taught by Lawler et al.), for the benefit of increasing the potential for personalized treatments and improved recovery rates across the population (see Lawler et al., Introduction, pg. 2796).
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 pM, 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 explictly teach the levels of kynurenine to be at least 1μM in saliva, the range given by Fraser of ≥ 3.1 pM for COVID-19 positive patients well emcompasses 1μM of kynurenine (see Fig. 1A, col. 18/lines 3-9, col. 53-54/lines 27-10), and it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to see that Fraser teaches that COVID-19 positive patients can be found with at least 1 μM of kynurenine in saliva under reletive dimensions (see MPEP §§ 2144.04.IV.A. In Gardnerv.TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984), the Federal Circuit held that, where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device).
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Fraser as applied to claim 13 above, and further in view of Rai et al. (US PG-Pub 20210302436 A1).
Regarding claim 14, Fraser et al. teaches 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 (see col. 6/lines 15-20).
Fraser et al. fails to teach that the kit of claim 13 is an 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.
However, in the analogous art of methods, systems, and a kit for detection, diagnosis, monitoring and treatment of COVID-19, Rai et al. teaches methods, systems, and kits for assaying saliva samples for diagnosing COVID-19 infections in patients. Modes of implementation may include, for example, assays such as lateral flow immunochromatographic assays (LFA) and enzyme-linked immunosorbent assays (ELISA), where salivary biomarkers may be qualitatively or quantitatively measured using these strategies for the detection, diagnosis, monitoring, and treatment of COVID-19 or other viral infections (see Rai et al. [0032]).
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 kit for diagnosing and assaying COVID-19 patients of Fraser et al. by incorporating lateral flow immunochromatographic assays (LFA) and enzyme-linked immunosorbent assays (ELISA) into the kit (as taught by Rai et al.), for the benefit of being able to implement the diagnostic method in a wide range of locations and environments for screening groups of people for the presents of COVID-19 in a "ready-to-use" assay (see Rai et al., [0088]).
Conclusion
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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/TRACY CHING-TIAN COLENA/ Examiner, Art Unit 1797
/JENNIFER WECKER/ Primary Examiner, Art Unit 1797