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 Amendment
Applicant’s amendment filed on 11/17/25 has been entered. Claims 1-5, 7, 9, and 15-18 are cancelled. Claim 19 is added. Claims 6, 8, 10-14, and 19 are pending and examined herein. Applicant’s amendment and remark have overcome each and every rejection under 112(b) set forth in Office Action mailed on 06/18/25.
Status of Rejection
The rejections of claims 1-5, 7, 9, and 15-18 are obviated by Applicant’s cancellation.
The rejections of claims 10-12 and 14 under 112(b) is withdrawn in light of Applicant’s amendment.
The rejections of claims 6, 10, 11, and 13 under 101 are withdrawn in light of Applicant’s amendment and remark.
The rejections of claims 6, 8, and 10-14 under 103 are maintained.
Claim Rejections - 35 USC § 101
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 8, 12, 14, and 19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to law of nature without significantly more.
Regarding claim 8, the claim(s) recite(s) “measuring suPAR in a sample of plasma obtained from the subject”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a law of nature in the form of a natural correlation. The claim recites detecting disease by measuring the amount of concentration of the biomarker compound in a biological sample. The amounts of biomarker/suPAR in the serum/plasma sample is/are naturally correlated with development of inflammatory disease and its severity. If a claim limitation, under its broadest reasonable interpretation, covers a natural correlation, then it falls within the law of nature grouping of natural phenomena. Accordingly, the claim recites a law of nature (Step 2A, Prong 1).
This judicial exception is not integrated into a practical application. In particular, the claim recites “measuring the suPAR level in a sample of plasma” to detect/diagnose disease, which constitutes a natural correlation under broadest reasonable interpretation. “Admitting or not discharging,” a subject is a mental decision, so another judicial exception so there is no integration of the measurement step much less a practical one. Accordingly, this additional element does not integrate the natural correlation into a practical application because it does not impose any meaningful limits on practicing the natural correlation. The claim is directed to a judicial exception (Step 2A, Prong 2).
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception (Step 2B). Admitting a patient to hospital appears to be routine and conventional ways of generic disease treatment methodology and is not instantly claimed with any particularity or specificity. Routine way of providing medical care is not significantly more. The claim is not patent eligible.
Claim 12 does not cure the deficiency of claim 8, the claim simply recites the sample used to measure suPAR. The sample is part of the natural correlation.
Claims 14 does not cure the deficiency of claim 8, respectively. The claims simply recite generically that suPAR level is determined by generic immunodiagnostic method. This does not practically apply, nor does it add significantly more as this is routine and conventional.
Claim 19 does not cure the deficiency of claim 8. They claim diagnosis which is a natural correlation judicial exception. Due to the level of generality a SARS-CoV-2 is detection assay is claimed, the limitation does not practically apply nor add significantly more.
Claim Rejections - 35 USC § 103
Claim(s) 6, 11, and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Eugen-Olsen (US 20140370527 A1) in view of Wrotek (Soluble urokinase plasminogen activator receptor: an indicator of pneumonia severity in children, 2015) and WHO (Oxygen sources and distribution for COVID-19 treatment centres, Interim guidance, Published April 4, 2020), as evidenced by Zhu (A Novel Coronavirus from Patients with Pneumonia in China, 2019, Published January 24, 2020) all cited in previous Office Action.
Regarding claims 6, Eugen-Olsen discloses a method of measuring and diagnosing inflammation, comprising:
measuring soluble urokinase type plasminogen activator receptor (suPAR) (claim 1, step a) in a sample of plasma obtained from the subject (claim 4).
Furthermore, Eugen-Olsen discloses suPAR can be a strong predictive indicator for the risk of development of chronic obstructive lung disease (Furthermore suPAR levels measured in a biological fluid derived from an individual are shown to be a strong predictive marker for risk of development of diseases that can originate from low-grade inflammation and metabolic disorders, including cardiovascular disease, chronic obstructive lung disease, para. [0099])).
In addition, Eugen-Olsen discloses the subject is at increased risk of developing an inflammation-related disease and/or metabolic syndrome-related disease if the suPAR level is more than 3.0, 4, 5, or 6 ng/mL in men and more than 3.5, 4.5, 5.5, or 6.5 ng/mL in women (para. [0030]).
However, Eugen-Olsen does not explicitly the method is used for treating a subject who has SARS-CoV-2 infection using invasive ventilation, and providing invasive ventilation to the subject having a suPAR plasma level of over 6 ng/ml.
In an analogous art, Wrotek discloses a correlation between pneumonia severity and suPAR level (Abstract). Wrotek discloses that suPAR concentration in patients with pneumonia was significantly higher than healthy individual (The finding were that the suPAR concentration in children with pneumonia was significantly higher (median 7.11 ng/mL) than in healthy individuals (4.68 ng/mL). We found a positive correlation between the suPAR and the following factors: fever, time for defeverscence, length of hospital stay, and elevated CRP and procalcitonin levels. Abstract). Furthermore, suPAR was concentration is higher for severe course of pneumonia compared with those with less severe pneumonia (Moreover, the suPAR level was significantly higher in children with a severe course of pneumonia compared with those having non-severe pneumonia (7.79 vs. 6.87 ng/mL; p = 0.006). Abstract).
It would have been obvious to one of ordinary skill in the art to have tried the method of Eugen-Olsen for monitoring COVID-19 patients,” as claimed with reasonable expectation of success based on the disclosure from Wrotek to derive the claimed invention. It is known some common symptoms of COVID-19 can include obstructive lung diseases such as pneumonia as evidenced by disclosure from Zhu (Abstract), and Wrotek discloses the correlation between severity of pneumonia and suPAR concentration. Therefore, one of ordinary skill in the art would have a reasonable expectation of success that the correlations disclosed by Wrotek is also applicable to patients with COVID-19 using the method of Wrotek.
Eugen-Olsen in view of Wrotek does not explicitly disclose providing invasive ventilation treatment. In an analogous art, WHO discloses relationship between severity classification of COVID-19 patients and likelihood requiring invasive ventilation with those classified as “critically ill” requiring invasive ventilation (Data from China suggests that although the majority of people with COVID-19…5% will be critically ill requiring intensive care unit treatment. In addition, most critically ill COVID-19 patients will require mechanical ventilation. COVID-19 and oxygen, Page 1, para. 1). As the severity of infection/likelihood of being prescribed to invasive ventilation are variables that positively corresponds to the suPAR concentration, with severity of pneumonia/likelihood of being prescribed to invasive ventilation both worsening/increasing as suPAR level is increased, the precise suPAR threshold of 6 ng/mL and its corresponding invasive ventilation treatment prescription would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed suPAR threshold and the type of oxygen treatment prescription cannot be considered critical. Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have optimized, by routine experimentation, the reference value in the Eugen-Olsen to obtain the desired balance between disease severity and likelihood of prescribing invasive ventilation as taught by Wrotek and WHO respectively (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223). “[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). “[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Regarding claim 11, Modified Eugen-Olsen discloses the claimed invention as discussed above in claim 6. Eugen-Olsen discloses the plasma level is determined indirectly by assaying a serum sample (para. [0008]).
Regarding claim 13, Modified Eugen-Olsen discloses the claimed invention as discussed above in claim 6. Eugen-Olsen discloses the suPAR level is determined by an immunodiagnostic method (ELISA assay, para. [0045]).
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Eugen-Olsenin view of Wrotek and WHO as discussed above in claim 6, and further in view of Zhu.
Regarding claim 10, Modified Eugen-Olsen discloses the claimed invention as discussed above in claim 6. Modified Eugen-Olsen does not explicitly disclose the SARS-CoV-2 infection is diagnosed using a SARS-CoV-2 detection assay. Zhu discloses that patients are diagnosed using PCR (RT-PCR) assay (Methods, Viral Diagnostic Methods). It would have been obvious to one of ordinary skill in the art before the effective filing date to have incorporated PCR such as those taught by Zhu to determine the patient is positive of coronavirus before determining if the patient requires invasive ventilation.
Claim(s) 8, 12, and 14is/are rejected under 35 U.S.C. 103 as being unpatentable over Eugen-Olsen in view of Wrotek and Rasmussen (Soluble urokinase plasminogen activator receptor (suPAR) in acute care: a strong marker of disease presence and severity, readmission and mortality. A retrospective cohort study, 2016; cited in previous Office Action), as evidenced in Zhu.
Regarding claim 8, Eugen-Olsen discloses a method of measuring and diagnosing inflammation, comprising:
determining subject’s soluble urokinase type plasminogen activator receptor (suPAR) (claim 1, step a) in a sample of plasma obtained from the subject (claim 4).
Furthermore, Eugen-Olsen discloses suPAR can be a strong predictive indicator for the risk of development of chronic obstructive lung disease (Furthermore suPAR levels measured in a biological fluid derived from an individual are shown to be a strong predictive marker for risk of development of diseases that can originate from low-grade inflammation and metabolic disorders, including cardiovascular disease, chronic obstructive lung disease, para. [0099])).
In addition, Eugen-Olsen discloses the subject is at increased risk of developing an inflammation-related disease and/or metabolic syndrome-related disease if the suPAR level is more than 3.0, 4, 5, or 6 ng/mL in men and more than 3.5, 4.5, 5.5, or 6.5 ng/mL in women (para. [0030]).
However, Eugen-Olsen does not explicitly the method is used for diagnosing a subject who has SARS-CoV-2 infection and admitting or not discharging the subject having a suPAR plasma level of over 6.0 ng/ml.
In an analogous art, Wrotek discloses a correlation between pneumonia severity and suPAR level (Abstract). Wrotek discloses that suPAR concentration in patients with pneumonia was significantly higher than healthy individual (The finding were that the suPAR concentration in children with pneumonia was significantly higher (median 7.11 ng/mL) than in healthy individuals (4.68 ng/mL). We found a positive correlation between the suPAR and the following factors: fever, time for defeverscence, length of hospital stay, and elevated CRP and procalcitonin levels. Abstract). Furthermore, suPAR was concentration is higher for severe course of pneumonia compared with those with less severe pneumonia (Moreover, the suPAR level was significantly higher in children with a severe course of pneumonia compared with those having non-severe pneumonia (7.79 vs. 6.87 ng/mL; p = 0.006). Abstract).
It would have been obvious to one of ordinary skill in the art to have tried the method of Eugen-Olsen for monitoring COVID-19 patients or “COVID 19 symptoms,” as claimed based with reasonable expectation of success based on the disclosure from Wrotek to derive the claimed invention. It is known some common symptoms of COVID-19 can include obstructive lung diseases such as pneumonia as evidenced by disclosure from Zhu (Abstract), and Wrotek discloses the correlation between severity of pneumonia and suPAR concentration. Therefore, one of ordinary skill in the art would have a reasonable expectation of success that the correlations disclosed by Wrotek is also applicable to patients with COVID-19 using the method of Wrotek.
Eugen-Olsen in view of Wrotek does not explicitly a step of admitting or not discharging the subject having a suPAR plasma level of over a threshold/reference value.
In another analogous art, Rasmussen discloses the suPAR is strongly associated with disease severity, readmission, and mortality (In this large unselected population of acute medical patients, suPAR is strongly associated with disease severity, readmission and mortality after adjusting for all other risk factors, indicating that suPAR adds information to established prognostic indicators. While patients with low suPAR levels have low risk of readmission and mortality, patients with high suPAR levels have a high risk of adverse events. Page 769, Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to have based on the decision of admitting or not discharging COVID-19 patients using the method of Eugen-Olsen in view of Wrotek based on the study disclosed by Ramussen. Doing so improves efficient resource allocation by correctly assess patient prognosis by reserving hospital care to those in urgent need (The number of elderly, frail, multimorbid patients is increasing rapidly, challenging our standardised, fast-track approach to medical treatment.5 At the same time, some patients admitted to the hospital could instead be treated in the primary sector. One way to improve the resource allocation is to rapidly and correctly assess the patient’s prognosis. Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that can be easily measured in plasma or serum. Rasmussen, Introduction, Page 769, left col., para. 1-2).
As the severity of COVID-19 infection is variable that positively corresponds to the suPAR concentration, with severity of pneumonia/COVID-19 symptoms both worsening as suPAR level is increased, the precise suPAR threshold of 6.0 ng/mL and its subsequent decision on admitting or not discharging patients would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed suPAR threshold cannot be considered critical. Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have optimized, by routine experimentation, the reference value/threshold in the Eugen-Olsen to obtain the desired balance between disease severity and likelihood of admission to urgent care/hospital as taught by Wrotek and Rasmussen (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223). “[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). “[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Regarding claim 12, Modified Eugen-Olsen discloses the claimed invention as discussed above in claim 8. Eugen-Olsen discloses the plasma level is determined indirectly by assaying a serum sample (para. [0008]).
Regarding claim 14, Modified Eugen-Olsen discloses the claimed invention as discussed above in claim 8. Eugen-Olsen discloses the suPAR level is determined by an immunodiagnostic method (ELISA assay, para. [0045]).
Claim(s)19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Eugen-Olsen in view of Wrotek and Rasmussen as discussed above in claim 8, and further in view of Zhu.
Regarding claim 19, Modified Eugen-Olsen discloses the claimed invention as discussed above in claim 8. Modified Eugen-Olsen does not explicitly disclose the SARS-CoV-2 infection is diagnosed using a SARS-CoV-2 detection assay. Zhu discloses that patients are diagnosed using PCR (RT-PCR) assay (Methods, Viral Diagnostic Methods). It would have been obvious to one of ordinary skill in the art before the effective filing date to have incorporated PCR such as those taught by Zhu to determine the patient is positive of coronavirus before determining if the patient requires invasive ventilation.
Response to Arguments
Applicant’s arguments, see Pages 5-7, filed 11/17/25, with respect to claims 6, 10, 11, and 13 have been fully considered and are persuasive. The 101 rejection of claims 6, 10, 11, and 13 has been withdrawn.
Applicant's arguments filed 11/17/25, regarding the 101 rejection directed to claim 8 and its dependent claims and 103 rejection, have been fully considered but they are not persuasive.
Regarding the 101 rejection of claim 8, Applicant argues, as amended, argues claim 8 recites eligible subject matter because the method offers an improvement over prior treatment practices by reducing the burden on medical facilities and personnel by reducing the extent to which patients are admitted, and therefore represents an improvement over previous SARS-CoV-2 patient assessment methods (Page 8 of remarks). Examiner respectfully disagrees.
MPEP 2106.06(d) states “If the additional element (or combination of elements) is a specific limitation other than what is well-understood, routine and conventional in the field, for instance because it is an unconventional step that confines the claim to a particular useful application of the judicial exception, then this consideration favors eligibility. If, however, the additional element (or combination of elements) is no more than well-understood, routine, conventional activities previously known to the industry, which is recited at a high level of generality, then this consideration does not favor eligibility.” Specifically, II states “The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity…iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011)”.
Even though the claims recite the decision of admitting or not discharging the subject is based on whether or not the subject suPAR level exceeds 6 ng/mL, the decision of admitting patients based on biomarkers result is a generally well-understood medical/diagnostic procedure for medical professional. Furthermore, medical professional typically takes into consideration of reducing expenditure of precious medical resources when making decision on admitting/discharging patients. Therefore, this additional element is no more than well-understood, routine, conventional activities previously known to the industry. Therefore, the incorporation of the step of admitting/not discharging patients does not render claim 8 patent eligible.
Regarding the 103 rejection of claims 6 and 8 and their respective dependents, Applicant argues that the Wrotek is not sufficient in curing the deficiency of Eugen-Olsen. Applicant points out Wrotek is not sufficient in providing motivation for one of ordinary skill in the art to have modified the method of Eugen-Olsen as conventional biomarkers for pneumonia (PCT) perform poorly as predictive biomarkers in the context of COVID-19, one of ordinary skill in the art would not have considered Wrotek when modifying the method of Eugen-Olsen (Page 12 of the remark).
MPEP 2143(I)(E) states: To reject a claim based on this rationale, Office personnel must resolve the Graham factual inquiries. Then, Office personnel must articulate the following:
(1) a finding that at the relevant time, there had been a recognized problem or need in the art, which may include a design need or market pressure to solve a problem;
(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;
(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success; and
(4) whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness.
First, Eugen-Olsen provides suPAR can be a strong predictive indicator for the risk of development of chronic obstructive lung disease (Furthermore suPAR levels measured in a biological fluid derived from an individual are shown to be a strong predictive marker for risk of development of diseases that can originate from low-grade inflammation and metabolic disorders, including cardiovascular disease, chronic obstructive lung disease, para. [0099])). The term “strong” suggests that suPAR can be a reliable indicator for chronic lung disorder; and the symptoms of coronavirus is known to cause such symptom (1).
Second, Wrotek provides a general positive correlation of suPAR and lung disorder such as pneumonia, which is a common yet severe symptom of coronavirus according to Zhu. Wrotek suggests that in addition to PCT, suPAR can also be reliable indicators (2).
Based on the findings of both Wrotek and Eugen-Olsen, one of ordinary skill in would have identified and pursued a finite number of potential solutions with a reasonable expectation of success (PCT or suPAR) (3). Even if PCT were to be proven to be poor indicators for COVID-19, one would have tried suPAR with a reasonable expectation of success as COVID symptoms share similarities to respiratory disease disclosed in Zhu and Wrotek.
As such, one of ordinary skill in the art would have a reasonable expectation of success to have modified the methods of Eugen-Olsen with the secondary references cited above to derive the claimed invention. Therefore, the rejections are maintained.
THIS ACTION IS MADE FINAL. 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.
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/M.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758