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 .
Detailed Action
Summary
This is the Final Office Action based on application 18/044752 election response filed 07/14/2026.
Claims 1-3, 5-18, 21-22, 25-27, 45-46, 49, 52 & 55-56 have been fully considered and examined.
Claims 47, 49, 52 & 54 are withdrawn from consideration.
Claims 4, 19-20, 23-24, 28-44, 48, 50-51, 53 & 57 have been cancelled.
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 ofmatter, or any new and useful improvement thereof, may obtain a patent therefor, subject to theconditions and requirements of this title.
Claims 1-3, 5-18, 21-22, 25-27, 45-46, 49, 52 & 55-56 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more.
The claim(s) recite(s) natural correlations/laws of nature and abstract ideas. This judicial exception is not integrated into a practical application. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The reasons for this are shown in the analysis below.
The invention of instant claims is drawn towards a method for determining Kawasaki disease in a subject, a method for administering a therapeutic intervention to a subject suspected of having Kawasaki disease, a method of detecting two or more protein markers in a subject that is suspected of having Kawasaki disease.
Claims 1, 25 & 26 of the elected claims are independent.
Through 101, inquiry:
Step 1 Inquiry: Are the claims directed to a statutory category of invention?
Yes, the independent claims 1, 25 & 26 are drawn towards a statutory category (a method).
Step 2A, Prong 1: Do the claims involve a Judicial Exception?
Yes, independent claims 1, 25 & 26 and those that depend therefrom involve the judicial exception of a natural correlation between the claimed biomarkers and presence or absence of Kawasaki disease. Natural correlations are law of nature judicial exceptions. They are also abstract ideas, as correlations are mathematical process/equations. Further, in all of these claims there are steps which include a subset of: calculating, log transforming, normalizing the log -transformation, calculating a score, assigning a score, classifying, selecting and determining. These are all either mental processes or mathematical calculations, which are both abstract idea judicial exceptions.
Step 2A, Prong: Has the natural correlation/ law of nature or abstract idea been integrated into a particular practical application?
For independent claims 1, 25 & 26 the answer is no.
For Claim 1, steps in addition to the claimed abstract ideas and laws of nature/natural correlations are:
providing a biological sample
applying the biological sample to an analytical device
detecting the concentration
For Claim 25, steps in addition to the claimed abstract ideas and laws of nature/natural correlations are:
determining the subject’s protein marker profile
administering to the subject a therapeutic intervention based on the positive, intermediate or negative score
For Claim 26, steps in addition to the claimed abstract ideas and laws of nature/natural correlations are:
providing a biological sample
applying the biological sample to an analytical device
detecting the concentration
With respect to the instantly claimed detecting, determining, providing a biological sample, and applying the biological sample to an analytical device, especially at the level of generality claimed all of these steps are just done to gather data to perform the judicial exception. Therefore, they are insignificant extra-solution activity and therefore they do nothing to practically apply the judicial exceptions. See MPEP 2106.05(g).
With respect to the claimed steps of treating the patients---specifically:
The independent Claims as amended 07/14/2026 further specify that the treatment is based on a score being negative, intermediate, or positive. They are left open to no treatment, so no practical application at all, if the score is negative no treatment would occur within the boundary of the claims and also does not offer a particular or specific therefore and therefore does not change the matters above.
The claims as amended 07/14/2026 further specify that pharmacological agents that could be used if there is a positive result. However, the claim is still left open to no treatment occurring so does not change the matters above. Further- it is not clear if some of the treatments such as “intravenous immunoglobin,” are specific since immunoglobins could be administered in almost anything, and “avoidance of ASA,” just avoidance of a treatment and no actual treatment itself, so therefore reading on no treatment and again, no practical application, even if a positive result/diagnosis is determined.
See Vanda memorandum.
Further, though the independent claims preamble are all now drawn towards treating, it is clear that this is still based on a diagnosis of Kawasaki disease in the claim even though not explicitly claimed, it is implicitly there. As this is the case and further because the abstract ideas are in the claim as well, the claimed treatment at the level of generality claimed is not particular or specific. Further—treatment is not required in every instance in which the claim is read, but instead it is only required “based on,” positive, intermediate, or negative score.” If negative score is found—no treatment occurs.
Step 2B: Do the claims recite any elements which are significantly more than the abstract idea or natural correlation/law of nature?
For independent claims 1, 25 & 26 the answer is no.
For Claim 1, steps in addition to the claimed abstract ideas and laws of nature/natural correlations are:
providing a biological sample
applying the biological sample to an analytical device
detecting the concentration
For Claim 25, steps in addition to the claimed abstract ideas and laws of nature/natural correlations are:
determining the subject’s protein marker profile
treating the subject based on the positive, intermediate or negative score
For Claim 26, the only steps in addition to the claimed abstract ideas and laws of nature/natural correlations are:
providing a biological sample
applying the biological sample to an analytical device
detecting the concentration
Especially at the level of generality claimed, the claimed detecting, determining, providing a biological sample, and applying the biological sample to an analytical device, and treating with a therapeutic intervention are all well understood, routine and conventional (WURC) in the art. Things that are WURC are not significantly more. See MPEP 2016.05(d)(II). “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.”
The independent Claims as amended 07/14/2026 further specify that the treatment is based on a score being negative, intermediate, or positive. They are left open to no treatment if the score is negative no treatment would occur within the boundary of the claims and also does not offer a particular or specific therefore and therefore does not change the matters above. No, treating, or a patient existing as normal is certainly WURC.
The claims as amended 07/14/2026 further specify that pharmacological agents that could be used if there is a positive result. However, the claim is still left open to no treatment occurring so does not change the matters above. Further- it is not clear if some of the treatments such as “intravenous immunoglobin,” are specific since immunoglobins could be administered in almost anything, and “avoidance of ASA,” just avoidance of a treatment and no actual treatment itself, so therefore reading on no treatment even if a positive result/diagnosis is determined. No, treating, or a patient existing as normal is certainly WURC.
Further, that the claimed treatments are WURC in the art, when used is evidenced by SPETZLER in US 20140148350. SPETZLER teaches that the treatment can be acetylsalicyclic acid (Table 9) methylprednisolone (paragraph 0794, 1072, 1073) and infliximab (paragraph 1044, 1126)
For the dependent claims we would look to see if they add limitations that change the above analysis (e.g. does the new limitation integrate into a practical application or amount to significantly more?)
Here, none of the dependent claims integrate the abstract idea or natural correlation into a practical application at step 2A/2 nor do they or amount to significantly more at step 2B.
With respect to Claims 2, 6-18, 55, specify a smaller set of biomarkers or clinical variables than in the independent claims. These are all part of the judicial exceptions themselves.
With respect to Claim 3, it specifies that a diagnostic score is calculated. This is a mathematical process and part of the judicial exception itself.
Claim 5 states what the sample is. The biological samples is part of the judicial exception /natural correlation itself, and is still only used to gather data--- therefore, not changing matters above with respect to practical application. Further biological samples and using them are WURC in the art so not significantly more.
Claims 21-22 make specifications of facilitating a mental determination by a medical practitioner. A mental determination is a mental process/abstract idea. Therefore, this does not change matters.
Claims 45-46 specify that the patient has already been diagnosed with other diseases. Diagnoses are natural correlations/law of nature judicial exceptions so this does not change matters above.
Claims 27 & 56-57 specifies that further calculating is done with an algorithm with weightings and clinical variables. This is still calculating and is part of the abstract idea judicial exceptions, and the clinical variables are biomarkers/part of the natural correlation Therefore, does not change matters above.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5-18, 21-22, 25-27, 45-46, 49, 52 & 55-56 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.
With respect to Claim 1, 25 & 26 the claim preamble is drawn to “a method of administering a therapeutic agent,” or a “method of treating,” or “detecting and treating,” however the claims do not require that a treatment is performed and it is only performed when a positive score is found. Therefore, it is not clear if there is actually any treatment in the claims as required by the preamble, but not required by the claim bodies.
2-3, 5-18, 21-22, 27, 45-46, 49, 52 & 55-56 are rejected by virtue of their dependency on Claims 1, 25 & 26.
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 non-obviousness.
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.
Claims 1-3, 5-18, 21-22, 25-27, 45, 49, 52 & 55-56 are rejected under 35 U.S.C. 103 as being obvious by SPETZLER in US 20140148350 in view of PREVENCIO in WO 2019090166 (as cited on IDS dated 05/19/2023).
With respect to Claim 1, SPETZLER teaches of a method for using biomarkers for diagnoses(abstract), and that the diagnoses can be for Kawasaki disease (paragraph 0796, 1103,1119).
SPETZLER further teaches of providing a sample from a subject who is suspected of having a disease--- any patient can be suspected of having a disease through broadest reasonable interpretation (paragraph 0164, 1306-1308),
applying the sample to a microfluidic device to detect the concentration of biomarkers (paragraph 0236).
SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173), and that
the detecting concentrations of at least two protein biomarkers (abstract, paragraph 0317, 0407, 0243) and that the biomarkers can be compared to a control or a reference (paragraph 0408), and that the control or reference standard can be a synthetic peptide or protein sequence (paragraph 0325, 0324).
Even further SPETZLER teaches of using log transform for cluster analysis of the samples (paragraph 0131) and
of forming a probability/diagnostic score for diagnostic, prognostic, and therapy related scores for the biosignature (paragraph 0881, 1225) and that the scores can be used for negative predictive value or positive predictive value (paragraph 1225) and of therapy related scores for the biosignature (paragraph 0881, 1225) and that the treatment choice can be determined by the score (paragraph 1225) and that the treatment in is therapeutic intervention (paragraph 0367).
Finally, SPETZLER teaches that the methods taught therein, including the scoring for a positive or negative prediction can be used for the diagnoses can be for Kawasaki disease (paragraph 0796, 1103,1119).
SPTEZLER further teaches that the intervention can be pharmaceutical or non-pharmaceutical (paragraph 0397). SPETZLER further teaches that the treatment can be acetylsalicyclic acid (Table 9) methylprednisolone (paragraph 0794, 1072, 1073) and infliximab (paragraph 1044, 1126).
Though SPETZLER teaches the general mathematical processing of data as claimed, in case this is not clear to one of ordinary skill in the art PREVENCIO is used to remedy this.
PREVENCIO teaches a method of administering a therapeutic intervention to a subject suspected of having peripheral artery disease (paragraph 0006) comprising: i: determining the subject's protein marker profile for a panel of protein markers comprising at least two protein markers selected (paragraph 0132 Table 1; note: several other protein markers are listed in Table 1); wherein the score is classified as a positive, intermediate, or negative score (the score is positive, intermediate, or negative; (paragraph 0141), said score algorithmically-derived from normalized and mathematically transformed concentrations of protein markers in the subject's sample and optionally, the status of at least one clinical variable (calculating a diagnostic score using an algorithm applied to the transformed and normalize concentrations of the two protein markers in the subject's sample and the status of the clinical variable; (paragraph 0141), and specifically of log transforming the protein concentration and data to normalize--- which reads on with respect to the normal distribution (paragraph 0122); and iii: administering to the subject a therapeutic intervention based on the positive, intermediate or negative score (administering a therapeutic intervention based on the positive, intermediate, or negative score; (paragraph 0141). Note: peripheral artery disease is a known to be related to Kawasaki disease-- Further, the method of administering a therapeutic intervention within the peripheral artery disease genus includes Kawasaki disease.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of success to process data as is done in PREVENCIO in the method of SPETZLER due to due to the need in the art for better methods for prognosing and predicting associated outcomes in patients with peripheral artery disease (PREVENCIO, paragraph 0004) and due to the advantage transforming and normalizing data has for designing values to fit specific populations (PREVENCIA, paragraph 0122).
With respect to Claim 2, SPETZLER teaches of detecting/determining and pooling data from samples with respect to the clinical variable of age (paragraph 0318).
With respect to Claim 3, SPETZLER teaches of detecting/determining and pooling data from samples with respect to the clinical variable of age (paragraph 0318). SPETZLER further teaches of applying weight expression to various biomarkers/markers in the score (paragraph 0881, 1225). SPEZTLER further teaches of using an algorithm (paragraphs 0351-0354, 1042, 1060, 1228).
With respect to Claim 5, SPETZLER teaches of detection of biomarkers in blood (paragraph 0005).
With respect to Claim 6, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173), and that
the detecting concentrations of at least two protein biomarkers (abstract, paragraph 0317, 0407, 0243) and that the biomarkers can be compared to a control or a reference (paragraph 0408), and that the control or reference standard can be a synthetic peptide or protein sequence (paragraph 0325, 0324). SPETZLER teaches of detecting/determining and pooling data from samples with respect to the clinical variable of age (paragraph 0318).
With respect to Claim 7, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173) and or/ N-terminal prohormone BNP (paragraph 1115).
With respect to Claim 8, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173) and or/ N-terminal prohormone BNP (paragraph 1115).
With respect to Claim 9, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173), and or/ N-terminal prohormone BNP (paragraph 1115).
With respect to Claim 10, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173) and or/ N-terminal prohormone BNP (paragraph 1115).
With respect to Claim 11, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173) and or/ N-terminal prohormone BNP (paragraph 1115).
With respect to Claim 12, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173) and or/ N-terminal prohormone BNP (paragraph 1115) and further of interleukin 1-Beta (IL-1B or IL-1beta) (Table 4 paragraph 1062, 0998).
With respect to Claim 13, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173) and or/ N-terminal prohormone BNP (paragraph 1115) and further of interleukin 1-Beta (IL-1B or IL-1beta) (Table 4 paragraph 1062, 0998).
With respect to Claim 14, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173) and or/ N-terminal prohormone BNP (paragraph 1115) and further of interleukin 1-Beta (IL-1B or IL-1beta) (Table 4 paragraph 1062, 0998). SPETZLER does not teach of thyroxine- binding globulin being a biomarker. PREVENCIO is used to remedy this and teaches of tyroxine binding globulin (paragraph 0112, 0127). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to used thyroxine binding globulin as a biomarker as is done in PREVENCIO in the method of SPETZLER since it shows advantage in being diagnostic and prognostic for peripheral artery disease (paragraph 0210, 0210).
With respect to Claim 15, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173) and or/ N-terminal prohormone BNP (paragraph 1115) and further of interleukin 1-Beta (IL-1B or IL-1beta) (Table 4 paragraph 1062, 0998). SPETZLER does not teach of thyroxine- binding globulin being a biomarker. SPETZLER does not teach of thyroxine- binding globulin being a biomarker. PREVENCIO is used to remedy this and teaches of tyroxine binding globulin (paragraph 0112, 0127). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to used thyroxine binding globulin as a biomarker as is done in PREVENCIO in the method of SPETZLER since it shows advantage in being diagnostic and prognostic for peripheral artery disease (paragraph 0210, 0210).
With respect to Claim 16, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173) and or/ N-terminal prohormone BNP (paragraph 1115) and further of interleukin 1-Beta (IL-1B or IL-1beta) (Table 4 paragraph 1062, 0998). SPETZLER does not teach of thyroxine- binding globulin being a biomarker. PREVENCIO is used to remedy this and teaches of tyroxine binding globulin (paragraph 0112, 0127). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to used thyroxine binding globulin as a biomarker as is done in PREVENCIO in the method of SPETZLER since it shows advantage in being diagnostic and prognostic for peripheral artery disease (paragraph 0210, 0210).
With respect to Claims 17-18, SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173) and or/ N-terminal prohormone BNP (paragraph 1115) and further of interleukin 1-Beta (IL-1B or IL-1beta) (Table 4 paragraph 1062, 0998). SPETZLER does not teach of T uptake being a biomarker. PREVENCIO is used to remedy this and teaches of tyroxine binding globulin (paragraph 0112, 0127). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to used thyroxine binding globulin as a biomarker as is done in PREVENCIO in the method of SPETZLER since it shows advantage in being diagnostic and prognostic for peripheral artery disease (paragraph 0210, 0210).
With respect to Claim 21, SPETZLER teaches of disease monitoring and treatment monitoring (paragraph 0302, 0309, 0316), in relation to the determination of the score. SPETZLER teaches of forming a probability/diagnostic score for diagnostic, prognostic, and therapy related scores for the biosignature (paragraph 0881, 1225) and that the scores can be used for negative predictive value or positive predictive value (paragraph 1225) and that the treatment choice can be determined by the score (paragraph 1225) and that the treatment in is therapeutic intervention (paragraph 0367).
With respect to Claim 22, SPETZLER teaches of disease monitoring and treatment monitoring (paragraph 0302, 0309, 0316), in relation to the determination of the score. SPETZLER teaches of forming a probability/diagnostic score for diagnostic, prognostic, and therapy related scores for the biosignature (paragraph 0881, 1225) and that the scores can be used for negative predictive value or positive predictive value (paragraph 1225) and that the treatment choice can be determined by the score (paragraph 1225) and that the treatment in is therapeutic intervention (paragraph 0367). SPETZLER also teaches that the biomarkers can be used for differential diagnosis (paragraph 0417).
With respect to Claim 25, SPETZLER teaches of a method for using biomarkers for diagnoses(abstract), and that the diagnoses can be for Kawasaki disease (paragraph 0796, 1103,1119). SPTEZLER teaches of using the method to select a candidate treatment and treat the patient (abstract).
SPETZLER further teaches of providing a sample from a subject who is suspected of having a disease--- any patient can be suspected of having a disease through broadest reasonable interpretation (paragraph 0164, 1306-1308),
applying the sample to a microfluidic device to detect the concentration of biomarkers (paragraph 0236).
SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173), and that
the detecting concentrations of at least two protein biomarkers (abstract, paragraph 0317, 0407, 0243) and that the biomarkers can be compared to a control or a reference (paragraph 0408), and that the control or reference standard can be a synthetic peptide or protein sequence (paragraph 0325, 0324). This reads on the claimed, “determining the subject’s protein marker profile,” for the claimed panel as the claimed does not required that all proteins in panel are found.
Even further SPETZLER teaches of using log transform for cluster analysis of the samples (paragraph 0131) and
of forming a probability/diagnostic score for diagnostic, prognostic, and therapy related scores for the biosignature (paragraph 0881, 1225) and that the scores can be used for negative predictive value or positive predictive value (paragraph 1225).
Finally, SPETZLER teaches that the methods taught therein, including the scoring for a positive or negative prediction can be used for the diagnoses can be for Kawasaki disease (paragraph 0796, 1103,1119).
Though SPETZLER teaches the general mathematical processing of data as claimed, in case this is not clear to one of ordinary skill in the art PREVENCIO is used to remedy this.
PREVENCIO teaches a method of administering a therapeutic intervention to a subject suspected of having peripheral artery disease (paragraph 0006) comprising: i: determining the subject's protein marker profile for a panel of protein markers comprising at least two protein markers selected (paragraph 0132 Table 1; note: several other protein markers are listed in Table 1); wherein the score is classified as a positive, intermediate, or negative score (the score is positive, intermediate, or negative; (paragraph 0141), said score algorithmically-derived from normalized and mathematically transformed concentrations of protein markers in the subject's sample and optionally, the status of at least one clinical variable (calculating a diagnostic score using an algorithm applied to the transformed and normalize concentrations of the two
of forming a probability/diagnostic score for diagnostic, prognostic, and therapy related scores for the biosignature (paragraph 0881, 1225) and that the scores can be used for negative predictive value or positive predictive value (paragraph 1225).
protein markers in the subject's sample and the status of the clinical variable; (paragraph 0141), and specifically of log transforming the protein concentration and data to normalize--- which reads on with respect to the normal distribution (paragraph 0122); and iii: administering to the subject a therapeutic intervention based on the positive, intermediate or negative score (administering a therapeutic intervention based on the positive, intermediate, or negative score; (paragraph 0141). Note: peripheral artery disease is a known to be related to Kawasaki disease-- Further, the method of administering a therapeutic intervention within the peripheral artery disease genus includes Kawasaki disease.
It would have been obvious to one of ordinary skill in the art to process data as is done in PREVENCIO in the method of SPETZLER due to due to the need in the art for better methods for prognosing and predicting associated outcomes in patients with peripheral artery disease (PREVENCIO, paragraph 0004) and due to the advantage transforming and normalizing data has for designing values to fit specific populations (PREVENCIA, paragraph 0122).
With respect to Claims 26-27, SPETZLER teaches of a method for using biomarkers for diagnoses(abstract), and that the diagnoses can be for Kawasaki disease (paragraph 0796, 1103,1119).
SPETZLER further teaches of providing a sample from a subject who is suspected of having a disease--- any patient can be suspected of having a disease through broadest reasonable interpretation (paragraph 0164, 1306-1308),
applying the sample to a microfluidic device to detect the concentration of biomarkers (paragraph 0236).
SPETZLER further teaches that the biomarkers can include CRP and BPN (paragraph 0545), a-1-antitrypsin (paragraph 0678), periosten (paragraph 0935), CRP and MMP9 (paragraph 1173), and that
the detecting concentrations of at least two protein biomarkers (abstract, paragraph 0317, 0407, 0243) and that the biomarkers can be compared to a control or a reference (paragraph 0408), and that the control or reference standard can be a synthetic peptide or protein sequence (paragraph 0325, 0324).
Even further SPETZLER teaches of using log transform for cluster analysis of the samples (paragraph 0131) and
of forming a probability/diagnostic score for diagnostic, prognostic, and therapy related scores for the biosignature (paragraph 0881, 1225) and that the scores can be used for negative predictive value or positive predictive value (paragraph 1225).
Finally, SPETZLER teaches that the methods taught therein, including the scoring for a positive or negative prediction can be used for the diagnoses can be for Kawasaki disease (paragraph 0796, 1103,1119).
Though SPETZLER teaches the general mathematical processing of data as claimed, in case this is not clear to one of ordinary skill in the art PREVENCIO is used to remedy this.
PREVENCIO teaches a method of administering a therapeutic intervention to a subject suspected of having peripheral artery disease (paragraph 0006) comprising: i: determining the subject's protein marker profile for a panel of protein markers comprising at least two protein markers selected (paragraph 0132 Table 1; note: several other protein markers are listed in Table 1); wherein the score is classified as a positive, intermediate, or negative score (the score is positive, intermediate, or negative; (paragraph 0141), said score algorithmically-derived from normalized and mathematically transformed concentrations of protein markers in the subject's sample and optionally, the status of at least one clinical variable (calculating a diagnostic score using an algorithm applied to the transformed and normalize concentrations of the two protein markers in the subject's sample and the status of the clinical variable; (paragraph 0141), and specifically of log transforming the protein concentration and data to normalize--- which reads on with respect to the normal distribution (paragraph 0122); and iii: administering to the subject a therapeutic intervention based on the positive, intermediate or negative score (administering a therapeutic intervention based on the positive, intermediate, or negative score; (paragraph 0141). Note: peripheral artery disease is a known to be related to Kawasaki disease-- Further, the method of administering a therapeutic intervention within the peripheral artery disease genus includes Kawasaki disease.
It would have been obvious to one of ordinary skill in the art to process data as is done in PREVENCIO in the method of SPETZLER due to due to the need in the art for better methods for prognosing and predicting associated outcomes in patients with peripheral artery disease (PREVENCIO, paragraph 0004) and due to the advantage transforming and normalizing data has for designing values to fit specific populations (PREVENCIA, paragraph 0122).
With respect to Claim 45, SPETZLER teaches of the patient having SARS coronavirus, which is what is claimed (paragraph 1143).
With respect to Claim 55, SPETZLER teaches of detecting/determining and pooling data from samples with respect to the clinical variable of age (paragraph 0318).
With respect to Claim 56, SPETZLER teaches of the invention as shown above but does not teach of the claimed weighting. PREVENCIO is used to remedy this and teaches of algorithmically weighting values (paragraph 0173, 0122). It would have beeo obvious to one of ordinary skill in the art to weight values due to the advantage this gives for making diagnostic or prognostic decisions based on factors which are more important (hence the weighting) (paragraph 0173).
Claim 46 is rejected under 35 U.S.C. 103 as being obvious by SPETZLER in US 20140148350 in view of PREVENCIO in WO 2019090166 (as cited on IDS dated 05/19/2023) and further in view of DURRANT in US 20210309733.
With respect to Claims 46, SPETZLER and PREVENCIO teach of the invention as shown above, but do not teach of the subject being diagnosed with MIS-C in relation to Kawasaki disease.
DURRANT is used to remedy this and teaches of a method for detection and treatment of inflammation resulting from coronavirus (abstract). DURRANT teaches that the coronavirus can be related to Kawasaki disease and also to MIS-C(paragraph 0013).
It would have been obvious to detect and co treat co-related diseases as is DURRANT in the methods of SPETZLER and PREVENCIO since the diseases are known to cause cytokines release syndrome and toxicity and since the same treatments are effective for both (DURRANT, paragraphs 0012-0013).
Response to Arguments
Applicant's arguments filed 07/14/2026 have been fully considered but they are not persuasive.
With respect to the 101 rejection, it is maintained. Notably, the claim amendments to the independent claims leave the claims open to no treatment occurring within the boundaries of the claim, since it is not always required that a positive score and treatment is needed. Further, some of the claim treatments themselves amount to no treatment, or “avoidance,” of treatment, which broadly reads as no treatment. Please see the 101 rejection above for more detail. In addition to the 101, rejection, there is also a 112 rejection with respect to related matters.
The prior Claim Objections are overcome.
Some of the prior 112 rejections are overcome due to the cancellation of prior Claims 23-24. However, due to amendments made 07/14/2026 others are maintained.
With respect to the prior art of SPETZLER in view of PREVENCIO, applicant argues that several important claim limitations would be missing. The examiner disagrees.
Specifically, applicant argues that the claims are “highly specific processing claims.” With respect to this, the examiner notes that as claimed, the processing in the independent claims is not considered really that specific, but more importantly as claimed it is just mathematical processing. This is an abstract idea, and rejected under 101. Further—the prior art in fact does teach of utilizing the claimed mathematical processing techniques like log transforming, normalizing and calculating.
Specifically, SPETZLER teaches of using log transform for cluster analysis of the samples (paragraph 0131). PREVENCIO teaches of using an algorithm applied to the transformed and normalize concentrations of the two, of forming a probability/diagnostic score for diagnostic, prognostic, and therapy related scores for the biosignature (paragraph 0881, 1225) and that the scores can be used for negative predictive value or positive predictive value (paragraph 1225). PREVENCIO further teaches of specifically of log transforming the protein concentration and data to normalize--- which reads on with respect to the normal distribution (paragraph 0122).
The prior art further teaches of classifying the scores as positive or negative for the claimed disease as shown in the above rejection.
All claims remain rejected.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
KENTSIS in US 20140161791 teaches of compositions and methods for diagnosing and treating Kawasaki disease. More specifically, the proteomes of patients with KD are enriched for the meprin A, filamin B, and filamin C, which serve as biomarkers (and potential therapeutic targets) for KD. Accordingly, detection of these biomarkers, using compositions and methods provided for herein, can inform the therapy delivered to the subject (abstract).
BULIK in US 20170052200 teaches of the determination of levels or expression of particular biomarkers in biological samples which can be utilized to diagnose, prognose, and treat Kawasaki disease in subjects, and further to select subjects who would benefit from a Kawasaki disease therapy other than, or in addition to, IVIG treatment. Accordingly, the present invention encompasses methods and compositions that utilize these biomarkers for the diagnosis, prognosis, and treatment of Kawasaki disease.
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 REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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