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 .
Remarks
This Office Action fully acknowledges applicant’s remarks filed 05/19/2026. Claims 1-18 are pending. Claims 1, 3-4, 6-7, and 10-11 have been amended. New claims 16-18 have been added.
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 1-18 are rejected under 35 U.S.C. 101 the claimed invention is directed to a natural correlation with no practical application and without significantly more.
That is, claim 1-18 are directed to identifying biomarkers for purposes of determining a risk of developing a circulatory disease – which is based on a natural correlation between the biomarkers and a circulatory disease.
The recited steps of “comparing” quantitative values in claims 1, 3, 4, and 10 do not preclude such comparison from being performed in one’s mind as a mental process that falls within the “mental processes” grouping of abstract ideas which are judicial exceptions. (See MPEP 2106.04(a)(2)(III)(C)).
As for the practical use of the claimed invention, the claims do not recite a particular practical application.
Claim 1 for examiner recites “administrating a treatment.”
Claim 16 recites administering a pharmacological treatment.
Claim 17 recites that the pharmacological treatment comprises a lipid-lowering medication, an anti-hypertensive medication, or a combination thereof.
Claim 18 recites that the pharmacological treatment comprises an anticoagulant, an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), a beta-blocker, an antiplatelet agent, a calcium channel blocker, a diuretic, a digitalis medication, a nitrate or a combination thereof.
These treatments are not “particular” since they broadly encompass generic treatments for circulatory diseases and not treatments that are particular to the biomarkers and quantitative values of the biomarkers claimed.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because: the additional steps of using a control sample, a plurality of biomarkers, specific biomarkers, consideration of the general health and risk factors of the subject, measuring biomarkers using nuclear magnetic resonance spectroscopy are nothing more than routine and conventional data gathering and comparison steps, i.e. insignificant extra-solution activity, and routine and conventional activity specified at a high level of generality.
Thus, in light of the above considerations the claims remain non-statutory, and are thus not patent eligible under 35 U.S.C. 101.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
1. Claims 1, 2, 5-11 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over International Patent Application No. WO2020242976 to Pritchard et al. in view of Das et al. (“Prevention and Management of Arrhythmias in Acute Myocardial Infarction,” International Journal of Contemporary Medical Research, Volume 3 | Issue 5 | May 2016) and Barb et al. (“The preparation and solution NMR spectroscopy of human glycoproteins is accessible and rewarding,” Methods Enzymol. 2019 ; 614: 239–261.).
Pritchard et al. teaches predicting the risk of an individual developing myocardial infarction using biomarker measurements selected from tyrosine, glycoprotein acetyls, and others. (claims 26 and 27).
Das et al. teaches that myocardial infraction is associated with arrhythmias. (page 1401 “Introduction”)
It would have been obvious to one of ordinary skill in the art to modify Prichard et al. to determine whether a subject is at risk for developing arrhythmias (heart flutter), using tyrosine and glycoprotein acetyls as biomarkers in view of Da et al. teaching myocardial infraction is associated with arrhythmias.
It would further be routine and otherwise obvious to compare the quantitative value of tyrosine and glycoprotein acetyls with control volumes.
Pritchard et al. in view of Das et al. does not teach using NMR spectroscopy to detect glycoprotein acetyls.
Barb et al, teaches it is known to use NMR spectroscopy to detect glycoproteins. (title)
It would have been obvious to modify Pritchard et al. in view of Das et al. to use NMR spectroscopy to detect glycoprotein acetyls in view of Barb et al.
I.) Regarding applicant’s claim 1, as noted above Pritchard et al. in view of Das et al. and Barb et al. teaches all the elements of claim 1.
Therefore, Pritchard et al. in view of Das et al. and Barb et al. renders claim 1 obvious.
II.) Regarding applicant’s claim 2, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 1 obvious from which claim 2 depends.
Claim 2 recites determining in the biological sample quantitative values of a plurality of the biomarkers.
Prichard et al. in view of Das et al. and Barb et al. teaches a plurality of the biomarkers.
Therefore, Pritchard et al. in view of Das et al. and Barb et al. renders claim 2 obvious.
III.) Regarding applicant’s claim 5, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 1 obvious from which claim 5 depends.
Claim 5 recites that the subject is generally healthy, or the subject has an already existing form of a circulatory disease and the risk of developing another or recurrent circulatory disease is determined.
It would have been obvious to select a subject in Prichard et al. in view of Das et al. and Barb et al. that is generally healthy to determine the subjects risk of developing a circulatory disease.
Therefore, Prichard et al. in view of Das et al. and Barb et al. renders claim 5 obvious.
IV.) Regarding applicant’s claim 6, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 1 obvious from which claim 6 depends.
Claim 6 recites quantitative value of the at least one biomarker is/are measured using nuclear magnetic resonance spectroscopy.
In Prichard et al. in view of Das et al. and Barb et al. NMR spectroscopy is used to measure at least one biomarker.
Therefore, Prichard et al. in view of Das et al. and Barb et al. renders claim 6 obvious.
V.) Regarding applicant’s claim 7, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 1 obvious from which claim 7 depends.
Claim 7 recites determining whether the subject is at risk of developing the circulatory disease using a risk score, hazard ratio, odds ratio, and/or predicted absolute risk or relative risk calculated on the basis of the quantitative value(s) of the at least one biomarker or of the plurality of the biomarkers.
Prichard et al. teaches developing risk scores based upon biomarkers. [0018]
Therefore, Prichard et al. in view of Das et al. and Barb et al. renders claim 7 obvious.
VI.) Regarding applicant’s claim 8, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 7 obvious from which claim 8 depends.
Claim 8 recites the risk score, hazard ratio, odds ratio, and/or predicted relative risk and/or absolute risk may be calculated on the basis of at least one further measure.
Prichard et al. teaches risk scores that can take into consideration of numerous factors listed in paragraph [00269].
Therefore, Prichard et al. in view of Das et al. and Barb et al. renders claim 8 obvious.
VII.) Regarding applicant’s claim 11, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 1 obvious from which claim 11 depends.
Claim 11 recites the subject is known not to suffer from a circulatory disease.
In Prichard et al. in view of Das et al. and Barb et al. it would have been obvious to select a subject that is known not to suffer from a circulatory disease for purposes of confirming any risks that the subject might develop a circulatory disease and/or to establish baseline measurements of biomarkers for the subject.
Therefore, Prichard et al. in view of Das et al. and Barb et al. renders claim 11 obvious.
VIII.) Regarding applicant’s claim 15, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 8 obvious from which claim 15 depends.
Claim 15 recites the at least one further measure comprises a characteristic of the subject.
In Prichard et al. teaches a list of characteristics of a subject in paragraph [00269] that can be taken into consideration.
Therefore, Prichard et al. in view of Das et al. and Barb et al. renders claim 15 obvious.
IX.) Regarding applicant’s claim 9, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 15 obvious from which claim 9 depends.
Claim 9 recites the characteristic of the subject includes one or more of age, height, weight, body mass index, race or ethnic group, smoking, and/or family history of circulatory diseases.
Prichard et al. teaches other factors that can be taken into consideration in paragraph [00269], including the health, social, physical, physiological and/or behavioral status of their relatives or acquaintances.
Therefore, Prichard et al. in view of Das et al. and Barb et al. renders claim 9 obvious.
2. Claims 3 and 12 are rejected under 35 USC 103 as being unpatentable over Prichard et al. in view of Das et al. and Barb et al. as applied to claims 1 and 2 above and further in view of González-Pacheco et al. (“Prognostic Implications of Serum Albumin Levels in Patients With Acute Coronary Syndromes,” The American Journal of Cardiology 2017).
I.) Regarding claim 3, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 1 obvious from which claim 3 depends.
Claim 3 recites determining in the biological sample obtained from the subject a quantitative value of the following biomarkers:
- glycoprotein acetyls;
- albumin; and
comparing the quantitative value(s) of the biomarkers to quantitative value(s) of the biomarkers in a control sample or to a control value(s); wherein an increase or a decrease in the quantitative value(s) of the biomarkers, when compared to the quantitative value(s) of the biomarkers in the control sample or to the control value, is/are indicative of the subject having an increased risk of developing the circulatory disease.
Prichard et al. in view of Das et al. and Barb et al. does not teach using albumin as a biomarker.
González-Pacheco et al. teaches that albumin is a biomarker for myocardial infarction.
It would have been obvious to modify Prichard et al. in view of Das et al. and Barb et al. to include albumin as a biomarker to determine myocardial in fraction in view of González-Pacheco et al. teaches that albumin is a biomarker for myocardial infarction.
Therefore, Prichard et al. in view of Das et al. Barb et al. and González-Pacheco et al. renders claim 3 obvious.
II.) Regarding applicant’s claim 12, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 2 obvious from which claim 12 depends.
Claim 12 recites determining in the biological sample quantitative values of three or more biomarkers.
As noted above, it would have been obvious to modify Prichard et al. in view of Das et al. and Barb et al. to include albumin as a biomarker to determine myocardial in fraction in view of González-Pacheco et al. teaches that albumin is a biomarker for myocardial infarction. Such a modification would add albumin to the tyrosine, glycoprotein acetyls taught by Prichard et al. resulting in three biomarkers.
Therefore, Prichard et al. in view of Das et al. Barb et al. and González-Pacheco et al. renders claim 12 obvious.
3. Claim 4 is rejected under 35 USC 103 as being unpatentable over Prichard et al. in view of Das et al. and Barb et al. as applied to claims 1 and 2 above and further in view of Campos et al. (“α-Linolenic Acid and Risk of Nonfatal Acute Myocardial Infarction,” Circulation Volume 118, Issue 4, 22 July 2008; Pages 339-345).
I.) Regarding applicant’s claim 4, as noted above Prichard et al.. in view of Das et al. and Barb et al. renders claim 1 obvious from which claim 4 depends.
Claim 4 recites determining in the biological sample obtained from the subject a quantitative value of the following biomarkers:
- glycoprotein acetyls,
- at least one fatty acid measure(s) of the following: ratio of linoleic acid to total fatty acids, linoleic acid, ratio of omega-6 fatty acids to total fatty acids, omega-6 fatty acids, ratio of saturated fatty acids to total fatty acids, fatty acid degree of unsaturation; and
comparing the quantitative value(s) of the biomarkers to quantitative value(s) of the biomarkers in a control sample or to a control value(s);
wherein an increase or a decrease in the quantitative value(s) of the biomarkers, when compared to the quantitative value(s) of the biomarkers in control sample or to the control value, is/are indicative of the subject having an increased risk of developing the circulatory disease.
Prichard et al. in view of Das et al. and Barb et al does not teach using the ratio of linoleic acid to total fatty acids as a biomarker.
Campos et al. teaches that linolenic acid is associated with myocardial infarction and teaches measuring the ratio of linolenic acid to other fatty acids.
It would have been obvious to modify Prichard et al. in view of Das et al. and Barb et al. to include the ratio of linolenic acid to other fatty acids a biomarker to determine myocardial in fraction in view of Campos et al. teaches that linolenic acid is associated with myocardial infarction and teaches measuring the ratio of linolenic acid to other fatty acids.
Therefore, Prichard et al. in view of Das et al. Barb et al. and González-Pacheco et al. renders claim 3 obvious.
4. Claims 13 and 14 are rejected under 35 USC 103 as being unpatentable over Prichard et al. in view of Das et al. and Barb et al. as applied to claim 1 and further in view of González-Pacheco et al. and Vermeulen et al. (“Clinical correlates of arterial lactate levels in patients with ST-segment elevation myocardial infarction at admission: a descriptive study,” Critical Care 2010).
I.) Regarding applicant’s claim 13, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 1 obvious from which claim 13 depends.
Claim 13 recites that determining in the biological sample quantitative values of four or more biomarkers.
As noted above, Prichard et al. teaches tyrosine and glycoprotein acetyls as biomarkers for myocardial infarction and González-Pacheco et al. teaches that albumin as a biomarker for myocardial infarction.
Vermeulen et al. teaches that muscle cells to preferentially use glycolysis and produce lactate from pyruvate, rather than oxidize pyruvate for mitochondrial energy production. In patients
with ischemic heart disease, the amount of lactate released by the myocardium has been shown to be
related to the severity of coronary artery disease. For patients with myocardial infarction, circulating venous lactate levels have been shown to be increased. (page 2, right-hand column).
It would have been obvious to modify Prichard et al. in view of Das et al. and Barb et al, to include a biomarkers albumin as taught by González-Pacheco et al., and lactate and pyruvate as biomarker in view of Vermeulen et al. teaching how these components contribute to myocardial infraction.
Therefore, Prichard et al. in view of Das et al. Barb et al. González-Pacheco et al., and Vermeulen et al. renders claim 13 obvious.
II.) Regarding applicant’s claim 14, as noted above Prichard et al. in view of Das et al. and Barb et al. renders claim 1 obvious from which claim 14 depends.
Claim 14 recites that determining in the biological sample quantitative values of five or more biomarkers.
As noted above, Prichard et al. teaches tyrosine and glycoprotein acetyls as biomarkers for myocardial infarction and González-Pacheco et al. teaches that albumin as a biomarker for myocardial infarction.
Vermeulen et al. teaches that muscle cells to preferentially use glycolysis and produce lactate from pyruvate, rather than oxidize pyruvate for mitochondrial energy production. In patients
with ischemic heart disease, the amount of lactate released by the myocardium has been shown to be
related to the severity of coronary artery disease [10]. For patients with myocardial infarction, circulating venous lactate levels have been shown to be increased. (page 2, right-hand column).
It would have been obvious to modify Prichard et al. in view of Das et al. and Barb et al, to include a biomarkers albumin as taught by González-Pacheco et al., and lactate and pyruvate as biomarker in view of Vermeulen et al. teaching how these components contribute to myocardial infraction.
Therefore, Prichard et al. in view of Das et al. Barb et al. González-Pacheco et al., and Vermeulen et al. renders claim 14 obvious.
5. Claim 10 is rejected under 35 USC 103 as being unpatentable over Prichard et al, in view of Das et al., International Patent Application Publication No. WO2009093077 to Mayr et al. (cited by applicant), Jian-Zhong et al. (“Use of Aromatic Hydroxylation of Phenylalanine to Measure Production of Hydroxyl Radicals After Myocardial Ischemia In Vivo” (cited by applicant), Moradi-Arzeloo et al. (“Effects of histidine and vitamin C on isoproterenol-induced acute myocardial infarction in rats,” Veterinary Research Forum. 2016; 7 (1) 47 – 54), Soininen et al. (“Quantitative Serum Nuclear Magnetic Resonance Metabolomics in Cardiovascular Epidemiology and Genetics) (cited by applicant) and Campos et al.
As noted above, Pritchard et al. teaches predicting the risk of an individual developing myocardial infarction using biomarker measurement selected from tyrosine, glycoprotein acetyls, and others. (claims 26 and 27).
Das et al. teaches that myocardial infraction is associated with arrhythmias. (page 1401 “Introduction.”
It would have been obvious to one of ordinary skill in the art to modify Prichard et al. to determine whether a subject is at risk for developing arrhythmias (heart flutter), using tyrosine and glycoprotein acetyls as biomarkers in view of Da et al. teaching myocardial infraction is associated with arrhythmias.
Mayr et al. teach various compounds that are associated with cardiac arrhythmia, including: fatty acids, acetate, lactate, pyruvate, acetoactetate, alanine, glutamine and tyrosine. (Table 2)
Jian-Zhong et al. teaches that phenylalanine is associated with myocardial stunning. (title)
Moradi-Arzeloo et al. teaches that histidine is associated with myocardial infraction. (Title)
Soininen et al. teaches that various fatty acids and their ratios are associated with various cardiovascular diseases. (page 198)
As noted above, Campos et al. teaches that linolenic acid is associated with myocardial infarction and teaches measuring the ratio of linolenic acid to other fatty acids.
It would have been obvious to modify Prichard et al. in view of Das et al. to use any and all of the compounds taught by Maye et al., Jain-Zhong et al., Moradi-Arzeloo et al., Soininen et al. and Campos et al. as biomarkers to access and determine a subject’s risk for developing a circulatory disease.
Therefore, Prichard et al. in view of Das et al. Maye et al., Jain-Zhong et al., Moradi-Arzeloo et al. and Campos et al. renders claim 10 obvious
Response to Arguments
Applicant's arguments filed 05/19/2026 have been fully considered but they are not persuasive.
On page 8 of applicant’s response applicant argues that claim 1 is not directed to a natural correlation, but instead recites a practical application for the detection of biomarkers of a particular disease, atrial fibrillation and/or flutter, and administration of a treatment.
As noted above, the biomarkers have a direct correlation to circulatory disease and the steps of “determining” under a broad reasonable interpretation are mental steps that are abstract ideas. Further, the generality of the treatments are not “particular” as applicant argues.
On pages 8-9 of applicant’s response applicant argues that Pritchard et al. does not teach predicting the risk of an individual developing atrial fibrillation and/or flutter.
Das et al. has been relied upon as teaching that myocardial infraction is associated with arrhythmias. (page 1401 “Introduction”)
It would have been obvious to one of ordinary skill in the art to modify Prichard et al. to determine whether a subject is at risk for developing arrhythmias (heart flutter), using tyrosine and glycoprotein acetyls as biomarkers in view of Da et al. teaching myocardial infraction is associated with arrhythmias.
Applicant’s arguments regarding the difference between mechanisms behind atrial fibrillation and myocardial infarction are distinct, are not germane since Das et al. teaches that myocardial infraction is associated with arrhythmias. One skilled in the art being aware of Das et al. teaching that myocardial infraction is associated with arrhythmias, would necessarily consider arrhythmias (heart flutter), using tyrosine and glycoprotein acetyls as biomarkers as taught by Pritchard et al.
On page 10 of applicant’s response applicant argues that Barb et al. is limited to using cultured human cells to produce homogenous glycoproteins with stable isotope labels and specific NMR experiments to probe glycans.
Barb et al. teaches “Solution NMR spectroscopy is a powerful tool to study biological macromolecules that is capable of characterizing mobile elements of molecules with atomic-level resolution. Methods to express glycoproteins, incorporate stable isotope labels, and analyze glycoproteins have recently opened new avenues to prepare and investigate glycoproteins. These methods are accessible to many laboratories with experience expressing and purifying proteins
from prokaryotic expression hosts.”
Thus Barb et al. generally teaches that glycoproteins can be detected by NMR spectroscopy.
Conclusion
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.S.G./Examiner, Art Unit 1798
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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