DETAILED ACTION
In application filed on 08/07/2023, Claims 1-4, 6-14 and 16-20 are pending. The claim set submitted on 08/07/2023 is considered because this is the most recent claim set. Claims 1-4, 6-14 and 16 are considered in the current office 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/07/2024, 05/23/2025 and 04/03/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation. All claims are directed to statutory categories, i.e., a method (Claim 1) (Step 1: YES).
Analysis:
Claim 1: Ineligible.
Step 1:
The claim recites a series of steps or acts, including “monitoring a subject's risk of premature death in a subject with metabolic malnutrition inflammation syndrome”. Thus, the claim is directed to a process, which is one of the statutory categories of invention (Step 1: YES).
Step 2A, Prong 1:
Claim 1 recites “(c) generating a sex-specific metabolic vulnerability index (MVX) value from the at least two simultaneously measured biomarkers, wherein the MVX value is sex-specific and comprises a sex-specific inflammation vulnerability index (IVX) and a sex-specific metabolic malnutrition index (MMX); (d) determining the subject's relative risk for premature death based on at least the MVX value; (e) repeating steps (a)-(d) at a later time point; and (f) evaluating the subject's relative risk for premature death and the MVX value over time; (g) determining that the subject's relative risk for premature death has increased over time; and (h) recommending a lifestyle change to promote the subject's cardiac health”. Therefore, the claim is directed towards an abstract idea, and more specifically to the abstract idea group of a math or mental process since claim 1 relates to using a math or mental process to perform the steps reciting the abstract ideas.
In addition, it appears that limitation of Claim 1 further recites a law of nature because it describes the naturally occurring relationship between subject's relative risk for premature death and the MVX value, where in the MVX value is generated from the measurement of at least two biomarkers. (Step 2A, Prong 1: YES).
Step 2A, Prong Two:
This judicial exception is not integrated into a practical application. In particular, the claim recites ‘additional elements’ which are the steps performed before and after the recited abstract ideas. However, the steps before the abstract ideas are performed in order to gather data necessary to perform the determination step. Thus, these steps do not add a meaningful limitation since these steps are insignificant pre-solution activity.
It appears that the steps of “(a) obtaining a sample of blood, serum, or plasma from the subject; and (b) measuring the Nuclear Magnetic Resonance (NMR) spectra of at least two biomarkers simultaneously from the sample” are recited at a high level of generality that they amount to mere data gathering (insignificant extra-solution activity). See MPEP 2106.05(g).
Accordingly, these steps are ‘additional elements’ which do not integrate the abstract ideas into a practical application because they do not impose meaningful limits on practicing the abstract ideas (Step 2A, Prong Two: NO).
Step 2B:
Furthermore, the courts have found that limitations adding insignificant extrasolution activity to the judicial exception, such as mere data gathering in conjunction with a law of nature or abstract idea, are limitations found not to be enough to qualify as ‘significantly more’ when recited in a claim with a judicial exception (see the 2014 Interim Guidance on Patent Subject Matter Eligibility of the Federal Register dated December 16, 2014; and MPEP 2106.05(I)(A)). Note that mere data gathering is not significantly more than the abstract idea. See MPEP 2106.05(g).
Here, there are no additional elements which are significantly more than the abstract idea.
The steps of “(a) obtaining a sample of blood, serum, or plasma from the subject; and (b) measuring the Nuclear Magnetic Resonance (NMR) spectra of at least two biomarkers simultaneously from the sample” appear to be well-understood, routine, and conventional (WURC) in the field of clinical diagnostics as evidenced by Otvos et al. (US20190072572A1, submitted in IDS 11/07/2024 as US11156621B2) in view of Anand et al. ("The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink." Journal of clinical and Diagnostic Research: JCDR 7.4 (2013): 763.).
Thus, the claims do not amount to significantly more (Step 2B: NO).
Therefore, Claim 1 is ineligible.
Further, the dependent claims 2-4, 6-14 and 16 , do not solve the issues of above the limitations of Claim 1. Moreover, Claims 2-4,6-14 and 16 are rejected by virtue of dependency on Claim 1.
Claims 2-4: Ineligible.
Step 2A, Prong One and Prong Two: Claims 2-4 provides at least two biomarkers in the sample. The claims do not provide any practical application.
Step 2B: The claims do not recite any elements which are significantly more.
Claims 9 and 16: Ineligible.
Step 2A, Prong One and Prong Two: Claims 5, 9 and 15-16 further define the data gathering steps which appear to be generic and WURC.
Step 2B: The claims do not recite any elements which are significantly more.
It is noted that these steps are insignificant. The steps appear to be more data gathering and are well-understood, routine, and conventional (WURC)
Therefore, Claims 9 and 16 are ineligible.
Claims 6-7 and 10-13: Ineligible.
Step 2A, Prong One: Claim recites equations of mathematical models (math step) is are abstract ideas.
Step 2A, Prong Two: Once the steps of “generating…”, “determining…”, “repeating…” and “evaluating…” (in claim 1) are done, No further action takes place, much less a particular practical application. Also the steps of “obtaining a sample of blood, serum, or plasma from the subject” and “measuring at least two biomarkers simultaneously from the sample” (in claim 1) are recited at a high level of generality that it amounts to mere data gathering (insignificant extra-solution activity). See MPEP 2106.05(g).
Step 2B: The claims do not recite any elements which are significantly more.
Therefore, Claims 6-7 and 10-13 are ineligible.
Claim 14: Ineligible.
Step 2A, Prong One: Claim recites “the MVX value is sex-specific and is determined in a subject deemed to be at low-risk for a cardiovascular event or in a subject deemed to be at high- risk for a cardiovascular event” (math or mental step), which is the abstract idea.
Step 2A, Prong Two: Once the steps of “generating…”, “determining…”, “repeating…” ; “evaluating…”; “determining…”; and “recommending…” (in claim 1) are done, No further action takes place, much less a particular practical application. Also the steps of “obtaining a sample of blood, serum, or plasma from the subject” and “(b) measuring the Nuclear Magnetic Resonance (NMR) spectra of at least two biomarkers simultaneously from the sample” (in claim 1) are recited at a high level of generality that it amounts to mere data gathering (insignificant extra-solution activity). See MPEP 2106.05(g).
Step 2B: The claims do not recite any elements which are significantly more.
Therefore, Claim 14 is ineligible.
As a result, Examiner submits that each of the dependent claims do not resolve the 101 issues of claim 1 above.
Claim Rejections - 35 USC § 112
Claims 1-4, 6-14 and 16 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.
Claim 1 recites the limitation "the Nuclear Magnetic Resonance (NMR) spectra" in Claim 1. There is insufficient antecedent basis for this limitation in the claim.
For the purpose of expedited prosecution, the limitation "the Nuclear Magnetic Resonance (NMR) spectra" is interpreted by the Examiner as "a Nuclear Magnetic Resonance (NMR) spectra".
Moreover, Claims 2-4, 6-14 and 16 are rejected by virtue of dependency on claim 1.
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.
Claims 1-4, 8-9, 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Otvos et al. (US20190072572A1, submitted in IDS 11/07/2024 as US11156621B2) in view of Anand et al. ("The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink." Journal of clinical and Diagnostic Research: JCDR 7.4 (2013): 763.).
Regarding Claim 1, Otvos teaches a method for monitoring a subject's risk of premature death (See Para 0083; See Fig. 3…a graph that shows the cumulative mortality rates over five years for 9 subgroups of high-risk cardiac catheterization patients enrolled in CATHGEN stratified by MVX score according to embodiments of the present disclosure…. As shown in FIG. 3, the higher the MVX score, the higher the risk was of dying prematurely, thereby teaching “monitoring a subject's risk of premature death”) in a subject with cardiovascular disease (See Para 0018… subject's overall health and risk for a fatal CV event; See Para 0003) comprising:
obtaining a sample of blood, serum, or plasma from the subject (See Para 0077…obtaining a sample from the subject; See Para 0051… “biosample” refers to in vitro blood, plasma, serum, CSF, saliva, lavage, sputum, or tissue samples of humans or animals; See Para 0157…a) obtaining a sample from the subject;);
(b) measuring the Nuclear Magnetic Resonance (NMR) spectra (See Claims 25 and 31… wherein the measuring is performed by NMR; See Para 0140… wherein the measuring is performed by NMR; See Para 0008…evaluating NMR spectra of an in vitro blood plasma or serum patient sample; Also see Para 0107-0109 for the NMR spectra of at least two biomarkers) of at least two biomarkers simultaneously from the sample (See Para 0077…measuring GlycA, at least one high density lipoprotein particle (HDLP) subclass, at least one branched chain amino acid (BCAA), and at least one ketone body (KetoneBody) and optionally at least one of citrate (Citrate) and serum protein (Protein); See Para 0158…b) measuring GlycA, at least one high density lipoprotein particle (HDLP) subclass, at least one branched chain amino acid (BCAA), and at least one ketone body (KetoneBody) and optionally at least one of citrate (Citrate) and serum protein (Protein) in the sample);
(c) generating a sex-specific ((See Para 0080… The MVX mathematical models can consider other clinical parameters such as gender…) metabolic vulnerability index (MVX) value from the at least two simultaneously measured biomarkers (See Para 0010…In some embodiments, the processor may be configured to calculate an MVX score based on the measurements of GlycA, at least one ketone body, at least one branched chain amino acid; See Para 0019…the system may be further configured to calculate a MVX score using a defined mathematical model of risk of all cause-mortality that uses the calculated measurements of GlycA, at least one ketone body, at least one branched chain amino acid, at least one of the HDLP subclass parameters, and optionally serum protein (Protein) and/or citrate (Citrate); See Para 0159…(c) determining a metabolic vulnerability index (MVX) value based on the measurements), wherein the MVX value is sex-specific See Para 0080… The MVX mathematical models can consider other clinical parameters such as gender…; See Para 0091… In some embodiments, gender may be included as a factor in the MVX model; See Para 0031-0031 for the MVX score for female participants and the MVX score for male participants) and comprises a sex-specific inflammation vulnerability index (IVX) (See Para 0013… the MVX value is defined as comprising an inflammation index (INFX) value. Under BRI, IVX is viewed as INFX; See Para 0031-0031 for the MVX score for female participants and the MVX score for male participants)) and a sex-specific metabolic malnutrition index (MMX) (See Para 0013… the MVX value is defined as comprising a…a metabolic malnutrition index (MMX) value; See Para 0030-0031 for the MVX score for female participants and the MVX score for male participants, thereby teaching “sex specific”);
(d) determining the subject's relative risk for premature death based on at least the MVX value (See Para 0066… the metabolic vulnerability index can provide short (1 year) to long (12 year) term premature death risk assessments; See Para 0075…Generally stated, it is contemplated that MVX scores can be used to stratify relative risk for premature death. MVX scores can stratify premature death risk for patients having the same age, gender, blood pressure, and BMI independently of these clinical factors; See Para 0159….);
(e) repeating steps (a)-(d) at a later time point (See Para 0160…(d) repeating steps (a)-(c) at a later time point; See Para 0161…evaluating at least whether the MVX value has increased or decreased over time. Examiner under BRI submits that the determination of the change of the MVX value over time, thereby teaches “repeating step d” since he metabolic vulnerability index can provide short (1 year) to long (12 year) term premature death risk assessments, as disclosed in Para 0066); and
(f) evaluating the subject's relative risk for premature death based on at least the MVX value over time (See Para 0066…the metabolic vulnerability index can provide short (1 year) to long (12 year) term premature death risk assessments);
(g) determining that the subject's relative risk for premature death has increased over time (See Para 0083; See Fig. 3…a graph that shows the cumulative mortality rates over five years for 9 subgroups of high-risk cardiac catheterization patients enrolled in CATHGEN stratified by MVX score according to embodiments of the present disclosure…. As shown in FIG. 3, the higher the MVX score, the higher the risk was of dying prematurely. For example, individuals with a high MVX score>70 (red line) had a rate of premature death more than 10 times greater than those with a low MVX score<35 (dark green line); In addition, Examiner, under BRI, submits that Cumulative Mortality Incidence increases over the follow-up time of five years);
(h) recommending a lifestyle change to promote the subject's cardiac health (See Para 0018… The MVX1 value may, in certain embodiments, be used as a guide to lifestyle changes that promote cardiac health).
Otvos does not explicitly teach “in subject with metabolic malnutrition inflammation syndrome”.
In the analogous art of the malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink, Anand teaches “in subject with metabolic malnutrition inflammation syndrome” (See Abstract…The patients who undergo Maintenance Haemodialysis (MHD) have a high prevalence of Protein-Energy Malnutrition (PEM) and inflammation. Because these two conditions often occur concomitantly in the MHD patients, they have been referred to together as the Malnutrition-Inflammation Complex Syndrome (MICS) or Mal nutrition-inflammation atherosclerosis, to underscore the atherosclerotic complications of this entity; Under BRI, Examiner submits that Malnutrition-Inflammation Complex Syndrome (MICS) is interpreted as MMIS (Metabolic Malnutrition-Inflammation Syndrome, as Malnutrition-Inflammation Complex Syndrome (MICS) can be analogous for MMIS (Metabolic Malnutrition-Inflammation Syndrome).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Otvos to include “in subject with metabolic malnutrition inflammation syndrome”, as taught by Anand for the benefit of disclosing the that malnutrition, inflammation, and/or oxidative stress, which are together known as the ‘malnutrition–inflammation complex (or Ca-chexia) Syndrome’ (MICS), may be a much stronger predictor of the death risk in dialysis patients than the traditional cardiovascular risk factors (Anand, Conclusion, Page 766), allowing for the confirmation that that the periodontal health was poor in haemodialysis patients and that it correlated with the markers of malnutrition and inflammation [21]. The treatment of periodontal diseases reduces the chronic systemic inflammation in maintenance haemodialysis patients [22] by inducing a decline in the systemic inflammatory response (Anand, Conclusion, Page 766).
Regarding Claim 2, the method of claim 1 is obvious over Otvos in view of Anand.
Otvos teaches wherein the at least two biomarkers comprise two or more of GlycA, at least one of a high density lipoprotein particle (HDLP) subclass, citrate, and a branched chain amino acid (BCAA) (See Para 0077…measuring GlycA, at least one high density lipoprotein particle (HDLP) subclass, at least one branched chain amino acid (BCAA), and at least one ketone body (KetoneBody) and optionally at least one of citrate (Citrate) and serum protein (Protein); See Para 0079… As disclosed herein, the MVX model(s) can include at least two inflammatory markers, such as GlycA and S-HDLP and at least two metabolic malnutrition biomarkers, such as at least one ketone body and at least one BCAA).
Regarding Claim 3, the method of claim 2 is obvious over Otvos in view of Anand.
Otvos teaches wherein the HDLP subclass is small HDLP (S-HDLP) (See Para 0009, In an embodiment, the HDLP subclass is small HDL particles (S-HDLP).
Regarding Claim 4, the method of claim 2 is obvious over Otvos in view of Anand.
Otvos teaches wherein the BCAA is at least one of leucine, isoleucine, or valine (See Para 0065… In some embodiments, the BCAA may be at least one of leucine, isoleucine, or valine).
Regarding Claim 8, the method of claim 1 is obvious over Otvos in view of Anand.
Otvos teaches wherein the measurement of the at least one of each BCAA and citrate (See Para 0015… In other embodiments, the measurements of at least one BCAA, at least one ketone body, citrate, and protein are used to generate an alternate MMX value), are used to generate the sex-specific metabolic malnutrition index (MMX) value (See Para 0013… the MVX value is defined as comprising a…a metabolic malnutrition index (MMX) value; See Para 0031-0031 for the MVX score for female participants and the MVX score for male participants, thereby teaching “sex specific”)).
Regarding Claim 9, the method of claim 1 is obvious over Otvos in view of Anand.
Otvos teaches wherein the measurement of the at least one HDLP subclass and GlycA (See Para 0143…using the measurement of GlycA and the at least one HDLP subclass to generate an inflammation index (INFX) value) are used to generate the sex- specific inflammation vulnerability index (IVX) (See Para 0013… the MVX value is defined as comprising an inflammation index (INFX) value. Under BRI, IVX is viewed as INFX; See Para 0031-0031 for the MVX score for female participants and the MVX score for male participants)).
Regarding Claim 14, the method of claim 1 is obvious over Otvos in view of Anand.
Otvos teaches wherein the MVX value is sex-specific (See Para 0030-0031… FIG. 8 Left Panel is a graph that shows cumulative mortality rates over 12 years of follow-up in female participants in the MESA… FIG. 8 Right Panel is a graph that shows cumulative mortality rates over 12 years of follow-up in male participants in the MESA study) and is determined in a subject deemed to be at low-risk for a cardiovascular event (See Para 0088… In some embodiments, it is contemplated that MVX can be used to stratify mortality risk among low risk populations, as seen in FIG. 8. FIG. 8 Left Panel is a graph that shows cumulative mortality rates over twelve years of follow-up in female participants in the MESA study stratified by quintile of the low risk MVX score (e.g., MVX1) according to embodiments of the present disclosure.). The claimed limitation “or in a subject deemed to be at high- risk for a cardiovascular event” is viewed as optional and thus not required by the claim.
Regarding Claim 16, the method of claim 1 is obvious over Otvos in view of Anand.
Otvos teaches wherein the metabolic vulnerability index (MVX) can provide short (1 year) to long (12 year) term risk of premature death risk assessments (See Para 0056… The terms “mathematical model” and “model” are used interchangeably and when used with “MVX”, “metabolic vulnerability index”, or “risk”, refer to a statistical model of risk used to evaluate a subject's risk of premature mortality in the future, typically within 1-12 years; See Para 0066… The metabolic vulnerability index can provide short (1 year) to long (12 year) term premature death risk assessments), and wherein evaluating the subject over time comprises following up with the subject after 12 years, after 10 years (See Para 0030-0031… FIG. 8 Left Panel is a graph that shows cumulative mortality rates over 12 years of follow-up… FIG. 8 Right Panel is a graph that shows cumulative mortality rates over 12 years of follow-up, thereby teaching “after 10 years”). The claimed “after 12 years”; “and/or every 6 years, every 5 years, every 4 years, every 3 years, every 2 years, or every 1 years” is viewed as optional and thus not required by the Claim.
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Otvos et al. (US20190072572A1, submitted in IDS 11/07/2024 as US11156621B2) in view of Anand et al. ("The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink." Journal of clinical and Diagnostic Research: JCDR 7.4 (2013): 763.) as applied to claim 1 above.
Regarding Claim 6, the method of claim 1 is obvious over Otvos in view of Anand.
Otvos teaches wherein the MVX value is sex-specific for females (See Para 0080… The MVX mathematical models can consider other clinical parameters such as gender…; See Para 0091… In some embodiments, gender may be included as a factor in the MVX model; See Para 0031-0031 for the MVX score for female participants, thereby teaching “sex specific”).
While Otvos does not explicity teach that the MVX value is sex-specific for females is determined using the following model: MVXF = (IVXF * 2.27278) + (InMMXF * 12.13511) + (IVXF * InMMXF) * -1.09312.
Otvos teaches that the MVX value is sex-specific for females (See Para 0080… The MVX mathematical models can consider other clinical parameters such as gender…; See Para 0091… In some embodiments, gender may be included as a factor in the MVX model; See Para 0031-0031 for the MVX score for female participants, thereby teaching “sex specific”) is determined using the following model: MVXF = (IVXF * 2.27278) + (InMMXF * 12.13511) + (IVXF * InMMXF) * -1.09312. (See Para 0013… the MVX value is defined as comprising an inflammation index (INFX) value. Under BRI, IVX is viewed as INFX.
Further See Para 0017…Examiner submits that the metabolic vulnerability index may be generally described as: MVX=βi*INFX+βm*MMX.
For application to normal (i.e., low) risk patient populations (e.g., people who have not had a known CV event) the metabolic vulnerability index may be described as MVX1=βi*INFX+βm*MMX1 (wherein βi and βm may have unique values depending upon the model used). Conversely, for application to high-risk patient populations (e.g., people who have had a known CV event) the metabolic vulnerability index may be described as MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model used and MMX=β9*MMX1+β10*MMX2. In some cases βm is the same for both the low-risk and the high-risk models (see e.g., FIG. 16)).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used. For example, β1 in the first above formula for MVX (i.e., the formula that does not include the term β3*(lnGlycA*lnS-HDLP)), will generally be a different value than β1 in the second above formula (i.e., the equation that does include that product term), respectively (Para 0011).
Further, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
In the calculation of INFX, MMX, and MVX, in a Cox proportional hazards prediction model for mortality, the predictive strengths (χ2) and statistical significance (p value) of parameters and the actual coefficients used (e.g., for MMX1, 34=−1.10056 and 135=0.2373) may vary depending upon the populations used and/or the analysis performed (Para 0137, 0026). Further, the MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model (Para 0017, Figs 5-6).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used (Para 0011).
Thus, the numerical coefficients in the sex-specific MVX value are a result effective variables.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provide MVX value that is sex-specific for females to be determined using the following model: MVXF = (IVXF * 2.27278) + (InMMXF * 12.13511) + (IVXF * InMMXF) * -1.09312 for the benefit of providing a method of determining the levels of markers associated with a person's risk of premature death (Otvos, Para 0010) which allows for the provision of risk calculators comprised of factors that can better predict or assess a person's risk of premature death from any cause as opposed to the risk of suffering a non-fatal event (Otvos, Para 0007).
Regarding Claim 7, the method of claim 1 is obvious over Otvos in view of Anand.
Otvos teaches wherein the MVX value is sex-specific for males (See Para 0080… The MVX mathematical models can consider other clinical parameters such as gender…; See Para 0091… In some embodiments, gender may be included as a factor in the MVX model; See Para 0031-0031 for the MVX score for male participants, thereby teaching “sex specific”).
While Otvos does not explicity teach that the MVX value is sex-specific for males is determined using the following model: MVXM= (IVXM * 3.54601) + (InMMXM * 14.414.28) + (IVXF * InMMXM) * -1.43438. (IVXF is viewed as IVXM in light of the objection (Supra))
Otvos teaches that the MVX value is sex-specific for males (See Para 0080… The MVX mathematical models can consider other clinical parameters such as gender…; See Para 0091… In some embodiments, gender may be included as a factor in the MVX model; See Para 0031-0031 for the MVX score for male participants, thereby teaching “sex specific”) is determined using the following model: MVXM= (IVXM * 3.54601) + (InMMXM * 14.414.28) + (IVXF * InMMXM) * -1.43438. (IVXF is viewed as IVXM in light of the objection (Supra)) (See Para 0013… the MVX value is defined as comprising an inflammation index (INFX) value. Under BRI, IVX is viewed as INFX.
Further See Para 0017…Examiner submits that the metabolic vulnerability index may be generally described as: MVX=βi*INFX+βm*MMX.
For application to normal (i.e., low) risk patient populations (e.g., people who have not had a known CV event) the metabolic vulnerability index may be described as MVX1=βi*INFX+βm*MMX1 (wherein βi and βm may have unique values depending upon the model used). Conversely, for application to high-risk patient populations (e.g., people who have had a known CV event) the metabolic vulnerability index may be described as MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model used and MMX=β9*MMX1+β10*MMX2. In some cases βm is the same for both the low-risk and the high-risk models (see e.g., FIG. 16)).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used. For example, β1 in the first above formula for MVX (i.e., the formula that does not include the term β3*(lnGlycA*lnS-HDLP)), will generally be a different value than β1 in the second above formula (i.e., the equation that does include that product term), respectively (Para 0011).
Further, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
In the calculation of INFX, MMX, and MVX, in a Cox proportional hazards prediction model for mortality, the predictive strengths (χ2) and statistical significance (p value) of parameters and the actual coefficients used (e.g., for MMX1, 34=−1.10056 and 135=0.2373) may vary depending upon the populations used and/or the analysis performed (Para 0137, 0026). Further, the MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model (Para 0017, Figs 5-6).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used (Para 0011).
Thus, the numerical coefficients in the sex-specific MVX value are a result effective variables.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provide MVX value that is sex-specific for females to be determined using the following model: MVXM= (IVXM * 3.54601) + (InMMXM * 14.414.28) + (IVXF * InMMXM) * -1.43438 for the benefit of providing a method of determining the levels of markers associated with a person's risk of premature death (Otvos, Para 0010) which allows for the provision of risk calculators comprised of factors that can better predict or assess a person's risk of premature death from any cause as opposed to the risk of suffering a non-fatal event (Otvos, Para 0007).
Claims 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Otvos et al. (US20190072572A1, submitted in IDS 11/07/2024 as US11156621B2) in view of Anand et al. ("The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink." Journal of clinical and Diagnostic Research: JCDR 7.4 (2013): 763.) as applied to claim 8 above.
Regarding Claim 10, the method of claim 8 is obvious over Otvos in view of Anand.
Otvos teaches the sex-specific MMX value for females (See Para 0013… the MVX value is defined as comprising a…a metabolic malnutrition index (MMX) value; See Para 0031-0031 for the MVX score for female participants, thereby teaching “sex specific”))
While Otvos does not explicity teach that MMX is determined using the following model:
MMXF = ((4 + (Leu * -0.03142) + (Leu2* 0.0000893)) * 0.353) + ((7 + (Val * -0.03362) + (Val2* 0.0000689)) * 0.684) + (Ileu * 0.00332) + ((1 + (Citr * -0.0072) + (Citr2* 0.0000573)) * 0.7135).
Otvos teaches that MMXF (See Para 0013… the MVX value is defined as comprising a…a metabolic malnutrition index (MMX) value; See Para 0031-0031 for the MVX score for female participants, thereby teaching “sex specific”)) is determined using the following model:
MMXF = ((4 + (Leu * -0.03142) + (Leu2* 0.0000893)) * 0.353) + ((7 + (Val * -0.03362) + (Val2* 0.0000689)) * 0.684) + (Ileu * 0.00332) + ((1 + (Citr * -0.0072) + (Citr2* 0.0000573)) * 0.7135) (See Para 0013… the MVX value is defined as comprising a…a metabolic malnutrition index (MMX) value; See Para 0031-0031 for the MVX score for female participants, thereby teaching “sex specific”)).
Otvos further teaches MMX=β4*lnBCAA+β5*lnKetoneBody+β6*lnCitrate+β7*lnProtein. Or, the MMX value may be determined using the following model: MMX=β4*lnBCAA+β5*lnKetoneBody+β6*lnCitrate+β7*lnProtein+β8*(lnCitrate*lnProtein). In such embodiments, MMX may be described as follows: MMX=β9*MMX1+β10*MMX2, where MMX1 is as described above, and MMX2=β6*lnCitrate+β7*lnProtein+β8*(lnCitrate*lnProtein) (Para 0015).
Otvos teaches The MVX models may include one or more BCAAs including one or more of isoleucine, leucine, and valine (as discussed herein). In some embodiments, one or more of the set of three BCAAs (valine, leucine, and isoleucine) can be quantified by NMR (Para 0102).
For application to normal (i.e., low) risk patient populations (e.g., people who have not had a known CV event) the metabolic vulnerability index may be described as MVX1=βi*INFX+βm*MMX1 (wherein βi and βm may have unique values depending upon the model used). Conversely, for application to high-risk patient populations (e.g., people who have had a known CV event) the metabolic vulnerability index may be described as MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model used and MMX=β9*MMX1+β10*MMX2. In some cases βm is the same for both the low-risk and the high-risk models (see e.g., FIG. 16)).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used. For example, β1 in the first above formula for MVX (i.e., the formula that does not include the term β3*(lnGlycA*lnS-HDLP)), will generally be a different value than β1 in the second above formula (i.e., the equation that does include that product term), respectively (Para 0011).
Further, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
In the calculation of INFX, MMX, and MVX, in a Cox proportional hazards prediction model for mortality, the predictive strengths (χ2) and statistical significance (p value) of parameters and the actual coefficients used (e.g., for MMX1, 34=−1.10056 and 135=0.2373) may vary depending upon the populations used and/or the analysis performed (Para 0137, 0026). Further, the MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model (Para 0017, Figs 5-6).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used (Para 0011).
Thus, the numerical coefficients in the sex-specific MMX value are a result effective variables.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provide MMXF value that is sex-specific for females to be determined using the following model: MMXF = ((4 + (Leu * -0.03142) + (Leu2* 0.0000893)) * 0.353) + ((7 + (Val * -0.03362) + (Val2* 0.0000689)) * 0.684) + (Ileu * 0.00332) + ((1 + (Citr * -0.0072) + (Citr2* 0.0000573)) * 0.7135) for the benefit of providing a method of determining the levels of markers associated with a person's risk of premature death (Otvos, Para 0010) which allows for the provision of risk calculators comprised of factors that can better predict or assess a person's risk of premature death from any cause as opposed to the risk of suffering a non-fatal event (Otvos, Para 0007).
Regarding Claim 11, the method of claim 8 is obvious over Otvos in view of Anand.
Otvos teaches the sex-specific MMX value for males (See Para 0013… the MVX value is defined as comprising a…a metabolic malnutrition index (MMX) value; See Para 0031-0031 for the MVX score for male participants, thereby teaching “sex specific”))
While Otvos does not explicitly teach that MMX is determined using the following model:
MMXM = ((4 + (Leu * -0.01594) + (Leu2 * 0.0000291)) * 1.076) + ((7 + (Val * -0.0239) + (Val2 * 0.00005)) * 0.414) + (Ileu * 0.01265) + ((1 + (Citr * 0.00906) + (Citr2 * -0.0000126)) * 0.5881).
Otvos teaches that MMXM (See Para 0013… the MVX value is defined as comprising a…a metabolic malnutrition index (MMX) value; See Para 0031-0031 for the MVX score for male participants, thereby teaching “sex specific”)) is determined using the following model:
MMXM = ((4 + (Leu * -0.01594) + (Leu2 * 0.0000291)) * 1.076) + ((7 + (Val * -0.0239) + (Val2 * 0.00005)) * 0.414) + (Ileu * 0.01265) + ((1 + (Citr * 0.00906) + (Citr2 * -0.0000126)) * 0.5881). (See Para 0013… the MVX value is defined as comprising a…a metabolic malnutrition index (MMX) value; See Para 0031-0031 for the MVX score for male participants, thereby teaching “sex specific”)).
Otvos further teaches MMX=β4*lnBCAA+β5*lnKetoneBody+β6*lnCitrate+β7*lnProtein. Or, the MMX value may be determined using the following model: MMX=β4*lnBCAA+β5*lnKetoneBody+β6*lnCitrate+β7*lnProtein+β8*(lnCitrate*lnProtein). In such embodiments, MMX may be described as follows: MMX=β9*MMX1+β10*MMX2, where MMX1 is as described above, and MMX2=β6*lnCitrate+β7*lnProtein+β8*(lnCitrate*lnProtein) (Para 0015).
Otvos teaches The MVX models may include one or more BCAAs including one or more of isoleucine, leucine, and valine (as discussed herein). In some embodiments, one or more of the set of three BCAAs (valine, leucine, and isoleucine) can be quantified by NMR (Para 0102).
For application to normal (i.e., low) risk patient populations (e.g., people who have not had a known CV event) the metabolic vulnerability index may be described as MVX1=βi*INFX+βm*MMX1 (wherein βi and βm may have unique values depending upon the model used). Conversely, for application to high-risk patient populations (e.g., people who have had a known CV event) the metabolic vulnerability index may be described as MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model used and MMX=β9*MMX1+β10*MMX2. In some cases βm is the same for both the low-risk and the high-risk models (see e.g., FIG. 16)).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used. For example, β1 in the first above formula for MVX (i.e., the formula that does not include the term β3*(lnGlycA*lnS-HDLP)), will generally be a different value than β1 in the second above formula (i.e., the equation that does include that product term), respectively (Para 0011).
Further, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
In the calculation of INFX, MMX, and MVX, in a Cox proportional hazards prediction model for mortality, the predictive strengths (χ2) and statistical significance (p value) of parameters and the actual coefficients used (e.g., for MMX1, 34=−1.10056 and 135=0.2373) may vary depending upon the populations used and/or the analysis performed (Para 0137, 0026). Further, the MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model (Para 0017, Figs 5-6).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used (Para 0011).
Thus, the numerical coefficients in the sex-specific MMX value are a result effective variables.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provide MMXM value that is sex-specific for males to be determined using the following model: MMXM = ((4 + (Leu * -0.01594) + (Leu2 * 0.0000291)) * 1.076) + ((7 + (Val * -0.0239) + (Val2 * 0.00005)) * 0.414) + (Ileu * 0.01265) + ((1 + (Citr * 0.00906) + (Citr2 * -0.0000126)) * 0.5881) for the benefit of providing a method of determining the levels of markers associated with a person's risk of premature death (Otvos, Para 0010) which allows for the provision of risk calculators comprised of factors that can better predict or assess a person's risk of premature death from any cause as opposed to the risk of suffering a non-fatal event (Otvos, Para 0007).
Regarding Claim 12, the method of claim 9 is obvious over Otvos in view of Anand.
Otvos teaches wherein the sex-specific IVX value for females (See Para 0013… the MVX value is defined as comprising an inflammation index (INFX) value. Under BRI, IVX is viewed as INFX; See Para 0031-0031 for the MVX score for female participants)) is determined using the following model:
IVXF = 9 + (GlycA * -0.000187) + (S-HDLP * -0.3585) + ((GlycA * S-HDLP) * 0.000348).
While Otvos does not explicitly teach that IVXF is determined using the following model: IVXF = 9 + (GlycA * -0.000187) + (S-HDLP * -0.3585) + ((GlycA * S-HDLP) * 0.000348).
Otvos teaches that IVXF (See Para 0013… the MVX value is defined as comprising an inflammation index (INFX) value. Under BRI, IVX is viewed as INFX; See Para 0031-0031 for the MVX score for female participants)) is determined using the following model:
IVXF = 9 + (GlycA * -0.000187) + (S-HDLP * -0.3585) + ((GlycA * S-HDLP) * 0.000348).
Otvos teaches that an INFX value using the following model: INFX=β1*lnGlycA+β2*lnS-HDLP+β3*(lnGlycA*lnS-HDLP). (Para 0114). Further Otvos teaches that the INFX value is determined using the following model: INFX=β1*lnGlycA+β2*lnS-HDLP+β3*(lnGlycA*lnS-HDLP) (Para 0140). In addition, the INFX value is determined using the following model: INFX=β1*lnGlycA+β2*lnS-HDLP+β3*(lnGlycA*lnS-HDLP) (Para 0145).
For application to normal (i.e., low) risk patient populations (e.g., people who have not had a known CV event) the metabolic vulnerability index may be described as MVX1=βi*INFX+βm*MMX1 (wherein βi and βm may have unique values depending upon the model used). Conversely, for application to high-risk patient populations (e.g., people who have had a known CV event) the metabolic vulnerability index may be described as MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model used and MMX=β9*MMX1+β10*MMX2. In some cases βm is the same for both the low-risk and the high-risk models (see e.g., FIG. 16)).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used. For example, β1 in the first above formula for MVX (i.e., the formula that does not include the term β3*(lnGlycA*lnS-HDLP)), will generally be a different value than β1 in the second above formula (i.e., the equation that does include that product term), respectively (Para 0011).
Further, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
In the calculation of INFX, MMX, and MVX, in a Cox proportional hazards prediction model for mortality, the predictive strengths (χ2) and statistical significance (p value) of parameters and the actual coefficients used (e.g., for MMX1, 34=−1.10056 and 135=0.2373) may vary depending upon the populations used and/or the analysis performed (Para 0137, 0026). Further, the MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model (Para 0017, Figs 5-6).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used (Para 0011).
Thus, the numerical coefficients in the sex-specific IVX (viewed as INFX) value are a result effective variables.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provide IVXF value that is sex-specific for females to be determined using the following model: IVXF = 9 + (GlycA * -0.000187) + (S-HDLP * -0.3585) + ((GlycA * S-HDLP) * 0.000348) for the benefit of providing a method of determining the levels of markers associated with a person's risk of premature death (Otvos, Para 0010) which allows for the provision of risk calculators comprised of factors that can better predict or assess a person's risk of premature death from any cause as opposed to the risk of suffering a non-fatal event (Otvos, Para 0007).
Regarding Claim 13, the method of claim 9 is obvious over Otvos in view of Anand.
Otvos teaches wherein the sex-specific IVX value for males (See Para 0013… the MVX value is defined as comprising an inflammation index (INFX) value. Under BRI, IVX is viewed as INFX; See Para 0031-0031 for the MVX score for male participants)) is determined using the following model:
IVXM = 9 + (GlycA * -0.00437) + (S-HDLP * -0.52307) + ((GlycA * S- HDLP) * 0.000817).
While Otvos does not explicitly teach that IVXM is determined using the following model: IVXM = 9 + (GlycA * -0.00437) + (S-HDLP * -0.52307) + ((GlycA * S- HDLP) * 0.000817).
Otvos teaches that IVXM (See Para 0013… the MVX value is defined as comprising an inflammation index (INFX) value. Under BRI, IVX is viewed as INFX; See Para 0031-0031 for the MVX score for male participants)) is determined using the following model:
IVXM = 9 + (GlycA * -0.00437) + (S-HDLP * -0.52307) + ((GlycA * S- HDLP) * 0.000817).
Otvos teaches that an INFX value using the following model: INFX=β1*lnGlycA+β2*lnS-HDLP+β3*(lnGlycA*lnS-HDLP). (Para 0114). Further Otvos teaches that the INFX value is determined using the following model: INFX=β1*lnGlycA+β2*lnS-HDLP+β3*(lnGlycA*lnS-HDLP) (Para 0140). In addition, the INFX value is determined using the following model: INFX=β1*lnGlycA+β2*lnS-HDLP+β3*(lnGlycA*lnS-HDLP) (Para 0145).
For application to normal (i.e., low) risk patient populations (e.g., people who have not had a known CV event) the metabolic vulnerability index may be described as MVX1=βi*INFX+βm*MMX1 (wherein βi and βm may have unique values depending upon the model used). Conversely, for application to high-risk patient populations (e.g., people who have had a known CV event) the metabolic vulnerability index may be described as MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model used and MMX=β9*MMX1+β10*MMX2. In some cases βm is the same for both the low-risk and the high-risk models (see e.g., FIG. 16)).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used. For example, β1 in the first above formula for MVX (i.e., the formula that does not include the term β3*(lnGlycA*lnS-HDLP)), will generally be a different value than β1 in the second above formula (i.e., the equation that does include that product term), respectively (Para 0011).
Further, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
In the calculation of INFX, MMX, and MVX, in a Cox proportional hazards prediction model for mortality, the predictive strengths (χ2) and statistical significance (p value) of parameters and the actual coefficients used (e.g., for MMX1, 34=−1.10056 and 135=0.2373) may vary depending upon the populations used and/or the analysis performed (Para 0137, 0026). Further, the MVX=βi*INFX+βm*MMX wherein βi and βm may have unique values depending upon the model (Para 0017, Figs 5-6).
Also, Otvos teaches that it is noted that throughout this disclosure, the empirical values for A and β1-βn may vary depending upon the model used (Para 0011).
Thus, the numerical coefficients in the sex-specific IVX (viewed as INFX) value are a result effective variables.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have provide IVXM value that is sex-specific for males to be determined using the following model: IVXM = 9 + (GlycA * -0.00437) + (S-HDLP * -0.52307) + ((GlycA * S- HDLP) * 0.000817) for the benefit of providing a method of determining the levels of markers associated with a person's risk of premature death (Otvos, Para 0010) which allows for the provision of risk calculators comprised of factors that can better predict or assess a person's risk of premature death from any cause as opposed to the risk of suffering a non-fatal event (Otvos, Para 0007).
Response to Arguments
Applicant’s arguments, see Page 7, filed 07/20/2026, with respect to the objections of the Drawings have been considered and persuasive.
Applicant submits that the submitted replacement sheets for Figures 1-22 are of sufficient resolution and requests that the objection be withdrawn.
Examiner submits that Applicants’ argument is persuasive and the objection is withdrawn.
Applicant’s arguments, see Page 7, filed 07/20/2026, with respect to the claim objections of Claims 7-9 and 10 have been considered and persuasive.
Applicant submits that Claim 7 is objected to for reciting the limitation "IVXF" in line 3, which the Examiner suggests should be "IVXM." Applicant thanks the Examiner for their suggestion and has amended the claim accordingly.
Claims 8 and 9 are objected to for reciting "the measurement," which the Examiner suggests should be "a measurement." Applicant thanks the Examiner for their suggestion and has amended the claim accordingly.
Claim 11 is objected to for reciting the limitation "fff' in lines 2-3, which the Examiner suggests is a likely typographical error. Applicant thanks the Examiner for their suggestion and has amended the claim to remove the "fff" limitation.
In view of the above, Applicant respectfully requests the objections to the claims be withdrawn.
Examiner submits that Applicants’ argument is persuasive and the Claims 7-9 and 10 objections are withdrawn.
Applicant’s arguments, see Page 7, filed 07/20/2026, with respect to the 35 U.S.C. §101 rejections on claims 1-4, 6-14 and 16 (Claims 5 and 15 are cancelled) have been fully considered and are not persuasive.
Applicant submits that amended claim 1 integrates any alleged judicial exception into a practical application, as the claim is directed to a method of treating a subject with an increased risk of premature death, reciting the steps of "determining that the subject's relative risk for premature death has increased over time" and treating the patient by "recommending a lifestyle change to promote the subject's cardiac health."
Applicant thus respectfully requests that the rejection under 35 U.S.C. § 101 be withdrawn.
Applicant’s arguments with respect to amended claim 1-4, 6-14 and 16 (Claims 5 and 15 are cancelled) has been considered and Examiner respectfully disagrees.
Examiner assertively identifies the judicial exception (abstract idea) in amended Claim 1 as “(c) generating a sex-specific metabolic vulnerability index (MVX) value from the at least two simultaneously measured biomarkers, wherein the MVX value is sex-specific and comprises a sex-specific inflammation vulnerability index (IVX) and a sex-specific metabolic malnutrition index (MMX); (d) determining the subject's relative risk for premature death based on at least the MVX value; (e) repeating steps (a)-(d) at a later time point; and (f) evaluating the subject's relative risk for premature death and the MVX value over time; (g) determining that the subject's relative risk for premature death has increased over time; and (h) recommending a lifestyle change to promote the subject's cardiac health” as a mental step (Step 2A Prong One) and found that the additional elements “(a) obtaining a sample of blood, serum, or plasma from the subject; and (b) measuring the Nuclear Magnetic Resonance (NMR) spectra of at least two biomarkers simultaneously from the sample” do not integrate the exception into a practical application (Step 2A Prong Two), as these additional elements appear to be insignificant post solution activities as they amount to just “data gathering” or “applying it” – both held as not practical applications (MPEP 2106.05f, MPEP 2106.05g).
Further these additional elements do not amount to significantly more than the exception (Step 2B) because they are well-understood, routine and conventional activities in the field of clinical diagnostics (See 101 rejection Supra). These elements are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity: See MPEP 2106.05(d), previously known in the field of clinical diagnostics as evidenced by Otvos et al. (US20190072572A1, submitted in IDS 11/07/2024 as US11156621B2) in view of Anand et al. ("The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink." Journal of clinical and Diagnostic Research: JCDR 7.4 (2013): 763.).
As a result, Examiner submits that the claims do not amount to significantly more that the judicial exception. The 101 rejection is maintained.
Applicant’s arguments, see Page 8, filed 07/20/2026, with respect to the rejection(s) of claim(s) 1-5, 8-9 and 14-16 under 35 U.S.C. §102(a)(1) 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 for Claim 1 by Otvos et al. (US20190072572A1, submitted in IDS 11/07/2024 as US11156621B2) in view of Anand et al. ("The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink." Journal of clinical and Diagnostic Research: JCDR 7.4 (2013): 763.).
Applicant has amended claim 1 to incorporate the features of claims 5 and 15 and recites in part "generating a sex-specific metabolic vulnerability index (MVX) value from the at least two simultaneously measured biomarkers, wherein the MVX value is sex-specific and comprises a sex-specific inflammation vulnerability index (IVX) and a sex-specific metabolic malnutrition index (MMX)."
Applicant respectfully submits that Otvos provides no disclosure, teaching, or motivation to a person of skill in the art to develop or apply sex-specific models for assessing metabolic malnutrition or inflammation vulnerability. While Otvos uses MVX to analyze mortality risk in cohorts of women (FIG. 8, left panel) and men (FIG. 8, right panel) in the multi-Ethnic Study of Atherosclerosis (MESA) and mentions that an MVX model could consider a clinical parameter such as gender (para. [0080]), Otvos fails to recognize the significance of sex differences in the context of metabolic malnutrition inflammation syndrome, nor does it provide any guidance as to how such differences might be incorporated into a sex-specific predictive model comprising a sex-specific inflammation vulnerability index (IVX) and a sex-specific metabolic malnutrition index (MMX). The present application addresses this technical gap by providing novel, sex- specific models that improve the accuracy and clinical utility of metabolic malnutrition inflammation syndrome assessment. The development of the claimed models required not only the identification and measurement of the relevant biomarkers but also the derivation and validation of the specific mathematical relationships that underpin the claimed indices, which are not disclosed or suggested by Otvos.
Thus, Applicant respectfully submits that amended claim 1 and its dependent claims are novel over Otvos and requests that the rejection under 35 USC § 102 be withdrawn. Furthermore, Applicant submits that, for at least the reasons set forth above, amended claim 1 and its dependent claims 1-4, 8-9, 14, and 16 are not obvious over Otvos.
Applicant’s arguments with respect to amended claim 1 has been considered and Examiner respectfully disagrees.
Examiner submits that the limitations of amended Claim 1 is taught as disclosed in the rejection of Claim 1 (Supra) by Otvos et al. (US20190072572A1, submitted in IDS 11/07/2024 as US11156621B2) in view of Anand et al. ("The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink." Journal of clinical and Diagnostic Research: JCDR 7.4 (2013): 763.).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., "significance of sex differences in the context of metabolic malnutrition inflammation syndrome, nor does it provide any guidance as to how such differences might be incorporated into a sex-specific predictive model comprising a sex-specific inflammation vulnerability index (IVX) and a sex-specific metabolic malnutrition index (MMX)") are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Examiner submits that Otvos discloses that the MVX scores can stratify premature death risk for patients having the same age, gender, blood pressure, and BMI independently of these clinical factors [Para 0075] and that the the MVX value is defined as comprising a…a metabolic malnutrition index (MMX) value [Para 0013].
Further, Examiner notes that Otvos discloses the MVX score for female participants and the MVX score for male participants, thereby teaching “sex specific”).
Applicant’s arguments, see Page 8, filed 07/20/2026, with respect to the rejection(s) of claim(s) 1-5, 8-9 and 14-16 under 35 U.S.C. §102(a)(1) 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 for Claim 1 by Otvos et al. (US20190072572A1, submitted in IDS 11/07/2024 as US11156621B2) in view of Anand et al. ("The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink." Journal of clinical and Diagnostic Research: JCDR 7.4 (2013): 763.).
Applicant’s arguments, see Page 9, filed 07/20/2026, with respect to the rejection(s) of claim(s) 6-7 and 11-13 under 35 U.S.C. §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 for Claims 6-7 and 11-13 in view of amended Claim 1 by Otvos et al. (US20190072572A1, submitted in IDS 11/07/2024 as US11156621B2) in view of Anand et al. ("The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink." Journal of clinical and Diagnostic Research: JCDR 7.4 (2013): 763.).
Applicant submits that claims 6-7 and 11-13 are inventive over Otvos and requests their rejection under 35 USC § 103 be withdrawn.
Applicant’s arguments with respect to claims 6-7 and 11-13 in view of amended claim 1 has been considered and Examiner respectfully disagrees.
Examiner submits that the limitations of claims 6-7 and 11-13 in view of amended Claim 1 is taught as disclosed in the rejection of claims 6-7 and 11-13 (Supra) by Otvos et al. (US20190072572A1, submitted in IDS 11/07/2024 as US11156621B2) in view of Anand et al. ("The malnutrition inflammation complex syndrome-the micsing factor in the perio-chronic kidney disease interlink." Journal of clinical and Diagnostic Research: JCDR 7.4 (2013): 763.).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OYELEYE ALEXANDER ALABI whose telephone number is (571)272-1678. The examiner can normally be reached on M-F 7:30am-5:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached on (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797
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