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. 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 appl icant regards as his invention. Claims 1-11 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. Regarding claim 1, the claim recites at “high altitudes”. The term “ high altitude ” in claim 1 is a relative term which renders the claim indefinite. The term “ high altitude ” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification provides an example in which t he subject is exposed to a n altitude that is greater than 4900 ft (1500 m ) above sea level . However, above 4900 ft (1500 m) in the embodiment is an example rather than a definition of “high altitude”. Claims 2-11 are also rejected for failing to cure the deficiency. 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 s 1-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to law of nature and abstract idea without significantly more. Regarding claim 1, the claim(s) recite(s) a “method of predicting AMS ”; the method comprises the step of analyzing for a quantity of at least one biomarker /metabolite compound ( creatine, taurine, N- methylhistidine , hypoxanthine…3-methylhistidine ) in an urine sample and compar ing the quantity to a threshold. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a law of nature in the form of a natural correlation. The claim recites detecting illness by measuring the amount of concentration of the biomarker compound in a biological sample. The amounts of biomarkers in the sample naturally correlated with diagnostic of altitude sickness . If a claim limitation, under its broadest reasonable interpretation, covers a natural correlation, then it falls within the law of nature grouping of natural phenomena. Accordingly, the claim recites a law of nature (Step 2A, Prong 1). This judicial exception is not integrated into a practical application. In particular, the claim recites “ analyzing the urine sample for a quantity of at least one metabolite ” and comparing the quantity to a threshold to detect/diagnose AMS , which constitutes a natural correlation under broadest reasonable interpretation. There is no integration of the measurement step much less a practical one since after the measurement, a generic and broadly recited diagnostic step is introduced. However, the diagnostic step does not impose any meaningful limit since the limitation is directed toward determining whether or not the subject is “susceptible” (In other word, likely) to experience AMS, and there is no particular threshold value (or how the threshold value is being determined). As such, the measuring of the biomarkers is mere natural correlation that is not significantly more than law of nature. See MPEP 2106.05(g). Accordingly, this additional element does not integrate the natural correlation into a practical application because it does not impose any meaningful limits on practicing the abstract idea. The claim is directed to a judicial exception (Step 2A, Prong 2). In addition, the claim also recites based on the comparison, determining whether the subject is susceptible to experience AMS at high altitudes. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers an abstract idea in the form of a mental process. The claim recites comparing the amount of concentration of a biomarker in a biological sample in a subject to a generically recited “threshold value” . Making decision whether or not the difference of the comparison, under broadest reasonable interpretation, is a mental process that can be performed in the human mind. Nothing in the claim precludes the user from manually comparing the data of a subject to an arbitrary preset threshold and deciding what would be constitute as “suggesting” the subject is “likely” to experience AMS . If a claim limitation, under its broadest reasonable interpretation, covers a mental process, then it falls within the mental process grouping. Accordingly, the claim recites an abstract idea (Step 2A, Prong 1). This judicial exception is not integrated into a practical application. In particular, the claim recites suggesting that the subject is likely to experience AMS if the quantity of the biomarker exceeds or falls below the threshold , which constitutes a mental process under broadest reasonable interpretation. There is no integration of the diagnostic step much less a practical one since after the determination of susceptibility is completed, nothing practical is being done afterward. Accordingly, this additional element does not integrate the mental process into a practical application because it does not impose any meaningful limits on practicing the abstract idea. The claim is directed to a judicial exception (Step 2A, Prong 2). The claim does not include additional elements that are sufficient to amount to significant more than the judicial exception. With respect to integration of the abstract idea into a practical application, the rest of the limitation, obtaining the sample and analyzing the samples for metabolites are conventional ways of data gathering. Routine and conventional data gathering cannot provide an inventive concept. The claim is not patent eligible. Claims 2-4 do not cure the deficiency of claim 1. The claims merely recite indicating susceptibility when the quantity of certain metabolites either exceeds or falls below the threshold value. As discussed above, the indication of susceptibility is, at best, an abstract idea that has not been practically integrated. Claim s 5- 8 do not cure the deficiency of claim 1. Claim 5 and 8 merely recite how the sample is being analyzed by a broad and generically recited method such as “metabolomic analysis, targeted quantitation, or semi-quantitative method” or “lab method or a point-of-care method” . Furthermore, claim s 6 and 7 further narrow the scope of claim 5 to analytical method such as NMR, LC/MS, HPLC/MS, GC/MS, ELISA, or LFA , with claim 7 focuses specifically on ELISA. However, analyzing urine samples for metabolites using these methods are generally well-known and conventional. Claim s 9 and 10 do not cure the deficiency of claim 1. The claim merely recites where the sample is being collected Claim 11 does not cure the deficiency of claim 1. The claim recites urine sample being normalized and standardized using creatine, which is a well-known and conventional standardization step when analyzing urine sample. For similar reason, claim 12 recite(s) a “method of evaluating acclimatization after exposure to high altitude and associated AMS ”; the method comprises the step of analyzing for a quantity of at least one biomarker /metabolite compound ( creatine, taurine, N- methylhistidine , hypoxanthine…3-methylhistidine ) in an urine sample and compar ing the quantity to a threshold. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a law of nature in the form of a natural correlation. The claim recites detecting illness by measuring the amount of concentration of the biomarker compound in a biological sample. The amounts of biomarkers in the sample naturally correlated with diagnostic of altitude sickness . If a claim limitation, under its broadest reasonable interpretation, covers a natural correlation, then it falls within the law of nature grouping of natural phenomena. Accordingly, the claim recites a law of nature (Step 2A, Prong 1). This judicial exception is not integrated into a practical application. In particular, the claim recites “ analyzing the urine sample for a quantity of at least one metabolite ” and comparing the quantity to a threshold to detect/diagnose AMS , which constitutes a natural correlation under broadest reasonable interpretation. There is no integration of the measurement step much less a practical one since after the measurement, a generic and broadly recited diagnostic step is introduced. However, the diagnostic step does not impose any meaningful limit since the limitation is directed toward determining whether or not the subject has acclimatized to the new altitude, and there is no particular threshold value (or how the threshold value is being determined). As such, the measuring of the biomarkers is mere natural correlation that is not significantly more than law of nature. See MPEP 2106.05(g). Accordingly, this additional element does not integrate the natural correlation into a practical application because it does not impose any meaningful limits on practicing the abstract idea. The claim is directed to a judicial exception (Step 2A, Prong 2). In addition, the claim also recites based on the comparison, determining whether the subject has acclimatized at high altitudes. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers an abstract idea in the form of a mental process. The claim recites comparing the amount of concentration of a biomarker in a biological sample in a subject at one altitude to a generically recited “threshold value” or a quantity of biomarkers collected from sample at a lower altitude . Making decision whether or not the difference of the comparison, under broadest reasonable interpretation, is a mental process that can be performed in the human mind. Nothing in the claim precludes the user from manually comparing the data of a subject to an arbitrary preset threshold and deciding what would be constitute as “suggesting” the subject has acclimatized . If a claim limitation, under its broadest reasonable interpretation, covers a mental process, then it falls within the mental process grouping. Accordingly, the claim recites an abstract idea (Step 2A, Prong 1). This judicial exception is not integrated into a practical application. In particular, the claim recites suggesting that the subject has acclimatized if the quantity of the biomarker exceeds or falls below the threshold or another quantity at a lower altitude , which constitutes a mental process under broadest reasonable interpretation. There is no integration of the diagnostic step much less a practical one since after the determination is completed, nothing practical is being done with the information afterward. Accordingly, this additional element does not integrate the mental process into a practical application because it does not impose any meaningful limits on practicing the abstract idea. The claim is directed to a judicial exception (Step 2A, Prong 2). The claim does not include additional elements that are sufficient to amount to significant more than the judicial exception. With respect to integration of the abstract idea into a practical application, the rest of the limitation, obtaining the sample at different location and analyzing the samples for metabolites are conventional ways of data gathering. Routine and conventional data gathering cannot provide an inventive concept. The claim is not patent eligible. Claim s 13-15 do not cure the deficiency of claim 1 2 . Claim 13 merely recite s how the sample is being analyzed by a broad and generically recited method such as “metabolomic analysis, targeted quantitation, or semi-quantitative method” . Furthermore, claims 14 and 15 further narrow the scope of claim 5 to analytical method such as NMR, LC/MS, HPLC/MS, GC/MS, ELISA, or LFA, with claim 15 focuses specifically on ELISA. However, analyzing urine samples for metabolites using these methods are generally well-known and conventional. Claim 1 6 does not cure the deficiency of claim 1 2 . The claim recites urine sample being normalized and standardized using creatine, which is a well-known and conventional standardization step when analyzing urine sample. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness . 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. Claim(s) 1 , 2 , and 5-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liao (Metabolite Modulation in Human Plasma in the Early Phase of Acclimatization to Hypobaric Hypoxia, 2016) in view of Wijemanne (Development and Validation of a Simple High Performance Liquid Chromatography/UV Method for Simultaneous Determination of Urinary Uric Acid, Hypoxanthine, and Creatinine in Human Urine, 2018) and Julian (Acute mountain sickness, inflammation, and permeability: new insights from a blood biomarker study, 2011) . Regarding claim s 1 and 2 , Liao discloses a method of predicting AMS, the method comprising: collecting plasma sample from a subject ( Fasting venous blood (with EDTA as an anticoagulant) was obtained from all subjects ; Experimental Procedures, para. 3); analyzing the sample for a quantity of at least one metabolite selected from the group consisting hypoxanthine (ESI + , Table 3); comparing the quantity to a respective threshold value (Ratio of High Altitude vs Plain, Table 3; plain as the threshold). Liao does not disclose urine samples are being collected and analyzed and a step of determining whether the subject is susceptible to experience AMS at high altitudes. Regarding the limitation of collecting urine and analyzing urinary hypoxanthine , Wijemanne discloses laboratory technique of analyzing for urinary hypoxanthine using chromatographic techniques (Abstract), thus confirming the presence of hypoxanthine in urine. Regarding the limitation of indicating susceptibility based on a threshold, Julian hypothesized and confirmed that individuals who remained healthy with hypobaric hypoxia exposure would have lower levels of proinflammatory, angiogenic, or chemotactic mediators and higher levels of anti-permeability or anti-inflammatory biomarkers compared with individuals who developed AMS (right col., para. 3, page 393) since the presence of “adequate” amount of anti-permeability or anti-inflammatory biomarkers may be an indication of a person’s susceptibility to hypoxic exposure ( In summary, our findings support the possibility that resistance to AMS may involve the ability to mount an adequate “defensive” anti-inflammatory or anti-permeability response during hypoxic exposure. We consider it likely that such effects may have prevented downstream pathophysiological events leading to AMS. Right col., page 398, para. 1). As hypoxanthine is an anti-inflammatory marker known for its potent anti-inflammatory effects, it would have been obvious to one of ordinary skill in the art before the effective filing date to have developed an alternative embodiment of analyzing hypoxanthine in the method of Liao with urine as disclosed by method of Wijemanne instead of blood sample with a reasonable expectation of success as both methods involves chromatographic analysis for hypoxanthine. Furthermore, one would have been motivated to make such substitution as it may be potentially less labor intensive in collecting urine sample compare to blood sample as urine sample simply requires excretion; collecting blood sample, on the other hand, requires withdrawing samples by needle and storing the sample with anticoagulant ( Liao , Experimental Procedures, para. 3). Furthermore, it would have been obvious to one of ordinary skill in the art to further testing fluid sample of both the AMS resistant and susceptible individuals to develop a threshold based on testing from resistant individuals with the expectation that a susceptible person would have a hypoxanthine level below the level of resistant individuals based on the disclosure of Julian ( our findings support the possibility that resistance to AMS may involve the ability to mount an adequate “defensive” anti-inflammatory or anti-permeability response during hypoxic exposure . Right col., page 398, para. 1) as lack of adequate anti-inflammatory markers presence is indicative of one’s readiness for high altitude sickness. Regarding claim 5, Modified Liao discloses the claimed invention as discussed above in claim 1. Liao discloses analyzing the sample includes a metabolomic analysis ( This is the first metabolomic study to determine plasma biochemical alterations of healthy individuals after four days at high altitude (5300 m) by using combined LC-MS and GC-MS . Conclusions). Regarding claim 6, Modified Liao discloses the claimed invention as discussed above in claim 5. Liao discloses the metabolomic analysis is selected from LC-MS or GC-MS ( This is the first metabolomic study to determine plasma biochemical alterations of healthy individuals after four days at high altitude (5300 m) by using combined LC-MS and GC-MS . Conclusions). Regarding claim 7, Modified Liao discloses the claimed invention as discussed above in claim 6. Liao discloses, in addition to GC/MS and LC-MS, an additional quantitation by capture element in ELISA is performed wherein the ELISA method includes evaluation of a peptide ( To validate the metabolic changes, the levels of key enzymes in these metabolic pathways were determined by ELISA . The Levels of Key Enzymes Involved in the Pathways of Altered Metabolites). Regarding claim 8, Modified Liao discloses the claimed invention as discussed above in claim 1. Liao discloses analyzing the urine samples includes a lab method (GC/MS or LC/MS). Regarding claim 9, Modified Liao discloses the claimed invention as discussed above in claim 1. Liao does not disclose the urine is collected at sea level. However, Liao discloses sample is collected at two altitudes, 1400m and 5300m. Therefore, it would have been obvious design choice to one of ordinary skill in the art to have chosen a different altitude than the one disclosed by Liao such as at sea level to derive the claimed invention, so long a second higher altitude is chosen for testing for AMS susceptibility. Regarding claim 10, Modified Liao discloses the claimed invention as discussed above in claim 1. Liao discloses the sample is collected at an altitude of 1400 m (Experimental Procedures, para. 1) . Regarding claim 11, Modified Liao discloses the claimed invention as discussed above in claim 1. Wijemanne, after incorporation with Liao, discloses normalization of the collected urine sample using creatine to standardize against urine sample volume ( The method can be employed for the analysis of purine metabolism defects using human urine samples with normalization with creatinine . 20. Conclusion). Claim(s) 1 and 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liao in view of Magiera (Determination of carnitine and acylcarnitines in human urine by means of microextraction in packed sorbent and hydrophilic interaction chromatography–ultra-high-performance liquid chromatography–tandem mass spectrometry, 201 5 ) and Horscroft (Metabolic basis to Sherpa altitude adaptation, 2017). Regarding claims 1 and 3 , Liao discloses a method of predicting AMS, the method comprising: collecting plasma sample from a subject ( Fasting venous blood (with EDTA as an anticoagulant) was obtained from all subjects ; Experimental Procedures, para. 3); analyzing the sample for a quantity of at least one metabolite selected from the group consisting acetylcarnitine (ESI + , Table 3); comparing the quantity to a respective threshold value (Ratio of High Altitude vs Plain, Table 3; plain as the threshold). Liao does not disclose urine samples are being collected and analyzed and a step of determining whether the subject is susceptible to experience AMS at high altitudes when the quantity of the acetylcarnitine is above the respective threshold value. Regarding the limitation of collecting urine and analyzing urinary acetylcarnitine , Magiera present s a laboratory method for analyzing urinary acetylcarnitine in the sample using chromatographic techniques (Abstract), thus confirming the presence of acetylcarnitine in urine. Regarding the limitation of indicating susceptibility based on a threshold, Horscroft discloses a study of Sherpa’s carnitine concentration compared to that of lowlander. Horscroft found that Sherpas, due to genetic difference and metabolic adaptations, allows their tissues to use oxygen more efficiently (Abstract) after analyzing carnitines present in the sample ( Half of the organic fraction and half of the aqueous fraction were combined with 200 μL of acetonitrile containing an internal standard mix of eight deuterated carnitines [1.63 μM (d9) free carnitine, 0.3 μM (d3) acetyl carnitine … ; Mass Spectrometry, para. 4]. Horscroft findings concludes lowlanders generally have higher carnitine present in their samples than Sherpas at baseline (35 m above sea level) (Fig. 2C-F). it would have been obvious to one of ordinary skill in the art before the effective filing date to have developed an alternative embodiment of analyzing acetylcarnitine in the method of Liao with urine as disclosed by Magiera instead of blood sample with a reasonable expectation of success as both methods involves chromatographic analysis for acetylcarnitine . Furthermore, one would have been motivated to make such substitution as it may be potentially less labor intensive in collecting urine sample compare to blood sample as urine sample simply requires excretion; collecting blood sample, on the other hand, requires withdrawing samples by needle and storing the sample with anticoagulant ( Liao , Experimental Procedures, para. 3). Furthermore, it would have been obvious to one of ordinary skill in the art to further testing fluid sample of both the AMS resistant and susceptible individuals to develop a threshold based on testing from resistant individuals with the expectation that a susceptible person would have a acetylcarnitine level above the level of resistant individuals based on the disclosure of Horscroft as lower level carnitine is indicative of oxygen utilization efficiency ( Horscroft , Abstract) . Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liao in view of Wijemanne and Julian as discussed above in claim 1, and further in view of Magiera and Horscroft . Regarding claim 4, Modified Liao discloses the claimed invention as discussed above in claim 1. Liao discloses the method is capable of analyzing the sample for a quantity of acetylcarnitine in addition of hypoxanthine (ESI + , Table 3). Neither Liao nor Wijemanne disclose s urine samples are being collected for analyzing acetylcarnitine and a step of determining whether the subject is susceptible to experience AMS at high altitudes when the quantity of the acetylcarnitine is above the respective threshold value. Regarding the limitation of collecting urine and analyzing urinary acetylcarnitine , Magiera presents a laboratory method for analyzing urinary acetylcarnitine in the sample using chromatographic techniques (Abstract), thus confirming the presence of acetylcarnitine in urine. Regarding the limitation of indicating susceptibility based on a threshold, Horscroft discloses a study of Sherpa’s carnitine concentration compared to that of lowlander. Horscroft found that Sherpas, due to genetic difference and metabolic adaptations, allows their tissues to use oxygen more efficiently (Abstract) after analyzing carnitines present in the sample ( Half of the organic fraction and half of the aqueous fraction were combined with 200 μL of acetonitrile containing an internal standard mix of eight deuterated carnitines [1.63 μM (d9) free carnitine, 0.3 μM (d3) acetyl carnitine … ; Mass Spectrometry, para. 4]. Horscroft findings concludes lowlanders generally have higher carnitine present in their samples than Sherpas at baseline (35 m above sea level) (Fig. 2C-F). it would have been obvious to one of ordinary skill in the art before the effective filing date to have developed an alternative embodiment of analyzing acetylcarnitine in the method of Modified Liao with urine as disclosed by Magiera instead of blood sample with a reasonable expectation of success as both methods involves chromatographic analysis for acetylcarnitine . Furthermore, one would have been motivated to make such substitution as it may be potentially less labor intensive in collecting urine sample compare to blood sample as urine sample simply requires excretion; collecting blood sample, on the other hand, requires withdrawing samples by needle and storing the sample with anticoagulant ( Liao , Experimental Procedures, para. 3). Furthermore, it would have been obvious to one of ordinary skill in the art to further testing fluid sample of both the AMS resistant and susceptible individuals to develop a threshold based on testing from resistant individuals with the expectation that a susceptible person would have a acetylcarnitine level above the level of resistant individuals based on the disclosure of Horscroft as lower level carnitine is indicative of oxygen utilization efficiency ( Horscroft , Abstract). Claim(s) 12 -16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liao in view of Wijemann e. Regarding claim 12, Liao discloses a method of predicting AMS, the method comprising: Collecting a first plasma sample from a subject ( Fasting venous blood (with EDTA as an anticoagulant) was obtained from all subjects ; Experimental Procedures, para. 3) at a first altitude not more than 1500 m above sea level (1400 m); Exposing and collecting a second plasma sample from a subject at a second altitude greater than 1500 m above sea level (5300 m); analyzing the first and second sample for first and second quantity of at least one metabolite selected from the group consisting hypoxanthine and acetylcarnitine (ESI + , Table 3); comparing the second quantity (High Altitude) to the first quantity (Plain) (Ratio of High Altitude vs Plain, Table 3) ; based on the comparison, determining whether the subject has acclimatized to the second altitude ( We have identified 50 significantly changed metabolites and predicted the major metabolites network by pattern recognition and pathway analysis….Identified differential metabolites and related pathways provide new insights for further understanding the pathophysiological mechanism of early acclimatization to hypobaric hypoxia and treatment of AMS-S individuals. Blocking or modifying these points of convergence are attractive approaches to promoting acclimatization to hypobaric hypoxia and the treatment of AMS-S individuals. Conclusions). Liao does not disclose urine samples are being collected and analyzed. Regarding the limitation of collecting urine and analyzing urinary hypoxanthine, Wijemanne discloses laboratory technique of analyzing for urinary hypoxanthine using chromatographic techniques (Abstract), thus confirming the presence of hypoxanthine in urine. I t would have been obvious to one of ordinary skill in the art before the effective filing date to have developed an alternative embodiment of analyzing hypoxanthine in the method of Liao with urine as disclosed by method of Wijemanne instead of blood sample with a reasonable expectation of success as both methods involves chromatographic analysis for hypoxanthine. Furthermore, one would have been motivated to make such substitution as it may be potentially less labor intensive in collecting urine sample compare to blood sample as urine sample simply requires excretion; collecting blood sample, on the other hand, requires withdrawing samples by needle and storing the sample with anticoagulant ( Liao , Experimental Procedures, para. 3). Regarding claim 13, Modified Liao discloses the claimed invention as discussed above in claim 12. Liao discloses analyzing the sample includes a metabolomic analysis ( This is the first metabolomic study to determine plasma biochemical alterations of healthy individuals after four days at high altitude (5300 m) by using combined LC-MS and GC-MS . Conclusions). Regarding claim 14, Modified Liao discloses the claimed invention as discussed above in claim 13. Liao discloses the metabolomic analysis is selected from LC-MS or GC-MS ( This is the first metabolomic study to determine plasma biochemical alterations of healthy individuals after four days at high altitude (5300 m) by using combined LC-MS and GC-MS . Conclusions). Regarding claim 15, Modified Liao discloses the claimed invention as discussed above in claim 14. Liao discloses, in addition to GC/MS and LC-MS, an additional quantitation by capture element in ELISA is performed wherein the ELISA method includes evaluation of a peptide ( To validate the metabolic changes, the levels of key enzymes in these metabolic pathways were determined by ELISA . The Levels of Key Enzymes Involved in the Pathways of Altered Metabolites). Regarding claim 16, Modified Liao discloses the claimed invention as discussed above in claim 13. Wijemanne, after incorporation with Liao, discloses normalization of the collected urine sample using creatine to standardize against urine sample volume ( The method can be employed for the analysis of purine metabolism defects using human urine samples with normalization with creatinine . 20. Conclusion). Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT MICKEY HUANG whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-7690 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 9:30-5:30 PM ET . 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, FILLIN "SPE Name?" \* MERGEFORMAT Maris Kessel can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 5712707698 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /M.H./ Examiner, Art Unit 1758 /MARIS R KESSEL/ Supervisory Patent Examiner, Art Unit 1758