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. 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. DETAILED ACTION This action is in response to claim amendments filed 3/8/24. Claims 1-3, 5-7, 9, 11- 19, and 24-27 are pending and under examination. Specification The disclosure is objected to because of the following informalities: Of the nine uses in the specification, there are eight recitations of “liquid chromatography” and only one of “liquid chromatograph”, though they appear to be used in the same context referring to a method of detection rather than the device (a chromatograph) . The use of “chromatograph” on p.13 at paragraph 51 appears to be a typographical misspelling. Appropriate correction is required. Claim Objections Claim 7 is objected to because of the following informalities: The claim recites “liquid chromatograph”, whereas other uses of the term in both the claims and specification are “chromatography”. The use of “chromatograph” appears to be a typographical misspelling. Appropriate correction is required. 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. Claim 12 is 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 12 recites “a healthy individual without hepatocellular carcinoma”. The phrase “healthy” is unclear. In one interpretation, the individual meets the limitations of healthy by not having hepatocellular carcinoma. However, this would make the two phrases redundant , suggesting that the word “healthy” is meant to add a limitation other than the lack of HCC . In a second interpretation, these are two separate requirements: individual must not have hepatocellular carcinoma as well as be “healthy”. In this second interpretation, the metes and bounds of “healthy” are indefinite. There is no definition or guidance in the specification as the term appears used solely in combination with the lack of HCC or a “liver disorder” (paragraph 39). Thus, “healthy” could mean, e.g., 1) does not have HCC, 2) does not have any liver disorder, or 3) does not have any diagnosed or suspected disorder at all. Further, claim 12 recites the term “individual”. The specification defines this term to be “a subject or patient” (paragraph 62). The term “patient” appears to be interchangeable with “subject” in the specification but there is no specific definition of the term. While claim 1 requires obtaining a sample from a human subject, the qualifier “human” clearly indicates that “subject” alone is not limited to humans. It is unclear from the claim language in light of the specification whether or not the “individual” in claim 12 must also be human or if this extends to other species and, if so, which ones. Therefore, claim 12 is indefinite. For the purpose of examination, the phrase “healthy individual without hepatocellular carcinoma” will be interpreted as “subject without hepatocellular carcinoma” without requiring this subject is human. Claim 18 is 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 18 recites “generating a report”. The specification does not define this phrase and does not define “report”. It is unclear if this “report” must be a physical item or if the phrase encompasses any potential means of “containing information”. Further, the claim recites the report “is useful” for diagnosing HCC. This term is also indefinite because there is no clear guidance on what the threshold for being “useful” is. The report must contain the information regarding the biomarkers; “generating the report” in line 4 incorporates the preamble limitations into the body of the claim. In one case, having this information, on its own, meets the limitation of “is useful”. However, this would make the “wherein” clause unnecessary. Alternately, having the information alone is not “useful” and there is some other limitation that must be met to define the scope of the claim. The specification does not provide adequate guidance on what those limitations might be. The requirement might be that the report must be useful to the one generating the report, or it might need to be useful to others. This might be an inherent property of the report and does not further distinguish the report. The report is not “used” in any way, only that it “is useful”, which creates indefiniteness as two skilled artisans could fairly disagree on whether or not a particular piece of information is useful. The claims do not specify how the information is used nor claim any specifics as to what the levels mean. Thus, given the amounts of biomarkers, one individual could conclude that the report indicates the subject has HCC and is therefore useful, while another could find those amounts inconclusive and not useful. MPEP § 2173.02 (II) states that one of the purposes of examination under 35 USC § 112, second paragraph is to determine whether the claim apprises one of ordinary skill in the art of its scope and, therefore, serves the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent. See, e.g., Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000). See also In re Larsen, No. 01-1092 (Fed. Cir. May 9, 2001) (unpublished). If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. See Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470, 28 USPQ2d 1190, 1195 (Fed. Cir. 1993). In this case , it is unclear when the data or information rises to the level of “useful” and so the metes and bounds are not sufficiently clear. Therefore, claim 18 is indefinite. 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 18 and 19 are rejected under 35 U.S.C. 101 because the claims recite a judicial exception without significantly more. Step 1: It must first be determined if the claim is to a statutory category and, if so, proceed to step 2A prong 1. Claims 18-19 are a method and fall within the statutory category of a process . Step 2A, prong 1: Prong 1 requ ires the Examiner to evaluate whether the claim recites a judicial exception and, if so, proceed to prong 2. In this case, the claims recite the natural correlation between information regarding biomarkers and their usefulness in diagnosis; the claim recites “wherein the report is useful for diagnosing hepatocellular carcinoma in the subject”. By reciting the report is useful in this way, the claim language amounts to reciting what the report “indicates”, which has been held to be the recitation of a judicial exception. For example, in Mayo v Prometheus ( Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) ), level of the metabolite "less than about 230 pmol per 8x10 8 red blood cells [indicated] a need to increase the amount of said drug”. Such claim limitations were found to be a description of the correlation itself and not “significantly more”. It was also found that steps prior to this constituted routine data gathering, instructing the artisan to engage in conventional, well-known practices and then "warning" the user of the implications of the data; this was not eligible in Mayo and thus the instant claim(s) are not patent eligible. Similar facts hold here, where a “report” containing the information about the biomarkers (similar to the “measurement” of the metabolites, which would have needed to be in some discernable form or “report” to be used in the claimed manner ) “is useful” (indicates) for diagnosing HCC (the indication was useful for determining the need to increase the drug). Step 2A, prong 2 : Prong 2 requires the Examiner to evaluate whether the claim recites additional elements that integrate the exception into a practical application of that exception and, if not, proceed to step 2B. In order to integrate the recited judicial exception into a practical application, the claim will apply, rely on, or use the judicial exception that imposes a meaningful limit such that the claim is more than a drafting effort to monopolize the judicial exception. Examiners evaluate integration by identifying additional elements in the claim beyond the judicial exception and evaluating those elements individually and in combination to determine whether they integrate the exception in to a practical application. Examples that have been found by the Courts in which the exception was not integrated into a practical application include: Mere instructions to implement an abstract idea on a computer Adding generic instructions that the judicial exception should be used ("apply it") Adding insignificant extrasolution activity to the exception ("mere data gathering") Generally linking the use of the exception to a particular technological environment or field of use In this case, the claims do no more than gather data and place that data in a report. This is “mere data gathering” and considered insignificant extrasolution activity. The data itself is not used, only claimed as “useful” for making a diagnosis. In other words, anyone who detected these biomarkers by any means and for any reason would infringe the claim as that data is useful for (indicates) a diagnosis whether one proceeds to actually diagnose a subject or use the data for some other reason. This is a clear attempt at monopolizing the relevance of these biomarkers to the diagnosis without integration into a practical application. Step 2B: Where a claim does not integrate the exception, a claim may nevertheless be patent eligible, for example where additional elements are “significantly more” tha n the exception such that the additional elements were unconventional in combination. Considerations include whether or not the claim adds a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; or simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present. In this case, there are two elements beyond the exception itself. The first is detecting the biomarkers. However, this falls into a recognized judicial category of well-understood, routine, and conventional activity. See MPEP §2106.05(d)(II), where the Courts have determined that “determining the level of a biomarker in blood by any means” is considered insufficient to meet this step of the analysis. The instant claims are not limited to blood and instead encompass any bodily fluid. The detection is recited at a high level of generality (any possible means of detection) such that this is a well-understood element. The second is “generating the report”. This also falls into a Court recognized category of well-understood, routine, and conventional. MPEP §2106.05(d)(II ) notes that “electronic recordkeeping” is insufficient to meet the requirements of this step when part of the data gathering (extrasolution) activity. The claimed report includes generating an electronic report but encompasses recording the data in any way which might somehow be “useful” for the diagnosis. As this is an even more generic element than that decided by the Court, this element is also a well-understood element. Claim 19 adds additional biomarkers. As these are part of the judicial exception itself (the correlation between the naturally occurring levels of these biomarkers as presented in a report and a diagnosis of HCC), claim 19 does not have “additional elements” to consider in step 2A prong 2 or 2B. Therefore, claims 18 and 19 are not patent eligible. C laim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale , or otherwise available to the public before the effective filing date of the claimed invention. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim(s) 1, 2, 7, 9, 11, 12, 18, and 1 9 is/are rejected under 35 U.S.C. 102 (a )( 1-2) as being anticipated by Ravenzwaay (US20110091929; form 892) . Regarding claim 1, Ravenzwaay teaches a method of detecting (determining the amount of) hep t adecanoic acid and eicosapentaenoic acid in a bodily fluid obtained from a subject (determining in a test body fluid sample of a male subject) (claim 23). The subject is human (paragraph 38; “ subject”… relates…preferably, to humans). The phrase “hepatocellular carcinoma biomarkers” (HCC) does not inform any additional structure or limitation on the compounds and so their detection meets the limitations of detecting “two or more hepatocellular carcinoma biomarkers”. However, it is further noted that Ravenzwaay teaches this detection as a method of diagnosing liver enzyme induction (claim 23) which indicates liver tumors (claim 40) , which is within the instant definition of HCC (instant specification paragraph 37) . Regarding claim 2, Ravenzwaay teaches detection of eicosanoic acid C20:0 (claim 23). Regarding claim 7, Ravenzwaay teaches the detection by gas chromatography-mass spectrometry (GS- MS) ( claim 42). Regarding claim 9, Ravenzwaay teaches the body fluid is blood (claim 43). Regarding claim 11, Ravenzwaay teaches determining the amounts of the marker (claim 23), which meets the limitations of determining concentrations; see also paragraphs 93-95 describing measuring the amounts in a specific volume of blood, i.e., determining a concentration. Regarding claim 12, Ravenzwaay teaches the detection of the biomarkers is compared to a “reference”, i.e., a control (claim 23), where the reference is derived from a subject not known to suffer from liver enzyme induction (LEI) and “diseases or disorders accompanied therewith” (claim 29). Liver tumors are such a disease as described above. A subject (individual) without any disease associated with LEI meets the limitations of both “without [HCC]” and “healthy”. Regarding claim 18, there is no special definition of “report” in the instant specification. Ravenzwaay teaches using methods such as GS-MS to detect the amounts of hep t adecanoic acid and eicosapentaenoic acid as described above . This inherently provides the relevant information in some fashion and therefore meets the broadest, reasonable interpretation for generating a report that contains information on results of the detection. Further, there is no special definition or guidance for interpreting “is useful for diagnosing” and so the broadest, reasonable interpretation is having the data at all is sufficient to meet this limitation. Ravenzwaay also teaches “comparing and/or analyzing the results obtained from the means for determination of analytes” comprising a database (paragraph 51), which also meets the limitations for such a report. This database may be on a computer where the computer facilitates the diagnosis (paragraphs 50-51), indicating the data (report) was useful for such a diagnosis. Regarding claim 19, Ravenzwaay teaches measuring 20:0-eicosanoic acid and 23:0-tricosanoic acid (table 2) . The table itself appears to meet the limitations of “generating a report” and the broadest, reasonable interpretation of “is useful for diagnosing” is having the data at all is sufficient to meet this limitation . Therefore, claims 1, 2, 7, 9, 11, 12, 18, and 19 are anticipated. Claim(s) 25-27 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Hutchinson (WO 2013022789; IDS 2/7/24 citation 1) . Hutchinson teaches diagnosing liver disorders such as HCC in a subject (abstract). Hutchinson teaches this subject “is currently receiving treatment for HCC” (p.17 L24-25). Hutchinson also teaches determining a response (monitoring) of a mammalian subject having HCC tumor cells to treatment with an HCC inhibitory agent (drug) or surgical technique (p.25 L13-17). This method includes determining a first level of a biomarker in a first sample from the subject “prior to treatment” and determining a second level from a second sample from the same subject “after initiation of treatment”. Thus, Hutchinson teaches selecting a subject and administering an effective amount of an anti-HCC treatment, including surgical treatment. This also meets the limitations in the preamble of a method of treating HCC in a subject. Regarding the “differential level” of biomarkers limitations, the instant claim does not recite that the “differential levels” of the biomarkers are ever measured. Rather, this differential level is claimed as an inherent property of the subject (“selecting a subject that has differential levels”). Throughout the instant specification , e.g., in table 2, it is disclosed that those with HCC have the required differential level. Thus, selecting any subject with HCC, such as in Hutchinson, meets the limitations of selecting a subject that has these differential levels in instant claims 25 and 26. See MPEP § 2112 (II ), which states, "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." . Therefore, claims 25-27 are anticipated. 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 . Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ravenzwaay (US20110091929) as applied to claim s 1, 2, 7, 9, 11, 12, 18, and 19 above, and further in view of Beretta (US20070202496; form 892) . Ravenzwaay is discussed above and incorporated herein. Ravenzwaay does not teach measuring osteopontin or alpha-fetoprotein. Like Ravenzwaay, Beretta is in the field of diagnosing liver cancer using biomarkers (title ; abstract ). Beretta teaches this includes HCC (claim 4). Like Ravenzwaay, Beretta teaches the biomarkers are also detected in blood (claim 10). Further, Beretta teaches this detection of liver cancer includes detecting alpha-fetoprotein (claim 9). It would have been obvious to one of ordinary skill in the art at the time of filing to include detection of alpha-fetoprotein according to Beretta into the method of Ravenzwaay with a reasonable expectation of success. Both are measuring blood biomarkers relevant to liver cancer and the biomarkers themselves are taught as useful in this respect, i.e., are performing their known function. It is further noted that Beretta also teaches establishing control values from those subjects without liver cancer (paragraph 33). Therefore, claims 1 -3 , 7, 9, 11, 12, 18, and 19 would have been obvious. Claim(s) 5-6 and 13 -14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ravenzwaay (US20110091929) as applied to claim s 1, 2, 7, 9, 11, 12, 18, and 19 above, and further in view of Schuppan (IDS 2/7/24 citation 18) . Ravenzwaay is discussed above and incorporated herein. Ravenzwaay does not teach performing the detection on a subject previously diagnosed with advanced liver cirrhosis. Ravenzwaay is concerned with using biomarkers for diagnostic purposes including liver disorders such as liver tumors (claim 40). Schuppan teaches that HCC is one of the most common solid organ tumors and that cirrhosis is “the major risk factor for progression to HCC” (p.6). Schuppan teaches “screening for HCC is one of the most important tasks in following patients with cirrhosis” (p.6). Schuppan teaches advanced liver cirrhosis is a known condition (p.12). It would have been obvious to one of ordinary skill in the art at the time of filing to perform the liver tumor diagnostic assay of Ravenzwaay on patients diagnosed with liver cirrhosis because Schuppan teaches that such diagnosis (screening) is one of the most important tasks for patients with cirrhosis since liver cirrhosis is the major risk factor for liver tumors such as HCC. While Schuppan does not explicitly suggest screening for those with “advanced” liver cirrhosis, Schuppan teaches the genus of liver cirrhosis and names advanced liver cirrhosis as a condition. MPEP 2141(II)(C): "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR, 550 U.S. at 421, 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418, 82 USPQ2d at 1396. In this case, given that liver cirrhosis is a risk factor for HCC, it would have been an ordinary inference that the “advanced” liver cirrhosis in Schuppan would similarly be a risk factor where screening was “one of the most important tasks”. Thus, it would have been obvious to include those with advanced liver cirrhosis with the teachings of liver cirrhosis and apply the screening method of Ravenzwaay. Regarding claim s 13, Schuppan teaches cirrhosis is “an advanced stage of liver fibrosis” (p.1). Since cirrhosis is a major risk factor for HCC and screening is important as discussed above, it would have been obvious to one of ordinary skill in the art to include those patients with cirrhosis, including those currently being treated for cirrhosis (advanced liver fibrosis) as there is no indication in the references cited that treating cirrhosis negates the increased risk or need for screening. With respect to the limitations of obtaining two samples at different time points from the same subject, Ravenzwaay teaches the method for monitoring a disease, such as the progression of the disease (paragraph 17). Similar to the above, the person of ordinary skill is also a person of ordinary creativity. When set to monitor the progression of a disease, it would have been obvious that a single measurement is insufficient as progression is a change over time, thus making it obvious to perform the measurement steps of Ravenzwaay at least twice. Further, if the sample were from a different subject, it would not provide information regarding how the subject’s disease has progressed, making it obvious to select both measurements from blood samples of the same individual. Regarding claim 14, Ravenzwaay teaches monitoring “the influence of a particular treatment on the progression of disease” (paragraph 17). Similar to the above, this would suggest and make obvious to the person of ordinary skill to take the above two time points where at least one sample was prior to treatment and the other was subsequent to treatment as this would provide the expected information regarding how the biomarkers (the disease) has responded to said treatment. Therefore, claims 1, 2, 5- 7, 9, 11 -1 4 , 18, and 19 would have been obvious. Claim(s) 11-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ravenzwaay (US20110091929) as applied to claim s 1, 2, 7, 9, 11, 12, 18, and 19 above, and further in view of Laing (US20160061849; form 892) . Ravenzwaay is discussed above and incorporated herein. While the §102 rejection above establishes that measurement as a concentration is anticipated in the disclosure of Ravenzwaay, in the alternative, Laing is also concerned with measuring lipid biomarkers relevant to HCC (abstract) , including in blood (e.g., paragraphs 27 and 50) . Laing teaches this measurement may be in terms of concentration (e.g., claims 13-18). Laing also teaches comparison to a control level (e.g., claims 14-18), where the control is a healthy individual (paragraph 26: “a control biological sample, which may be a sample of one or more healthy individuals”). A person with HCC would not be a “healthy individual” within the ordinary definition of the term. As Liang teaches this is a viable method of measuring and diagnosing lipid biomarkers in the context of the liver and liver disorders, one would have found it obvious that the same methods could be applied to the measurement and analysis steps of Ravenzwaay in the same manner. Claim(s) 13-17 and 25-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ravenzwaay (US20110091929 ) as applied to claim s 1, 2, 7, 9, 11, 12, 18, and 19 above, and further in view of Hutchinson (WO 2013022789; IDS 2/7/24 citation 1 ) Ravenzwaay is discussed above and incorporated herein. Regarding claim s 13 -14 , Ravenzwaay t eaches the method for monitoring a disease, such as the progression of the disease as well as monitoring treatment (paragraph 17). However, Ravenzwaay does not explicitly teach doing so by detecting two samples, where one sample was obtained from a different time point. Ravenzwaay does not teach the treatment to be monitored is treatment for HCC or advanced liver fibrosis ( cirrhosis ) . Hutchinson is also concerned with diagnosing liver disorders such as HCC in a subject (abstract). Hutchinson teaches this subject “is currently receiving treatment for HCC” (p.17 L24-25). Hutchinson also teaches determining a response (monitoring) of a mammalian subject having HCC tumor cells to treatment with an HCC inhibitory agent (drug) or surgical technique (p.25 L13-17). This method includes determining a first level of a biomarker in a first sample from the subject “prior to treatment” and determining a second level from a second sample from the same subject “after initiation of treatment”. It would have been obvious to a person of ordinary skill in the art to perform the monitoring method of Ravenzwaay using the techniques of Hutchinson. Ravenzwaay suggests monitoring treatment using biomarkers and Hutchinson teaches one way of doing so it so measure the biomarkers before and after treatment using different samples from the same subject. One would reasonably expect the method of Hutchinson to apply to the detection of other biomarkers, such as those in Ravenzwaay, providing a reasonable expectation of success. The teaching of two samples before and after treatment meets the limitations of claim 14 (one of the samples is prior to start of treatment), while administering the treatment meets the limitations of “undergoing treatment”. Regarding claim 16, Hutchinson teaches treatment with an HCC inhibitory agent as above, which meets the limitations of an anti-[HCC] treatment. Regarding claims 15 and 17, Hutchinson teaches treatment of HCC with surgery as above, meeting the limitations of the treatment or anti-HCC treatment being a surgical treatment. Regarding claim 25, Ravenzwaay teaches heptadecanoic acid and eicosapentaenoic acid which differ from a control (differential) are indicative of a predisposition to liver tumors while Hutchinson teaches HCC is a primary cancer of the liver (p.1 L12). This would have suggested to the ordinary artisan at the time of filing that these biomarkers, indicative of a predisposition to the disease, would reasonably indicate the disease itself , motivating one of ordinary skill in the art to select a subject having these differential levels . Thus, one would have found it obvious to measure these biomarkers as in Ravenzwaay, confirm a diagnosis of HCC by means such as in Hutchinson, and administer the anti-HCC treatment to that subject as in Hutchinson. R egarding claim 26, Ravenzwaay meets this limitation as described, e.g., in the analysis of claims 2 and 19. Regarding claim 27, Hutchinson teaches treatment of HCC with surgery as above. Therefore, claims 1, 2, 7, 9, 11, 12 - 19 and 25-27 would have been obvious. Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ravenzwaay (US20110091929) as applied to claim s 1, 2, 7, 9, 11, 12, 18, and 19 above, and further in view of Li (IDS 2/7/24 citation 48). Ravenzwaay is discussed above and incorporated herein. Ravenzwaay does not utilize the method of instant claim 24 to detect the lipid biomarkers; however, Ravenzwaay does teach using LC-MS (claim 42). Li teaches an improved LC-MS method for determination of fatty acids in red blood cells (title). Li teaches: - extracting the fatty acids from the red blood cells : “fatty acid extraction from red blood cells (RBC)”; “[fatty acid] standards and RBC samples underwent the same extraction” (p.1); “MS chromatogram of fatty acids extracted from 20 µL of red blood cells” (figure 3). Extraction from red blood cells meets the limitations of extraction from the sample as Ravenzwaay teaches the sample is blood as above. - converting the extracted free fatty acids to acyl chloride intermediates : “free fatty acids were first converted to the acyl chloride intermediate” (p.4). The derivatization phase of the protocol—of which the acyl chloride conversion is part of—occurs after the extraction step; see p.1 “the same extraction, hydrolysis, and derivatization steps”. - derivatizing the acyl chloride intermediates to form derivatized products : “free fatty acids were first converted to the acyl chloride intermediate …followed by coupling with an amine or alcohol to form the corresponding amide or ester” (p.4). These amides and esters meet the instant recitation of a derivatized product. - analyzing the derivatized product : Li uses a technology known as orbitrap to “analyze a wide range of biological and clinical relevant fatty acids” (p.5) and analyzes the derivatized products via LC-MS (figure 2). It would have been obvious to the ordinary artisan at the time of filing to use the methodology of Li in the detection method of Ravenzwaay. Ravenzwaay teaches analyzing certain fatty acids using LC-MS and Li provides an effective procedure for preparing those fatty acids for LC-MS. Li explicitly detects some of the fatty acids of Ravenzwa a y such as eicosapentaenoic acid (table 1), providing a reasonable expectation of success when applying the Li method to the biomarker analysis of Ravenzwa a y. Therefore, claims 1, 2, 7, 9, 11, 12, 18, 19 and 24 would have been obvious. Conclusion The art made of record and not relied upon is considered pertinent to applicant's disclosure: US12523658 (form 892) was considered for double patenting purposes. The reference patent is also directed to diagnostic methods of HCC in blood. However, the reference claims utilize proteins such as VCAM-1 or IL-6, not the fatty acids of the instant claims. While fatty acids are found in the reference claims, such as eicosapentaenoic acid in claim 1, this is in the context as a therapeutic to be administered, not as a biomarker. As such, the claims are considered patentably distinct. Rejections under §101 were considered for all pending claims. Other than claims 18 and 19 (rejected above), the claims do not recite a judicial exception. For example, claim 1 is a detection method, claim 5 designates who that detection method should be practiced on, claim 13 repeats the detection method, and claim 25 is a method of treatment. Notably, the non-rejected claims do not use the gathered data in any way. The biomarkers are detected, but they are never used to make a diagnosis, inform a treatment decision, nor otherwise used to describe their relevance. Thus, the answer to step 2A prong 1 is ”no ” and the claims are patent eligible. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT ADAM M WEIDNER whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-3045 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-T 9-18; W-R 9-15 . 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 Jeffrey Stucker can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-0911 . 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. /Adam Weidner/ Primary Examiner, Art Unit 1675