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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on August 11, 2026 has been entered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 261-262, 265-266, 268-269, 276, 278 and 283 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 261 is indefinite since it is not clear whether the detection of the level of the at least 5 lipids which differs from the reference level of the at least 5 lipids in the healthy subject in step (a) of the method means that the subject is at risk of having or developing NASH or NAFL. Claim 261 does not positively recite any correlation of the measurements made in step (a) of the method to the subject either having or not having a risk of developing either NASH or NAFL. It is not clear what the determination of the level of the at least 5 lipids that is different from the level of these same lipids in a healthy subject means in step (a) of claim 261. See this same problem in claim 283. For purposes of examination, claims 261 and 283 are being interpreted as meaning a difference of the detected at least 5 lipids in the subject from the level of these same lipids in a healthy subject as meaning that the subject has or is at risk of having either NASH or NAFL.
Claim 262 is indefinite since it is not clear what the determination of the level of the additional recited lipids that is different from a reference level of the additional lipids in a healthy subject means. Do the different levels of the additional lipids from the reference level mean that the subject has a risk of developing either NASH or NAFL?
Inventorship
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 Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 261-262, 265-269, 278 and 283 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation between the at least five lipids comprising DG(34:1), LPC(20:0e), PC(40:8), PE(38:1) and SM(d40:1) in a blood sample from a subject and whether the subject is at risk of having or developing nonalcoholic steatohepatits (NASH) or nonalcoholic fatty liver (NAFL) without significantly more. The claim(s) recite(s) a method of detecting lipids in a blood sample from a subject and then administering a treatment for NASH or NAFL to the subject, wherein the lipids detected comprise at least DG(34:1), LPC(20:0e), PC(40:8), PE(38:1) and SM(d40:1) present in the blood sample. This judicial exception is not integrated into a practical application because the claims do not apply or use the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment or field of use (i.e. disease diagnosis). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional steps in the method concerning measurement of the lipids in the sample using either liquid or gas chromatography and mass spectrometry constitutes a “well understood, routine and conventional activity” under 35 USC 101.
When considering the claims under the 2019 Revised Patent Subject Matter Eligibility Guidance (January 2019), it is noted that the claims meet step 1 of the guidance since the claims are directed to one of the statutory categories of invention (i.e. are directed to a process). The claims meet prong one of revised step 2A since the claims recite the judicial exception comprising the natural correlation between the at least five lipids comprising DG(34:1), LPC(20:0e), PC(40:8), PE(38:1) and SM(d40:1) in a blood sample from a subject and whether the subject is at risk of having or developing nonalcoholic steatohepatits (NASH) or nonalcoholic fatty liver (NAFL).
The claims do not meet prong two of revised step 2A since the claims do not recite additional elements that integrate the judicial exception into a practical application. With regards to claims 261, 267, 269 and 283, the step of administering a treatment for NASH or NAFL to the subject is not a practical application of the natural correlation that renders the claims patent eligible under prong two of revised step 2A of the 35 USC 101 analysis because according to MPEP 2106.04(d)(2), in order for a treatment step to be a practical application of a judicial exception, “The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). The claim also recites "administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype." This administration step is particular, and it integrates the mental analysis step into a practical application. Conversely, consider a claim that recites the same abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application.” Since claims 261, 267, 269 and 283 only recite generally “administering a treatment for NASH or NAFL to the subject” without specifying what the treatment is with any particularity, these claims do not recite a practical application of the natural correlation/judicial exception. Nothing about the treatment “for NASH or NAFL” administered to the subject is particular or specific to the measurement and correlation performed in step (a) of claim 261 and in the measurement/correlation steps of the method recited in claims 267 and 283. With regards to claims 262 and 265-266, these claims do not recite a practical application of the natural correlation since these claims merely recite the measurement of additional natural substances found in a biological sample from the subject. With regards to claim 268, the recitation of the reference level being established by training a machine learning algorithm using a reference dataset of healthy subjects does not amount to a practical application of the natural correlation because comparing measured levels of analytes in a diagnostic procedure to a reference level is commonly performed by a doctor or medical professional in order to assess the meaning of the analyte levels and make a diagnosis. In addition, the use of a machine learning algorithm to establish a reference level amounts to extra-solution activity that is well-known and is only nominally or tangentially related to the invention. With regards to claim 278, the recitation of the types of measurement methods or techniques used to measure the biomarkers in the method (i.e. chromatography, mass spectrometry, etc.) does not amount to a practical application of the judicial exception since each of the techniques are well-known and routinely used to measure metabolic biomarkers in a biological sample, and therefore, only amount to insignificant extra-solution activity to the judicial exception.
The claims also do not meet step 2B of the guidance since the additional elements of the claims concerning obtaining a sample from a subject and determining the presence and/or amounts of the lipids in the sample using techniques such as chromatography and mass spectrometry are both well-understood, conventional and routine sample analysis steps that must be taken by those of skill in the art in order to establish the conditions under which the product of nature exception exists. The additional steps recited in the claims are merely well understood, routine and conventional limitations that are necessary for all practical applications of the exception, such that everyone practicing the exception would be required to perform those steps. See the references to Le Naour et al (WO 2017/167821, submitted in the IDS filed on April 11, 2023), and the references to Sa et al, Iruarrizaga-Lejarreta et al, Peng et al and Gorden et al included in the Information Disclosure Statement filed on November 29, 2023), which all demonstrate that measuring lipids in a biological sample using a technique such as chromatography and mass spectrometry are well understood, routine and conventional in the prior art. For this reason, the additional steps recited in the method do not recite an inventive concept that renders the claims patent eligible under step 2B of the 35 USC 101 analysis.
Allowable Subject Matter
Claims 260, 275 and 282 are allowable since none of the prior art of record teaches or fairly suggests a method for detecting at least five lipids in a blood sample from a subject comprising DG(34:1), LPC(20:0e), PC(40:8), PE(38:1) and SM(d40:1) using mass spectrometry, wherein the at least five lipids detected differ from these same at least five lipids detected in a reference healthy subject. In addition, claims 260, 275 and 282 are patent eligible under 35 USC 101 since the at least five lipids are transformed from their natural state in a blood sample by the mass spectrometry performed in the method since mass spectrometry serves to ionize the lipids to form protonated, deprotonated or adducted derivatives of the lipids. Therefore, claims 260, 275 and 282 recite a method for measuring a non-natural product (i.e. ionized lipids) in a blood sample using mass spectrometry.
Claims 279-280 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims since claims 279-280 recite specific and particular types of medication to administer to the subject in the method in order to treat NASH or NAFL in the subject, which is a practical application of the judicial exception recited in the claims.
Claim 276 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims since claim 276 recites specific and particular types of medication to administer to the subject in the method in order to treat NASH or NAFL in the subject, which is a practical application of the judicial exception recited in the claims.
Response to Arguments
Applicant's arguments filed August 11, 2026 have been fully considered but they are not persuasive.
The previous objections to the claims made in the last Office action mailed on April 13, 2026 have been withdrawn in view of the amendments made to the claims. The previous rejection of claim 281 under 35 USC 112(a) made in the last Office action has also been withdrawn in view of the cancelation of claim 281.
Applicant argues the rejection of claims 260, 275, and 282 under 35 USC 101 as being directed to a natural product by stating that the lipids detected by mass spectrometry in the method recited in these claims are not naturally occurring lipids, but rather ionized forms thereof, such as protonated, deprotonated or adducted derivative of the lipids, and therefore, the naturally occurring lipids in the blood sample analyzed are transformed into ionized species that are not naturally found in blood. This argument is found persuasive, and therefore, the rejection of claims 260, 275 and 282 under 35 USC 101 has been withdrawn. However, it is noted that the rejection of claims 261-262, 265-269, 278 and 283 under 35 USC 101 is maintained since these claims recite the natural correlation between the at least five lipids comprising DG(34:1), LPC(20:0e), PC(40:8), PE(38:1) and SM(d40:1) in a blood sample from a subject and whether the subject is at risk of having or developing nonalcoholic steatohepatits (NASH) or nonalcoholic fatty liver (NAFL). The mass spectrometry recited in these claims is simply used as a tool to obtain the data (i.e. the measurements of the amounts or presence of the at least five lipids in a blood sample) used to establish the natural correlation/naturally occurring relationship recited in the claims. The mass spectrometry in these claims only transforms the lipids into a form that is measurable so that the naturally occurring correlation can be made, and therefore, the transformation of the lipids into ionized lipids in the mass spectrometry step of claims 261-262, 265-269, 278 and 283 amounts to simple routine, pre-solution activity and data gathering necessary for establishing the natural correlation.
Applicant also argues the rejection of claims 261-262, 265-269, 278 and 283 under 35 USC 101 by stating that the claims do recite a specific and particular “treatment for NASH or NAFL to the subject”, and thus, recite a practical application of the judicial exception recited in these claims since the claims are similar to claim 2 in Example 43 of the 2019 Revised Patent Subject Matter Eligibility Guidance. Applicant argues that claim 1 in Example 43 was found ineligible under 35 USC 101 since it recited any possible treatment that a doctor decides to administer to the patient, whereas claim 2 in Example 43 was found patent eligible under 35 USC 101 because it recited administering a “non-steroidal agent capable of treating NAS-3” as the treatment. Similarly, Applicant argues that pending claims 261-262, 265-269, 278 and 283 recite a “treatment for NASH or NAFL to the subject”, which satisfies the “particular treatment or prophylaxis” prong of revised step 2A of the 35 USC 101 analysis. This argument is not found persuasive since claim 2 in Example 43 of the 2019 Revised Patent Subject Matter Eligibility Guidance does limit the treatment to a “non-steroidal agent” so it at least identifies and narrows the treatment to a particular genus of drugs or medications to administer to the patient, and the treatment recited in claim 2 of Example 43 uses the natural correlation recited in the claim in a manner that imposes a meaningful limit on it. In instant claims 261-262, 265-269, 278 and 283, the claims do not use the results of the natural correlation (whether or not the measured at least 5 lipids differ from the 5 lipids in the reference sample obtained from a healthy subject) in any meaningful way to tailor the treatment for NASH or NAFL administered to the subject. The results of the natural correlation do not have any effect on which type of “treatment for NASH or NAFL” that is administered to the subject. Therefore, any non-specific treatment known to be useful to treat NASH or NAFL, even treatments known to be used to treat other diseases besides NASH and NAFL, such as diabetes or heart disease (i.e. with cholesterol lowering medications or type 2 diabetes medications, etc), are encompassed by the “treatment for NASH or NAFL”. In instant claims 261-262, 265-269, 278 and 283, there is no nexus or link between the results of the natural correlation and the treatment chosen to treat the identified NASH or NAFL subject as with claim 2 in Example 43 that recites the particular treatment of the patient with a “non-steroidal agent capable of treating NAS-3” since the patient in the method was identified as having a non-responder phenotype non-responsive to steroids based upon the recited natural correlation. In the instant claims, the natural correlation is not used in any way to identify which of many particular treatments for NASH or NAFL to use, and nothing about the “treatment for NASH or NAFL” is particular or specific to the measurement and correlation performed in step (a) of claim 261 and in the measurement/correlation steps of the method recited in claims 267 and 283.
For all of the above reasons, Applicant’s arguments are not found persuasive. However, as noted above, 260, 275 and 282 are now allowable, and claims 279-280 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims for the reasons set forth above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAUREEN M WALLENHORST whose telephone number is (571)272-1266. The examiner can normally be reached on Monday-Thursday from 6:30 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander, can be reached at telephone number 571-272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MAUREEN WALLENHORST/Primary Examiner, Art Unit 1797 August 18, 2026
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