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 Objections
Claims 261-262, 265-266, 268-269, 276, 278 and 283 are objected to because of the following informalities: In both independent claims 261 and 283, the full meanings for the abbreviations “NASH” and “NAFL” (nonalcoholic steatohepatitis and nonalcoholic fatty liver) should be recited. Dependent claims 262, 265-266, 268-269, 276 and 278 are objected to based upon their dependency from claim 261. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 281 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. New claim 281 recites that the subject has not been previously diagnosed as having or being at risk of developing NASH or NAFL by magnetic resonance imaging (MRI), computed tomography (CT) scan, ultrasound, and/or liver biopsy. This recitation in new claim 281 represents new matter not disclosed in the specification as originally filed because the specification only states that “these diagnostic methods can be used individually or in combination with another diagnostic method for NAFL, NASH, or liver fibrosis, such as imaging (e.g. abdominal ultrasound, computerized tomography scanning, magnetic resonance imaging, transient elastography, or magnetic resonance elastography) or liver biopsy” (see paragraph 0215 in the corresponding PG publication of the instant application, U.S. 2023/0064246), not that the subject has not been previously diagnosed as having or being at risk of developing NASH or NAFL by magnetic resonance imaging (MRI), computed tomography (CT) scan, ultrasound, and/or liver biopsy. Therefore, it is unclear whether the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention as recited in new claim 281.
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 260-262, 265-269, 275-276, 278-279 and 281-283 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature exception without significantly more. The claim(s) recite(s) a method of detecting lipids in a blood sample from a subject, or 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 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 are drafted in such a way that they are no different in substance from a product claim that recites a product of nature (i.e. the at least 5 lipids comprising DG(34:1), LPC(20:0e), PC(40:8), PE(38:1) and SM(d40:1) present in a blood sample from a subject at risk of having or developing nonalcoholic steatohepatitis (NASH) or nonalcoholic fatty liver (NAFL) in the subject). The instant claims simply recite blood with identified lipids, which are naturally found in blood (i.e. the lipids are a product of nature). According to MPEP 2106.04(c), when a claim recites a product of nature, a markedly different characteristics analysis is performed as part of Step 2A, prong 1 of the 35 USC 101 analysis. If the claim includes a nature-based product that has markedly different characteristics from the natural product, then the claim does not recite a product of nature exception and is eligible under 35 US 101. However, if a claim reciting a natural product does not exhibit markedly different characteristics from its naturally occurring counterpart in its natural state, then the claim recites a “product of nature” exception, and requires further analysis in the Step 2A, prong two of the 35 USC 101 eligibility analysis. In this case, the at least 5 naturally occurring lipids detected in a blood sample using a conventional technology (i.e. mass spectrometry) do not have markedly different characteristics from the at least 5 lipids found naturally in blood, and therefore, the claims recite a “product of nature” exception and are not patent eligible at step 2A, prong one of the analysis. See MPEP 2106.04(c)(I)(C) where it states :
For a process claim, the general rule is that the claim is not subject to the markedly different analysis for nature-based products used in the process. This is because the analysis of a process claim should focus on the active steps of the process rather than the products used in those steps. For example, when evaluating a claimed process of cryopreserving hepatocyte cells comprising performing density gradient fractionation to separate viable and non-viable hepatocytes, recovering the viable hepatocytes, and cryopreserving the recovered viable hepatocytes, the court did not subject the claim to the markedly different characteristics analysis for the nature-based products (the hepatocytes) used in the process. Rapid Litig. Mgmt. v. CellzDirect, Inc., 827 F.3d 1042, 1049, 119 USPQ2d 1370, 1374 (Fed. Cir. 2016) (claims are directed to a process of creating a preparation of multi-cryopreserved hepatocytes, not to the preparation itself).[AltContent: rect]
However, in the limited situation where a process claim reciting a nature-based product is drafted in such a way that there is no difference in substance from a product claim, the claim is subject to the markedly different analysis for the recited nature-based product. These types of claims are drafted in a way that focuses on the product rather than the process steps. For example, consider a claim that recites, in its entirety, "a method of providing an apple." Under the broadest reasonable interpretation, this claim is focused on the apple fruit itself, which is a nature-based product. Similarly, claims to detecting naturally occurring cell-free fetal DNA (cffDNA) in maternal blood were held to be directed to the cffDNA, because the "existence and location of cffDNA is a natural phenomenon [and thus] identifying its presence was merely claiming the natural phenomena itself." Rapid Litig. Mgmt., 827 F.3d at 1048, 119 USPQ2d at 1374, (explaining the holding in Ariosa Diagnostics, Inc. v. Sequenom, 788 F.3d 1371, 115 USPQ2d 1152 (Fed. Cir. 2015)).
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 independent claims 260 and 282, this claim simply recites detecting a product of nature (i.e. the at least 5 lipids comprising DG(34:1), LPC(20:0e), PC(40:8), PE(38:1) and SM(d40:1 present in a blood sample from a subject at risk of having or developing nonalcoholic steatohepatitis (NASH) or nonalcoholic fatty liver (NAFL) in the subject) with nothing more. With regards to claims 261, 267, 269 and 283, the step of administering a treatment for NASH or NAFL to the subject, and doing so in order to prevent or delay the development of NASH in the subject into NAFL, 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 and 269 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. With regards to claims 262, 265-266 and 275, 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 claims 276 and 279, these claims are also not patent eligible under 35 USC 101 since not all of the recited “treatments” are specific and particular treatments in accordance with MPEP 2106.04(d)(2). Specifically, weight loss, a dietary change, increased physical activity, an anti-apoptosis agent, a medication to treat insulin resistance or type 2 diabetes, a medication to improve cholesterol, a glucagon-like peptide agonist, a peroxisome proliferator-activated receptor gamma agonist, a SGLT2 inhibitor, and/or an anti-fibrotic agent are not particular treatments for NASH or NAFL since each of these actions and/or medications are routinely taken by individuals for many other reasons. In addition, the general descriptions of an anti-inflammatory agent, an anti-apoptosis agent, a medication to treat insulin resistance or type 2 diabetes, a medication to improve cholesterol, a peroxisome proliferator-activated receptor (PPAR) agonist, an anti-hypertensive drug, and a farnesoid X receptor agonist are not specific and particular treatments of a subject since these types of medications have not been specifically identified. 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. With regards to claim 281, this claim simply recites characteristics of the subject upon which the method is performed, which is not a practical application of the product of nature exception recited in the claims.
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
Claim 280 is 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 claim 280 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 product of nature exception recited in the claims.
Response to Arguments
Applicant's arguments filed February 27, 2026 have been fully considered but they are not persuasive.
The previous rejections of the claims under 35 USC 112(b) made in the last Office action mailed on October 27, 2025 have been withdrawn in view of the amendments made to the claims. However, claims 261-262, 265-266, 268-269, 276, 278 and 283 are objected to for minor informalities as noted above, and new claim 281 is rejected under 35 USC 112(a) for reciting new matter not supported by the specification as originally filed.
Applicant argues the rejection of the claims under 35 USC 101 by stating that the claims have been amended to remove any alleged natural correlation or phenomenon since the claims are now directed to methods requiring a step of “performing mass spectrometry” on a blood sample from a “subject at risk of having or developing” NASH or NAFL in order to “detect a level of… DG(34:1), LPC(20:0e), PC(40:8), PE(38:1) and SM(d40:1)”. Therefore, Applicant argues that the claims do not recite an alleged judicial exception because they recite a specific analytical assay on a specific biological sample obtained from a specific subject to detect a level of lipids, which is similar to Example 29, claim 1 of the USPTO’s Subject Matter Eligibility Examples: Life Sciences (published May 4, 2016). This argument is not persuasive since the claims are now drafted in such a way that they are no different in substance from a product claim that recites a product of nature (i.e. the at least 5 lipids comprising DG(34:1), LPC(20:0e), PC(40:8), PE(38:1) and SM(d40:1) present in a blood sample from a subject at risk of having or developing nonalcoholic steatohepatitis (NASH) or nonalcoholic fatty liver (NAFL). The instant claims simply recite blood with identified lipids, which are naturally found in blood (i.e. the lipids are a product of nature). According to MPEP 2106.04(c), when a claim recites a product of nature, a markedly different characteristics analysis is performed as part of Step 2A, prong 1 of the 35 USC 101 analysis. If the claim includes a nature-based product that has markedly different characteristics from the natural product, then the claim does not recite a product of nature exception and is eligible under 35 US 101. However, if a claim reciting a natural product does not exhibit markedly different characteristics from its naturally occurring counterpart in its natural state, then the claim recites a “product of nature” exception, and requires further analysis in the Step 2A, prong two of the 35 USC 101 eligibility analysis. In this case, the at least 5 naturally occurring lipids detected in a blood sample using a conventional technology (i.e. mass spectrometry) do not have markedly different characteristics from the at least 5 lipids found naturally in blood, and therefore, the claims recite a “product of nature” exception and are not patent eligible at step 2A, prong one of the analysis. See MPEP 2106.04(c)(I)(C) where it states :
For a process claim, the general rule is that the claim is not subject to the markedly different analysis for nature-based products used in the process. This is because the analysis of a process claim should focus on the active steps of the process rather than the products used in those steps. For example, when evaluating a claimed process of cryopreserving hepatocyte cells comprising performing density gradient fractionation to separate viable and non-viable hepatocytes, recovering the viable hepatocytes, and cryopreserving the recovered viable hepatocytes, the court did not subject the claim to the markedly different characteristics analysis for the nature-based products (the hepatocytes) used in the process. Rapid Litig. Mgmt. v. CellzDirect, Inc., 827 F.3d 1042, 1049, 119 USPQ2d 1370, 1374 (Fed. Cir. 2016) (claims are directed to a process of creating a preparation of multi-cryopreserved hepatocytes, not to the preparation itself).[AltContent: rect]
However, in the limited situation where a process claim reciting a nature-based product is drafted in such a way that there is no difference in substance from a product claim, the claim is subject to the markedly different analysis for the recited nature-based product. These types of claims are drafted in a way that focuses on the product rather than the process steps. For example, consider a claim that recites, in its entirety, "a method of providing an apple." Under the broadest reasonable interpretation, this claim is focused on the apple fruit itself, which is a nature-based product. Similarly, claims to detecting naturally occurring cell-free fetal DNA (cffDNA) in maternal blood were held to be directed to the cffDNA, because the "existence and location of cffDNA is a natural phenomenon [and thus] identifying its presence was merely claiming the natural phenomena itself." Rapid Litig. Mgmt., 827 F.3d at 1048, 119 USPQ2d at 1374, (explaining the holding in Ariosa Diagnostics, Inc. v. Sequenom, 788 F.3d 1371, 115 USPQ2d 1152 (Fed. Cir. 2015)).
Also, see Example 43, claim 1 in Appendix 1 to the October 2019 Update: Subject Matter Eligibility Life Sciences & Data Processing Examples.
For these reasons, Applicant’s arguments are not persuasive.
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 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 April 9, 2026
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