DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The present Application, filed June 22, 2023, is a national stage entry under 35 U.S.C. § 371 of International Patent Application No. PCT/US2021/052863, filed September 30, 2021, which claims the benefit of Provisional U.S. Patent Application Nos. 63/239,656, 63/165,395, and 63/085,706, filed September 1, 2021 and March 24, 2021, and September 30, 2020, respectively.
Status of the Claims
In the amendment filed July 14, 2026, claims 5, 7-10, 15-16, 18, 21, 27, and 29-30 are canceled. Claims 4, 13, 17, 20, and 31 are amended. Claims 4, 6, 12-14, 17, 20, and 31-32 are currently pending.
Previous Rejections and/or Objections
Any objections and/or rejections raised in the previous Office Action but not reiterated below are considered to have been withdrawn.
Claim Rejections - 35 USC § 101 – Modified in View of Amendment, but Substantially Maintained
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 4, 6, 12-14, 17, 20, and 31-32 are rejected for failure to recite eligible subject matter:
Claims 4, 6, 12-14, 17, 20, and 31-32 are rejected under 35 U.S.C. § 101 because the claimed invention is directed to an abstract idea without significantly more.
In its Remarks of July 14, 2026, Applicant states that the previous rejections for subject matter ineligibility are believed to have been overcome by the present amendments. However, the amendment does not overcome the subject matter ineligibility of claim 4. Claim 4 is amended, inter alia, to add a step of administering to the subgroup of subjects from the stratifying step one of a number of enumerated drugs or drug types. This, however fails to integrate the judicial exception into a practical application because the administering step has no more than a nominal or insignificant relationship to the exceptions (the mental steps) and is thus merely extra-solution activity. See MPEP 2106.04(d)(2) and cases cited therein, and see particularly MPEP 2106.04(d)(2)(b-c).
It is noted that previous claim 5 recited an administering step that did not recite a particular therapy to be administered, but merely said generically that the therapy was to be “determined by the unique and specific mitochondrial metabolic profile of the subgroup of subjects.” While amended claim 4 recites particular drugs, or drug types (e.g. PPAR agonists), the method makes no connection between the mental steps (calculating, determining, stratifying) and the drug to be administered. Specifying certain drugs or drug types, by itself, is not sufficient to make a prophylaxis step sufficiently particular to confer subject matter eligibility on an otherwise abstract mental process; rather the prophylaxis must have a relationship to the exception (the abstract ideas). In the present case, one of the specified drugs or drug types is administered to the subjects in the subgroup, but nothing about the drug administration is tied to any of the exceptions; for example, the choice of drug does not depend on the subgroup to which the subject is stratified or on the determination whether there is a branched chain amino acid or SCFA deficiency. Rather, the mental steps are performed, and then any one of the recited drugs is administered, with no connection to the exceptions.
Substantially reiterated rejection:
Claim 4 recites a method for stratifying and treating a subject having a neurological disorder, comprising steps of (i) calculating ratios of metabolite levels, (ii) determining if the subject has a mitochondrial defect based on metabolic measurements, (iii) stratifying the subject into a subgroup of subjects, and (iv) administering to the subgroup of subjects an effective amount of one or more enumerated pharmaceutical compounds. Each of steps (i)-(iii) constitutes a mental process: (i) calculating ratios (basic arithmetic), (ii) mentally determining the presence of a metabolic defect based on a known correlation to a metabolite measurement, and (iii) stratifying (mentally categorizing) the subject into a subgroup. The fourth step, administering, is mere extra-solution activity that fails to integrate the judicial exceptions into a practical application. This is because there is insignificant connection between the judicial exceptions and the administering step; the manner in which the administering step is performed is unaffected by the results of the calculating, determining, and stratifying steps. This is unlike the situation in Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d 1117 (Fed. Cir. 2018), where the Court found subject matter eligibility for a method having a step of performing a genotyping assay and a step of administering a dose of a drug, precisely because the dose of the drug was determined by the outcome of the genotyping assay and the manner in which it was determined was recited in the claim. Contrast that to Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012) where a method having a step of administering a drug providing 6-thioguanine to a subject was found ineligible when the judicial exception (mental step) did not alter the administration step in any way, similar to the situation with instant claim 4. As such, the administration step of amended claim 4 fails to integrate the judicial exceptions (calculating, determining, and stratifying steps) into a practical application, and the claim is subject matter ineligible.
Claim 6 recites constraints on the manner in which the mental “determining” step is performed (specifically, limiting the biomarker metabolite options). Such constraint on the manner in which the mental step is performed does not transform the recited subject matter into patent eligible subject matter.
Claim 12 narrows the preambular recitation of the neurological disorder, but does not integrate the mental steps into a practical application or cause the claim to amount to significantly more than the judicial exception, as the only effect of this claim is to narrow the population of suitable subjects.
The method of claim 13 is substantially the same as the method of claim 4, but omits the “stratifying” step (included in claim 14), and recites measuring expression levels of mitochondrial enzymes or transporters rather than levels of metabolites. The generalized step of measuring expression or activity levels of enzymes or transporters fails to integrate the mental steps into a practical application, or to cause the claim as a whole to be significantly more than the mental steps, for the same reasons as does the step of measuring metabolite levels in claim 5. Claims 13 and 14 therefore fail to recite patent-eligible subject matter for the same reason as does claim 4.
Claim 17, depending from claim 13, recites constraints on the manner in which the mental “determining” step is performed (specifically, limiting the mitochondrial metabolic disrupted acylcarnitine homeostasis options). Such constraint on the manner in which the mental step is performed does not transform the recited subject matter into patent eligible subject matter.
Claim 20 is substantially the same as claim 4, but omits the “stratifying” step (like claim 13), and also in that claim 20 further includes a step of comparing the presence, concentration levels, and ratios of one or more biomarker metabolites related to mitochondrial function in the sample from the subject to the presence, concentration levels, and ratios of the one or more biomarker metabolites in a control sample. This added step also recites a mental step (an abstract idea, i.e. a judicial exception), and thus does not confer subject matter eligibility on the claim. Claim 20 thus recites ineligible subject matter for essentially the same reasons as does claim 4.
Claims 31-32, depending from claim 4, are likewise subject matter ineligible as these claims, in different respects, narrow the available treatment options, but do not specify a particular treatment and, more importantly, do not specify any particular connection between a given treatment and an output or result of the mental steps.
Claim Rejections - 35 USC § 112(b) - Maintained
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.
Claim 20 is indefinite:
Claim 20 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 20 is indefinite for reciting “determining the…ratios of one or more biomarker metabolites,” because one of skill in the art could not reasonably determine the metes and bounds of this limitation. In particular, it would be unclear what it means to determine the ratio of one biomarker metabolite, as a ratio requires two values by definition.
Claim 20 is further indefinite for reciting one or more biomarker metabolites related to mitochondrial function, because a person of ordinary skill in the art could not reasonably determine the metes and bounds of this limitation. As a first matter, it would not be clear what constitutes a biomarker metabolite related to mitochondrial function. This could be any metabolite consumed or produced in the mitochondrion, it could be any metabolite whose level is directly or indirectly influenced by the rate of metabolism, or it could be defined in some other way. For the purpose of compact prosecution, a biomarker metabolite related to mitochondrial function will be construed as being any listed “mitochondrial biomarker metabolite” or “biomarker metabolite” of paragraph [0008] of the specification.
Claim Rejections - 35 USC § 112(b) – Necessitated by Amendment
Claims 4, 6, 12-14, 17, and 31-32 are indefinite:
Claims 4, 6, 12-14, 17, and 31-32 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 4 is indefinite for reciting a “determining” step that has no measured values on which the determining is based. Specifically, claim recites “determining if the subject has a deficiency in branched chain amino acids, short chain fatty acids,” but no measurement is made of either short chain fatty acids or branched chain amino acids in the measuring step of claim 4 as currently amended. As such, one of skill in the art could not reasonably ascertain how the determining step is performed, in the absence of such measurements. Claim 4 is therefore indefinite, and claims 6, 12, and 31-32 are indefinite for depending from claim 4 without curing this indefiniteness.
Claim 13 is similarly indefinite for reciting a “determining” step that has no measured values on which the determining is based. Specifically, the claim recites “determining if the subject has disrupted acylcarnitine homeostasis.” Claim 17 (and the specification) indicate that “disrupted acylcarnitine homeostasis” can be determined by, e.g., lower levels of all acylcarnitines and increases in certain acylcarnitine ratios. However, the measuring step of claim 13 does not include measurement of acylcarnitines, but is limited to measurements of the expression levels or activity of various enzymes. As such, it would be unclear how the determination of “acylcarnitine homeostasis” and whether it is “disrupted” would be made, at least in some of its manifestations. As such, claim 13 is indefinite and claims 14 and 17 are indefinite for depending from claim 13 without curing this indefiniteness.
Claim 14 is further indefinite for reciting “the mitochondrial metabolic defect,” a phrase which has no antecedent basis due to the amendment to claim 13.
Conclusion
THIS ACTION IS MADE FINAL. 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 extension fee 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 ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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