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 .
Remarks
This Office Action fully acknowledges Applicant’s remarks filed on February 23rd, 2026. Claims 1-3 and 5-12 are pending. Claims 4, 13, and 14 are canceled.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 February 23rd, 2026 has been entered.
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 1-3 and 5-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim(s) individually (and including both of independent claims 1 and 8, and dependents thereof) and as an ordered combination recite(s) well as being drawn to the abstract idea of determining a peak area ratio of teriflunomide in a blood sample to an internal standard (and likewise with respect to a second internal standard as in cl. 8) that is representative of a mental step/judgment as well as a mathematical concept that may be accomplished by mental steps, and further wherein in which the “identifying the administered treatment as being below an internal standard threshold…” is drawn to a characterization that may be accomplished through mental steps in assessing data. This is drawn to Step 2A, Prong 1 (i.e. judicial exception/abstract idea portion) of the analysis.
As in Step 2A, Prong 2 (i.e. integration portion) -
This/these judicial exception(s) is(are) not integrated into a practical application because claims the claims do not provide an application of the judicial exception let alone a particularly integrated practical application. The claims provided a mass spectrometer, which is a well-known, routine and conventional device for generating peaks of target compounds and those of an internal standard therefor (see, for example, Barfield et al. “Application of dried blood spots…” as previously cited that discloses such a mass spectrometer to generate peaks of the target and peaks of an internal standard thereof as by isotopically-labeled internal standards, and likewise through Thomassian (US 2012/0171151) and Anderson (US 2016/0282361), and appending a general computer-readable memory and one or more processors to carry out the abstract idea does not itself provide an integrated practical application thereof.
Discussion to the particular compound of interest, teriflunomide, has no particular bearing herein as it, along with an extracted dried blood spot sample (and from a pregnant subject and a filter paper pretreated with an internal standard), is/are not positively provided within the systems of claims 1 and 8.
This is likewise seen with respect to the point of origin in that of the DBS sample being from a pregnant subject after a treatment for multiple sclerosis that has no particular bearing to the claim, nor does the claim require any steps to a treatment of any kind let alone particularly to multiple sclerosis.
Examiner further notes that while the claims have recited that the various steps have been done by a processor(s), such steps could have been done mentally as one may assess the data to make such determination and identification and further, a general purpose computer has been recited and is not a particular machine. See MPEP 2106.05(b), I.
As in Step 2B (i.e. significantly more portion) –
As in claims 1, the claims do not contain anything beyond that of the abstract ideas to the above-discussed mental steps in the “determining” and “identifying.”
Further, as in cl. 8 (and likewise as in cls. 2,3, 9, and 10), the recitations to the defining of peak area ratios (i), (ii) represents insignificant extra-solution activity.
Claims 5-7 are drawn to prospective compounds that have no particular bearing on the claim as discussed above, wherein the claim is drawn to the analytical device of a mass spectrometer itself.
Claims 11 and 12 are merely descriptive to first and second internal standards and in which no such treatment and criteria therewith to provide any particularity to “minimum effective concentration” and “minimum toxic concentration”, in which they themselves are given by functionality of a conventional mass spectrometer (such as in Thomassian, Anderson as cited above)
See also - Limitations that the courts have found not to be enough to qualify as “significantly more” when recited in a claim with a judicial exception include:
i. Adding the words “apply it” (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer, e.g., a limitation indicating that a particular function such as creating and maintaining electronic records is performed by a computer, as discussed in Alice Corp., 573 U.S. at 225-26, 110 USPQ2d at 1984 (see MPEP § 2106.05(f));
ii. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, e.g., a claim to an abstract idea requiring no more than a generic computer to perform generic computer functions that are well-understood, routine and conventional activities previously known to the industry, as discussed in Alice Corp., 573 U.S. at 225, 110 USPQ2d at 1984 (see MPEP § 2106.05(d));
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-3, and 5-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Barfield et al. (“Application of dried blood spots combined with HPLC-MS/MS for the quantitation of acetaminophen in toxicokinetic studies, Journal of Chromatography, vol. 870, 2008) in view of Thomassian (US 2012/0171151), hereafter Thomassian, and Lebrun-Frenay et al. (Terfiflunomide international pregnancy registry; Neurology, April 10th, 2018; https://doi.org/10.1212/WNL.90.15_supplemental.P4.371), hereafter Lebrun-Frenay.
With regard to claim 1, Barfield discloses a mass spectrometry device configured to (i) generate a peak representing acetaminophen drug in an extracted DBS sample, and (ii) generate a peak representing an internal standard (isotopically-labeled acetaminophen). Barfield further discloses computer-readable memory comprising computer-executable instructions and one or more processors coupled to the mass spectrometry device (implicit to an HPLC-MS/MS and further discussed with the processing of the integrated Analyst software in section 2.6) and configured to carry out operations comprising determining a peak area ratio of acetaminophen in the extracted DBS sample to the internal standard (abstract; section 2.1, 2.6, fig. 2, for example).
Barfield provides a commensurately-disclosed mass spectrometer that is configured as in item (i) and fully capable of use therewith the recited prospective teriflunomide (and wherein the DBS sample, its point of origin, and pre-processing therewith are not positively provided elements of the system) is also fully capable of generating as in item (ii) with respect to an internal standard, wherein the internal standard is 0.02 micrograms/mL, in which teriflunomide, nor the DBS sample itself and its recited point of origin and pre-processing thereof are not required by the claim.
With regards to claims 5-7, the recitations are drawn to prospective workpieces not afforded patentable weight, wherein teriflunomide is not a positively claimed element of the device, and Barfield commensurately a mass spectrometer as claimed that is fully capable of use to generate a peak representative of teriflunomide those particulars thereof as in cls. 5-7 in as much as recited and required herein.
With regard to claim 1, Barfield does not specifically the one or more processors being configured to carry out the operations as claimed with respect to teriflunomide.
Thomassian discloses a test kit and system for a teriflunomide quantitation assay, including an isotopically labeled internal standard (pars.[0061-0065], for example). Thomassian further discloses utilizing standards of teriflunomide starting at about 10ng/mL (0.1 microgram/mL) (pars.[0008,0100-0103], for example). Further, Thomassian discloses suitable isotopic labels include deuterium (2H), 13C, and 15 N, and one or more isotopic labels can be incorporated at one more positions in the molecule and one more kinds of isotopic labels can be used on the same isotopically labeled molecule(pars.[0081,0082]).
Lebrun-Frenay discloses that teriflunomide is contraindicated (i.e. the drug should not be used) in pregnancy based on embryo-fetal toxicity (abstract).
It would have been obvious to one of ordinary skill in the art to modify Barfield to provide a quantitative assay to teriflunomide in a similar mass spectrometry system such as taught by Thomassian in which Thomassian likewise provides that teriflunomide is another clinically significant drug benefiting from a mass spec. analysis for assaying the drug’s elimination from the body and which analogously utilizes a isotopically labeled standard (and including those as in cls. 5-7 for representative peaks) to accurately determine a relative amount of the drug to such an internal standard. While Thomassian discloses internal standards starting at 0.1 micrograms/mL and assessing teriflunomide levels at a target of 20ng/mL or less to assess effectiveness of cholestyramine drug elimination, it would have been obvious to one of ordinary skill in the art to provide such an assessment of at a much lower target level of the drug as in 0.02 micrograms/mL such as suggested by Lebrun-Frenay in which it is seen that teriflunomide is a contraindicated drug during pregnancy due to its fetal toxicity and thereby should be evaluated to be effectively completely absent from the patient given the sensitive circumstances to best provide evaluation for a healthy pregnancy.
Additionally, while Barfield (and as would be subsequently applied in view of the applied, analogous disclosures of Thomassian and Lebrun-Frenay) discloses utilizing determining a peak area ratio of acetaminophen in the extracted DBS sample to the internal standard to assess the relative amount of acetaminophen in the sample, Barfield as modified does not particularly disclose that the chosen ratio is 1. However, this represents an obvious engineering choice in the statistical analysis of the data that is of no particular consequence as it remains that the evaluation is predicated on assessing the target’s level being below that of the level of the internal standard to inform the patient/practitioner that the drug level is acceptable/unacceptable for safe pregnancy.
With regards to claims 2 and 3, these recitations are descriptive to the ratio and do not add any further, particular processing steps to that of claim 1, wherein modified-Barfield, as discussed above, provides for such processed ratio in as much as claimed and consistent with the relative assessment thereof in which being less than 1 represents a lack of toxicity to the fetus (less than the threshold given by the internal standard) and greater than 1 (greater than the threshold given by the internal standard) indicating a level of the drug that is harmful to the fetus.
Claim(s) 8-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Barfield in view of Thomassian, Lebrun-Frenay, and Anderson (US 2016/0282361).
Barfield, Thomassian, and Lebrun-Frenay have been discussed above.
With regard to claim 8, Barfield does not specifically disclose a mass spectrometer for generating a peak representing a second internal standard, and the one or more processors are configured to identify the administrated treatment as being effective as in (i) and (ii) as recited therein, and wherein the generated peaks are with respect to a drug from a pregnant subject after treatment for multiple scelerosis.
Anderson discloses methods for interpretation of mass spectrometric tests for clinical biomarkers in which amounts of internal standards are set to equal clinical evaluation threshold, and utilizing isotope-labeled peptides for accurate assessment (abstract). Anderson discloses utilizing first and second internal standard stable-isotope labeled peptides added to the sample to establish a clinical reference interval lower limit and a clinical reference upper limit, wherein the result of the test is read directly by comparison of the height of the predominant analyte peak with the height of the predominant peaks of each internal standard to determine if the analyte is below, within, or above the reference interval (pars.[0006,0116], for example).
It would have been obvious to one of ordinary skill in the art to modify Barfield to provide a quantitative assay to teriflunomide (a “drug…” herein) in a similar mass spectrometry system such as taught by Thomassian/Lebrun-Frenay in which Thomassian likewise provides that teriflunomide is another clinically significant drug benefiting from a mass spec. analysis, and utilizing a first and second internal standard at the lower and upper clinical limits, respectively, as taught by Anderson in which the patient’s sample can then be suitably assessed for the drug’s clinical significance against both the lower limit (minimal therapeutic efficacy) and upper limit (maximal therapeutic efficacy) in a single mass spec. assay to thus provide a more accurate and full assessment of the target drug of interest to better inform the practitioner of the patient’s health.
Additionally, while Barfield (and as would be subsequently applied in view of the applied, analogous disclosures of Thomassian, Lebrun-Frenay, and Anderson) discloses utilizing determining a peak area ratio of acetaminophen in the extracted DBS sample to the internal standard to assess the relative amount of acetaminophen in the sample, Barfield as modified does not particularly disclose that the chosen ratio is 1. However, this represents an obvious engineering choice in the statistical analysis of the data that is of no particular consequence as it remains that the evaluation is predicated on assessing the target drug level being above the lower limit, but below the upper limit to provide an assessment of a relative safe level of the drug in the patient while maintaining the drug’s desired therapeutic effect.
Further, with regards to claims 9 and 10, these recitations are descriptive to the ratio and do not add any further, particular processing steps to that of claim 8, wherein modified-Barfield, as discussed above, provides for such processed ratios in as much as claimed herein and are representative of such in as much as required herein.
With regards to claims 11 and 12, these recitations are drawn to intended usage that are not afforded patentable weight, and wherein the above-discussed prior art generates peaks representing these internal standards in as much as claimed and required herein.
Response to Arguments
Applicant's arguments filed February 23rd, 2026 have been fully considered but they are not persuasive.
With regards to claims 1-3 and 5-7 rejected under 35 USC 103 as being unpatentable over Barfield in view of Thomassian and Lebrun-Frenay, Applicant traverses the rejection.
Applicant asserts that the claim 1 has been amended as recited therein and with respect to claims 8-14, Applicant asserts that claim 8 has been amended as recited therein.
Applicant asserts that none of Barfield, Thomassian, and Lebrun-Frenay disclose or suggest the system as amended in claim 1, and likewise with respect to the cited prior art and independent claim 8.
Examiner maintains that claims 1-3 and 5-7, and 8-14 are properly rejected under 35 USC 103 as being unpatentable over the cited art of record.
Examiner further asserts that Applicant has not provided any substantive remarks or arguments thereto beyond referencing the amendments made herein within clause (i) to the mass spectrometer.
Examiner reiterates a likewise discussion as presented previously in the Office Action mailed on December 23rd, 2025 that remain pertinent herein with respect to the amendments of claims 1 and 8.
The claims system (including the system of independent claim 8 and dependents thereof), which are drawn to a system, do not require/necessitate active steps of a course of action or treatment let alone positively providing a provision/step of a subject who is administered teriflunomide.
The claims do not necessitate teriflunomide as a positive elements of the systems, and likewise with respect to its base sample in that of DBS sample, nor does the point of origin with respect to a pregnant subject and having gone through a treatment for multiple sclerosis have any particular bearing to the claims. This is likewise seen with respect to the further discussion to the DBS sample being obtained from the pregnant subject and a filter paper pretreated with an internal standard, which has no particular positive bearing to the claims.
The claims provide are drawn to comprising a mass spectrometer as claimed and CRM/processor(s) for executing those steps as recited therein.
The prior art of Barfield (and likewise as in Thomassian) commensurately provides a mass spectrometry device configured as in items (i) and (ii) as the prior art of Barfield provides a mass spectrometer commensurately as claimed wherein there is no structural distinction in the claims from that of the mass spectrometer of Barfield, and wherein the provided functionalities to the configurations (i) and (ii) represent intrinsic capabilities given to a mass spectrometer at is baseline. A mass spectrometer is configured to generate a mass spectrum as a “fingerprint” of the compound/sample introduced thereto wherein the spectrum is comprised of plotted peaks on a graph that is commensurate with the configurations (i), (ii) provided in the claim.
Further, the amended recitation to “generate a peak representing teriflunomide in an extracted dried blood spot (DBS)…from a pregnant subject after a treatment for multiple scleorisis has been administered…wherein the DBS sample comprises blood obtained from the pregnant subject and a filter paper pretreated with an internal standard…” the recitations to the DBS sample, its point of origin (obtained from the pregnant subject and a filter paper pretreated with an internal standard), and administration of a treatment of multiple sclerosis are not drawn to positively claimed elements and/or actions/steps afforded to the methodology.
The recitation remains drawn to a mass spectrometer and its functionality, wherein the mass spectrometer of Barfield is commensurately configured as claimed.
A mass spectrometer is configured to generate a mass spectrum as a “fingerprint” of the compound/sample introduced thereto wherein the spectrum is comprised of plotted peaks on a graph that is commensurate with the configurations (i), (ii) provided in the claims.
As discussed above, the sample itself, its point of origin, and administration of a treatment of multiple sclerosis are not positively claimed elements and/or actions afforded to the methodology and are drawn to prospective workpieces to be utilized with a mass spectrometer as it pertains to a subject sample to be investigated by a mass spectrometer.
Claims 1-3, 5-7, and 8-12 (in which claims 13&14 are canceled herein) are maintained rejected under 35 USC 103 as being unpatentable over the above-cited prior art for these reasons and those discussed above.
Further, and upon further consideration of the claims, claims 1-3 and 5-12 are rejected under 35 USC 101 as being drawn to a judicial exception without significantly more for the reasons discussed above in the body of the action.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NEIL N TURK whose telephone number is (571)272-8914. The examiner can normally be reached M-F 930-630.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi can be reached at 571-270-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NEIL N TURK/ Primary Examiner, Art Unit 1798
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