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 .
Response to Amendment
The amendment filed on June 30, 2026 is acknowledged. Claims 1-14 and 16-25 are pending. Applicant amended claims 1, 3-6, 8, 9, 13, 16 and 20, and added new claims 23-25. Applicant also filed a replacement abstract.
Response to Arguments
Applicant's arguments directed to the patentability of the claims have been fully considered but they are not persuasive.
Regarding the outstanding 35 U.S.C. 101 rejection, Applicant argues that the rejection should be withdrawn because the rejection incorrectly identifies a mental process in the language of claim 1. Remarks 15. The basis for the argument is that “a person is clearly not going to generate an admixture, determine a chromatogram of the admixture…, and compare peak properties in the human mind”. Id.
The argument is not persuasive. Contrary to Applicant’s remarks, the rejection is not indicating that the entirety of claim 1 constitutes a mental process. Rather, the rejection identifies only step c) of claim 1 as a mental process. Based on the broadest reasonable interpretation of step c), the step can be performed in the human mind (regardless of whether it is actually done in the human mind), making step c) a mental process in the context of 35 U.S.C. 101 analysis.
Applicant also argues that the admixing in step a) of claim 1 integrates the mental process of step c) into a practical application because the admixing involves effecting a transformation or reduction of a particular article to a different state or thing. Remarks 16.
The argument is not persuasive for multiple reasons:
admixing, without specifying the nature of the admixing, does not convey transformation with particularity as required by MPEP 2106.05(c). “Admixing”, based on the broadest reasonable interpretation, encompasses mixing two substances without inducing transformation.
even if the admixing induces transformation, the claim is not particular regarding the article(s) being admixed as required by MPEP 2106.05(c). Claim 1 recites “a sample” and “an interferent monitoring compound”, which are both broad in scope and can potentially refer to any combination of substances that can be analyzed by chromatography-mass spectrometry.
The “transformation” alleged by Applicant (i.e. admixing) is so untethered to the judicial exception (comparing peaks) identified in the rejection such that the “admixing” cannot be considered a practical application of the “comparing” recited in claim 1. As indicated in the rejection, the admixing step is instead considered an “insignificant extra-solution activity” that is tangentially affiliated with the comparing step. See MPEP 2106.05(g).
Applicant also argues that the claim “adds a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field”. Remarks 17. To support the argument, Applicant cites to the Office action’s treatment of claims 5, 8, 9 and 16 with respect to prior art (i.e. the claims were not rejected). Remarks 18.
The argument is not persuasive for multiple reasons:
First, the subject matter of the dependent claims does not affect the analysis of claim 1. Each claim is analyzed on its own merits. Consequently, the subject matter of claims 5, 8, 9 and 16 cannot be the basis for overcoming the rejection of claim 1.
Second, the subject matter of claims 8, 9 and 16 recite an additional judicial exception (claim 8 recites a new mathematical calculation). To obviate a rejection under 35 U.S.C. 101, the claims must recite an additional element, apart from the judicial exception, that “adds a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field”. In other words, “the specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field” cannot itself be a judicial exception. Consequently, Applicant’s arguments that claims 8, 9 and 16 “add[s] a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field” so as to obviate a rejection under 35 U.S.C. 101 is not persuasive.
Regarding the prior art rejections, despite the new grounds of rejection set forth below, some of Applicant’s arguments remain pertinent. That said, Applicant’s arguments have been fully considered but they are not persuasive.
Regarding Applicant’s argument that the prior art must teach a step of “providing a verified analyte measurement” (see Remarks 20), the argument is not persuasive because a method claim is defined by its step(s), and claim 1 does not recite a step of verifying analyte measurement of a sample. While the preamble recites that the claimed method is “for providing a verified analyte measurement of a sample”, the recitation merely conveys the purpose/intended use of the claimed method (i.e. it does not “breathe life” into the claim). See MPEP 2111.02(II). Consequently, Applicant’s argument that the claims are patentable because the prior art does not teach a step of “providing a verified analyte measurement of a sample” is not persuasive.
Claim Objections
Claims 4-6, 20 and 22 are objected to because of the following informalities:
In step b) of claim 20, the “chromatogram of the sample” should be changed to “chromatogram of the admixture”. The claim explicitly associates the chromatogram with data points of the internal standard and the interferent monitoring compound, which are present in the admixture, not the sample. Claim 1 was previously objected to and Applicant made the correction to claim 1, but the correction was not made to claim 20.
In claims 4-6 and 22, the limitation “based on” should be amended/deleted in the same manner as claim 3. The limitation suggests the existence of a condition, which does not appear to be the intent of the claims. Applicant amended claim 3 to obviate this suggestion without traversing the rejection.
Appropriate corrections are required.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 23 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 23 is indefinite because the limitation “is selected” is recited in passive voice. It is unclear whether the limitation intends to convey a method step (i.e. further recite a step of selecting the peak property). Method steps should be recited in active voice (e.g. “further comprising selecting the property…”).
Claim Rejections - 35 USC § 101
Claims 1-4, 6-14 and 16-25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 1 recites the steps of determining a chromatogram of an admixture of a sample and an interferent monitoring compound, and subsequently comparing the peaks in said chromatogram, wherein the comparing step constitutes an abstract idea in the form of a mental process. This judicial exception (i.e. abstract idea) is not integrated into a practical application because nothing is done with the mental process. Moreover, while the claim further recites steps of admixing the interferent monitoring compound and the sample and acquiring data points, these steps are considered insignificant extra-solution activity, not a practical application of the mental process identified above. In addition, the claim does not recite additional elements that are sufficient to amount to significantly more than the judicial exception so as to obviate a rejection under 35 U.S.C. 101. In this instance, the admixing step and gathering data discussed above constitute additional elements of the claimed method apart from the judicial exception. However, admixing a sample and an interferent monitoring compound and subsequently gathering data on the admixture is not deemed to be “significantly more” than the judicial exception. As discussed above, they are considered insignificant extra-solution activity. Moreover, they are considered well-understood, routine and conventional activity (see art rejection of claim 1 set forth below).
As for the rejected dependent claims, they fail to cure the deficiencies of claim 1. Like claim 1, they fail to integrate the mental process identified above into a practical application, and as indicated below (see art rejections below), the additional elements are not deemed to be “significantly more” than the judicial exception.
In some cases (e.g. claims 7-9 and 13), the dependent claims recite additional mental processes (identifying/determining/calculating/verifying/evaluating steps) that are not integrated into a practical application or reciting additional elements sufficient to amount to significantly more than the respective judicial exceptions. Consequently, these claims may remain rejected even if the issues of claim 1 identified above are resolved. Each claim is analyzed on its own merits.
Claim Interpretation
When a method step is introduced, it should be recited in active voice (e.g. “admixing”) as opposed to passive voice (e.g. “are admixed”) (see claim 4). Otherwise, the scope of the claim(s) may be rendered ambiguous because it is unclear whether certain verbs convey method steps or intent. For claims that recite verbs in passive voice, they will be appropriately interpreted based on context. Applicant is advised to amend the claims as necessary to obviate the potential for indefiniteness.
Applicant amended claim 4 based on the example cited above. However, the example was not meant to be exhaustive, and the claims remain replete with other instances of verbs recited in passive voice (e.g. “is determined” in claim 4). Applicant is advised to review ALL of the claims and make appropriate changes, including making further changes to claim 4.
Claim Rejections - 35 USC § 102
Claim 14 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Horak et al. (“Horak”) (WO 2020/065047 A1).
With respect to claim 14, Horak discloses a system for determining an amount of at least one analyte in a sample, the system comprising:
at least one chromatography-mass spectrometer device (UHPLC-QTOF-ESI-MS) configured to determine a chromatogram of an admixture of an analyte and a interferent monitoring compound (see Fig. 2c and [0009]); and
at least one evaluation device (software) configured to compare a property of two peaks (see [0014]).
Claim 14 is directed to a system. While the claim refers to the method of claim 1, the patentability of the claim is based on the system itself and what it is configured to do. That said, prior art need not teach the method of claim 1 to anticipate claim 14. In this instance, the system taught by Horak can perform steps b) and c) of claim 1. Hence, it is “configured to” perform steps b) and c).
Claim Rejections - 35 USC § 103
Claims 1-4, 6, 7, 10, 12, 13, 17, 18 and 20-25 are rejected under 35 U.S.C. 103 as being unpatentable over Horak.
With respect to claim 1, Horak discloses a method for providing a verified analyte measurement of a sample with a chromatography mass spectrometer device, said method comprising the following steps:
admixing an interferent monitoring compound (internal standard) to the sample to create an admixture (see [0076]), wherein the interferent monitoring compound is configured for monitoring an interferent (see [0028] disclosing that the interferent monitoring compound is used for “accurate quantification of…samples containing chiral amino acids and analogs”, which interfere with one another); and
analyzing eluents for the presence of the interferent monitoring compound using a mass analyzer (see [0076]).
The method taught by Horak differs from the claimed invention in that Horak does not explicitly teach the steps of determining a chromatogram of the admixture and subsequently comparing a property of an interferent monitoring compound peak to a property of an analyte peak.
However, based on Horak’s disclosure of “analyzing the eluent for the presence of [the interferent monitoring compound]…using a mass analyzer” (see [0076]) and given that the interferent monitoring compound is used as an internal standard, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have:
determined a chromatogram of the admixture by acquiring a plurality of data points for signal intensities over time for the interferent monitoring compound and the analyte; and
comparing a property (e.g. relative intensity) of the peaks of the interferent monitoring compound and the analyte.
With respect to step b), Horak explicitly discloses producing chromatograms in other methods in which eluents are analyzed (see Figs. 1c, 2c). With respect to step c), the step is considered a conventional way of determining the concentration of the analyte in the sample using an internal standard (i.e. comparing intensities of internal standard and analyte).
With respect to claims 2 and 3, because the interferent monitoring compound is an isotopologue of the analyte (see abstract), the chromatogram would comprise non-identical signals for the analyte and the interferent monitoring compound (see also Fig. 2 illustrating how use of isotopes produces chromatograms with different peak patterns).
With respect to claim 4, the interferent monitoring compound is a part of a composition comprising a plurality of isotopologues of the analyte (see abstract), wherein each isotopologue constitutes an internal standard. In other words, one of the isotopologues anticipates the claimed “interferent monitoring compound” and another isotopologue anticipates the claimed “internal standard”. That said, step a) comprises admixing the interferent monitoring compound and an internal standard to the sample, wherein the interferent monitoring compound and the internal standard are isotopically labeled. Moreover, because the interferent monitoring compound and the internal standard are isotopologues of the analyte, the chromatogram would comprise non-identical signals for the analyte, the interferent monitoring compound and the internal standard. Lastly, step c) would comprise comparing the peaks belonging to all three entities.
With respect to claim 6, as discussed above (see rejection of claims 1 and 2), the subject matter of the first alternative is rendered obvious in view of Horak.
With respect to claim 7, as discussed above (see rejection of claim 1), the peaks corresponding to the analyte and the interferent monitoring compound would be compared. Naturally, said step encompasses performing peak identification of at least one interferent monitoring compound peak and at least one analyte peak.
With respect to claims 10, 17 and 18, the interferent is not a part of the claimed method. The identity of the interferent merely provides context for analyte and the interferent monitoring compound. That said, as discussed above (see rejection of claim 1), the interferent is a chiral compound of the analyte (e.g. epimer, stereoisomer) (see also [0028]).
With respect to claim 12, the subject matter of the claim is directed to an intended use of the claimed method. A method is defined by its step(s). In this case, because Horak renders obvious all of the steps of the claimed method (see rejection of claim 1), claim 12 is also rejected. Nevertheless, the method taught by Horak is a method of routine analyte measurement.
With respect to claim 13, while Horak does not explicitly disclose the use of a chromatography-mass spectrometer for conducting the method disclosed in [0076], Horak teaches other methods in which chromatograms are produced using LC-MS (see [0009]). In light of the disclosure, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used LC-MS to conduct the method of claim 1. Moreover, given that the interferent monitoring compound is used as an internal standard, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have evaluated the quality of the LC-MS measurement based on the degree of calibration required to determine the concentration of the analyte.
With respect to claim 20, as discussed above (see rejection of claim 4), step a) further comprises admixing an internal standard to the sample, step b) comprises determining a chromatogram of the admixture by acquiring a plurality of data points for signal intensities over time for said interferent monitoring compound, said analyte, and said internal standard, and step c) comprises comparing the property of the interferent monitoring compound peak to the property of an internal standard peak and/or to the property of the analyte peak.
With respect to claim 21, as discussed above (see rejection of claim 4), the internal standard is an isotopologue of the analyte.
With respect to claim 22, as discussed above (see rejection of claims 3 and 4), because the isotopic composition of the analyte and the interferent monitoring compound are different, the signals corresponding to them would be non-identical.
With respect to claim 23, in order to compare a property of the peaks, the property to be compared must first be mentally selected. As for the recitation “to allow establishing…interferent monitoring compound peak”, the recitation is directed to the intended use of the selection made. It is not a tangible step. Because a method is defined by its step(s), prior art need not teach the recitation to reject claim 23.
With respect to claim 24, as discussed above (see rejection of claim 1), the property comprises peak height.
With respect to claim 25, the chromatogram also exhibits retention time (e.g. see Fig. 2c), and Horak teaches determining the retention times of the peaks when analyzing the chromatogram (see [0106]). In light of the disclosure, it would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have compared the retention times of the peaks corresponding to the analyte and the interferent monitoring compound in step c).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Horak as applied to claims 1-4, 6, 7, 10, 12, 13, 17, 18 and 20-25 above, and further in view of Shah et al. (“Shah”) (“Misleading measures in Vitamin D analysis: A novel LC-MC/MS assay to account for epimers and isobars” (cited on IDS).
With respect to claim 11, Horak does not explicitly disclose a method of quantifying vitamin D in a sample.
Shah discloses an analogous method of quantifying biomarkers in serum (see abstract and Materials and methods, p. 2-3), wherein the biomarkers comprise Vitamin D (see abstract). According to Shah, Vitamin D plays a vital role in the body and it can be used as a biomarker for diagnosing diseases, hence there is a need to quantify it (see Introduction). In light of the disclosure of Shah, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the method taught by Horak to quantify Vitamin D in serum. If the method of Horak is modified, then the analyte would be Vitamin D, the interferent would be an epimer of vitamin D (see abstract of Shah), and the interferent monitoring compound would be an isotopically-labeled epimer of vitamin D.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Horak as applied to claims 1-4, 6, 7, 10, 12, 13, 17, 18 and 20-25 above, and further in view of Zhou et al. (“Zhou”) (“Simultaneous measurement of total estradiol and testosterone in human serum by isotope dilution liquid chromatography tandem mass spectrometry” (cited on IDS).
With respect to claim 19, Horak does not explicitly disclose a method of quantifying testosterone in a sample.
Zhou discloses an analogous method of quantifying biomarkers in serum (see abstract), wherein the biomarkers comprise testosterone (see abstract). According to Zhou, testosterone can be used as a biomarker for diagnosing diseases (see abstract). In light of the disclosure of Zhou, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the method taught by Horak to quantify testosterone in serum. If the method of Horak is modified, then the analyte would be testosterone, the interferent would be an epimer of testosterone, and the interferent monitoring compound would be an isotopically-labeled epimer of testosterone.
Allowable Subject Matter
Claim 5 would be allowable if it is rewritten to overcome the applicable objection(s) set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
As discussed above, Horak discloses a method for determining an amount of at least one analyte in a sample using an internal standard and an interferent monitoring compound. However, Horak does not disclose a method in which the signals of the internal standard and the interferent monitoring compound are identical, as recited in claim 5, and based on the disclosure of Horak, there is no motivation to modify the method such that the internal standard and the interferent monitoring compound produce identical signals.
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 PAUL S HYUN whose telephone number is (571)272-8559. The examiner can normally be reached M-F 8:30-5:00.
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, Luan Van can be reached at 571-272-8521. 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.
/PAUL S HYUN/Primary Examiner, Art Unit 1796
Prosecution Insights