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 preliminary amendment filed on June 12, 2023 is acknowledged. The application will be examined accordingly.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on September 30, 2023 and December 1, 2025 are being considered by the examiner.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it is replete with the legal terminology “said”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 1, 4-6 and 20 are objected to because of the following informalities:
In line 7 of claim 1, the limitation “compound, said analyte” should be changed to “compound and said analyte”.
In step b) of claim 1, the “chromatogram of the sample” should be “chromatogram of the admixture”. The claim explicitly associates the chromatogram with the interferent monitoring compound, which is present in the admixture, not the sample. Corresponding change should be made in claim 20.
In claims 4-6 and 20, all instances of the limitation “an interferent monitoring compound” should be changed to “the interferent monitoring compound”. Claim 1 establishes antecedent basis for the limitation.
Similarly, “a property of an interferent monitoring compound peak” and “a property of an analyte peak” in claim 20 should be changed. Antecedent basis for the limitations are established in claim 1.
Appropriate corrections are required.
Claim Rejections - 35 USC § 112
In the event the determination of the status of the application as subject to AIA (or as subject to pre-AIA ) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the rationale supporting the rejection would be the same under either status.
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.
Claims 3-6, 8-11, 13, 16-19 and 22 are 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.
In claims 3-5, the scope of the recitation, “the chromatogram is determined based on signals being identical/non-identical” is unclear. The limitation “based on” suggests the existence of a condition under which the chromatogram is determined (i.e. the chromatogram is determined only if the signals are identical/non-identical). It is unclear whether the claim intends to convey the existence of a condition.
In addition, the scope of the limitation “signals being identical” in claims 3, 5, 6 and 22 is unclear. According to the claim, the signals of the internal standard and the interferent monitoring compound peak are “identical”, yet the claim further recites a step of comparing the peaks of the two. If the signals are identical (i.e. they completely overlap), it is unclear how two peaks exist for comparison.
Claims 4-6 recite “the property of the internal standard peak”. There is no antecedent basis for the limitation.
Claim 8 recites “the first peak” and “the second peak”. There is no antecedent basis for the limitations.
Claim 9 recites “the internal standard peak”. There is no antecedent basis for the limitation.
In addition, claim 9 recites a value of the resolution without any units. Consequently, it is unclear how the resolution is determined. It appears that claim 9 should be dependent on claim 8.
Claims 10, 11 and 19 recite “said/the interferent”. There is no antecedent basis for the limitations. The claims previously recite “interferent monitoring compound”, which refers to a completely different compound/molecule.
Claim 13 recites “the chromatography mass spectrometer device”. There is no antecedent basis for the limitation.
Claim 13 is indefinite because it recites redundant subject matter. Claim 13 is dependent on claim 1, which involves determining a chromatogram. Yet, claim 13 recites a separate step of determining at least one chromatogram. It is unclear whether the claim intends to recite two separate steps of determining a chromatogram.
Claim 16 is indefinite because it recites a unitless number without any context.
Claims not explicitly rejected are rejected due to dependency.
Any changes made to the claims may require additional changes to claims not explicitly rejected above. For example, claim 17 also recites “said interferent” but it is not rejected because claim 10 provides antecedent basis.
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 1-14 and 16-22 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, which constitute an abstract idea in the form of mental processes. This judicial exception (i.e. abstract idea) is not integrated into a practical application because nothing is done with the mental processes. Moreover, while the claim further recites a step of admixing the interferent monitoring compound and the sample, this step is considered insignificant extra-solution activity, not a practical application of the mental processes 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 discussed above constitutes an additional element of the claimed method apart from the judicial exception. However, admixing a sample and an interferent monitoring compound is not deemed to be “significantly more” than the judicial exception. As discussed above, it is considered insignificant extra-solution activity. Moreover, the admixing step is considered a well-understood, routine and conventional activity (see art rejection 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 processes 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.
Claim Interpretation
Notwithstanding the definition set forth in the specification, the limitation “interferent” is context-sensitive because the nature of the interferent is dependent on an analyte being analyzed. Absent the claim(s) providing said context (e.g. identifying the analyte so as to enable one to deduce the identity of the interferant, see claims 11 and 19), the limitation “interferent” can presumably correspond to any molecule/compound. Likewise, the limitation “interferent monitoring compound” is also context-sensitive. It is dependent on the interferent, which itself is dependent on the analyte. Consequently, the interferent monitoring compound can also presumably correspond to any compound. The claims will be examined accordingly.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4, 6, 7, 10, 12-14 and 17-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by 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 1, Zhou discloses a method for providing a verified analyte measurement of a sample with a chromatography mass spectrometer device, said method comprising the following steps:
a) admixing an interferent monitoring compound (isotopically-labeled testosterone/isotopically-labeled 17β-estradiol, see Materials and Methods, p. 5944) to the sample (serum) (see abstract);
b) determining a chromatogram of the admixture by acquiring a plurality of data points for signal intensities over time for said interferent monitoring compound and said analyte (see Data analysis, p. 5946); and
c) comparing a property (peak area) of an interferent monitoring compound peak to a property of an analyte peak (see Data analysis, p. 5946).
With respect to claim 2, the interferent monitoring compound (e.g. isotopically-labeled testosterone) is an isotopologue of an interferent (testosterone).
With respect to claim 3, the subject matter of the claim recites encompasses all possible scenarios. Consequently, it is inherently anticipated by Zhou.
With respect to claim 4, step a) further comprises a step of admixing an isotope-labeled internal standard (isotopically-labeled 17β-estradiol) with the sample (see Materials and chemicals, p. 5944). In addition, the chromatogram determined in step b) is based on signals being non-identical between the analyte, the internal standard, and the interferent monitoring compound (they have different masses due to different chemical structure and/or use of isotopes), and step c) further comprises a step of comparing a property (peak area) of an internal standard peak to the property of the interferent monitoring compound peak (see Data analysis, p. 5946).
With respect to claim 6, as discussed above (see rejection of claim 1), in step a) the interferent monitoring compound is admixed with the sample, and the interferent monitoring compound is isotope-labelled. Moreover, in step b) the chromatogram is determined based on signals being non-identical between the analyte and the interferent monitoring compound, as discussed above (see rejection of claim 4). Lastly, in step c) the property of the analyte peak is compared to the property of the interferent monitoring compound peak (see rejection of claim 1).
With respect to claim 7, as discussed above (see rejection of claim 1), the peaks corresponding to the analyte and the interferent monitoring compound are 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, as discussed above, there is no antecedent basis for the limitation “said/the interferent”. In other words, the method of claim 1 does not involve an interferent. Moreover, given the abstract nature of the analyte, the interferent, and the interferent monitoring compound, the claims specifying an isomeric relationship between the interferent and the analyte does not appear to further limit the interferent monitoring compound. Consequently, the method taught by Zhou is deemed to anticipate the claims. Nevertheless, the interferant (epitestosterone) in the sample taught by Zhou is an isomer of the analyte (testosterone), and the interferent monitoring compound (isotopically-labeled testosterone) taught by Zhou is deemed to satisfy the requirements of “interferent monitoring compound” with respect to the analyte and the interferent as defined in the specification.
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 Zhou teaches all of the steps of the claimed method (see rejection of claim 1), claim 12 is also anticipated. Nevertheless, the method taught by Zhou is a method of routine analyte measurement.
With respect to claim 13, the method taught by Zhou involves measuring the admixture using a chromatography mass spectrometer device (see p. 5945), and the method further comprises evaluating the quality of the measurement based on the comparison of the peaks to each other and to a known value (see Method validation, p. 5946).
With respect to claim 14, Zhou discloses a system that performs the method discussed above, the system comprising at least one chromatography mass spectrometer device for carrying out step b) (see p. 5945 disclosing use of LC-MS/MS), and at least one evaluation device (AB Sciex software) configured for performing at least step c) (see Data analysis, p/ 5946).
With respect to claim 19, the analyte is testosterone (see abstract) and the interferent is epitestosterone (see table 1 listing analytes that are considered interferents for analytes of intertest).
With respect to claim 20, as discussed above (see rejection of claim 4), step a) further comprises admixing an internal standard (isotopic 17β-estradiol) with 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 an interferent monitoring compound peak to the property of an internal standard peak and/or to the property of an analyte peak (see Data analysis, p. 5946).
With respect to claim 21, the internal standard (isotopic 17β-estradiol) is an isotopologue of the analyte (17β-estradiol) (see abstract disclosing that 17β-estradiol and testosterone are analytes of interest).
With respect to claim 22, as discussed above (see rejection of claim 4), because the isotopic composition of the analyte and the interferent monitoring compound are different, the signals corresponding to them are non-identical (i.e. subject matter IV of the claim).
Claim Rejections - 35 USC § 103
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 11 is rejected under 35 U.S.C. 103 as being unpatentable over Zhou 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, Zhou’s method is intended to quantify testosterone and estradiol in serum (see abstract). Consequently, Zhou does not disclose that the sample comprises Vitamin D.
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 Zhou to quantify Vitamin D in serum. If the method of Zhou is modified, then the analyte would be Vitamin D, and the interferent monitoring compound would be isotopically-labeled Vitamin D. Regarding the interferent, it is not part of the claimed method, hence the prior art need not teach the interferent to reject the claim. Nevertheless, Epi-Vitamin D is an interferent of Vitamin D (see abstract of Shah).
Allowable Subject Matter
Claims 5, 8, 9* and 16* are not rejected based on prior art. With respect to claim 5, it appears to recite contradictory subject matter (see 35 U.S.C. 112(b) rejection above) and hence it cannot be examined on the merits absent further clarification. Regarding claims 8, 9 and 16, due to the 35 U.S.C. 101 rejection set forth above, they are not deemed to contain allowable subject matter.
*As indicated above, claim 9 and its dependent claim 16 are being interpreted to be dependent on claim 8, not claim 1.
As discussed above, Zhou discloses a method for providing a verified analyte measurement of a sample with a chromatography mass spectrometer device. However, Zhou does not disclose a method of determining a resolution based on the formula recited in claim 8. Moreover, while determining resolution between signals in LC-MS/MS is considered conventional, based on how the limitations “analyte peak” and “interferent monitoring compound peak” have been mapped to the disclosure of Zhou, there is no motivation to perform the claimed calculation.
Conclusion
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.
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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.
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/PAUL S HYUN/Primary Examiner, Art Unit 1796
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