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
This application filed 07/29/2022 is a National Stage entry of PCT/CN2021/083495, with an International Filing Date of 03/29/2021, and claims foreign priority to 202010429597.7, filed 05/20/2020. The claims are therefore examined as filed on 05/20/2020, the effective filing date. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further review of the priority application(s).
Claim Status
Claims 1-10 are pending.
Claims 2, 4-5 are objected to.
Claims 1-10 are examined.
Claims 1-10 are rejected.
Information Disclosure Statement
The Information Disclosure Statements are in compliance with the provisions of 37 CFR 1.97. Accordingly, all references have been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see sections [050, and 78-79]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 2 and 4-5 are objected to because of the following informalities:
Claims 2, 4-5 contain the phrase “mixing same” which appears to be a translation error. The Examiner recommends changing this phrase to refer to the specific solutions being mixed.
Claims 4-5 similarly contain the phrase “concentrating same” which appears to be a translation error. The Examiner recommends changing this phrase to refer to the specific solutions being concentrated.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 1-10 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 1 recites the limitation "selecting the optimal isotope internal standard" in step f. There is insufficient antecedent basis for this limitation in the claim, and no clear definition for what is considered “the optimal isotope internal standard” or how it is selected. Section [052] of the specification describes one potential embodiment for selecting an optimal isotope internal standard, but this does not clarify the full metes and bound of the claim limitation. The Examiner recommends integrating this section into the claim to clearly define and provide antecedent basis for the optimal isotope internal standard/how it is selected.
Claims 2-10 are rejected as they depend from claim 1 and do not resolve the issue of indefiniteness.
Claim 2 is also rejected because the term “appropriate amount” in claim 2, is a relative term which renders the claim indefinite. The term “appropriate amount” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The amounts of the internal standards/solutions used are rendered indefinite as a result, and the claim is therefore indefinite due to lack of clarity.
No Rejection Under 35 USC § 101
Claim 1 recites the additional elements of using a single UPLC/HRMS platform to collect mass spectrometry data, and doing so through formulation of an isotope internal standard mixed solution based on multiple isotope internal standards, by formulating relative quantitative standard curve correction solutions in a series of concentration gradients by using a relative quantitative correction sample and the isotope internal standard mixed solution, and by formulating a metabolomics sample solution using a metabolomics sample and isotope internal standard mixed solution. This combination of additional elements with the analysis represents an improvement to UPLC/HRMS technology as it allows for simultaneous qualitative and relative quantitative analysis of metabolomics samples based on one platform, and therefore integrates the abstract ideas of the claim (the analysis of metabolites) into a practical application.
No Rejection Under 35 USC § 102/103
No art rejection is applied to claims 1-10. Close art, such as LIU 2020 (as cited on the 07/29/2022 "Notice of References Cited" form 892), while addressing the use of multiple internal standards, obtaining raw mass spectrometry data, and identification of metabolites, does not teach formulating relative quantitative standard curve correction solutions in a series of concentration gradients by using the relative quantitative correction sample and the isotope internal standard mixed solution, then selecting the optimal isotope internal standard for linear fitting, and performing linear fitting by using concentrations of the relative quantitative standard curve correction solutions in a series of concentration gradients and variable information based on mass spectrum transposed data to acquire a linear equation used to obtain relative quantitative results. No combinable art before the effective filing date could be found to render the claims as obvious.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
SYSI-AHO 2007 “Normalization method for metabolomics data using optimal selection of multiple internal standards teaches using multiple internal standard compounds to find an optimal normalization factor for individual molecular species
DUNN 2011 “Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry” describes different protocols for metabolic profiling that include UPLC-MS
CHEKMENEVA 2018 “Ultra-Performance Liquid Chromatography−High-Resolution Mass Spectrometry and Direct Infusion−High-Resolution Mass Spectrometry for Combined Exploratory and Targeted Metabolic Profiling of Human Urine” teaches UPLC−HRMS methods for metabolic profiling
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY C LEVERETT whose telephone number is (571)272-5494. The examiner can normally be reached 8:00am - 5:00pm M-Th.
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, Karlheinz R. Skowronek can be reached at (571) 272-9047. 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.
/MARY C LEVERETT/ Examiner, Art Unit 1687