Prosecution Insights
Last updated: April 19, 2026
Application No. 18/276,323

CALIBRANT FOR USE IN MASS SPECTROMETER AND METHOD FOR PRODUCING SAME

Non-Final OA §102§103
Filed
Aug 08, 2023
Examiner
WASHINGTON, BRITNEY NICOLE
Art Unit
1797
Tech Center
1700 — Chemical & Materials Engineering
Assignee
Shimadzu Corporation
OA Round
1 (Non-Final)
85%
Grant Probability
Favorable
1-2
OA Rounds
3y 5m
To Grant
99%
With Interview

Examiner Intelligence

Grants 85% — above average
85%
Career Allow Rate
40 granted / 47 resolved
+20.1% vs TC avg
Strong +15% interview lift
Without
With
+15.1%
Interview Lift
resolved cases with interview
Typical timeline
3y 5m
Avg Prosecution
28 currently pending
Career history
75
Total Applications
across all art units

Statute-Specific Performance

§101
2.4%
-37.6% vs TC avg
§103
45.7%
+5.7% vs TC avg
§102
37.8%
-2.2% vs TC avg
§112
12.0%
-28.0% vs TC avg
Black line = Tech Center average estimate • Based on career data from 47 resolved cases

Office Action

§102 §103
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 Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. JP2021-026450, filed on 02/22/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Claim Rejections - 35 USC § 102 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 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. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim(s) 1, 3, and 5-6 are rejected under 35 U.S.C. 102(a)(1) based upon a public use or sale or other public availability of the invention. The closest prior art is Andreas Leinenbach, Josef Pannee, Thomas Dülffer, Andreas Huber, Tobias Bittner, Ulf Andreasson, Johan Gobom, Henrik Zetterberg, Uwe Kobold, Erik Portelius, Kaj Blennow, on behalf of the IFCC Scientific Division Working Group on CSF proteins, Mass Spectrometry–Based Candidate Reference Measurement Procedure for Quantification of Amyloid-β in Cerebrospinal Fluid, Clinical Chemistry, Volume 60, Issue 7, 1 July 2014, Pages 987–994, https://doi.org/10.1373/clinchem.2013.220392 herein referred to as Leinenbach et al. Regarding Claim 1, Leinenbach et al. teaches a calibrant for use in a mass spectrometer (See the Background section and the calibration curve illustrated in Fig. 1 pg. 991), the calibrant comprising not less than two calibration substances, wherein a ratio of, relative to a concentration of one calibration substance of the not less than two calibration substances, a concentration of another calibration substance of the not less than two calibration substances is a predetermined value (See how the calibration samples are made by spiking a CSF pool with different concentrations of [15N]Aβ42 {CSF concentrations: 150, 500, 1000, 2000, 3000, and 4000 pg/mL} and a constant concentration of [13C]Aβ42 {CSF concentration: 1600pg/mL} as internal standard in the Calibration and Sample Preparation section pg. 988). Regarding Claim 3, Leinenbach et al. teaches the device and/or method limitations of claim 1. Leinenbach et al. further teaches a calibrant for use in a mass spectrometer (See the Background section and the calibration curve illustrated in Fig. 1 pg. 991),wherein the calibration substances are Aβ related peptides (See Fig. 1-4). Regarding Claim(s) 5-6, Leinenbach et al. teaches the device and/or method limitations of claim 1. Leinenbach et al. further teaches a calibrant for use in a mass spectrometer (See the Background section and the calibration curve illustrated in Fig. 1 pg. 991), wherein the calibrant comprises a plurality of calibrants which are respectively different in a concentration of at least one calibration substance of the not less than two calibration substances (See in the Calibration and Sample Preparation section pg. 988); wherein a ratio of, relative to a concentration of one calibration substance of the not less than two calibration substances, a concentration of another calibration substance of the not less than two calibration substances is in a range of 1/4 to 4 (See Fig. 1-4 and in Tables 1-2). Claim(s) 7-13 and 14-16 are rejected under 35 U.S.C. 102(a)(1) based upon a public use or sale or other public availability of the invention. The closest prior art is Li et al. (CN107765015A). Regarding Claim 7, Li et al. teaches a method for producing a calibrant for use in a mass spectrometer (See the Abstract and the Claim(s) 1-7 in [0043]-[0045], [0048]-[0051], [0075], [0078] in Fig. 1), the calibrant comprising not less than two calibration substances, wherein a ratio of, relative to a concentration of one calibration substance of the not less than two calibration substances, a concentration of another calibration substance of the not less than two calibration substances is a predetermined value (See how an Aβ40 standard protein and an internal standard material Aβ42 for evaluating a linear dependency relating to Aβ measurements using MALDI-TOF in [0043]-[0045]), and the method comprising: a previous step of preparing: a solution A which comprises one calibration substance (S 1) of the not less than two calibration substances at a predetermined concentration, and a solution B which comprises the one calibration substance (S1) of the not less than two calibration substances at a concentration equal to the predetermined concentration, and further comprises another calibration substance (S2) of the not less than two calibration substances; and a preparation step of obtaining a calibrant in which a ratio of, relative to a concentration of the one calibration substance (SI), a concentration of the another calibration substance (S2) is a predetermined value by using the solution A and the solution B (See how mixing these materials in different proportions, and as such the Aβ40 standard protein and the internal standard material Aβ42 are considered to be calibrants for which the concentration ratio is a prescribed value (See in [0021], [0043]-[0045]). Regarding Claim(s) 8-13, Li et al. teaches the method limitations of claim 7. Li et al. further teaches a method for producing a calibrant for use in a mass spectrometer (See the Abstract and the in [0043]-[0045], [0048]-[0051], [0075], [0078] in Fig. 1), wherein, in the preparation step, a plurality of calibrants which are constant in a concentration of the one calibration substance (S1) and respectively different at least in a concentration of the another calibration substance (S2) are obtained; wherein, in the preparation step, the calibrant in which the ratio of, relative to the concentration of the one calibration substance (S1), the concentration of the another calibration substance (S2) is the predetermined value is obtained by using the solution A and the solution B, a mixing operation is performed to separate a part of the calibrant from the resulting calibrant and further mix the part of the calibrant separated with the solution A, and thereby another calibrant in which a ratio of, relative to a concentration of the one calibration substance (S 1), a concentration of the another calibration substance (S2) is a different value from the predetermined value is obtained; wherein, in the preparation step, the calibrant in which the ratio of, relative to the concentration of the one calibration substance (S 1), the concentration of the another calibration substance (S2) is the predetermined value is obtained by using the solution A and the solution B, a mixing operation is performed to separate a part of the calibrant from the resulting calibrant and further mix the part of the calibrant separated with the solution A in an amount equal to the part of the calibrant separated, and thereby another calibrant in which a ratio of, relative to a concentration of the one calibration substance (S1), a concentration of the another calibration substance (S2) is 1/2 of the predetermined value is obtained; wherein, in the preparation step, the mixing operation is performed two or more times sequentially; wherein, in the preparation step, the calibrant in which the ratio of, relative to the concentration of the one calibration substance (S1), the concentration of the another calibration substance (S2) is the predetermined value is obtained by using the solution A and the solution B, a mixing operation is performed to separate a part of the calibrant from the resulting calibrant and further mix the part of the calibrant separated with the solution B, and thereby another calibrant in which a ratio of, relative to a concentration of the one calibration substance (SI), a concentration of the another calibration substance (S2) is a different value from the predetermined value is obtained; wherein, in the preparation step, the calibrant in which the ratio of, relative to the concentration of the one calibration substance (S 1), the concentration of the another calibration substance (S2) is the predetermined value is obtained by using the solution A and the solution B, a mixing operation is performed to separate a part of the calibrant from the resulting calibrant and further mix the part of the calibrant separated with the solution B in an amount equal to the part of the calibrant separated, and thereby another calibrant in which a ratio of, relative to a concentration of the one calibration substance (SI), a concentration of the another calibration substance (S2) is a different value from the predetermined value is obtained (For the instant claim(s) 8-14 one with ordinary skills in the arts would know to adjust a reagent solution through mixing and separation steps based on an predetermined concentration value in Claim(s) 1-7 in [0043]-[0045], [0048]-[0051], [0075], [0078] in Fig. 1). Regarding Claim(s) 14-16, Li et al. teaches the method limitations of claim(s) 7 and 12. Li et al. further teaches a method for producing a calibrant for use in a mass spectrometer (See the Abstract and the in [0043]-[0045], [0048]-[0051], [0075], [0078] in Fig. 1), wherein, in the preparation step, the mixing operation is performed two or more times sequentially; wherein the preparation step using the solution A and the solution B is performed by volume measuring; wherein the preparation step using the solution A and the solution B is performed by weight measuring (See in [0048]-[0068]; Also, one with ordinary skills in the arts would know that mixing more than once is necessary for complex reactions and analytical measurements, and how to measure or convert substances and solutions volume concentrations and molecular weight concentrations). Claim(s) 19-22 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kaneko et al. (US20240266158A1). The applied reference has a common joint inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. Regarding Claim(s) 19-22, Kaneko et al. teaches a calibrant kit for use in a mass spectrometer (See the Abstract and the Claim(s) 1-2, 4-5, and 8 in [0065]-[0066], [0075], [0124]), the kit comprising a plurality of calibrants which comprises not less than two calibration substances, wherein the plurality of calibrants are respectively different in a concentration of at least one calibration substance of the calibration substances; the kit comprising not less than two calibration substances (See in Claim 7); wherein the kit further comprises a solvent (See in [0071]-[0078]); wherein the kit further comprises a container to accommodate a calibrant (See how the data processing unit 2 would most likely have a container or storage to hole calibrants during preparation and analysis in [0127]-[0132] in Fig. 20). 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. 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) 2 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Leinenbach et al. (https://doi.org/10.1373/clinchem.2013.220392) as applied to claim 1 above, and further in view of Kaneko et al. (US20240266158A1). Regarding Claim 2, Leinenbach et al. teaches the device and/or method limitations of claim 1. Leinenbach et al. fails to explicitly teach a calibrant for use in a mass spectrometer, wherein the calibration substances include a substance labeled with a stable isotope and a substance not labeled with a stable isotope. However, in the analogous art of correction methods for mass spectrometry, Kaneko et al. teaches a calibrant for use in a mass spectrometer (See the Abstract and the Claim(s) 1-2, 4-5, and 8 in [0065]-[0066], [0075], [0124]), wherein the calibration substances include a substance labeled with a stable isotope and a substance not labeled with a stable isotope (See how a substance labeled with a stable isotope may be used in [0065]). Thus, it would be obvious to one with ordinary skills in the arts to modify the invention of Leinenbach et al. by incorporating a substance labeled with a stable isotope and a substance not labeled with a stable isotope (as taught by Kaneko et al.) for the benefit of quantifiably creating a calibration substance for mass spectrometry. Regarding Claim 4, Leinenbach et al. teaches the device and/or method limitations of claim 1. Leinenbach et al. fails to explicitly teach a calibrant for use in a mass spectrometer, wherein the calibration substances are Aβ1-38 and a stable isotope-labeled Aβ1-38. However, in the analogous art of correction methods for mass spectrometry, Kaneko et al. teaches a calibrant for use in a mass spectrometer (See the Abstract and the Claim(s) 1-2, 4-5, and 8 in [0065]-[0066], [0075], [0124]), wherein the calibration substances are Aβ1-38 and a stable isotope-labeled Aβ1-38 (See in [0065] in Fig.1). Thus, it would be obvious to one with ordinary skills in the arts to modify the invention of Leinenbach et al. by incorporating calibration substances are Aβ1-38 and a stable isotope-labeled Aβ1-38 (as taught by Kaneko et al.) for the benefit of quantifiably creating a calibration substance for mass spectrometry. Claim(s) 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (CN107765015A) as applied to claim 7 above, and further in view of Kaneko et al. (US20240266158A1). Regarding Claim 17, Li et al. teaches the method limitations of claim 7. Li et al. fails to explicitly teach a method for producing a calibrant for use in a mass spectrometer, wherein the one calibration substance (S 1) is a substance labeled with a stable isotope, and the another one calibration substance (S2) is a substance not labeled with a stable isotope. However, in the analogous art of correction methods for mass spectrometry, Kaneko et al. teaches a calibrant for use in a mass spectrometer (See the Abstract and the Claim(s) 1-2, 4-5, and 8 in [0065]-[0066], [0075], [0124]), wherein the one calibration substance (S 1) is a substance labeled with a stable isotope, and the another one calibration substance (S2) is a substance not labeled with a stable isotope (See how a substance labeled with a stable isotope may be used in [0065]). Thus, it would be obvious to one with ordinary skills in the arts to modify the method of Li et al. by incorporating one calibration substance (S 1) is a substance labeled with a stable isotope, and the another one calibration substance (S2) is a substance not labeled with a stable isotope (as taught by Kaneko et al.) for the benefit of quantifiably creating a calibration substance for mass spectrometry. Regarding Claim 18, Li et al. teaches the method limitations of claim 7. Li et al. fails to explicitly teach a method for producing a calibrant for use in a mass spectrometer, wherein the one calibration substance (S1) is Aβ1-38 labeled with a stable isotope, and the another one calibration substance (S2) is Aβ1-38 not labeled with a stable isotope. However, in the analogous art of correction methods for mass spectrometry, Kaneko et al. teaches a calibrant for use in a mass spectrometer (See the Abstract and the Claim(s) 1-2, 4-5, and 8 in [0065]-[0066], [0075], [0124]), wherein the one calibration substance (S1) is Aβ1-38 labeled with a stable isotope, and the another one calibration substance (S2) is Aβ1-38 not labeled with a stable isotope (See in [0065] in Fig.1). Thus, it would be obvious to one with ordinary skills in the arts to modify the invention of Li et al. by incorporating one calibration substance (S1) is Aβ1-38 labeled with a stable isotope, and the another one calibration substance (S2) is Aβ1-38 not labeled with a stable isotope(as taught by Kaneko et al.) for the benefit of quantifiably creating a calibration substance for mass spectrometry. Conclusion The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The following prior art teaches similar devices and methods: Bateman et al. (US20170146557A1). Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRITNEY N WASHINGTON whose telephone number is (703)756-5959. The examiner can normally be reached Monday-Friday 7:00am - 3:30pm CT. 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, Lyle Alexander can be reached at (571) 272-1254. 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. /BRITNEY N. WASHINGTON/Examiner, Art Unit 1797 /JENNIFER WECKER/Primary Examiner, Art Unit 1797
Read full office action

Prosecution Timeline

Aug 08, 2023
Application Filed
Mar 21, 2026
Non-Final Rejection — §102, §103 (current)

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Prosecution Projections

1-2
Expected OA Rounds
85%
Grant Probability
99%
With Interview (+15.1%)
3y 5m
Median Time to Grant
Low
PTA Risk
Based on 47 resolved cases by this examiner. Grant probability derived from career allow rate.

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