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.
Response to Arguments
Applicant's arguments filed 06/24/2026 have been fully considered but they are not persuasive.
The Examiner acknowledges and agrees with the applicant’s argument that Kaneko et al. and the instant application are commonly owned, and that Kaneko et al. is an exception under 35 USC 102(b)(2)(C). Therefore, Kaneko et al. cannot be considered prior art with respect to the instant application.
The applicant recites the instant Specification [0053] as support for the original claim 1 amendment. However, this paragraph only discloses the topic of calibration substance concentration, and does not teach or further describe the limitation(s) of “the calibration substances include a substance labeled with a stable isotope and a substance not labeled with a stable isotope, and both the substance labeled with the stable isotope and the substance not labeled with the stable isotope are the same compound” as argued. One with ordinary skills in the arts could replicate or better understand the instant invention “calibration substances” with the current Specification. Therefore, the application amendment to combine the original claim 1 with the original claim 2 cannot overcome the previous rejection.
Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Applicant's arguments do not comply with 37 CFR 1.111(c) because they do not clearly point out the patentable novelty which he or she thinks the claims present in view of the state of the art disclosed by the references cited or the objections made. Further, they do not show how the amendments avoid such references or objections.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Thus, Leinenbach et al. (https://doi.org/10.1373/clinchem.2013.220392) still reads on the claim(s) 1, 3-19, and 23 as currently presented in the application.
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.
Claim(s) 1 and 3-19 and 23 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.
The term “same compound” in claim 1 is a relative term which renders the claim indefinite. The term “same compound” 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. One with ordinary skills in the arts could replicate or better understand the instant invention “calibration substances” with the current Specification. Furthermore, it is unclear how both the substance labeled with the stable isotope and the substance not labeled with the stable isotope are the same compound as one is labeled and one is not. The application amendment to combine the original claim 1 with the original claim 2 cannot overcome the previous rejection, and renders an indefinite claim.
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, 5-6, 19, and 23 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 instant invention is anticipated by 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);
the calibration substances include a substance labeled with a stable isotope and a substance not labeled with a stable isotope, and both the substance labeled with the stable isotope and the substance not labeled with the stable isotope are the same compound (See the quantification of Aβ42 in CSF. The reference measurement procedure is validated using two different stable isotope-labelled Aβ peptides, namely [15N]Aβ42 and [13C]Aβ42, and the native, unlabeled Aβ42 of CSF samples in the "Methods" on pg.987 in the "Calibration and sample preparation" on pg.988 and in the "Discussion" on pg.992 in Fig. 2; Also, since [15N]Aβ422 and native Aβ42 may not have the same MS responses, the [15N]Aβ42 concentration is adjusted according to the peak area ratio compared to the native Aβ42 at a given concentration (2000 pg/ml) in artificial CSF. In this way native Aβ42 concentrations can be determined by calculating the endogenous Aβ42/[13C]Aβ42 ratio with the calibration curve ([15N]Aβ42 /[[13C]Aβ42)).
Regarding Claim 3, Leinenbach et al. teaches the device 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 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).
Regarding Claim(s) 19 and 23, Leinenbach et al. teaches a calibrant kit for use in a mass spectrometer (See the Background section and the calibration curve illustrated in Fig. 1 pg. 991), 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 (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);
the calibration substances include a substance labeled with a stable isotope and a substance not labeled with a stable isotope, and both the substance labeled with the stable isotope and the substance not labeled with the stable isotope are the same compound; wherein the kit further comprises a container to accommodate a calibrant; wherein the calibrant is used for calibrating a machine difference between mass spectrometer machines (See the quantification of Aβ42 in CSF. The reference measurement procedure is validated using two different stable isotope-labelled Aβ peptides, namely [15N]Aβ42 and [13C]Aβ42, and the native, unlabeled Aβ42 of CSF samples in the "Methods" on pg.987 in the "Calibration and sample preparation" on pg.988 and in the "Discussion" on pg.992 in Fig. 2; Also, since [15N]Aβ422 and native Aβ42 may not have the same MS responses, the [15N]Aβ42 concentration is adjusted according to the peak area ratio compared to the native Aβ42 at a given concentration (2000 pg/ml) in artificial CSF. In this way native Aβ42 concentrations can be determined by calculating the endogenous Aβ42/[13C]Aβ42 ratio with the calibration curve ([15N]Aβ42 /[[13C]Aβ42)).
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 instant invention is anticipated by 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]),
wherein the one calibration substance (S1) is a substance labeled with a stable isotope, and the another one calibration substance (S2) is a substance not labeled with a stable isotope; and both the substance labeled with the stable isotope and the substance not labeled with the stable isotope are the same compound (See in the Example 1).
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) 8-1 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 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.
Claim 4 is 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 West et al. (US20140065636A1).
Regarding Claim 4, Leinenbach et al. teaches the device 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 methods for measuring concentrations in biomolecules, West et al. teaches a calibrant for use in a mass spectrometer (See the Abstract and the Claim(s) 1-7, in [0008]-[0103] in Fig. 1-5), wherein the calibration substances are Aβ1-38 and a stable isotope-labeled Aβ1-38 (See in [0024]-[0028] in Fig.1-5).
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 that are Aβ1-38 and a stable isotope-labeled Aβ1-38 (as taught by West 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 West et al. (US20140065636A1).
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 methods for measuring concentrations in biomolecules, West et al. teaches a calibrant for use in a mass spectrometer (See the Abstract and the Claim(s) 1-7, in [0008]-[0103] in Fig. 1-5), 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 in [0024]-[0028] in Fig.1-5).
Thus, it would be obvious to one with ordinary skills in the arts to modify the invention of Leinenbach et al. by incorporating one calibration substance (S 1) that is a substance labeled with a stable isotope, and the another one calibration substance (S2) that is a substance not labeled with a stable isotope (as taught by West et al.) for the benefit of quantifiably creating a calibration substance for mass spectrometry.
Regarding Claim 18, Leinenbach et al. teaches the method limitations of claim 7.
Leinenbach et al. fails to explicitly teach 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 methods for measuring concentrations in biomolecules, West et al. teaches a calibrant for use in a mass spectrometer (See the Abstract and the Claim(s) 1-7, in [0008]-[0103] in Fig. 1-5), 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 [0024]-[0028] in Fig.1-5).
Thus, it would be obvious to one with ordinary skills in the arts to modify the invention of Leinenbach et al. by incorporating one calibration substance (S1) that is Aβ1-38 labeled with a stable isotope, and the another one calibration substance (S2) that is Aβ1-38 not labeled with a stable isotope (as taught by West et al.) for the benefit of quantifiably creating a calibration substance for mass spectrometry.
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 BRITNEY N. WASHINGTON whose telephone number is (703)756-5959. The examiner can normally be reached Monday-Friday 9:00am - 5:30pm CT.
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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.
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/BRITNEY N. WASHINGTON/Examiner, Art Unit 1797
/JENNIFER WECKER/Primary Examiner, Art Unit 1797
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