DETAILED ACTION
Applicant's response, filed 7/22/2026, has been fully considered. The following rejections and/or
objections are either reiterated or newly applied. They constitute the complete set presently being
applied to the instant application.
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 the instant application, filed on 7/18/2022. As such the effective filing date of claims 1-15 is 12/17/2019.
Claim Status
Claims 1-3, and 5-15 are pending.
Claims 1-3, and 5-15 are rejected.
Withdrawn Rejections/Objections
The objection to the drawings in the Office Action mailed 4/22/2026 is withdrawn in view of the amendments filed 7/22/2026.
The rejection of claims 3-5, 10-12, and 14 under 35 U.S.C. 112(b) for indefiniteness in the Office Action mailed 4/22/2026 are withdrawn in view of the amendments filed 7/22/2026.
Drawings
Response to Amendment
In view of applicant’s amendments to the drawings, previous objections to the drawings as failing to show items described within the specification are withdrawn.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that use the word “means” or “step” but are nonetheless not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph because the claim limitation(s) recite(s) sufficient structure, materials, or acts to entirely perform the recited function. Such claim limitation(s) is: an “evaluation device” in claim 15. However, the specification, particularly paragraph [0045] provides sufficient structure.
Because this/these claim limitation(s) is/are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are not being interpreted to cover only the corresponding structure, material, or acts described in the specification as performing the claimed function, and equivalents thereof.
If applicant intends to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to remove the structure, materials, or acts that performs the claimed function; or (2) present a sufficient showing that the claim limitation(s) does/do not recite sufficient structure, materials, or acts to perform the claimed function.
Claim Rejections - 35 USC § 112
Response to Amendment
In view of applicant’s amendments to the claims, previous rejections to claims 3-5, 10-12, and 14 under 35 U.S.C. 112(b) for indefiniteness are withdrawn.
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 13 is 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 “substantially” in claim 13 is a relative term which renders the claim indefinite. The term “substantially” 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. Substantially here modifies the conditions under which the measurements are taken, and in this context renders the conditions unclear as to the range of difference that may occur between the various measurements.
Response to Arguments
Applicant's arguments filed 7/22/2026 have been fully considered but they are not persuasive.
Applicant asserts that the word substantially, that renders the claim indefinite, is described within the specification, pointing to paragraph [0096] of the specification, however, the specification only has up to paragraph [0093], as such upon review examiner believes the cited portion to be from paragraph [0024] or paragraph [0075] where it states “The reference measurements and the measuring of the transition of the analyte may be performed under substantially the same conditions. For example, the reference measurement and the measuring of the transition of the analyte may be performed under constant chromatographic conditions, specifically with the same LC column and eluents” or “The reference measurements and the measuring of the transition of the analyte may be performed under substantially the same conditions. For example, the reference measurement and the measuring of the transition of the analyte may be performed under constant chromatographic conditions, specifically with the same LC column and eluent”. However, these are exemplary cases, not a definitions of the metes and bounds of the word substantially, and as such the claim remains rejected under 35 U.S.C. 112(b) for indefiniteness.
Claim Rejections - 35 USC § 101
Response to Amendment
In view of applicant’s amendments to the claims, previous rejections of claims 1-15 under 35 U.S.C. 101 for being directed to abstract ideas without significantly more, have been reviewed, updated, and provided below.
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 1-3, and 5-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more. The claims recite a method and device for transition monitoring using liquid chromatography mass spectrometry. The judicial exception is not integrated into a practical application because while claims 1-3, and 5-15 attempt to integrated the exception into a practical application, said application is either generically recited computer elements that do not add a meaningful limitation to the abstract idea or it is insignificant extra solution activity and merely implementing the abstract idea on a computer. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the computer elements only store and retrieve information in memory as well as perform basic calculations that are known to be well-understood, routine and conventional computer functions as recognized by the decisions listed in MPEP § 2106.05(d).
Framework with which to Analyze Subject Matter Eligibility:
Step 1: Are the claims directed to a category of stator subject matter (a process, machine, manufacture, or composition of matter)? [see MPEP § 2106.03]
Claims are directed to statutory subject matter, specifically a method (Claims 1-3 and 5-14), and a device (Claims 15)
Step 2A Prong One: Do the claims recite a judicially recognized exception, i.e., an abstract idea, a law of nature, or a natural phenomenon? [see MPEP § 2106.04(a)]
The claims herein recite abstract ideas, specifically mental processes and mathematical concepts.
With respect to the Step 2A Prong One evaluation, the instant claims are found herein to recite abstract ideas that fall into the grouping of mental processes.
Claim 1: Determining at least one data set, determining at least one reference peak using an initial setting defined by a time frame, determining an actual setting of the measurement window, adjusting the time frame, and determining a measured peak information of the transition are process of comparing/contrasting, calculating, and selecting information that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes. One or both of a mean value or a moving average being used as a reference measurement are merely further limiting the data itself which is an abstract idea, specifically a mental process.
Claim 2: Updating the data set is a process of comparing/contrasting, and selecting information that can be done via pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 3: Performing steps a) – d) repeatedly is a process of comparing/contrasting, calculating, and selecting information that can be done via pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process. Using the most recent measurement as a reference, and determining reference peak information using the most recent determined actual setting are merely further limiting the data itself which is an abstract idea, specifically a mental process.
Claim 5: Performing an in-situ adjustment step during step d), monitoring and comparing the transition during measurement, and stopping if the intensity falls below a threshold are process of comparing/contrasting, calculating, and selecting information that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes.
Claim 6: One or both of the reference peak information or the measured peak information comprising one of those specified is merely further limiting the data itself which is an abstract idea, specifically a mental process.
Claim 7: One or both of the reference peak information or the measured peak information comprising the full width half maximum is merely further limiting the data itself which is an abstract idea, specifically a mental process.
Claim 8: The method comprising at least one initial calibration step, and determining one or both of the reference measurement or initial setting are processes of comparing/contrasting, calculating, and selecting information that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes.
Claim 9: Performing the initial calibration step at the specified step is a process of comparing/contrasting, calculating, and selecting information that can be done via pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 10: The initial start of the calibration being triggered by one or more the specified events/thresholds is a process of comparing/contrasting, calculating, and selecting information that can be done via pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 11: The initial setting comprising a broad time frame of retention times compared to the actual setting is merely further limiting the data itself which is an abstract idea, specifically a mental process.
Claim 12: Repeating method steps a) – d), and a width of the measurement window narrows with number of repetitions are process of comparing/contrasting, calculating, and selecting information that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes.
Claim 13: The reference measurements and the measuring of the transition of the analyte are performed under substantially the same conditions is merely further limiting the data itself which is an abstract idea, specifically a mental process.
Claim 14: The method steps b) – c) and in step d) determining the measured peak information is performed by at least one computer, is a process of comparing/contrasting, calculating, and selecting information that can be done via pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 15: Determining at least one data set, determining at least one reference peak using an initial setting defined by a time frame, determining an actual setting of the measurement window, adjusting the time frame, and determining a measured peak information of the transition are process of comparing/contrasting, calculating, and selecting information that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes. One or both of a mean value or a moving average being used as a reference measurement are merely further limiting the data itself which is an abstract idea, specifically a mental process.
Step 2A Prong Two: If the claims recite a judicial exception under prong one, then is the judicial exception integrated into a practical application? [see MPEP § 2106.04(d) and MPEP § 2106.05(a)-(c) & (e)-(h)]
Because the claims do recite judicial exceptions, direction under Step 2A Prong Two provides that the claims must be examined further to determine whether they integrate the abstract ideas into a practical application.
The following claims recite the following additional elements in the form of non-abstract elements:
Claim 1: Measuring the transition with a liquid chromatography mass spectrometry device is an insignificant extra solution activity, specifically mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989), PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis), Cutting hair after first determining the hair style, In re Brown, 645 Fed. App'x 1014, 1016-1017 (Fed. Cir. 2016) (non-precedential), and Printing or downloading generated menus, Ameranth, 842 F.3d at 1241-42, 120 USPQ2d at 1854-55) [See MPEP § 2106.05(g)].
Claim 3: Measuring the transition repeatedly with a liquid chromatography mass spectrometry device is an insignificant extra solution activity, specifically mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989), PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis), Cutting hair after first determining the hair style, In re Brown, 645 Fed. App'x 1014, 1016-1017 (Fed. Cir. 2016) (non-precedential), and Printing or downloading generated menus, Ameranth, 842 F.3d at 1241-42, 120 USPQ2d at 1854-55) [See MPEP § 2106.05(g)].
Claim 5: Measuring the transition with a liquid chromatography mass spectrometry device is an insignificant extra solution activity, specifically mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989), PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis), Cutting hair after first determining the hair style, In re Brown, 645 Fed. App'x 1014, 1016-1017 (Fed. Cir. 2016) (non-precedential), and Printing or downloading generated menus, Ameranth, 842 F.3d at 1241-42, 120 USPQ2d at 1854-55) [See MPEP § 2106.05(g)].
Claim 9: A quality control run and internal standards run are insignificant extra solution activities, specifically mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989), PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis), Cutting hair after first determining the hair style, In re Brown, 645 Fed. App'x 1014, 1016-1017 (Fed. Cir. 2016) (non-precedential), and Printing or downloading generated menus, Ameranth, 842 F.3d at 1241-42, 120 USPQ2d at 1854-55) [See MPEP § 2106.05(g)].
Claim 10: The changing of the liquid chromatography column is an insignificant extra solution activity, specifically mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989), PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis), Cutting hair after first determining the hair style, In re Brown, 645 Fed. App'x 1014, 1016-1017 (Fed. Cir. 2016) (non-precedential), and Printing or downloading generated menus, Ameranth, 842 F.3d at 1241-42, 120 USPQ2d at 1854-55) [See MPEP § 2106.05(g)].
Claim 12: Measuring the transition repeatedly with a liquid chromatography mass spectrometry device is an insignificant extra solution activity, specifically mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989), PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis), Cutting hair after first determining the hair style, In re Brown, 645 Fed. App'x 1014, 1016-1017 (Fed. Cir. 2016) (non-precedential), and Printing or downloading generated menus, Ameranth, 842 F.3d at 1241-42, 120 USPQ2d at 1854-55) [See MPEP § 2106.05(g)].
Claim 14: A computer is a generic and nonspecific element of a computer that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)].
Claim 15: A database, and an evaluation device are generic and nonspecific elements of computers that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)]. A liquid chromatography device, and measuring the transition with a liquid chromatography mass spectrometry device is an insignificant extra solution activity, specifically mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989), PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis), Cutting hair after first determining the hair style, In re Brown, 645 Fed. App'x 1014, 1016-1017 (Fed. Cir. 2016) (non-precedential), and Printing or downloading generated menus, Ameranth, 842 F.3d at 1241-42, 120 USPQ2d at 1854-55) [See MPEP § 2106.05(g)].
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept? [see MPEP § 2106.05]
Because the additional claim elements do not integrate the abstract idea into a practical application, the claims are further examined under Step 2B, which evaluates whether the additional elements, individually and in combination, amount to significantly more than the judicial exception itself by providing an inventive concept.
The claims do not recite additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are generic, conventional or nonspecific. These additional elements include:
The additional elements of a computer, database, and an evaluation device are all generic and nonspecific elements of a computer that do not improve the functioning of any computer or technology described herein (Receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), Performing repetitive calculations, Flook, 437 U.S. at 594, 198 USPQ2d at 199 (recomputing or readjusting alarm limit values), and Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)]. Therefore, taken both individually and as a whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
The additional elements of a liquid chromatography mass spectrometry device (Conventional: Scheduled MRM Algorithm Pro), quality control run (Conventional: Zabell et al. page 32, column 1, paragraph 3, and Dong et al. page 1529, column 1, paragraph 2), internal standards run (Conventional: Garofolo et al. Section 13.3), changing of the liquid chromatography column (Conventional: Zabell et al. page 32, column 1, paragraph 3, and Dong et al. page 1529, column 1, paragraph 2), and measuring the transition with a liquid chromatography mass spectrometry device (Conventional: Scheduled MRM Algorithm Pro) are insignificant extra solution activities, specifically mere data gathering and necessary data outputting (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989), PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis), Cutting hair after first determining the hair style, In re Brown, 645 Fed. App'x 1014, 1016-1017 (Fed. Cir. 2016) (non-precedential), and Printing or downloading generated menus, Ameranth, 842 F.3d at 1241-42, 120 USPQ2d at 1854-55) [See MPEP § 2106.05(g)]. Therefore, taken both individually and as a whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
Therefore, claims 1-15, when the limitations are considered individually and as a whole, are rejected
under 35 USC § 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant's arguments filed 7/22/2026 have been fully considered but they are not persuasive. Applicant asserts on page 12 of the remarks filed 7/22/2026 that the features of claim 1 cannot be practically performed in the human mind as they are performed with a LC-MS device. However, examiner reminds applicant that according to MPEP 2106.04(a)(III) - The courts consider a mental process (thinking) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea…Accordingly, the "mental processes" abstract idea grouping is defined as concepts performed in the human mind, and examples of mental processes include observations, evaluations, judgments, and opinions…The courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation…Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. In the case of claim 1, it is true that the method uses an LC-MS device, however this device is merely required for gathering of data, not the steps of determining at least one data set, determining at least one reference peak, determining an actual setting of the measurement window, or measuring the transition of analyte, all of which while they might be performed on the device are not required to be performed on the device, similar to the use of a generic computer in calculating information and decision making.
Applicant asserts on page 13 of the Remarks filed 7/22/2026 that the examiner alleged recitations of mathematical process/concepts. However, the Office Action does not allege such recitations merely that the claims recite mental processes.
Applicant asserts on page 15 of the Remarks filed 7/22/2026 that the claim limitations impose meaningful limits on the abstract ideas, citing specifically the use a mean value or moving average as a reference measurement. This is however, as previously described, part of the abstract idea as it is merely limiting the data itself, not a meaningful limitation on the abstract idea.
Applicant asserts on page 15 of the Remarks filed 7/22/2026 that the claims represent an integration into an improvement to the technological field, where specifically the improvement is the increasing of reliability of the transition monitoring. However, examiner reminds applicant that according to MPEP 2106.05(a) - It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements. In addition, the improvement can be provided by the additional element(s) in combination with the recited judicial exception. Here the improvement is directed to the abstract idea itself, improving reliability, not to any of the additional elements.
Applicant asserts on page 15 of the Remarks filed 7/22/2026 that the claims represent a practical application as they “enable the extension of the lifetime of a liquid chromatography column” and as such are representative of an improvement to a technological field. However examiner reminds applicant that merely instructing a user to use conventional chromatography steps and columns in accordance with a newly discovered rule or optimization algorithm does not fundamentally improve the underlying technology of the column or instrument, i.e. the column itself is not modified nor is the process fundamentally re-engineered in an un-conventional way. As such this amounts to mere instructions to apply an abstract idea, not an improvement to technology.
Applicant asserts on page 17 of the Remarks filed 7/22/2026 that “the claimed features that are not taught by the art of record constitute significantly more than the abstract idea”, and specifically that the additional features are not well-understood, routine, or conventional. However, examiner has provided cited references regarding the additional elements (See Above) and their respective conventionality, such as Scheduled MRM Algorithm Pro, Zabell et al. page 32, column 1, paragraph 3, and Dong et al. page 1529, column 1, paragraph 2, and Garofolo et al. Section 13.3.
Applicant asserts on page 18 of the Remarks that the directive Ex Parte Desjardins was not followed in so much as the claims were evaluated at too high of a granularity. However, examiner reminds applicant that each of the claim limitations, as well as their combination were thoroughly examined and outlined in the OA above.
Claim Rejections - 35 USC § 103
Response to Amendment
In view of applicant’s amendments to the claims previous rejections of claims 1-15 under 35 U.S.C. 103 for obviousness have been reviewed, updated, and provided below.
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.
Claims 1, 6, and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Sumiyoshi et al. (WO 2016125271 A1) and Wolf-Yadlin et al. (Proceedings of the National Academy of Sciences U.S.A. (2007) 5860-5865).
Claim 1 is directed to a method for monitoring transition using liquid chromatography mass spectrometry.
Claim 15 is directed to a device for monitoring transition using liquid chromatography mass spectrometry.
Sumiyoshi et al. teaches in the description under Technical Field “The present invention relates to a mass spectrometry method and a program for mass spectrometry that are used for optimizing conditions for measuring multiple reaction monitoring (MRM) of a target compound contained in a sample”, under Background Art “There is a technique called MS / MS analysis (tandem analysis) as one of mass spectrometry techniques for identifying and quantifying target compounds contained in a sample. The MS / MS analysis is performed using, for example, a mass spectrometer having a front-stage mass separation unit that sorts precursor ions, a collision cell that cleaves the precursor ions to generate product ions, and a rear-stage mass separation unit that sorts product ions”, in paragraph 2 of the Background Art “One of the measurements in MS / MS analysis is MRM measurement. In the MRM measurement, the mass-to-charge ratio of ions passing through the former mass separator and the latter mass separator is fixed, and the intensity (amount) of a specific product ion with respect to a specific precursor ion is measured. This pair of precursor ion and product ion is called an MRM transition”, and in paragraph 16 of the Drawing Description “When the normalization function is created, the spectrum intensity normalization unit 46 reads the product ion scan measurement data from the storage unit 41”, reading on a device for multiple transition monitoring of at least one analyte in a sample comprising: at least one liquid chromatography mass spectrometer device configured for multiple transition monitoring; at least one data base configured for storing at least one data set comprising at least one reference measurement of at least one transition of at least one analyte; at least one evaluation device. Furthermore, Sumiyoshi et al. teaches in paragraph 2 of the Background Art “One of the measurements in MS / MS analysis is MRM measurement. In the MRM measurement, the mass-to-charge ratio of ions passing through the former mass separator and the latter mass separator is fixed, and the intensity (amount) of a specific product ion with respect to a specific precursor ion is measured. This pair of precursor ion and product ion is called an MRM transition”, and further in paragraph 11 of the Drawing Description “First, the analyst determines the time zone (the peak start time and peak end time of the chromatogram) during which the target compound contained in the sample is introduced… The reference measurement is executed once every peak start time, peak top time, and peak end time, and the product ion scan measurement is executed between the reference measurement and the reference measurement”. Sumiyoshi et al. teaches in paragraph 13 of the Drawing Description “The reference measurement is executed once every peak start time, peak top time, and peak end time, and the product ion scan measurement is executed between the reference measurement and the reference measurement. In addition, the execution time of the reference measurement and the product ion scan measurement (including the switching time of the voltage applied to each part of the mass analyzer 2) is determined based on the length of the introduction time and the number of measurement executions…When the above measurement is completed, the peak function creation unit 44 reads the three reference measurement data from the storage unit 41 and creates a peak function (step S8). In the present embodiment, a peak function is created by fitting three points of reference measurement data using a Gaussian function and stored in the storage unit 41. This peak function represents the change of the target compound to the mass spectrometer 2 within the introduction time of the target compound”, reading on wherein in step a) one or both of a mean value or a moving average of a plurality of preceding measurements is used as reference measurement. Finially it would be obvious that any method for chromatography would have as one of its goals to prolong the use of the instrument itself, thereby reading on thereby enabling extension of a liquid chromatography column lifetime.
Wolf-Yadlin et al. teaches in the abstract “we have developed a new MS-based strategy, based on multiple reaction monitoring of stable isotope-labeled peptides, that enables highly reproducible quantification of hundreds of nodes (phosphorylation sites) within a signaling network and across multiple conditions simultaneously. We have applied this strategy to quantify temporal phosphorylation profiles of 222 tyrosine phosphorylated peptides across seven time points following EGF treatment, including 31 tyrosine phosphorylation sites not previously known to be regulated by EGF stimulation. With this approach, 88% of the signaling nodes were reproducibly quantified in four analyses, as compared with only 34% by typical information-dependent analysis. As a result of the improved reproducibility, full temporal phosphorylation profiles were generated”, on page 5862, column 1, paragraph 2 “For each half of the time course, a single analysis consisted of five separate MRM methods, with 300 precursor-fragment ion transitions for the first four methods and 1,428 total MRM transitions”, on page 5862, column 2, paragraph 2 “To confirm the accuracy of quantification results obtained with the MRM method, we compared these results to IDA-based analysis of the same samples. In this comparison, we selected 903 iTRAQ peaks with intensities between 50 and 1,500 counts (to avoid low signal-to-noise measurements or detector saturation) from IDA data and compared them to the same iTRAQ peaks as detected by MRM; all data from both methods are relative to the 4-min time point for the given time course”, in Figure 2, “Accumulation times can also be adjusted”, which in view of Sumiyoshi et al. reads on determining at least one data set from at least one data base, the data set comprising at least one reference measurement of at least one transition of at least one analyte with the liquid chromatography mass spectrometry device; determining at least one reference peak information of the transition of the analyte using an initial setting of a measurement window, wherein the initial setting is a setting of the measurement window which is used for determining the reference peak information, wherein the measurement window is defined by a time frame of retention times; determining an actual setting of the measurement window considering the reference peak information, wherein the determining comprises adjusting the time frame, wherein the actual setting is a setting of the measurement window determined by considering the reference peak information determined in step b); measuring the transition of the analyte with the liquid chromatography mass spectrometry device and determining a measured peak information of the transition of the analyte using the actual setting of the measurement window.
It would have been obvious at the time of first filing to have modified the teachings of Sumiyoshi et al. for a mass spectrometry method using MRM and the specific liquid chromatography mass spectrometry with the teachings of Wolf-Yadlin et al. for the method steps determining data, reference peak, measurement windows and finally the transition as the latter teaches in the abstract “With this approach, 88% of the signaling nodes were reproducibly quantified in four analyses, as compared with only 34% by typical information-dependent analysis. As a result of the improved reproducibility, full temporal phosphorylation profiles were generated for an additional 104 signaling nodes with the multiple reaction monitoring strategy, an 88% increase in our coverage of the signaling network”. One would have had a reasonable expectation of success in combining the two as both are performing MRM using mass spec with the former specifically describing the tools being used and the latter focusing on the process/method. Therefore, it would have been obvious at the time of first filing to have modified the teachings of each and to be successful.
Claim 6 is directed to the method of claim 1 but further specifies that the reference peak information comprise one of the specified types.
Wolf-Yadlin et al. teaches on page 5865, column 2, paragraphs 2-3 “Data from each analysis were normalized to the 4-min peak area for time-course integration. For MRM experiments, peak detection and automatic quantification methods were built for each method by using Analyst 1.4.1 (Applied Biosystems). Peak detection was inspected visually to ensure correct peak identification (coelution) and shape (smoothness)”, reading on wherein one or both of the reference peak information or the measured peak information comprise one or more of: peak maximum, retention time, peak start time, peak end time, peak width peak shape, tailing factor, or any type of peak fitting and filtering.
Claim 13 is directed to the method of claim 1 but further specifies that the reference measurements and the actual measurements are performed under substantially the same conditions.
It is inherent to a reference measurement that it is performed under similar conditions as an actual measurement as a reference by definition attempts to establish a comparative measurement in order to ensure accuracy, traceability, and consistency in methodology across experimental runs, thereby reading on wherein the reference measurements and the measuring of the transition of the analyte are performed under substantially the same conditions.
Claim 14 is directed to the method of claim 1 but further specifies that the method steps are performed by at least one computer.
Wolf-Yadlin et al. teaches on page 5865, column 2, paragraphs 2-3 “Data from each analysis were normalized to the 4-min peak area for time-course integration. For MRM experiments, peak detection and automatic quantification methods were built for each method by using Analyst 1.4.1 (Applied Biosystems). Peak detection was inspected visually to ensure correct peak identification (coelution) and shape (smoothness)”, reading on wherein the method steps b) to c) and in step d) the determining of the measured peak information of the transition of the analyte are performed by at least one computer.
Claims 2-3, 8, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Sumiyoshi et al. (WO 2016125271 A1) and Wolf-Yadlin et al. (Proceedings of the National Academy of Sciences U.S.A. (2007) 5860-5865) as applied to claim 1, 6, and 13-15 above, and further in view of Analyst 1.6 Software Guide (AB ScieX (2011) 1-56).
Claim 2 is directed to the method of claim 1 but further specifies the updating of the data set by adding the measurement to the data set.
Sumiyoshi et al. and Wolf-Yadlin et al. teach the method and device of claims 1 and 15.
Sumiyoshi et al. and Wolf-Yadlin et al. do not teach the updating of the data set by adding the measurement to the data set.
Analyst 1.6 Software Guide teaches on page 15, paragraph 4 “The compound database stores information about compounds, including optimization specifications. Use the compound database when you have large numbers of samples and need to optimize a large number of compounds quickly. The Automaton software automatically fills the database. The Compound Database window stores optimized conditions for compounds that can be retrieved to run samples”, and on page 22, paragraph 2 “The Library Search feature compares unknown spectra to known MS spectra contained in a library database and generates a list of possible matches. With Library Search you can: • Compare library contents against an unknown spectrum. • Add records to the library. • Edit existing records. You can store library data in the following locations: • MS Access on a local database. • MS SQL Server.”, reading on wherein the method further comprises updating the data set by adding the measurement of the transition of the analyte to the data set.
It would have been obvious at the time of first filing to have modified the teachings of Sumiyoshi et al. and Wolf-Yadlin et al. for the method and device of claims 1 and 15, with the teachings of the Analyst 1.6 Software Guide as this is the same software (albeit updated) that was used for in the cited reference Wolf-Yadlin et al. for their protocol. One would have had a reasonable expectation of success given that this was the cited software used previously in the cited reference. Therefore, it would have been obvious at the time of first filing to have modified the teachings of each and to be successful.
Claim 3 is directed to the method of claim 2 and thus claim 1, but further specifies that the method is performed repeatedly, the most recent reference is used and is calculated using the most recent settings.
Wolf-Yadlin et al. teaches on page 5860, column 2, paragraph 1 “In this mode, the mass spectrometer continuously repeats a cycle consisting of a full-scan mass spectrum, followed by selection and fragmentation of the n (typically n 1–10) most abundant m/z ratios for peptide identification and quantification”.
Analyst 1.6 Software Guide teaches on page 15, paragraph 1 “A chromatogram displays the variation of some quantity with respect to time in a repetitive experiment; for example, when the instrument is programmed to repeat a given set of mass spectral scans several times… In the case of LC/MS, the chromatogram is often displayed as a function of time, the time at which a particular scan was obtained, which can be derived from the scan number”, which in view of Wolf-Yadlin et al. reads on wherein method steps a) to d) are performed repeatedly, wherein in step a) the most recent measurement is used as reference measurement, wherein in step b) the reference peak information of the transition of the analyte is determined using the most recently determined actual setting as initial setting.
Claim 8 is directed to the method of claim 1 but further specifies the use of a calibration step to determine reference measurements or initial settings.
Sumiyoshi et al. and Wolf-Yadlin et al. teach the method and device of claims 1 and 15.
Sumiyoshi et al. and Wolf-Yadlin et al. do not teach the use of a calibration step to determine reference measurements or initial settings.
Analyst 1.6 Software Guide teaches on page 13, paragraph 6, “The calibration options define the parameters for a calibration curve, which are used to determine the calculated concentration of the samples. The curve is a plot of the concentration of the standard against the area or height of the standard if no internal standard is used. If an internal standard is used, the curve is a plot of the concentration ratio against the area or height ratio. This curve is used, along with the area (or height) for the unknowns, to interpolate the calculated concentration”, reading on wherein the method comprises at least one initial calibration step, wherein in the initial calibration step one or both of the reference measurement or the initial setting are determined.
Claim 11 is directed to the method of claim 1 but further specifies the initial setting comprising a broad frame of retention times.
Sumiyoshi et al. and Wolf-Yadlin et al. teach the method and device of claims 1 and 15.
Sumiyoshi et al. and Wolf-Yadlin et al. do not teach the initial setting comprising a broad frame of retention times.
Analyst 1.6 Software Guide teaches on page 29, in Figure 1-7 “The actual retention time for a peak is not simply the point identified as described previously. Instead, it is determined from a quadratic fit based on the three highest data points”, where if a retention time is calculated then its initial setting is infinitely broad compared to its absolute retention time which is then calculated, reading on wherein the initial setting comprises a broad time frame of retention times compared to the actual setting.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Sumiyoshi et al. (WO 2016125271 A1) and Wolf-Yadlin et al. (Proceedings of the National Academy of Sciences U.S.A. (2007) 5860-5865) as applied to claims 1, 6, and 13-15 above, and further in view of Scheduled MRM Algorithm Pro (Technical Note RUO-MKT-02-8539-A (2018) 1-6).
Claim 5 is directed to the method of claim 1 but further specifies the use of in-situ adjustments based on intensity compared to a predefined threshold, where if it falls below the process is stopped.
Sumiyoshi et al., and Wolf-Yadlin et al. teach the method and device of claims 1 and 15.
Sumiyoshi et al., and Wolf-Yadlin et al. do not teach the use of in-situ adjustments based on intensity compared to a predefined threshold, where if it falls below the process is stopped.
Scheduled MRM Algorithm Pro teaches on page 3, column 1, paragraph 4 “For many applications, it is preferable to monitor more than one MRM transition for each compound. This can help to optimize assay robustness and quantitative accuracy. But because this adds to the overall number of MRM transitions to monitor for the assay, this can adversely affect the total number of compounds that can be analyzed. To combat this, an MRM triggered MRM acquisition strategy can be used (Figure 3). With MRM triggered MRM acquisition, one primary transition (or more) is monitored and triggers secondary MRMs for the same compound only when the intensity of the primary transition exceeds the defined threshold. Secondary MRMs are monitored until primaries drop back below the threshold, thus are monitored across the LC peak. The secondary transitions maintain accurate intensity and, with appropriate threshold settings, also maintain accurate and quantifiable areas”, reading on wherein the method further comprises at least one in-situ adjustment step, wherein the in-situ adjustment step is performed during step d), wherein in the in-situ adjustment step intensity of the transition of the analyte is monitored during the measurement and compared to at least one predetermined or predefined threshold level, wherein if the intensity falls below the threshold level acquisition of the transition is stopped.
It would have been obvious at the time of first filing to have modified the teachings of Sumiyoshi et al. and Wolf-Yadlin et al. for the method and device of claims 1 and 15, with the teachings of the Scheduled MRM Algorithm Pro for the use of intensity thresholds in adjustment steps during MRM acquisition, as the latter is a reference for the MRM platform manufactured by the same company and uses the same software as Wolf-Yadlin et al. is using. One would have had a reasonable expectation of success given that this is a similar platform using the same software used previously in the cited reference. Therefore, it would have been obvious at the time of first filing to have modified the teachings of each and to be successful.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Sumiyoshi et al. (WO 2016125271 A1) and Wolf-Yadlin et al. (Proceedings of the National Academy of Sciences U.S.A. (2007) 5860-5865) as applied to claims 1, 6, 13-15 above, and further in view of Lange et al. (Molecular Cell Proteomics (2008) 1489-500).
Claim 7 is directed to the method of claim 6 and thus claim 1, but further specifies that the reference information used comprise the full width half maximum.
Sumiyoshi et al., and Wolf-Yadlin et al. teach the method and device of claims 1, 6 and 15.
Sumiyoshi et al., and Wolf-Yadlin et al. do not teach the reference information used comprise the full width half maximum.
Lange et al. teaches in the abstract “In many studies, particularly in the field of systems biology, it is essential that identical protein sets are precisely quantified in multiple samples such as those representing differentially perturbed cell states. The high degree of reproducibility required for such experiments has not been achieved by classical mass spectrometry-based proteomics methods. In this study we describe the implementation of a targeted quantitative approach by which predetermined protein sets are first identified and subsequently quantified at high sensitivity reliably in multiple samples”, and on page 1491, column 1, paragraph 3 “Three MS/MS spectra were acquired in the linear ion trap per each FT-MS scan that was acquired at 100,000 full-width half-maximum nominal resolution settings…”, reading on wherein one or both of the reference peak information or the measured peak information comprise the full width half maximum.
It would have been obvious at the time of first filing to have modified the teachings of Sumiyoshi et al. and Wolf-Yadlin et al. for the method and device of claims 1 and 15, with the teachings of Lange et al. for the use of the full-width half-maximum as the latter teaches in the abstract “Applying this approach we were able to reliably quantify low abundance virulence factors from cultures of the human pathogen Streptococcus pyogenes exposed to increasing amounts of plasma. The resulting quantitative protein patterns enabled us to clearly define the subset of virulence proteins that is regulated upon plasma exposure”. One would have had a reasonable expectation of success given that the only integration necessary is the data type and the authors provided their protocol through a set of software tools for MRM. Therefore, it would have been obvious at the time of first filing to have modified the teachings of each and to be successful.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Sumiyoshi et al. (WO 2016125271 A1) and Wolf-Yadlin et al. (Proceedings of the National Academy of Sciences U.S.A. (2007) 5860-5865) as applied to claims 1, 6, 13-15 above, and further in view of Dong et al. (Journal of chromatographic science (2015) 1528-1535).
Claim 12 is directed to the method of claim 1 but further specifies the repeating of the method steps and narrowing of the measurement window.
Sumiyoshi et al., and Wolf-Yadlin et al. teach the method and device of claims 1 and 15.
Sumiyoshi et al., and Wolf-Yadlin et al. do not teach the narrowing of the measurement window.
Dong et al. teaches on page 1534, column 2, paragraph 2 “The narrower the peak widths, the more reproducible the RTs are, and the narrower the dMRM detection window shall be. With increased narrow detection windows, the number of concurrent MRMs is reduced, and this inverse relationship means that higher dwell times can be used for each MRM transition”, reading on wherein the method comprises repeating method steps a) to d), wherein a width of the measurement window narrows with number of repetitions.
It would have been obvious at the time of first filing to have modified the teachings of Sumiyoshi et al. and Wolf-Yadlin et al. for the method and device of claims 1 and 15, with the teachings of Dong et al. for the narrowing of detection windows across subsequent runs as the latter teaches in the abstract “The result showed that the signal response and quality of the chromatograms for each stimulant improved significantly with dMRM over cMRM”. One would have had a reasonable expectation of success given that according to the abstract it’s a “novel, reliable and sensitive liquid chromatography–tandem mass spectrometry (LC–MS-MS) method…developed with dynamic multiple reaction monitoring (dMRM) mode”, that is according to page 1534, column 2, paragraph 3 “simple, fast and efficient and increases productivity”. Therefore, it would been obvious at the time of first filing to have modified the teachings of each and to be successful.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Sumiyoshi et al. (WO 2016125271 A1), Wolf-Yadlin et al. (Proceedings of the National Academy of Sciences U.S.A. (2007) 5860-5865), and Analyst 1.6 Software Guide (AB ScieX (2011) 1-56) as applied to claim 2-4, 8, and 11 above, and further in view of Dong et al. (Journal of chromatographic science (2015) 1528-1535).
Claim 9 is directed to the method of claim 8 and thus claim 1, but further specifies the performing of a calibration step during or subsequent to a control run and internal standard sample run.
Sumiyoshi et al., Wolf-Yadlin et al., and the Analyst 1.6 Software Guide teach the method and device of claims 1 and 15.
Sumiyoshi et al., Wolf-Yadlin et al. and the Analyst 1.6 Software Guide do not teach the performing of a calibration step during or subsequent to a control run and internal standard sample run.
Dong et al. teaches on page 1529, column 1, paragraph 2 “Stock solutions of individual stimulant and metabolite were prepared in methanol at a concentration of 1 mg/mL. Low, medium and high concentration quality control (QC) samples (10, 100, 500 ng/mL) were prepared by serial dilution of the stock solution with blank urine. Single point calibration was applied for method validation since multiple components qualitative analysis was carried out. The calibration standards were prepared with pooled blank urine at concentrations of 10, 100, 500 ng/mL respectively. The stock solution of internal standard (IS), mefruside (1 mg/mL) was prepared in methanol and diluted with methanol to a final concentration of 10 mg/mL. QC sample solutions were stored at 2208C and used within 1 month after preparation”, reading on wherein the initial calibration step is one or more of performed during or subsequent to at least one quality control run of the liquid chromatography mass spectrometry device, performed during or subsequent to at least one internal standard samples run.
It would have been obvious at the time of first filing to have modified the teachings of Sumiyoshi et al., Wolf-Yadlin et al., and the Analyst 1.6 Software Guide for the method and device of claims 2-4, 8, and 11, with the teachings of Dong et al. for the use of a calibration step during a quality control run and internal samples run, as the latter teaches in the abstract “The result showed that the signal response and quality of the chromatograms for each stimulant improved significantly with dMRM over cMRM”. One would have had a reasonable expectation of success given that according to the abstract it’s a “novel, reliable and sensitive liquid chromatography–tandem mass spectrometry (LC–MS-MS) method…developed with dynamic multiple reaction monitoring (dMRM) mode”, that is according to page 1534, column 2, paragraph 3 “simple, fast and efficient and increases productivity”. Therefore, it would been obvious at the time of first filing to have modified the teachings of each and to be successful.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Sumiyoshi et al. (WO 2016125271 A1), Wolf-Yadlin et al. (Proceedings of the National Academy of Sciences U.S.A. (2007) 5860-5865), and Analyst 1.6 Software Guide (AB ScieX (2011) 1-56) as applied to claim 2-4, 8, and 11 above, and further in view of Zabell et al. (Clinical Mass Spectrometry (2017) 25-33).
Claim 10 is directed to the method of claim 8 and thus claim 1, but further specifies performing a calibration step after one or more specified events.
Sumiyoshi et al., Wolf-Yadlin et al., and the Analyst 1.6 Software Guide teach the method and device of claims 2-4, 8 and 1.
Sumiyoshi et al., Wolf-Yadlin et al. and the Analyst 1.6 Software Guide do not teach the performing of a calibration step after one or more specified events.
Zabell et al. teaches on page 32, column 1, paragraph 3 “The common industrial practice of generating a new calibration curve for each analytical run only answers the question, ‘‘is this curve good,” when the true question should be, ‘‘has the instrument changed.””, which makes obvious the idea of running a new calibration when the instrument has changed, i.e. when a new column has been inserted, thereby reading on wherein a start of the initial calibration step is triggered by one or more of changing of a column of the liquid chromatography mass spectrometry device after a predefined or predetermined time or after a predefined or predetermined number of runs, or other suitable counters.
It would have been obvious at the time of first filing to have modified the teachings of Sumiyoshi et al., Wolf-Yadlin et al. and the Analyst 1.6 Software Guide for the method of claim 8, with the teachings of Zebell et al. for the recalibration of the instrument after a new column has been inserted as the latter is a review of best practices for calibration and provides an “explanation for the calibrator minimum and provide recommendations for curve building, which include improved outlier detection for high-volume mass spectrometry laboratories”. One would have had a reasonable expectation of success given that the latter is a review and recalibration does not impact the overall methodology merely the accuracy of the results. Therefore, it would have been obvious at the time of first filing to have modified the teachings of each and to be successful.
Response to Arguments
Applicant's arguments filed 7/22/2026 have been fully considered but they are not persuasive.
Applicant asserts on page 20 of the Remarks filed 7/22/2026 that the limitations of the amended independent claims are not taught, specifically citing wherein in step a) one or both of a mean value or a moving average of a plurality of preceding measurements is used as a reference measurement. However, examiner reminds applicant that this was merely the limitation of claim 4 in the preceeding set of claims that was rejected over Sumiyoshi et al., merely requiring it to be rejected in concert with the art of claim 2 as it was dependent on the latter claim.
Conclusion
No claims are allowed.
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.
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/K.N.A./Examiner, Art Unit 1687
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686
