DETAILED ACTION
Claim Status
Claims 1-25 are rejected.
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 .
Information Disclosure Statement
The Information Disclosure Statement(s) filed on 09/14/2022, 05/31/2024, 10/15/2024, 03/04/2025 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of list of references cited from each IDS is included with this Office Action.
Priority
This application is a continuation of PCT/EP2021/058432, filed 03/31/2021. This application claims Foreign Priority to European Patent Application # EP20167557.6, filed 04/01/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Foreign priority is acknowledged. Therefore, the effective filing date of this application is 04/01/2020.
Drawings
The Drawings filed on 09/14/2022 are accepted.
Specification
The use of the term “Bluetooth,” (specification ¶ 50) which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “evaluation device” in claim 14.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof. The “evaluation device” is described by ¶ 47 of the instant application, and is adapted to perform the method described in ¶ 6. As such, this claim is being interpreted in light of those sections of the specification.
If applicant does not intend 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 avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 16 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 claim recites “The system of claim 10” and “the evaluation device,” which lack antecedent basis in the claims it is dependent upon.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 13, 15-16, and 20 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 13 merely states an intended use of the method claim but does not actively further limit the method of claim 1. Claims 15 and 16 are restating the occurrence of the steps of claim 1 and 14, respectively, without reciting further limitations. Claim 20 also restates the steps of claim 1 without introducing a further limitation. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 24-25 are non-statutory as they recite “a computer program product”. The claims as instantly recited read on carrier waves or on data per se, which are transitory propagating signals or stored information and therefore are not proper patentable subject matter because they do not fit within any of the four statutory categories of invention (In re Nuijten, Federal Circuit, 2007). It is noted that the recitation of a "non-transitory computer readable medium" would overcome the rejection with respect to claims 24-25 reading on signals. However, the amendment to only "non-transitory computer readable medium" would not overcome the rejection under 35 U.S.C. 101 since the claims would still be directed to a judicial exception without significantly more (see below).
Claims 1-25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea/law of nature/natural phenomenon without significantly more.
In accordance with MPEP § 2106, claims found to recite statutory subject matter ( Step 1 : YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). While it is noted that claims 24-25 do not recite a statutory category of invention (see above), the analysis of these claims under the remaining steps of the subject matter eligibility analysis is continued in the interest of compact prosecution. In the instant application, the claims recite the following limitations that equate to an abstract idea/law of nature/natural phenomenon:
Claim 1 recites (b) determining a background height of the chromatogram; and (c) determining the carry over of the analyte from said previous sample into the sample of interest based on the background height.
Claim 4 recites using a predetermined relationship between the background height and a parameter correlating with the carry over
Claim 5 recites b1) identifying a peak corresponding to the analyte in the chromatogram; and b2) determining an upper and a lower peak boundary of said peak.
Claim 6 recites b3) determining at least one minimum signal intensity value within the upper and lower peak boundary.
Claim 7 recites that background height is determined shortly upstream of the upper peak boundary and/or shortly downstream of the lower peak boundary.
Claim 8 recites the confirmation step comprises determining the reliability of the background height
Claim 9 recites the reliability of the background height is determined by calculating a reliability parameter and comparing said reliability parameter to a pre-defined reference
Claim 10 recites (i) by determining an average of quantifier/qualifier ratios of background data points, and comparing said average to a pre-defined average reference;
Claim 10 recites (ii) by determining a variation parameter of background data points, and comparing said variation parameter to a pre-defined variation reference.
Claim 11 recites The method of claim 10, wherein in step (i) the background data points are used for determining background height of the chromatogram
Claim 12 recites The method of claim 10, wherein in step (ii) the background data points are used for determining background height of the chromatogram.
Claim 13 recites The method of claim 1, wherein said method is or is comprised in a method of quality control.
Claim 14 recites (II) at least one evaluation device, wherein the evaluation device is configured to determine a background height of the chromatogram and for determining a carry over based on the background height.
Claim 15 recites the system of claim 14, configured to perform a method for determining a carry over of an analyte
Claim 16 recites the evaluation device is adapted to perform a method for determining a carry over of an analyte
Claim 17 recites (C) determining a carry over from the first sample into the second sample with the method for determining a carry over according to claim 1
Claim 18 recites in case a carry over of the analyte from the first sample to the second sample exceeding a pre-determined threshold is determined, for the analyte in the second sample (i) no determination is provided, (ii) it is indicated that the result of determination is unreliable, and/or (iii) a repeat of the measurement is initiated
Claim 19 recites quantitatively determining an amount of the analyte in the second sample, and subtracting the carry over determined from the quantified result of the analyte of the second sample
Claim 20 recites The method of claim 19, wherein said amount is corrected by: (b) determining a background height of the chromatogram; and (c) determining the carry over of the analyte from said previous sample into the sample of interest based on the background height.
Claim 21 recites (iv) determining a background height of the chromatogram
Claim 21 recites (v) repeating steps (i) to (iv) for at least two further first samples, said first samples comprising non-identical concentrations of said analyte,
Claim 21 recites (vi) correlating the apparent amount of the analyte or a signal corresponding thereto determined in steps (iii) with the background heights determined in step (iv)
Claim 21 recites (vii) thereby, determining a relationship between a background height and a carry over of an analyte
Claim 21 recites repeating step (iv)
Claim 24 recites performing at least steps b) and c) of the method according to claim 1 when the program code means are executed on a computer or on a computer network
Claim 25 recites performing at least step (vi) of the method according to claim 21 when the program code means are executed on a computer or on a computer network
The limitations of claims 1, 5-10, and 14-21 all make reference to “determining” a numerical value based on the information from the chromatogram. These determinations are verbal equivalents for mathematical calculations that could be performed by a human being with a pen and paper.
Claim 4 makes reference to using a predetermined relationship between a value and a parameter in the steps of claim 1. This is a verbal equivalent to a mathematical relationship between the background height and the parameter.
Claim 5, step b1) makes reference to “identifying a peak”, which could be pratically performed by a human being looking at a chart, making it a type of mental process. It is also a verbal equivalent for a type of mathematical relationship between the identified point and the chart.
Claims 11-13 add further limitations to the steps of claim 1, or in the case of claim 13 as discussed in the section on § 112 above , do not add any limitations at all. As such they are directed to the judicial exception of claim 1, and are part of the mathematical relationship of claim 1.
Step (vi) of claim 21 makes reference to correlating two values determined earlier. A correlation is a type of mathematical relationship.
Claim 18 recites decisions that can be made in the case of a determination of a value. These decisions could be practically made and carried out by a human being, making it a type of mental process.
While claims 14, 16, 24, and 25 recite performing some aspects of the analysis with an “evaluation device” or “computer program product,” there are no additional limitations that indicate that this analysis engine requires anything other than carrying out the recited mental process or mathematical concept in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then if falls within the “Mental processes” grouping of abstract ideas. As such, claims 1-25 recite an abstract idea ( Step 2A, Prong 1 : YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception to effect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or mere instructions to apply the recited judicial exception via a generic treatment. Specifically, the claims recite the following additional elements:
Claim 1 recites determining at least one chromatogram of said sample of interest on said LC-MS device
Claim 2 recites wherein said chromatogram is a representation of intensity of an analyte-specific signal over elution time.
Claim 3 recites The method of claim 2, wherein said chromatogram is a representation of analyte quantifier signal intensity over elution time.
Claim 14 recites (I) at least one liquid chromatography mass spectrometer (LC-MS) device, wherein the LC-MS device is configured for measuring the analyte in the sample and for determining at least one chromatogram
Claim 14 recites at least one evaluation device
Claim 17 recites (A) conducting at least one first measurement on a first sample
Claim 17 recites (B) conducting at least one second measurement on a second sample;
Claim 19 recites (a) determining at least one chromatogram of said sample of interest on said LC-MS device;
Claim 20 recites (a) determining at least one chromatogram of said sample of interest on said LC-MS device;
Claim 21 recites (i) conducting at least one first measurement for a first sample
Claim 21 recites (ii) conducting at least one second measurement for a second sample and determining at least one chromatogram thereof, wherein said second sample is devoid of said analyte;
Claim 21 recites (iii) determining an apparent amount or a signal corresponding thereto of the analyte in said second sample; and (v) repeating steps (i) to [(iii)] for at least two further first samples, said first samples comprising non-identical concentrations of said analyte,
Claim 22 recites The method of claim 21, wherein said second sample is a control sample.
Claim 23 recites The method of claim 21, wherein said second sample is a buffer control sample, a blank control sample, or a matrix control sample.
Claim 24 recites A computer program product having program code means, wherein the program code means can be stored or are stored on a storage medium
Claim 25 recites A computer program product having program code means, wherein the program code means can be stored or are stored on a storage medium
There are no limitations that indicate that the claimed “evaluation device” or “computer program product” require anything other than generic computing systems. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984.
The additional elements of claims 1, 14, 17, 19, 20, and 21 do not add a meaningful limitation to the abstract idea because they amount to mere data gathering steps that would be required for the claimed mental processes. These limitations serve to gather data that is used as input for the abstract idea and there is no indication that the abstract idea has any impact on those data gathering steps. The courts have indicated that mere data gathering activity is insignificant extra-solution activity that does not provide a practical application (see MPEP 2106.05(g)).
Claims 2-3 and 22-23 add further limitations to the determined chromatogram of claim 1, which is an additional element because it is a mere data gathering step. Therefore, these claims are also part of the data gathering step.
As such, claims 1-25 are directed to an abstract idea ( Step 2A, Prong 2 : NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment. The instant claims recite the following additional elements:
Claim 1 recites determining at least one chromatogram of said sample of interest on said LC-MS device
Claim 2 recites wherein said chromatogram is a representation of intensity of an analyte-specific signal over elution time.
Claim 3 recites The method of claim 2, wherein said chromatogram is a representation of analyte quantifier signal intensity over elution time.
Claim 14 recites (I) at least one liquid chromatography mass spectrometer (LC-MS) device, wherein the LC-MS device is configured for measuring the analyte in the sample and for determining at least one chromatogram
Claim 14 recites at least one evaluation device
Claim 17 recites (A) conducting at least one first measurement on a first sample
Claim 17 recites (B) conducting at least one second measurement on a second sample;
Claim 19 recites (a) determining at least one chromatogram of said sample of interest on said LC-MS device;
Claim 20 recites (a) determining at least one chromatogram of said sample of interest on said LC-MS device;
Claim 21 recites (i) conducting at least one first measurement for a first sample
Claim 21 recites (ii) conducting at least one second measurement for a second sample and determining at least one chromatogram thereof, wherein said second sample is devoid of said analyte;
Claim 21 recites (iii) determining an apparent amount or a signal corresponding thereto of the analyte in said second sample; and (v) repeating steps (i) to (iv) for at least two further first samples, said first samples comprising non-identical concentrations of said analyte,
Claim 22 recites The method of claim 21, wherein said second sample is a control sample.
Claim 23 recites The method of claim 21, wherein said second sample is a buffer control sample, a blank control sample, or a matrix control sample.
Claim 24 recites A computer program product having program code means, wherein the program code means can be stored or are stored on a storage medium
Claim 25 recites A computer program product having program code means, wherein the program code means can be stored or are stored on a storage medium
Applicant states that the terms “LC-MS device” and “chromatogram” are known to the skilled person (spec ¶ 28-29), and they list a number of embodiments that the LC-MS device and chromatogram could take. Applicant states: “As will be understood by the skilled person, the aforesaid representation may be, but does not have to be, a graphical representation; the representation may, however, also be provided, e.g., as a list of value pairs, e.g., elution time / quantifier value pairs and/or elution time / qualifier value pairs, or as a mathematical model. In an embodiment, said quantitative measure of signals comprises an analyte signal intensity and/or an internal standard signal intensity. In an embodiment, said quantitative measure of signals comprises an analyte quantifier, an internal standard quantifier, an analyte qualifier and/or an internal standard qualifier. Thus, in an embodiment, in particular in case the MS is tandem MS, determining at least one chromatogram comprises measuring at least one of an analyte quantifier, an internal standard quantifier, an analyte qualifier and/or an internal standard qualifier over time and/or elution time, as specified above” (spec ¶ 29). Zeng writes: “In recent years, due to the coupling of tandem mass spectrometry (MS/MS) with HPLC, HPLC methods have become more selective and sensitive.” (abstract) This means that LC-MS is well-understood enough to cause people to invent new liquid chromatography methods to accommodate it.
Grebe et al. (Clin Biochem Rev. 2011 Feb;32(1):5–31.) writes: “Now, as we are entering the second decade of the 21st century, LC mass spectrometry (LC-MS) has become a widespread technology within clinical reference and referral laboratories world-wide, and has started to penetrate into large and medium sized hospitals and regional clinical laboratories.” (introduction ¶ 3)
A person of ordinary skill in the art would recognize LC-MS as a conventional laboratory technique, and that it can be repeated over multiple samples. These limitations do not provide more than nominal relation to the carry-over monitoring of the invention, and are a necessary data gathering step to monitor the carry-over. As a result, the limitations of claims 1, 17, 19, and 21 amount to insignificant extra-solution activity.
As discussed above, there are no additional limitations to indicate that the claimed “evaluation device” or “computer program product” requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984.
The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself ( Step 2B : No). As such, claims 1-25 is/are not patent eligible.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 13-15, 17-18, and 21-25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zeng et al. (Rapid Commun. Mass. Spectrum. 2006; 20; 635-40) (hereafter “Zeng”).
Regarding claim 1, Zeng teaches a method for determining a carry over of an analyte from a previous sample into a sample of interest on a liquid chromatography mass spectrometer (LC-MS) device (Zeng pg 636 left column ¶ 2, 4).
Zeng teaches determining at least one chromatogram of said sample of interest on said LC-MS device (Zeng pg 636 left column ¶ 2 – the name of the LCMS device for taking chromatograms is given, and the process is described in the abstract).
Zeng teaches determining a background height of the chromatogram and determining the carry over of the analyte from said previous sample into the sample of interest based on the background height. (Zeng pg 636 right column ¶ 3: “it is reasonable to use the peak area ratio of the blank sample and the preceding sample to measure carryover”)
Regarding claim 2, Zeng teaches that said chromatogram is a representation of intensity of an analyte-specific signal over elution time. Zeng gives intensity values in m/z for analyte signals in a chromatogram run on page 636 right column ¶ 1.
Regarding claim 3, Zeng teaches that said chromatogram is a representation of analyte quantifier signal intensity over elution time. Table 2 of Zeng gives measurements of the analyte in terms of their concentrations.
In the section regarding 35 U.S.C. § 112, claim 13 was determined not to include any further limitations on claim 1, as it is an “intended use.” This makes claim 13 anticipated by Zeng.
Regarding claim 14, A system for determining a concentration of at least one analyte in a sample comprising (I) at least one liquid chromatography mass spectrometer (LC-MS) device, wherein the LC-MS device is configured for measuring the analyte in the sample and for determining at least one chromatogram, (II) at least one evaluation device, wherein the evaluation device is configured to determine a background height of the chromatogram and for determining a carry over based on the background height is taught by Zeng (Zeng pg 636 left column ¶ 2, 4 – the LCMS device is named in ¶ 2 and the Analyst software is named in ¶ 4 as completing all steps of the analysis of the paper including the configuration configured to determine a background height of the chromatogram and for determining a carry over based on the background height).
Regarding claim 15, the combined system with the Analyst software and the LCMS device are configured to perform a method for determining a carry over of an analyte (abstract).
Claim 17 restates the limitations of claim 1, and is taught by Zeng (Zeng pg 636 left column ¶ 2, 4).
Regarding claim 18, these limitations are contingent because they only occur when the carry over exceeding a predetermined threshold, which is a condition that is not required to occur. The BRI of method claims does not include contingent limitations (see MPEP 2111.04.II). Therefore, claim 18 is anticipated by Zeng et al. because the limitations of claim 18 are not required to occur.
Regarding claim 21, this is a restatement of claim 1 that is taught by Zeng in the referenced sections above, but containing repetition of the steps at different concentrations. Zeng teaches repeated measurements of the same sample at different concentrations (table 2).
Regarding claim 22, that the second sample is a control sample is taught by Zeng (pg 636 left col ¶ 1).
Regarding claim 23, Zeng uses the term “blank sample” in their abstract, so this claim is taught by Zeng.
Claim 24 restates the limitations of claim 1 but implements them as a computer program product, which is taught by the Analyst software of Zeng (abstract).
Regarding claim 25, the Analyst software in Zeng completes steps (b) and (c) of claim 1 of the instant application and is a computer program product, so these claims are taught by Zeng (pg 636 left col ¶ 2).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 4-6 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng, as applied to claims 1-3, 13-15, 17-18, and 21-25 above, and further in view of Maekawa (US 2020/0103380A1).
Claims 4-6 are dependent from claim 1, which is taught by Zeng.
Regarding claim 4, using a predetermined relationship between the background height and a parameter correlating with the carry-over is taught by Maekawa (specification ¶ 47: “In a related art, there is a case in which it is difficult detect the peak due to a minute amount of the target analyte, and there is a case in which the peak cannot be detected due to an influence of a relatively large amount of contaminants which causes the peak to be determined as noise. However, by determining the peak of the target analyte from the retention time of the peak start point and the peak end point of the internal standard material, the measurement value of the target component can be obtained even in the above - described circumstances, and the robustness is excellent.”) The retention time of the peak start point is the parameter correlating with the carryover in Maekawa.
Regarding claim 5, determining an upper and a lower peak boundary of said peak is taught by Maekawa (specification ¶ 44: “the peak is determined by the peak detection part,” “a peak range detection part extracts a peak start time and a peak end time from the peak start point and the peak end point.”).
Regarding claim 6, determining at least one minimum signal intensity value within the upper and lower peak boundary is taught by Maekawa (specification ¶ 67: “In the chromatogram of the internal standard material, a section in the vicinity of the peak of the internal standard material is defined as a noise determination region, and a half value of a difference between the maximum value and the minimum value of the signal intensity in the section is defined as N”).
Regarding claim 19, Maekawa spec ¶ 36: “In the liquid chromatograph - mass spectrometer, it generally performed that an element labeled with a stable isotope with respect to the target analyte is used as the internal standard material, and separated and detected by the mass spectrometry part from a difference in the mass - to charge ratio”
Regarding claim 20, this is a restatement of claim 1 that is taught by Zeng in the referenced sections above, but dependent from claim 19.
An invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the invention if some teaching, suggestion or motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. Zeng discloses the steps of claim 1 that these claims are dependent on, and the determination of carry-over from two samples. Maekawa teaches the concepts of these dependent claims, but does not incorporate them into the same series of steps as Zeng. Maekawa writes: “According to the present invention , a measurement value can be calculated without affecting the quality of a chromatogram of a target analyte.” (¶ 12) Maekawa teaches subtracting one sample from another to determine carry over. A person of ordinary skill in the art would recognize wanting to employ what is “generally performed” in LC-MS analysis. As a result, a person of ordinary skill in the art would recognize a reason to combine the LC-MS analysis inventions to obtain the advantages of Maekawa’s method. Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time to modify the method of Zeng with the teachings of Maekawa, in order to obtain the measurement values without affecting the quality of the chromatogram, and to employ what is generally performed in LC-MS analysis.
Claims 7 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng, as applied to claims 1-3, 13-15, 17-18, and 21-25 above, and further in view of Skyline (https://skyline.ms/home/software/Skyline/wiki-page.view?name=tip_peak_calc).
Regarding claim 7, that the background height is determined shortly upstream of the upper peak boundary and/or shortly downstream of the lower peak boundary is taught by Skyline (“Background height: minimum intensity at peak boundaries… NOTE: Skyline uses points that have been linear interpolated from the raw data onto a uniform interval over the duration of the chromatogram in detecting its peak boundaries and calculating its peak areas” ¶ 1). Since the graph it is using is a linear interpolation of points, it is determining background height using points shortly upstream/downstream of the boundaries.
An invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the invention if some teaching, suggestion or motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. Zeng discloses the steps of claim 1 that these claims are dependent on. Skyline discloses the determination of the background height based on peak boundaries. Skyline discloses a motivation that its background determination is for “speed and simplicity” (¶ 2). A person of ordinary skill in the art would recognize why someone might want to combine aspects of multiple LC-MS analysis methods to achieve greater efficiency in the method. Therefore, It would have been prima facie obvious to one of ordinary skill in the art at the time to modify the method of Zeng with the teachings of Skyline in order to optimize the background determination for speed and simplicity.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng, as applied to claims 1-3, 13-15, 17-18, 21-25 above, and further in view of Pelikan (IEEE/ACM Transactions on Computational Biology and Bioinformatics, Vol. 7 Issue 1, 2007, 126-137).
Regarding claim 8, that the method further comprises at least one confirmation step, wherein the confirmation step comprises determining the reliability of the background height is taught by Pelikan (spec pg 7 left col ¶ 3 – the “reliability parameter”).
Regarding claim 9, that the reliability of the background height is determined by calculating a reliability parameter is taught by Pelikan (spec pg 7 left col ¶ 3).
Zeng and Pelikan are silent as to comparing said reliability parameter to a pre-defined reference. Pelikan gives a suggestion: “Each peak position in the analyzed spectra may also be assigned its own reliability parameter, pi,0. This parameter should be set to reflect the expectation that the ith molecule generates a detectable peak in the MS signal. In experiments where affinity surfaces selectively bind molecules for analysis, molecules which should not bind should have their pi,0 parameter set to reflect the probability with which they will remain in the analysis. In both our simulated and real experiments, we set these parameters to a single value p0.”
An invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the invention if some teaching, suggestion or motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. Zeng discloses the steps of claim 1 that these claims are dependent on. Pelikan teaches the reliability determination by a calculated reliability parameter, and suggests a situation where it is compared to a pre-defined value and changed to the calculated value in some cases. Pelikan writes: “In the baseline method, we observed a dramatic effect of varying p0, which uses only peak location information. A higher value of p0 heavily discourages a label if the location of a peak is far from the expected mass of a molecule. This results in a conservative labeling beyond p0 0:5. The probability of peaks not occurring begins to outweigh all but the closest location-based matches. Thus, few, if any, peak-to-label matches are made beyond this point, resulting in recall and precision close to 0.” The reliability parameter therefore allows one to vary the conservatism of the calculation. A person of ordinary skill in the art could recognize why one might want to add an additional parameter to an analysis method, so that the method could work in different experimental cases. Therefore, It would have been prima facie obvious to one of ordinary skill in the art at the time to modify the method of Zeng with the teachings/suggestions of Pelikan, in order to improve the method for various experimental cases.
Claims 10-12 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng and Pelikan as applied to claims 1-3, 13-15, 17-18, 21-25 and 8-9 above, and further in view of Skyline and St. George et al. (Environmental Pollution, Vol. 159, Issue 2, pg 481-486).
Regarding claim 10, determining an average of quantifier/qualifier ratios of background data points, and comparing said average to a pre-defined average reference is taught by St. George, in the context of identifying water contaminants (Section 5.5, pg 3 right col ¶ 4 – “Peaks were quantified when S/N 3, and when the quantifier/qualifier ratio was within 15% of the standard.”) “Background data points” is not defined by the specification and so can be read to mean any data points that help calculate the background height, such as the points that make up the line of the peak. Since the peaks are quantified as an average of the “background data points”, this reads on the claim.
Regarding claim 10, determining a variation parameter of background data points, and comparing said variation parameter to a pre-defined variation reference is taught by Pelikan (spec pg 7 left col ¶ 3 – the intensity variation parameter is scaled to its expected value) (Pelikan explains the motivation for this in spec pg 6 right col ¶ 1 – “The abundance variation parameter is intended to represent the relationship between the content of a given ion species in a sample, and the mass spectrometer's observation of that ion species in terms of relative intensity. Accurately expressing this relationship is an ongoing process.”).
Regarding claims 11 and 12, that the background data points are used for determining background height of the chromatogram is taught by Skyline (¶ 1). The authors state that the calculation is made in this way for “speed and simplicity” (¶ 1).
Regarding claim 16, Zeng teaches the combined system with the Analyst software and the LCMS device are configured to perform a method for determining a carry over of an analyte (abstract). Zeng states that their goal is to evaluate the influence of carry over on the quantitation of LC-MS samples.
An invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the invention if some teaching, suggestion or motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. Zeng discloses the steps of claim 1 that these claims are dependent on, and the software-based method for determining carry-over, to evaluate the influence of carry over on the quantitation of LC-MS samples. St. George teaches comparing the average of quantifier/qualifier to a reference, as a way of understanding whether it is a normal or abnormal amount of the analyte in the sample. Pelikan teaches comparing the variation parameter to a reference, as a means of representing the relationship between the content of an ion species in a sample and the mass spectrometer’s observation of the ion species. Skyline teaches the use of the background data points “for speed and simplicity”. There would have been a reasonable expectation of success in attempting to combine these inventions, as all of these similar LC-MS pipelines’ advantages, and their reasoning for deploying them, are explained in their documentation and have been implemented on LC-MS data. Therefore, It would have been prima facie obvious to one of ordinary skill in the art at the time to modify the method of Zeng with the methods of St. George, Skyline and Pelikan in order to improve the quality control and speed of the analysis.
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/G.M.H./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685