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 .
Status of the Claims
Claims 1-2, 4-8, 10-12, 16, 18-21, 23, 25-26, were subject to a restriction requirement and were elected without traverse, are currently pending and under exam herein.
Claims 58, 66, 72, 77, 83, 88 were subject to a restriction requirement and were not elected for examination.
Claims 1-2, 4-8, 10-12, 16, 18-21, 23, 25-26 are rejected.
Claims 3, 9, 13-15, 17, 22, 24, 27-57, 59-65, 67-71 are cancelled.
Claims 1, 6, 7, 8, 10, 12, 16, 18, 19, 20, 21, 23, 25, 26 are amended.
Election/Restrictions
The restriction requirement sent on 01/23/2026 is withdrawn. The application is only subject to the restriction requirement sent on 08/29/2025. Applicant’s election without traverse of Group I to claims 1, 2, 4-8, 10-12, 16, 18-21, 23, 25 and 26 in reply filed on 10/29/2025 is acknowledged.
Applicant’s election without traverse of: Species Group 1: peptide structure ID NO.: PS-3
Species Group 2: Pembrolizumab, PS-3
Species Group 3: SEQ ID NO. 45
in reply filed on 10/29/2025 is acknowledged.
Claims 58, 66, 72, 77, 83, 88 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in reply filed on 10/29/2025.
Priority
The instant application claims priority from 63/158,283 filed on 3/08/2021, 63/246,293 filed on 9/20/2021 and 63/251,023 filed on 9/30/2021. Thus, the earliest effective filing date of the instant application is 03/08/2021.
Claim interpretation
Claim 16 depends from cancelled claim 14. Examiner will examine claim 16 as if it depends from claim 1. Applicant elected peptide structure ID NO.: PS-3 and referred to it as IGG1-297_5410. However, structure ID NO.: PS-3 actually corresponds to IGG1-297_5510. Examiner will assume applicant elected structure ID NO.: PS-3 which corresponds to IGG1-297_5510 for the purpose of examination.
Drawings
The Drawings filed on 3/07/2022 were considered.
Information Disclosure Statement
The information disclosure statements (IDS) submitted are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 6, 7, 16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The claims reference Tables 1, 2, 3, 12, 14, 16. The tables contain information on the peptide sequence and attached sugar groups. Examiner recommends to incorporate the information on these tables directly into the claims. Claim 16 recites “the first response classification” , “the second response classification” and “the sustained period of time” there is a lack of antecedent basis for these.
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.
Claim 7, 16 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 7 references peptides from Table 3, however Table 3 only includes species that were not included in the elected species from claim 1 from which it depends. This increases the scope of possible peptides. Claim 16 depends from cancelled claim 14.
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 1-2, 4-8, 10-12, 16, 18-21, 23, 25-26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite: (a) mathematical concepts, (e.g., mathematical relationships, formulas or equations, mathematical calculations); and (b) mental processes, i.e., concepts performed in the human mind, (e.g., observation, evaluation, judgement, opinion).
Subject matter eligibility evaluation in accordance with MPEP 2106:
Eligibility Step 1: Claims 1-2, 4-8, 10-12, 16, 18-21, 23, 25-26 are directed to methods for identifying and treating melanoma or other cancer types.
[Step 1: YES]
Eligibility Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if
so, then it is determined in Prong Two whether the recited judicial exception is integrated into a
practical application of that exception.
Eligibility Step 2A Prong One: In determining whether a claim is directed to a judicial exception,
examination is performed that analyzes whether the claim recites a judicial exception, i.e., whether a
law of nature, natural phenomenon, or abstract idea is set forth or described in the claim.
Independent claim 1 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
computing a treatment score using quantification data identified from the peptide structure data for a set of peptide structures, wherein the set of peptide structures includes at least one peptide structure identified from a plurality of peptide structures listed in Table 1, Table 12, Table 14, or Table 16; and (mathematical concept)
generating a treatment output that indicates a predicted response to the treatment for the subject using the treatment score (mathematical concept, mental process)
Dependent claim 2 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
generating the predicted response to the treatment based on whether the treatment score is above a selected threshold (mathematical concept, mental process)
Dependent claim 4 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
identifying a first predicted response classification for the subject when the treatment score is above 0.5; and (mathematical concept, mental process)
identifying a first predicted response classification for the subject when the treatment score is above 0.5; and (mathematical concept, mental process)
Dependent claim 5 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the first predicted response classification is sustained control and wherein the second predicted response classification is early disruption (mathematical concept, this just limits the math)
Dependent claim 6 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the treatment is pembrolizumab and wherein the set of peptide structures includes at least one peptide structure identified from a plurality of peptide structures listed in Table 2. (mathematical concept, this just limits the math)
Dependent claim 7 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the condition is melanoma and the treatment comprises a combination of nivolumab and ipilimumab and wherein the set of peptide structures includes at least one peptide structure identified from a plurality of peptide structures listed in Table 3. (mathematical concept, this just limits the math)
Dependent claim 8 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the treatment outcome comprises a recommendation to modify a treatment plan for the subject.
Dependent claim 10 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
computing a proportion of the set of peptide structures having a selected abundance greater than a reference abundance (mathematical concept, mental process)
Dependent claim 11 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the reference abundance for a peptide structure of the set of peptide structures is a median of a plurality of abundances for the peptide structure across a sample population and wherein the selected abundance for a glycopeptide structure of the set of peptide structures is a relative abundance and the selected abundance for an a glycosylated peptide structure of the set of peptide structures is an absolute abundance (mathematical concept, mental process)
Dependent claim 12 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
identifying the set of peptide structures using sample data and a statistical algorithm that identifies a relative significance for each peptide structure of a collection of peptide structures corresponding to the sample data (mathematical concept)
Dependent claim 16 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
the first response classification is sustained control which indicates an absence of disruption events during a sustained period of time after treatment administration; (mathematical concept)
the second response classification is early disruption which indicates a presence of at least one disruption event during an initial period of time after treatment; and the sustained period of time is longer than the initial period of time. (mathematical concept)
Dependent claim 18 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the at least one peptide structure comprises a glycopeptide structure defined by a peptide sequence and a glycan structure linked to the peptide sequence at a linking site of the peptide sequence, as identified in Table 1, with the peptide sequence being one of SEQ ID NOS: 21-46 as defined in Table 7 (mathematical concept, this just limits what the math is done on)
Dependent claim 19 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the quantification data for a peptide structure of the set of peptide structures comprises at least one of an adjusted abundance, a relative abundance, an absolute abundance, a normalized abundance, a relative quantity, an adjusted quantity, a normalized quantity, a relative concentration, an adjusted concentration, or a normalized concentration (mathematical concept, this just limits what the math is done on)
Dependent claim 23 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
wherein the treatment output comprises at least one of a design for the treatment or a therapeutic dosage for the treatment (mental process, under the broadest reasonable interpretation the treatment is never administered to the patient and can be simply generated in the mind)
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification. As noted in the foregoing section, the claims are determined to contain limitations that can practically be performed in the human mind with the aid of a pencil and paper, and therefore recite judicial exceptions from the mental process grouping of abstract ideas. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Therefore, claims 1-2, 4-8, 10-12, 16, 18-21, 23, 25-26 recite an abstract idea as the dependent claims will inherit the abstract ideas from the independent claims.
[Step 2A Prong One: YES]
Eligibility Step 2A Prong Two: In determining whether a claim is directed to a judicial exception, further
examination is performed that analyzes if the claim recites additional elements that when examined as a
whole integrates the judicial exception(s) into a practical application (MPEP 2106.04(d)). A claim that
integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception
in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements
are analyzed to determine if the abstract idea is integrated into a practical application (MPEP
2106.04(d)(I); MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the abstract
idea, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d)(III)).
The judicial exceptions identified in Eligibility Step 2A Prong One are not integrated into a practical application because of the reasons noted below.
The additional element in independent claim 1 includes:
A method for managing a treatment for a subject diagnosed with a melanoma or non-small cell lung cancer condition, the method comprising:
receiving peptide structure data corresponding to a set of glycoproteins in a biological sample obtained from the subject;
The additional element in dependent claim 20 includes:
wherein the peptide structure data is generated using multiple reaction monitoring mass spectrometry (MRM-MS).
The additional element in dependent claim 21 includes:
creating a sample from the biological sample; and
preparing the sample using reduction, alkylation, and enzymatic digestion to form a prepared sample that includes a set of peptide structures.
The additional element in dependent claim 25 includes:
administering a therapeutic dosage of the treatment based on the predicted response being a predicted response classification that indicates the treatment will be successful (contingent limitation)
The additional element in dependent claim 26 includes:
administering a therapeutic dosage of the treatment based on the predicted response being sustained control (contingent limitation)
The additional elements of receiving peptide structure data corresponding to a set of glycoproteins in a biological sample obtained from the subject (Claim 1), wherein the peptide structure data is generated using multiple reaction monitoring mass spectrometry (MRM-MS) (Claim 20), creating a sample from the biological sample; and (Claim 21), preparing the sample using reduction, alkylation, and enzymatic digestion to form a prepared sample that includes a set of peptide structures (Claim 21) are insignificant extra-solution activity that are part of the data gathering process used in the recited judicial exceptions (see MPEP 2106.05(g)).
The additional elements of administering a therapeutic dosage of the treatment based on the predicted response being a predicted response classification that indicates the treatment will be successful (Claim 25, contingent limitation), administering a therapeutic dosage of the treatment based on the predicted response being sustained control (Claim 26, contingent limitation), are contingent limitations. The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. Therefore, under the broadest reasonable interpretation no drug needs to be administered. Therefore, they do not integrate a judicial exception into a practical application.
The additional elements of a method for managing a treatment for a subject diagnosed with a melanoma or non-small cell lung cancer condition, the method comprising (claim 1) fail to integrate a judicial exception into a practical application merely reciting the words "apply it" (or an equivalent) with the judicial exception, or merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f).
Thus, the additionally recited elements merely invoke a computer as a tool, and/or amount to insignificant extra-solution data gathering activity, and as such, when all limitations in claims 1-2, 4-8, 10-12, 16, 18-21, 23, 25-26 have been considered as a whole, the claims are deemed to not recite any additional elements that would integrate a judicial exception into a practical application, and therefore claims 1-2, 4-8, 10-12, 16, 18-21, 23, 25-26 are directed to an abstract idea (MPEP 2106.04(d)).
[Step 2A Prong Two: NO]
Eligibility Step 2B: Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they amount to significantly more than the judicial exception (MPEP 2106.05A i-vi).
The claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception(s) because of the reasons noted below.
The additional elements identified above, and carried over from Step 2A: Prong Two along with their conclusions for analysis at Step 2B. Any additional element or combination of elements that was considered to be insignificant extra-solution activity at Step 2A: Prong Two was re-evaluated at Step 2B, because if such re-evaluation finds that the element is unconventional or otherwise more than what is well-understood, routine, conventional activity in the field, this finding may indicate that the additional element is no longer considered to be insignificant; and all additional elements and combination of elements were evaluated to determine whether any additional elements or combination of elements are other than what is well-understood, routine, conventional activity in the field, or simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, per MPEP 2106.05(d).
The additional elements of receiving peptide structure data corresponding to a set of glycoproteins in a biological sample obtained from the subject (Claim 1), wherein the peptide structure data is generated using multiple reaction monitoring mass spectrometry (MRM-MS) (Claim 20), creating a sample from the biological sample; and (Claim 21), preparing the sample using reduction, alkylation, and enzymatic digestion to form a prepared sample that includes a set of peptide structures (Claim 21), are conventional and part of the data gathering process used in the recited judicial exceptions (see MPEP 2106.05(g)). Evidence for conventionality is shown by Gillet et al. (Gillet et al. Mass Spectrometry Applied to Bottom-up Proteomics: Entering the High-Throughput Era for Hypothesis Testing. Annual Review of Analytical Chemistry 2016, 9 (1), 449–472.) which is a mass spectrometry review for bottom-up proteomics. They discuss the current state of using MRM and enzymatic digestion for proteomics (pg. 450, paragraphs 2-3)
The additional elements of administering a therapeutic dosage of the treatment based on the predicted response being a predicted response classification that indicates the treatment will be successful (Claim 25, contingent limitation), administering a therapeutic dosage of the treatment based on the predicted response being sustained control (Claim 26, contingent limitation) are contingent limitations. The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. Therefore, under the broadest reasonable interpretation no drug needs to be administered. Therefore, they do not integrate a judicial exception into a practical application.
The additional element of a method for managing a treatment for a subject diagnosed with a melanoma or non-small cell lung cancer condition, the method comprising (claim 1) fails to integrate a judicial exception into a practical application merely reciting the words "apply it" (or an equivalent) with the judicial exception, or merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f).
Therefore, when taken alone, all additional elements in claims 1-2, 4-8, 10-12, 16, 18-21, 23, 25-26 do not amount to significantly more than the above-identified judicial exception(s). Even when evaluated as a combination, the additional elements fail to transform the exception(s) into a patent-eligible application of that exception. Thus, claims 1-2, 4-8, 10-12, 16, 18-21, 23, 25-26 are deemed to not contribute an inventive concept, i.e., amount to significantly more than the judicial exception(s) (MPEP 2106.05(II)).
[Step 2B: NO]
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 4-8, 10-12, 16, 18-21, 23, 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Weber et al. (Weber et al. A Serum Protein Signature Associated with Outcome after Anti–PD-1 Therapy in Metastatic Melanoma. Cancer Immunology Research 2017, 6 (1), 79–86.) in view of Li et al. (Li, Q.; Kailemia, M. J.; Merleev, A. A.; Xu, G.; Serie, D.; Danan, L. M.; Haj, F.; Emanual Michael Maverakis; Lebrilla, C. B. Site-Specific Glycosylation Quantitation of 50 Serum Glycoproteins Enhanced by Predictive Glycopeptidomics for Improved Disease Biomarker Discovery. Analytical chemistry 2019, 91 (8), 5433–5445.) in further view of Padmanabhan et al. (Padmanabhan, R.; Meskin, N.; Haddad, W. M. Reinforcement Learning-Based Control of Drug Dosing for Cancer Chemotherapy Treatment. Mathematical Biosciences 2017, 293, 11–20.). The italicized text corresponds to the instant claim limitations.
With respect to the limitations of Claims 1, Weber et al. teaches developed a pretreatment serum test utilizing mass spectrometry to identify a group of serum proteins that distinguish metastatic melanoma patients that went on to have prolonged survival after receiving anti–PD-1 antibodies. The test was validated in a blinded manner in three independent sets of patients treated with PD-1 checkpoint inhibitors. The test measures the relative abundance of 209 circulating proteins or protein fragments via mass spectrometry with MALDI-TOF, and generates a test classification, designated either “sensitive” or “resistant,” by using machine learning. This would identify patients with the best outcomes. (pg. 83, col. 1 paragraph 2 – col. 2 paragraph 2, computing a treatment score using quantification data identified from the peptide structure data for a set of peptide structures (Claim 1), generating a treatment output that indicates a predicted response to the treatment for the subject using the treatment score (Claim 1)
With respect to the limitations of Claims 2, 4, Weber et al. teaches the use of a binary classifier to determine effectiveness of melanoma treatment. A binary classifier uses 0.5 as the threshold for classification with 29% of patients were classified as sensitive.(pg. 81, col. 1, paragraph 3, wherein generating the treatment output comprises: generating the predicted response to the treatment based on whether the treatment score is above a selected threshold (Claim 2), wherein the generating the predicted response comprises: identifying a first predicted response classification for the subject when the treatment score is above 0.5: and identifying a second predicted response classification for the subject when the treatment score is not above 0.5 (Claim 4)
With respect to the limitations of Claims 5, 16, Weber et al. teaches that a signature consisting of 209 proteins or peptides was associated with progression-free and overall survival in a multivariate analysis and significantly better overall survival for "sensitive" relative to "resistant" patients which are the two outcomes for their binary classifier. This is equivalent to sustained control and early disruption. As both sensitive and resistant as well as sustained control and early disruption are merely labels for the favorable and unfavorable survival groups (abstract, wherein the first predicted response classification is sustained control and wherein the second predicted response classification is early disruption (Claim 5), wherein: the first response classification is sustained control which indicates an absence of disruption events during a sustained period of time after treatment administration; the second response classification is early disruption which indicates a presence of at least one disruption event during an initial period of time after treatment; and the sustained period of time is longer than the initial period of time (Claim 16)
With respect to the limitations of Claims 6, 7, Weber et al. teaches mass spectrometry analysis was performed using serum from patients receiving checkpoint inhibitors to define baseline protein signatures associated with outcome in metastatic melanoma. Pretreatment serum was obtained from a development set of 119 melanoma patients on a trial of nivolumab with or without a multipeptide vaccine and from patients receiving pembrolizumab, nivolumab, ipilimumab, or both nivolumab and ipilimumab (abstract, wherein the treatment is pembrolizumab (Claim 6), wherein the condition is melanoma and the treatment comprises a combination of nivolumab and ipilimumab (Claim 7)
With respect to the limitations of Claim 8, Weber et al. teaches delivering treatments only to those patients likely to benefit would also result in substantial health care savings and decreased morbidity due to elimination of unnecessary toxicity. The potential treatment is adjusted based on the prediction of it being successful. (pg. 79, col. 2, paragraph 1, wherein the treatment outcome comprises a recommendation to modify a treatment plan for the subject (Claim 8))
With respect to the limitations of Claim 10, 11, Weber et al. teaches each of these subtests assigns a good or poor prognosis classification to a sample (by comparing this sample with the samples in the development subset of the test). Samples where at least one of the seven subtests indicated poor prognosis were labeled as "resistant." The seven subtests utilize different numbers of MS peaks (n = 56, 69, 75, 82, 84, 85, and 85). The MS peaks are directly representative of different peptides in the sample and their relative abundance directly affects the peak intensity including being greater than the reference intensity. In addition, it is an obvious variant to use a simple greater abundance of the same peptides in classification or to median of a plurality of abundances for the peptide structure across a sample population. (pg. 81, col. 1, paragraph 3, wherein computing the treatment score comprises: computing a proportion of the set of peptide structures having a selected abundance greater than a reference abundance (Claim 10), wherein the reference abundance for a peptide structure of the set of peptide structures is a median of a plurality of abundances for the peptide structure across a sample population (Claim 11)
With respect to the limitations of Claim 12, Weber et al. teaches that the spectra were processed to render them comparable between patients and 351 MS peaks were selected for further analysis by assessing their reproducibility and stability. Each MS peak is representative of a different peptide structure which was chosen for further analysis (pg. 80, col 2, paragraph 2, further comprising: identifying the set of peptide structures using sample data and a statistical algorithm that identifies a relative significance for each peptide structure of a collection of peptide structures corresponding to the sample data (Claim 12))
With respect to the limitations of Claim 19, Weber et al. teaches a test that measures the relative abundance of 209 circulating proteins or protein fragments via mass spectrometry with MALDI-TOF (pg. 83, cols 1, paragraph 2, col. 2, paragraph 1, wherein the quantification data for a peptide structure of the set of peptide structures comprises at least one of an adjusted abundance, a relative abundance, an absolute abundance, a normalized abundance, a relative quantity, an adjusted quantity, a normalized quantity, a relative concentration, an adjusted concentration, or a normalized concentration (Claim 19)
With respect to the limitations of Claim 25, Weber et al. teaches the availability of a validated serum assay to predict outcome with PD-1 blockade could provide guidance in selecting metastatic melanoma patients for immunotherapy. It is an obvious variant to use this model to select patients for a favorable treatment when the author predicted treatment favorability and explicitly suggests using (pg. 85, col. 1, paragraph 1, further comprising: administering a therapeutic dosage of the treatment based on the predicted response being a predicted response classification that indicates the treatment will be successful (Claim 25)
Weber et al. does not explicitly teach
receiving peptide structure data corresponding to a set of glycoproteins in a biological sample obtained from the subject (Claim 1)
wherein the set of peptide structures includes at least one peptide structure identified from a plurality of peptide structures listed in Table 1, Table 12, Table 14, or Table 16, and (Claim 1)
wherein the set of peptide structures includes at least one peptide structure identified from a plurality of peptide structures listed in Table 2. (Claim 6), wherein the set of peptide structures includes at least one peptide structure identified from a plurality of peptide structures listed in Table 3. (Claim 7)
wherein the at least one peptide structure comprises a glycopeptide structure defined by a peptide sequence and a glycan structure linked to the peptide sequence at a linking site of the peptide sequence, as identified in Table 1, with the peptide sequence being one of SEQ ID NOS: 21-46 as defined in Table 7 (Claim 18)
wherein the peptide structure data is generated using multiple reaction monitoring mass spectrometry (MRM-MS), (Claim 20)
further comprising: creating a sample from the biological sample; and preparing the sample using reduction, alkylation, and enzymatic digestion to form a prepared sample that includes a set of peptide structures (Claim 21)
a method for managing a treatment for a subject diagnosed with a melanoma or non-small cell lung cancer condition, the method comprising: (Claim 1), wherein the treatment output comprises at least one of a design for the treatment or a therapeutic dosage for the treatment (Claim 23)
With respect to the limitations of Claims 1, Li et al. teaches the abundances of over 600 glycopeptides were simultaneously monitored in blood serum to identify biomarkers for human disease the abundances of over 600 glycopeptides were simultaneously monitored (abstract, receiving peptide structure data corresponding to a set of glycoproteins in a biological sample obtained from the subject (Claim 1)
With respect to the limitations of Claims 1, 6, 7, 18, Li et al. teaches a peptide fragment IgG1 studies corresponds to a triply-charged (z=3) glycosylated peptide (glycopeptide) located at the conserved Fc region with a sequence of EEQYNSTYR, with a G2FS N-glycan structure. This is the same structure that applicant elected. The authors related this peptide fragment as a potential biomarker for disease progression, such as cancer. (Supporting Information, Full transition list, wherein the set of peptide structures includes at least one peptide structure identified from a plurality of peptide structures listed in Table 1, Table 12, Table 14, or Table 16, and (Claim 1), wherein the set of peptide structures includes at least one peptide structure identified from a plurality of peptide structures listed in Table 2. (Claim 6), wherein the set of peptide structures includes at least one peptide structure identified from a plurality of peptide structures listed in Table 3. (Claim 7), wherein the at least one peptide structure comprises a glycopeptide structure defined by a peptide sequence and a glycan structure linked to the peptide sequence at a linking site of the peptide sequence, as identified in Table 1, with the peptide sequence being one of SEQ ID NOS: 21-46 as defined in Table 7 (Claim 18)
With respect to the limitations of Claims 20, Li et al. teaches the glycoproteomic data were used to develop the MRM method. The standard curve of RTs varying with the hydrophobicities of synthesized peptide standards was used to acquire the predicted RT of glycopeptides. Then, the RT of each glycopeptide was included in the MRM method for developing the dMRM method, which was used for simultaneous quantitation of glycopeptides and peptides (pg. 5436, col 1., paragraph 2, wherein the peptide structure data is generated using multiple reaction monitoring mass spectrometry (MRM-MS), Claim 20)
With respect to the limitations of Claims 21, Li et al. teaches that for quantitative analysis, tryptic-digested serum samples were injected into an Agilent 1290 infinity ultrahigh-pressure liquid chromatography (UHPLC) system coupled to an Agilent 6495 QqQ mass spectrometer.
(pg. 5434, col. 2, paragraph 3, further comprising: creating a sample from the biological sample; and preparing the sample using reduction, alkylation, and enzymatic digestion to form a prepared sample that includes a set of peptide structures (Claim 21)
With respect to the limitations of Claims 1, 23, Padmanabhan et al. teaches a reinforcement learning (RL)-based, model-free method is proposed for the closed-loop control of cancer chemotherapy drug dosing. Specifically, the Q -learning algorithm is used to develop an optimal controller for cancer chemotherapy drug dosing. Numerical examples are presented using simulated patients to illustrate the performance of the proposed RL-based controller (abstract, a method for managing a treatment for a subject diagnosed with a melanoma or non-small cell lung cancer condition, the method comprising: (Claim 1), wherein the treatment output comprises at least one of a design for the treatment or a therapeutic dosage for the treatment (Claim 23)
A person of ordinary skill in the art would be motivated to combine Weber et al. with Li et al. with Padmanabhan et al. as Weber et al. teaches a machine learning model to predict outcome after Anti–PD-1 therapy in metastatic melanoma. The same problem the applicant is trying to solve. Li et al. adds mass spectrometry techniques to find biomarkers in blood serum and identifies the same biomarker as the applicant and even suggests in the future these identified biomarkers can be used to treat cancer further giving a motivation to combine. Padmanabhan et al. adds a machine learning method to modify dosing of cancer treatment based on patient response. This model only works on the output and there is no need to modify any method to combine them. Therefore, there is a reasonable expectation of success because each method is expected to continue to work on its own. All of these works deal directly with identifying biomarkers of cancer progression or directly treating cancer therefore a person of ordinary skill in the art would be motivated to look at each of the works. Li et al. method was used as a simple substitution of Weber et al. Maldi TOF MS method for a more informative MRM method (Li et al.) with digestion enzymatic beforehand to get increased structural characterization. It’s also a simple substitution of one known MS technique for another well-known MS technique which will give a reasonable expectation of success.
Conclusion
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/C.H.B./Examiner, Art Unit 1687
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