DETAILED ACTION
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 .
Restriction/Election
Applicant's election of Species 1A (glycoprotein acetyls (Claims 1 and 10)) without traverse in the reply filed on 04 November 2025 is acknowledged.
In a telephonic correspondence held on 09 December 2025, the Attorney had been requested to elect either Species 2A or 2B, which had not been indicated in Applicants' reply to the Restriction/Election Office Action. The Attorney elected Species 2A (glycoprotein acetyls and albumin (Claim 3)).
Claim 4 is withdrawn from further consideration as being drawn to nonelected species (i.e., Species 2B). In addition, all limitations relating to said nonelected species are withdrawn from further consideration at this time. Election was made without traverse, in the timely reply filed on 04 November 2025 to the Restriction/Election Office Action mailed on 04 September 2025.
Status of Claims
Claim 4 shows an incorrect status identifier. Applicant is reminded that claim 4 should be labeled: “(Withdrawn; Currently Amended)”; remaining claims should be identified appropriately (MPEP 714 (II)(C)(A)) (See 37 CFR 1.121 (c)).
Appropriate correction is required.
Applicant is required to provide a new claim set showing correct status identifiers in the response to this Office Action.
Claims 1-14 are pending.
Claim 4 is withdrawn.
Claims 1-3 and 5-14 are rejected.
Claims 1, 5 and 10 are objected to.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. §119(e) or under 35 U.S.C. §120, §121, or §365(c) is acknowledged. This application is a 371 of PCT/FI2021/050888, filed on 12/16/2021.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. §119 (a)-(d). The certified copy of FINLAND 20206343, filed on 12/18/2020, was submitted on 16 June 2023.
Applicant has complied with all of the conditions for receiving the benefit of an earlier filing date under 35 U.S.C. §120 or §365(c).
Claims 1-3 and 5-14 have the effective filing date of 18 December 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 20 June 2023 and 23 December 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
Drawings
The drawings were received on 16 June 2023. These drawings are accepted.
Claim Objections
Claims 1, 5 and 10 are objected to because of the following informalities:
(1) Claim 1 recites: "A method for determining whether a subject is at risk of developing a musculoskeletal disease; wherein the method comprises...", which should read: "A method for determining whether a subject is at risk of developing a musculoskeletal disease, wherein the method comprises..." or "A method for determining whether a subject is at risk of developing a musculoskeletal disease, the method comprising..." Other language will be considered.
(2) Claim 5 recites: "..., wherein the musculoskeletal disease comprises or is polyosteoarthritis (M15); osteoarthritis of knee (M17); and/or other and unspecified osteoarthritis (M19)", which should read: "..., wherein the musculoskeletal disease is polyosteoarthritis; osteoarthritis of knee; and/or an unspecified osteoarthritis."
That is, the parenthetical designations should be removed from the claim. Also see Claim Rejections section under 35 USC §112(b) below.
Allowable Subject Matter
(3) Claim 10 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 U.S.C. § 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 1-3 and 5-14 are rejected under 35 U.S.C. §101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The judicial exception is not integrated into a practical application, and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The instant claims were analyzed for eligibility pursuant to the Patent Subject Matter Eligibility Guidance as presented in MPEP 2106. The instant claims are drawn to a method for quantifying at least one biomarker.
As such, the instant claims are drawn to a process, which is a statutory category of invention. (STEP 1: YES).
The claimed method for determining whether a subject is at risk of developing a musculoskeletal disease, comprises the following steps: 1) performing the laboratory step of determining the quantitative value of at least one biomarker, as listed in claim 1, such as glycoprotein acetyls [species election], which is, in turn, obtained from a biological sample of a subject; 2) correlating whether the quantitative value of the at least one biomarker is increased or decreased vs a control sample or value; and 3) deciding whether or not the subject has an increased risk of a musculoskeletal disease, such as osteoarthritis.
The broadest reasonable interpretation of step 1) is that it is considered to be a data gathering step. The broadest reasonable interpretation of steps 2) and 3) is that they fall within the mental process groupings of abstract ideas, because it covers concepts performed in the human mind, including observation, evaluation, judgment, and opinion. See MPEP 2106.04 (a)(2)(III).
As such, claim 1 recites a judicial exception (abstract ideas) in the form of a method for quantifying at least one biomarker (STEP 2A, PRONG ONE: YES).
The instant claims are drawn to a method for determining whether a subject is at risk of developing a musculoskeletal disease which is a judicial exception (i.e., abstract ideas). The claims do not improve the functioning of a computer or other technology.
Claims 2-3, 10 and 11-13 recite limitations which are related to the number of and/or type of biomarkers to be determined as per their quantitative value(s).
Claim 5 describes the type(s) of musculoskeletal diseases which can be identified as those which the subject is at risk of developing.
Claim 6 describes the instrumental protocol for determining the quantitative value(s) of the biomarker(s), i.e., nuclear magnetic resonance spectroscopy.
Claims 7-9 and 14 describe other assessments that can be used to determine whether the subject is at risk of developing a musculoskeletal disease.
That is, these claims also recite data gathering or mental process steps. Therefore, there are no additional elements recited in the claimed subject matter beyond the judicial exception. See MPEP 2106.04 (d).
It is noted that the 2019 PEG includes a 'treatment/prophylaxis' consideration, under which a claim can integrate a judicial exception into a practical application by applying or using the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. The treatment or prophylaxis limitation must be 'particular', i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). See the October 2019 Update: Subject Matter Eligibility, pg. 13, part (III)(C) at https://uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf.
As such, the instant claims do not recite additional elements that integrate the judicial exception(s) into a practical application of the exception(s) (STEP 2A, PRONG TWO: NO).
The claims as a whole do not describe significantly more than the recited judicial exception (i.e., an abstract idea). The use of nuclear magnetic resonance (NMR) spectroscopy, as an extra-solution activity performed to gather data, as specified in claim 6, is considered to be well-understood, routine and conventional. The use of such spectroscopy to analyze biological compounds or molecules, is considered to be well-understood, routine and conventional. See MPEP 2106.05 (d)(II). For example, Kettunen et al. (cited below in the 103 rejection) shows nuclear magnetic resonance (NMR) spectroscopy being used to measure the abundance of circulating glycated proteins (pg. 1, para. Background).
As noted above, the rest of the claims describe limitations related to the data gathering or mental process steps.
As such, the instant claims as a whole do not describe significantly more than the recited judicial exception (Step 2B: NO).
In summary, the claimed subject matter describes a judicial exception which is not integrated into a practical application, and, as individual elements and as a combination of elements, does not recite ‘significantly more’ than the judicial exception.
Accordingly, the instant claims do not constitute patent eligible subject matter under 35 USC §101.
Claim Rejections - 35 U.S.C. § 112
35 U.S.C. § 112(b)
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 1-3 and 5-14 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 pre-AIA the applicant regards as the invention.
[Claims 2-3 and 5-14 are dependent on claim 1, contain the limitations of claim 1, and, therefore, are rejected for the same reason.]
Claims 1-3 and 5-14 are indefinite because the metes and bounds of the claimed subject matter are not clear.
Claim 1 recites: "A method for determining whether a subject is at risk of developing a musculoskeletal disease;...; and wherein the musculoskeletal disease comprises or is osteoarthritis."
Claim 5 recites: "The method according to any one of claim 1, wherein the musculoskeletal disease comprises or is polyosteoarthritis (M15); osteoarthritis of knee (M17); and/or other and unspecified osteoarthritis (M19)."
However, it is not clear if the subject is at risk of developing one (a) musculoskeletal disease or at least one such disease because the transitional phrase of 'comprises or is' suggests that the disease can contain or include other diseases. One of ordinary skill in the art would understand that a subject with a musculoskeletal disease would be evaluated as exhibiting just one disease.
For the purpose of compact prosecution the claims will be interpreted to read: Claim 1. "A method for determining whether a subject is at risk of developing a musculoskeletal disease;...; and wherein the musculoskeletal disease is osteoarthritis"; and Claim 5: "The method according to any one of claim 1, wherein the musculoskeletal disease is polyosteoarthritis; osteoarthritis of knee; and/or an unspecified osteoarthritis." See Claim Objections section above.
Claim Interpretations
(1) Claims 1, 3 and 10 recite the term "glycoprotein acetyls".
The specification recites: "In the context of this specification, the term 'glycoprotein acetyls', 'glycoprotein acetylation', or 'GlycA' may refer to the abundance of circulating glycated proteins, and/or to a nuclear magnetic resonance spectroscopy (NMR) signal that represents the abundance of circulating glycated proteins, i.e. N-acetylated glycoproteins" (clean copy specification filed on 22 January 2024, pg. 19, para. 1).
Therefore, any references which recite any of the terms cited above will be considered to be applicable prior art.
(2) Claims 1, 3, 5, 7 and 9-10 recite the term "musculoskeletal disease".
The specification recites: "Musculoskeletal and connective tissue diseases comprise disorders related to the locomotor system (clean copy specification filed on 22 January 2024, pg. 1, para. 3); and "...predicting whether an individual person is at an elevated risk of developing a broad range musculoskeletal system and connective tissue diseases as well as specific types of these disorders, such as rheumatoid arthritis, other arthritis, gout, osteoarthritis, joint disorders, spondylosis and/or soft tissue disorders" (spec., pg. 2, lines 1-5).
Therefore, any references which recite any of the terms cited above or which show a disorder related to the locomotor system will be considered to be applicable prior art.
Claim Rejections - 35 U.S.C. § 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 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 of this title, 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.
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 1-3, 5-9 and 14 are rejected under 35 U.S.C. §103 as being unpatentable over Kettunen et al. (Circ. Genom. Precis. Med. 2018, 11: 1-7) in view of Jemmett et al. (Ortho. Proc. 2012, 94-B, Supp. XVIII, pg. 1).
[Both references cited on the IDS submitted 20 June 2023 and on the record. The Supplemental Material of Kettunen et al. is also on the record.]
Kettunen et al. addresses some of the limitations of claim 1.
Regarding claim 1, pertaining to a method for determining whether a subject is at risk of developing a musculoskeletal disease; determining at least one biomarker such as glycoprotein acetyls [species election],
Kettunen et al. teaches that there has been recent interest in the glycoprotein acetyls (GlycA) as a biomarker. GlycA predicts risk of diverse outcomes, including cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality. New associations with GlycA and, minimally, inflammatory polyarthropathies, have been uncovered, and known disease associations were replicated (pg. 1, para. Background & Results [polyarthropathies comprise musculoskeletal diseases such as arthritis]). GlycA was predictive of myriad incident diseases across many major internal organs. GlycA independently contributed to mortality risk, suggesting chronic inflammation as an etiological factor. GlycA may be useful in improving risk prediction in specific disease settings (pg. 1, para. Conclusions).
Further regarding claim 1, pertaining to the method comprises determining in a biological sample obtained from the subject a quantitative value of at least one biomarker; comparing the quantitative value(s) of the at least one biomarker to a control sample or to a control value; wherein an increase or a decrease in the quantitative value(s) of the at least one biomarker, when compared to the control sample or to the control value, is/are indicative of the subject having an increased risk of developing a musculoskeletal disease,
Kettunen et al. shows that GlycA was evaluated as a biomarker for future risk of hospitalization or death across the spectrum of all common diseases of two independent population-based cohorts with complete 8-yr follow-up electronic health record (EHR) follow-up (pg. 2, column 1, para. 3). A serum- or plasma-derived nuclear magnetic resonance spectroscopy signal represents the abundance of circulating glycated proteins (pg. 1, para. Background).
To elucidate the cause specificity of the disease burden predicted by elevated GlycA, high-throughput nuclear magnetic resonance (NMR) spectroscopy data was utilized with matched EHRs obtained from national care register for health care and causes of death registries from the independent population-based FINRISK 1997 and DILGOM. Baseline cohort characteristics are reported in the Table. GlycA was considered to be the biomarker for any outcome that was nominally significant (P<0.05) in both FINRISK 1997 and DILGOM. In total, strong and consistent associations between elevated GlycA concentrations and increased risk for 16 disease outcomes was observed (pg. 2, column 2, para. Results thru pg. 3, column 1, para. 1; and pg. 3, Table).
Figure S3 shows the 8-year disease risk for GlycA among several different types of disease manifestations, including inflammatory polyarthropathies (Suppl. Mater., pg. 13, Figure S3).
Kettunen et al. further teaches that GlycA is a heterogeneous biomarker associated with both acute and chronic inflammation that has been of intense, recent interest as a biomarker for diverse disease outcomes both in asymptomatic people and in those with preexisting chronic disease. The evaluation of GlycA as a reproducible biomarker for onset of all common disease outcomes, using data from 11,861 adults from 2 independent population-based cohorts with complete EHR during an 8-year follow-up period was conducted. Novel associations between elevated GlycA and 8-year risk of alcoholic liver disease, chronic renal failure, glomerular diseases, chronic obstructive pulmonary disease, and inflammatory polyarthropathies was observed (pg. 5, column 1, last para.).
That is, Kettunen et al. shows that a biological sample, such as serum or plasma, obtained from a subject has been analyzed by NMR in order to determine a quantitative value representing the presence of GlycA. The quantitative values were compared among subjects in a retrospective study at the start of an 8-yr study through the final GlycA determinations (e.g., Suppl. Mater., pg. 10, Fig. S1; and pg. 13, Fig. S3). The quantitative values are used to show the risk of disease contraction vs the level of the biomarker GlycA, one of these diseases being inflammatory polyarthropathies, which comprise musculoskeletal diseases such as arthritis.
Kettunen et al. does not explicitly show that the musculoskeletal disease is osteoarthritis.
Jemmett et al. shows the differences in synovial fluid metabolite profiles between osteoarthritis and meniscal tears. Meniscal tears commonly occur after a traumatic twisting injury to the knee (acute) or can form over time (degenerate). Symptoms include pain, swelling, and 'locking' of the knee. These symptoms are also commonly associated with osteoarthritis (OA) (pg. 1, Abstract [nexus to Kettunen et al.- obtain metabolite profiles in a biological sample in subjects with an inflammatory polyarthropathy]). Synovial fluid samples have been obtained from patients with varying degrees of joint pathology (cartilage graded 0-4; meniscal tears classified as acute or degenerative). Chemical shifts were referenced to known concentration NMR (nuclear magnetic resonance) internal standard peaks identified by reference to published synovial fluid NMR spectra (pg. 1, para. Method [nexus to Kettunen et al.- compare quantitative values with control sample or value]).
Regarding claim 1, Jemmett et al. shows that samples obtained during arthroscopy or knee replacement surgery were analyzed using NMR spectroscopy, which revealed a number of differences in metabolites between OA, meniscal tear and ACL (anterior cruciate ligament) pathologies. These included significantly increased concentrations of, minimally, n-acetyl glycoprotein (pg. 1, para. Method and Results). For example, concentrations of, minimally, n-acetyl glycoprotein was significantly increased in OA without tears compared to OA plus meniscal tears (pg. 2, lines 1-3). OA samples have increased concentrations of n-acetyl glycoprotein. The differing levels of metabolites seen in OA alone compared to OA with meniscal tears may ultimately be a useful indicator of whether cartilage or meniscal pathology predominates within the joint (pg. 2, para. Discussion).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified the method for determining whether a subject is at risk of developing a musculoskeletal disease, comprising determining the quantitative value of glycoprotein acetyls [species election] in a biological sample and determining an increase or decrease in said value, as shown by Kettunen et al., by determining the risk of osteoarthritis (OA) as the musculoskeletal disease [Claim 1], with a reasonable expectation of success, because Jemmett et al. shows that an increased level of n-acetyl glycoprotein has been measured in subjects with OA, which is a type of the inflammatory polyarthropathies, which are shown by Kettunen et al. (MPEP 2143 (I)(G)).
One of ordinary skill in the art would have been motivated to have made that modification, because Jemmett et al. shows that the level of n-acetyl glycoprotein (GlycA) in the biological sample can be used to differentiate between different grades of joint pathology (e.g., OA with or without meniscal tears). That is, GlycA would appear to be an important diagnostic tool with regard to its high specificity in discriminating different grades of joint pathology, which could potentially be extrapolated to diagnosing or determining the risk of other types of inflammatory polyarthropathy conditions.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Kettunen et al. further addresses the limitations of claims 2, 3, 6, 7, 8, 9 and 14.
Regarding claims 2 and 3, Kettunen et al. shows the associations between glycoprotein acetyls (GlycA) and 8-yr disease risk assessed by electronic health records (EHR). Cox models were fit using age as the time scale adjusting for sex, smoking status, body mass index, blood pressure, alcohol consumption, and previously discovered biomarkers for 5-yr all-cause mortality (i.e., citrate, albumin, and VLDL [very-low-density lipoprotein] particle size) to elucidate biology behind GlycA specific mortality risk (pg. 3, Figure 1 legend).
That is, Kettunen et al. measures citrate, as one of the biomarkers cited in claim 1, and albumin is cited as a biomarker with regard to claim 3.
Regarding claim 6, a serum- or plasma-derived nuclear magnetic resonance (NMR) spectroscopy signal represents the abundance of circulating glycated proteins (pg. 1, para. Background).
Regarding claim 7, pertaining to hazard ratio,
Kettunen et al. shows that GlycA had hazard ratios of 4.87 and 5.00 for 12-year risk of mortality in the fourth and fifth quintiles by GlycA levels, demonstrating its prognostic potential for identification of high-risk individuals (pg. 1, para. Results). To facilitate future meta-analyses, hazard ratios and standard errors are provided for all outcomes analyzed in the EHR analyses in Table S2 (Suppl. Mater., pg. 4, para. 2; and pg. 18, Table S2 legend). The disease risk association analyses in DILGOM and FINRISK97 were conducted using Cox proportional hazards analyses to account for the time to first event of each diagnosis outcome (Suppl. Mater., pg. 4, para. 3).
That is, a hazard ratio appears to be a calculation known in the art based on Cox proportional hazards analyses which determines disease risk.
Regarding claims 8 and 14, and
regarding claim 9, pertaining to, minimally, body mass index and smoking,
Kettunen et al. shows that Cox proportional hazards models were fit for each outcome separately with age as time scale and adjusting for smoking, body mass index, sex, systolic blood pressure, alcohol consumption, as well as 3 all-cause mortality biomarkers previously identified alongside GlycA in FINRISK 1997: citrate, VLDL (very-low-density lipoprotein) particle size, and albumin (pg. 2, column 2, para. Results).
Jemmett et al. further addresses the limitations of claim 5.
Regarding claim 5, pertaining to osteoarthritis of knee,
Jemmett et al. shows an increased level of n-acetyl glycoprotein in the synovial fluid obtained from patients during arthroscopy or knee replacement, the patients suffering from varying degrees of (knee) joint pathology (pg. 1, para. Method and Results).
Claims 11-13 are rejected under 35 U.S.C. §103(a) as being unpatentable over Kettunen et al. in view of Jemmett et al., as applied to claims 1-3, 5-9 and 14 above, and further in view of Werdyani et al. (Rheumatol. 2021, 60: 2735-2744; first published 7 Nov. 2020).
Kettunen et al. in view of Jemmett et al., as applied to claims 1-3, 5-9 and 14 above, do not show determining in the biological sample quantitative values of three or more biomarkers; or four or more biomarkers; or five or more biomarkers [Claims 11, 12 and 13].
Werdyani et al. addresses the limitations of claims 11-13.
Werdyani et al. shows a study to identify endotypes of osteoarthritis (OA) by a metabolomics analysis. Study participants included hip/knee OA patients and controls. Logistic regression was utilized to identify the most significant metabolites contributing to the endotypes. Clinical and epidemiological factors were examined in relation to the identified OA endotypes (pg. 2735, Abstract- Objective and Methods [nexus to Jemmett et al.- metabolite analysis of knee/joint patients with OA to identify diagnostic or risk of disease] [endotype- a subtype of a disease defined by a distinct biological or pathophysiological mechanism, as opposed to a phenotype, which is an observable characteristic of the disease]).
Regarding claims 11, 12 and 13, Werdyani et al. shows that metabolic profiling was performed on plasma using the Biocrates AbsoluteIDQ p180 kit, which measures the concentrations of 186 metabolites (pg. 2736, column 2, lines 1-4). The subjects were total hip or knee replacement patients due to primary OA (pg. 2736, column 1, para. 2). Supplementary Table S1 provides the full list of the metabolites measured in the study (pg. 2736, column 2, lines 5-7; and Suppl. Mater., pg. 1, Table S1). Table S1 shows that the concentrations of twenty-one (21) amino acids were measured, and include all of the amino acids as listed in claim 1 (and claim 10). For example, claim 1 cites glutamine, glycine, histidine, isoleucine, leucine, phenylalanine, and valine, which are listed in Table S1 in Werdyani et al. (Suppl. Mater. appended at the end of Werdyani et al. reference).
Werdyani et al. further shows that three distinct endotypes of OA patients were identified. The significant metabolite contributors to each of the three endotypes implied that the primary OA patients can be classified as having muscle weakness, arginine deficient, and low inflammatory OA (pg. 2740, column 2, para. Discussion [nexus to Kettunen et al.- an inflammatory polyarthropathy]). The findings provide new insights into the pathogenesis of primary OA and could help to develop personalized tools for OA management (pg. 2740, column 2, para. Discussion). Factors were ranked to identify certain endotypes and Table S2 shows that glutamine was included in one of the factors (Factor 17) (Suppl. Mater., pg. 2, Table S2, Factor 17). Glutamine is cited in claim 1.
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified the method for determining whether a subject is at risk of developing a musculoskeletal disease, comprising determining the quantitative value of glycoprotein acetyls [species election] in a biological sample and determining an increase or decrease in said value, as shown by Kettunen et al. in view of Jemmett et al., as applied to claims 1, 3, 5-9 and 14 above, by also determining the quantitative values of three, four or five or more biomarkers as listed in claim 1 [Claims 11, 12 and 13], with a reasonable expectation of success, because Werdyani et al. shows that a metabolomic profile of subjects with OA can include an analysis of many different metabolites, including several amino acids, as cited in claim 1. It is noted that Table S1 shows the biological relevance of the selected examples which include, minimally, amino acid metabolism, and oxidative stress (Table S1, last column). Werdyani et al. also shows that glutamine was a factor leading to the identification of a specific OA endotype, which is one of the amino acids cited in claim 1 (MPEP 2143 (I)(G)).
Although Werdyani et al. does not explicitly show whether there is a measured increase or decrease in each metabolite with regard to a control sample or value, it would have been obvious to one of ordinary skill in the art of determining in a subject the risk of developing a musculoskeletal disease, specifically osteoarthritis, to have been motivated by the information shown by Werdyani et al. to have incorporated the amino acids, which Werdyani et al. teaches have biological relevance to OA, into the method shown by Kettunen et al. (MPEP 2143 (I)(G)).
One of ordinary skill in the art would have been motivated to have made that modification, because measuring as many metabolites as possible associated with OA (and, in turn, compared their increase or decrease to control samples or values) would optimize or improve the accuracy of determining the risk of such a debilitating disease, and/or to more accurately differentiate a subset of the OA (e.g., with or without meniscal tears, as shown by Jemmett et al.)
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
This Office action is a Non-Final action. A shortened statutory period for reply to this action is set to expire THREE MONTHS from the mailing date of this action.
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/SMP/Examiner, Art Unit 1651
/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651