DETAILED ACTION
Claims 1-21 are pending.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 03/07/2023, 04/10/2023, and 08/24/2024 have been considered by the examiner.
Priority
Claims 19-21 do not qualify for the earlier priority date of the provisional application 63/075,807 because ‘807 does not teach or reference a kit for assessing preterm birth and preeclampsia risk biomarkers in a sample, wherein the kit comprises a detecting agent(s) for each metabolite in a panel of metabolites consisting essentially of thyroid stimulating hormone (TSH), galactose 1-phosphate uridylyltransferase (GALT), 17- hydroxyprogesterone (17-OHP), 5-oxoproline, glycine, leucine/isoleucine, ornithine, phenylalanine, proline, tyrosine, C-2 acylcarnitine, C-3 acylcarnitine, C-4 acylcarnitine, C-5 acylcarnitine, C-10 acylcarnitine, C-12 acylcarnitine, C-12:1 acylcarnitine, C-16:1 acylcarnitine, and C-18:2 acylcarnitine.
Due to claims 19-21 of the instant application not being supported by ‘807, claims 19-21 of the instant application do not qualify for the earlier filing date of the provisional application 63/075,807.
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 16-17 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.
Claims 16 and 17 refer to tables. See MPEP 2173.05 (s) which states “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table" is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted)”.
Claims 9-12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “higher” in claims 9-12 is a relative term which renders the claim indefinite. The term “higher” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term “higher” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. One of ordinary skill in the art would not know to what degree would the risk be.
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 1-18 are rejected under 35 U.S.C. 101 because the claimed method is directed towards a judicial of an abstract idea and laws of nature/natural phenomena without significantly more.
Step 1
Claims 1-18 are to a statutory category of a method of determining risk of adverse outcomes of infants by measuring various biomarkers.
Step 2A prong 1: Does the claim recite a judicial exception?
The claims recite methods for observing the law of nature of naturally occurring expression levels of biomarkers (thyroid stimulating hormone (TSH), galactose 1-phosphate uridylyltransferase (GALT), 17- hydroxyprogesterone (17-OHP), 5-oxoproline, glycine, leucine/isoleucine, ornithine, phenylalanine, proline, tyrosine, C-2 acylcarnitine, C-3 acylcarnitine, C-4 acylcarnitine, C-5 acylcarnitine, C-10 acylcarnitine, C-12 acylcarnitine, C-12:1 acylcarnitine, C-16:1 acylcarnitine, and C-18:2 acylcarnitine) and correlating it a risk for various diseases and disorders. The correlation between biomarkers and the presence of medical conditions is a naturally occurring phenomenon.
The claim recites “calculating” which is directed towards an abstract idea (i.e., math).
Step 2A prong 2: Does the claim recite additional elements that integrate the exception into a practical application?
Regarding the method of using the judicial exception, the data gathering steps do not add a meaningful limitation to the methods as they are insignificant extra-solution or mere data gathering steps.
Step 2B:
The claim does not include additional elements that are sufficient to amount to
significantly more than the judicial exception because the claimed elements when
considered separately and in combination, do not add significantly more to the
exceptions. The natural law/phenomenon is analogous to the correlation of biomarkers
found ineligible by the courts, for example, in Mayo Collaborative Servs. v. Prometheus
Labs., Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012), Cleveland Clinic
Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081,
1088 (Fed. Cir. 2017) (Using well -known standard laboratory techniques to detect
enzyme levels in a bodily sample such as blood or plasma), and Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015) (ineligible claims were directed to a method of detecting paternally inherited cell free fetal DNA, which is naturally occurring in maternal blood).
Regarding claim 1, the method of using the judicial exception, the extra solution activity of measuring the levels of metabolites comprising two or more of the group consisting of thyroid stimulating hormone (TSH), galactose 1-phosphate uridylyltransferase (GALT), 17- hydroxyprogesterone (17-OHP), 5-oxoproline, glycine, leucine/isoleucine, ornithine, phenylalanine, proline, tyrosine, C-2 acylcarnitine, C-3 acylcarnitine, C-4 acylcarnitine, C-5 acylcarnitine, C-10 acylcarnitine, C-12 acylcarnitine, C-12:1 acylcarnitine, C-16:1 acylcarnitine, and C-18:2 acylcarnitine), assigning a risk indicator or predictor for each of the measured metabolites; inputting the obtained risk indicator value into a computer-implemented predicative multivariate logistic model that is built using a training set and a testing set from a population of infants with any mortality or major morbidity to healthy infants; and calculating a risk assessment score for the biological sample obtained from the newborn infant using the predicative multivariate logistic model is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more.
Further, the claim recites “calculating” which is directed towards an abstract idea (i.e., math).
See prior art cited in the section below under 35 USC 102.
Regarding claim 2, wherein the newborn infant is a preterm infant is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 102 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 3, wherein the sample is obtained from a preterm infant that is born at a gestation age of 32-36 weeks is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 102 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 4, wherein the sample is obtained from a preterm infant that is born at a gestation age of under 32 weeks is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 102 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 5, wherein the newborn infant is a full-term infant is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 102 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 6, wherein the sample is a serum or a blood sample is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 102 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 7, wherein the one or more metabolites are measured using tandem mass spectrometry (MS/MS), high-performance liquid chromatography, and/or a fluorometric enzyme assay is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 102 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 8, wherein the predicative multivariate logistic model further includes risk indicator values or predictor values for one or more characteristics selected from sex of preterm infant, cesarean delivery, maternal education, maternal race/ethnicity, gestational age, and birthweight is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 102 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 9, wherein the preterm infant is at higher risk for a morbidity selected from patent ductus arteriosus (PDA), respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), jaundice, infections, sepsis, longer term, cerebral palsy, and/or neurodevelopmental disability is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. See prior art cited in the section below under 35 USC 102.
Regarding claim 10, wherein the infant is at higher risk for Sudden Infant Death Syndrome (SIDS) is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. See prior art cited in the section below under 35 USC 103.
Regarding claim 11, wherein the preterm infant is at a higher risk for morbidity or mortality if there is an increased measured concentration for phenylalanine, glycine, 17-OHP, proline, C-4 acylcarnitine, and C-5 acylcarnitine, and a decreased measured concentration for TSH, GALT, 5- oxoproline, ornithine, tyrosine, C-2 acylcarnitine, and C-12 acylcarnitine is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. See prior art cited in the section below under 35 USC 102.
Regarding claim 12, wherein the preterm infant is at a higher risk for morbidity or mortality if there is an increased measured concentration for 17-OHP, glycine, proline, and C-4 acylcarnitine and a decreased measured concentration for TSH, GALT, 5-oxoproline, ornithine, and C-2 acylcarnitine is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more. See prior art cited in the section below under 35 USC 102.
Regarding claim 13, wherein the panel of metabolites are measured using a quantitative multiplex assay is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 103 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 14, wherein the quantitative multiplex assay is a quantitative bead-based multiplex immunoassay is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 103 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 15, wherein the predicative multivariate logistic model is a linear discriminant analysis model is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 103 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 16, wherein the linear discriminant analysis model uses the coefficients for the biomarkers presented in Table 2 or 9 is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 103 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 17, wherein the predictive multivariate logistic model uses the coefficients for the biomarkers presented in Table 2 or 9 is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 103 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Regarding claim 18, further comprising: clinical monitoring and investigating etiologic metabolic pathways of the preterm infant that are related or give rise to the morbidity/mortality predictive value generated from the metabolic vulnerability regression model is an insignificant extra solution activity that does not add a meaningful limitation. See prior art cited in the section below under 35 USC 103 that teaches that this insignificant extra solution activity is routine and conventional in the art.
Thus, claims 1-18 are rejected under 35 USC 101.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-9, 11-12, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McCarthy et al. “Newborn Metabolic Profile Associated with Hyperbilirubinemia With and Without Kernicterus.” Clinical and translational science vol. 12,1 (2019): 28-38. doi:10.1111/cts.12590 (IDS filed on 08/24/2024).
Regarding claim 1, McCarthy teaches a method of generating a risk assessment score for a biological sample obtained from a newborn infant (see page 29 “Here, we explore whether 42 metabolites collected as part of routine newborn screening (NBS) in California are associated with hyperbilirubinemia occurring with and without kernicterus and whether patterns may aid in identification of infants at increased risk of hyperbilirubinemia and new targets for treatment.”), comprising:
measuring the level of a panel of metabolites in the sample, wherein the panel of metabolites comprises two or more the group consisting of thyroid stimulating hormone (TSH), galactose 1-phosphate uridylyltransferase (GALT), 17- hydroxyprogesterone (17-OHP), 5-oxoproline, glycine, leucine/isoleucine, ornithine, phenylalanine, proline, tyrosine, C-2 acylcarnitine, C-3 acylcarnitine, C-4 acylcarnitine, C-5 acylcarnitine, C-10 acylcarnitine, C-12 acylcarnitine, C-12:1 acylcarnitine, C-16:1 acylcarnitine, and C-18:2 acylcarnitine (see abstract teaching TSH, C-18:2, phenylalanine, C-3 acylcarnitine, ornithine, isoleucine/leucine, see table 2);
assigning a risk indicator value or predictor for each of the measured metabolites (see table 2 under p value, see page 29 “A number of investigators have explored creation of screening tools that utilize characteristics to identify high-risk infants. Existing predictive models are based upon characteristics, such as TSB levels, mode of delivery, gestational age (GA), and body mass loss”);
inputting the obtained risk indicator value into a computer-implemented predicative multivariate logistic model that is built using a training set and a testing set from a population of infants with any mortality or major morbidity to healthy infants (see page 29 “Backward stepwise multivariable logistic regression was used to determine which variables were associated with hyperbilirubinemia with and without kernicterus after adjustment for other factors… All statistical analyses were performed using the software SAS version 9.4 (SAS Institute, Cary, NC).”, see tables 1-3);
and calculating a risk assessment score for the biological sample obtained from the newborn infant using the predicative multivariate logistic model (the odds ratio (OR) of tables 2-4 are calculated risk scores using a predictive multivariate logistic model (see titles of tables 3-4)).
Regarding claims 2-3, McCarthy teaches wherein the newborn infant is a preterm infant wherein the preterm infant is born at a gestation age of 32-36 weeks (see table 1, see table 4).
Regarding claim 4, McCarthy teaches wherein the sample is obtained from a preterm infant that is born at a gestation age of under 32 weeks (see page 32 “When stratified by GA, several patterns remained consistent across GA groups for hyperbilirubinemia without kernicterus. TSH and C-18: 2 were found to be decreased (OR: 0.93; 95% CI: 0.92–0.93; OR: 0.96; 95% CI: 0.93–0.99; OR: 0.82; 95% CI: 0.70–0.96, > 36, 34–36 and < 32 weeks, respectively, for TSH, and OR: 0.89; 95% CI: 0.88–0.90; OR: 0.90; 95% CI: 0.86–0.95; OR: 0.69; 95% CI: 0.53–0.90, 36, 34–36, and <32 weeks, respectively, for C-18: 2) while tyrosine and C-3 were increased in infants across groupings (OR: 1.29; 1.27–1.35; OR: 1.18; 95% CI: 1.12–1.25; OR: 1.37; 95% CI: 1.07–1.75, >36, 34–36 and <32 weeks, respectively, for tyrosine and OR: 1.12; 95% CI: 1.10–1.14; OR: 1.34; 95% CI: 1.25–1.43; OR: 1.96; 95% CI: 1.42–2.69, >36, 34–36, and < 32 weeks, respectively, for C-3; Table 4).”).
Regarding claim 5, McCarthy teaches wherein the newborn infant is a full-term infant (see page 29 “GA outside the range of 22–41 weeks at birth, lacked full metabolic data, or were discharged after more than 7 days.”, see page 35 “Elevated levels of leucine and isoleucine are consistent with abnormal metabolism of amino acids among infants with hyperbilirubinemia, and have been observed previously in term infants.”).
Regarding claim 6, McCarthy teaches wherein the sample is a blood sample (see page 29 “The California Department of Public Health screens all newborn infants for inborn metabolic diseases by measuring markers in a heel-stick blood spot taken between 12 hours and 8 days after birth.”).
Regarding claim 7, McCarthy teaches wherein the one or more metabolites are measured using tandem mass spectrometry (MS/MS), high-performance liquid chromatography, and/or a fluorometric enzyme assay (see page 29 “Amino acids and carnitines were measured using standardized mass spectrometry. Fluorometric enzyme assay was used to measure galactose-1-phosphate uridyl transferase and high-performance liquid chromatography was used to measure thyroid stimulating hormone (TSH) and 17-hydroxyprogesterone. All metabolites were measured in units of μmol/L (see Table 2 for a complete list of metabolites measured and included in analyses).”).
Regarding claim 8, McCarthy teaches wherein the predicative multivariate logistic model further includes risk indicator values or predictor values for one or more characteristics selected from sex of preterm infant, cesarean delivery, maternal education, maternal race/ethnicity, gestational age, and birthweight (see tables 1-3 showing sex, maternal education, maternal race/ethnicity, gestational age, birthweight).
Regarding claim 9, McCarthy teaches wherein the preterm infant is at higher risk for a morbidity selected from patent ductus arteriosus (PDA), respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), jaundice, infections, sepsis, longer term, cerebral palsy, and/or neurodevelopmental disability (see page 29 “Here, we explore whether 42 metabolites collected as part of routine newborn screening (NBS) in California are associated with hyperbilirubinemia occurring with and without
kernicterus and whether patterns may aid in identification of infants at increased risk of hyperbilirubinemia and new targets for treatment.”, hyperbilirubinemia is known as jaundice).
Regarding claim 11, McCarthy teaches wherein the preterm infant is at a higher risk for morbidity or mortality if there is an increased measured concentration for phenylalanine, glycine, 17-OHP, proline, C-4 acylcarnitine, and C-5 acylcarnitine, and a decreased measured concentration for TSH, GALT, 5- oxoproline, ornithine, tyrosine, C-2 acylcarnitine, and C-12 acylcarnitine (see tables 2 and 4).
Regarding claim 12, McCarthy teaches wherein the preterm infant is at a higher risk for morbidity or mortality if there is an increased measured concentration for 17-OHP, glycine, proline, and C-4 acylcarnitine and a decreased measured concentration for TSH, GALT, 5-oxoproline, ornithine, and C-2 acylcarnitine (see tables 2 and 4).
Regarding claim 19, McCarthy teaches detecting agent(s) for each metabolite in a panel of metabolites consisting essentially of thyroid stimulating hormone (TSH), galactose 1-phosphate uridylyltransferase (GALT), 17- hydroxyprogesterone (17-OHP), 5-oxoproline, glycine, leucine/isoleucine, ornithine, phenylalanine, proline, tyrosine, C-2 acylcarnitine, C-3 acylcarnitine, C-4 acylcarnitine, C-5 acylcarnitine, C-10 acylcarnitine, C-12 acylcarnitine, C-12:1 acylcarnitine, C-16:1 acylcarnitine, and C-18:2 acylcarnitine (see table 2, where all biomarkers are taught). While McCarthy does not explicitly state the use of a kit, it would have been obvious to one of ordinary skill in the art at the time of the instant invention to combine the biomarker detecting agents together in order to simultaneously detect the markers in a sample as taught by McCarthy. The use of a kid is widely known in the art.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 10, 17-18, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over McCarthy et al., as applied to claims 1, 5, and 19 above, and in view of Morrow et al., (WO 2014/152985 A1) (IDS filed on 03/07/2023).
The teachings of McCarthy as it pertains to claims 1, 5, and 19 are discussed in the 35 USC 102 rejection above. McCarthy is silent towards SIDS, the use of coefficients, the use of antibodies, an ELISA or antibody microarray, and clinical monitoring and investigating etiologic metabolic pathways of the preterm infant that are related or give rise to the morbidity/mortality predictive value generated from the metabolic vulnerability regression model.
Regarding claim 10, Morrow teaches herein the infant is at higher risk for Sudden Infant Death Syndrome (SIDS) (see abstract “Methods for identifying a preterm infant having or at risk for necrotizing enterocolitis (NEC) based on metabolomics biomarkers in urine samples and/or microbial biomarkers in stool samples. Preterm birth contributes disproportionately to the global burden of morbidity and mortality in infancy. Necrotizing enterocolitis (NEC) is a devastating emergency of preterm infants that affects about IO% of infants born <29 weeks gestational age, with a case-fatality of about 30%.”).
It would have been prima facia obvious to one of ordinary skill in the art at the time of the instant application to combine the teaching of detecting a risk for SIDS taught by Morrow with the methods of generating a risk assessment score for a biological sample obtained from a newborn infant as taught by McCarthy. Morrow teaches that these claimed limitations are beneficial because they teach that metabolite biomarkers can be used to detect a risk of NEC and would allow for earlier interventions (such as treatments (see page 24)).
Regarding claim 17, McCarthy teaches the biomarkers in table 2.
Morrow teaches wherein the predictive multivariate logistic model uses the coefficients for biomarkers (see page 37 “Urinary metabolites, including alanine, pyridoxine, histidine, and tyrosine, were identified in samples collected DOL 4 to 9. Differences were observed between case types and between case type and controls, compared using generalized estimating equation (GEE) models. Data are presented as β-coefficients, 95% confidence intervals (Cl) and p-values.”, see table 4).
It would have been prima facia obvious to one of ordinary skill in the art at the time of the instant application to combine the teaching using coefficients taught by Morrow with the methods of generating a risk assessment score for a biological sample obtained from a newborn infant as taught by McCarthy. One of skill in the art would have been motivated to use the coefficients for the biomarkers present because it is a common way to express regression in clinical research as it represents the change in the log odds of the outcome.
Regarding claim 18, Morrow teaches further comprising: clinical monitoring and investigating etiologic metabolic pathways of the preterm infant that are related or give rise to the morbidity/mortality predictive value generated from the metabolic vulnerability regression model (see abstract, see figure 16, see pages 24-25).
It would have been prima facia obvious to one of ordinary skill in the art at the time of the instant application to combine the teaching of clinical monitoring and investigating etiologic metabolic pathways of the preterm infant that are related or give rise to the morbidity/mortality predictive value generated from the metabolic vulnerability regression model as taught by Morrow with the methods of generating a risk assessment score for a biological sample obtained from a newborn infant as taught by McCarthy. One of skill in the art would have considered investigating etiologic metabolic pathways as it allows for the root cause to be determined, which then allows for more effective and efficient treatments.
Regarding claim 20, Morrow teaches wherein the detecting agents are antibodies (see page 25 lines 9-11 “For example, the kit can contain antibodies specific to one or more of the metabolite biomarkers or more or more oligonucleotides that are specific to the 16s rRNA of a specific microbial marker.”).
It would have been prima facia obvious to one of ordinary skill in the art at the time of the instant application to combine the teaching of using antibodies as detecting agents taught by Morrow with the methods of generating a risk assessment score for a biological sample obtained from a newborn infant as taught by McCarthy. Morrow teaches that these claimed limitations are beneficial because antibodies are known in the art to be included in kits as detection agents (see page 25).
Regarding claim 21, Morrow teaches wherein the kit is an ELISA or antibody microarray (see page 24 lines 1-6 “Various computational programs can be applied in the methods of this disclosure to aid in analysis of expression data. Examples include, but are not limited to, Prediction Analysis of Microarray (PAM; see Tibshirani et al., PNAS 99(10):6567-6572, 2002); Plausible Neural Network (PNN; see, e.g., US Patent 7,287,014), PNNSulotion software and others provided by PNN Technologies Inc., Woodbridge, VA, USA, and Significance Analysis of Microarray (SAM).”).
It would have been prima facia obvious to one of ordinary skill in the art at the time of the instant application to combine the teaching using an antibody microarray in a kit taught by Morrow with the methods of generating a risk assessment score for a biological sample obtained from a newborn infant as taught by McCarthy. One of ordinary skill in the art would have considered adding an ELISA or an antibody microarray to the kit as they are commonly used immunoassays in the art that can measure various metabolites.
Claims 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over McCarthy et al., as applied to claim 1 above and in view of Jelliffe et al., (WO 2019/068092) (IDS filed on 03/07/2023).
The teachings of McCarthy as it pertains to claim 1 are discussed in the 35 USC 102 rejection above. McCarthy is silent towards multiplex immunoassays, linear discriminant analysis models, and coefficients.
Regarding claims 13-14, Jelliffe teaches wherein metabolites are measured using a quantitative multiplex assay and the assay is bead-based (see claims 10-11).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the teaching of using a bead-based quantitative multiplex assay taught by Jelliffe with the methods of generating a risk assessment score for a biological sample obtained from a newborn infant as taught by McCarthy. Jelliffe teaches these limitations are beneficial because the assays are known in the art for enabling the detection of multiple immune- or growth-related biomarkers at once (see [0042], see [0074], see [00113]).
Regarding claim 15, Jelliffe teaches wherein the predicative multivariate logistic model is a linear discriminant analysis model (see [0006] “Linear discriminate analysis was used to create a discriminate function.”, see claims 12-13).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the teaching of using a linear discriminant analysis model taught by Jelliffe with the methods of generating a risk assessment score for a biological sample obtained from a newborn infant as taught by McCarthy. Jelliffe teaches these limitations are beneficial because additional risk indicia useful as markers can be identified using algorithms known in the art, such as linear discriminant analysis (see [0050]).
Regarding claim 16, McCarthy teaches the biomarkers in table 2.
Jelliffe teaches wherein the linear discriminant analysis model uses coefficients (see claim 13).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the teaching using coefficients in the linear discriminant analysis model taught by Jelliffe with the methods of generating a risk assessment score for a biological sample obtained from a newborn infant as taught by McCarthy. Jelliffe teaches these limitations are beneficial because the output of the discriminant function can be a classifier indicating that the subject is at risk for a disease/disorder (see [00103]).
Conclusion
No claim is allowed.
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/MCKENZIE A DUNN/ Examiner, Art Unit 1678
/Ann Montgomery/ Primary Examiner, Art Unit 1678