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 .
Detailed Action
Summary
This is the Non-Final Office Action based on application 18/039883 filed 06/01/2023.
Claims 1-20 are pending and have been fully examined.
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.
The claimed invention of claims 1-20 are directed to a natural correlation without significantly more.
Through 101, inquiry analysis:
Is the claim directed to a statutory category of invention?
Yes, the claims including and depending form independent Claim 1 is drawn towards a statutory category of a method.
Step 2A, Prong One: Identify if there is a law of nature/natural phenomenon/abstract ideas.
For independent Claim 1 and those dependent therefrom, they recite the relationship/natural correlation of the claimed biomarkers (wherein the biomarker is glycoprotein acetyls and possibly an additional biomarker/biomarkers) with a metabolic condition related to the nutritional state of blood which is a vitamin deficiency or disorder of mineral metabolism. The notice of increase or decrease in comparison to a control and the presence or absence of the disease is part of the natural correlation itself. Natural correlations are law of nature and abstract idea judicial exceptions.
Claim 1 and those dependent therefrom also contain limitations for “determining,” “risk,” and “comparing,” values to a control. These things as claimed are mental processes which are abstract idea judicial exceptions.
Step 2A Prong Two: Are the judicial exceptions integrated into practical application?
The judicial exceptions are not integrated into a practical application in independent claim 1.
Claim 1 most closely follows USPTO eligibility Example 29, Claim 2. Though the word “diagnosis,” is not explicitly used, the diagnosis based on the natural correlation is still implicitly in the claims.
As generally claimed in claim one, no actual measuring or detecting takes place and instead the levels of the claimed biomarkers are done through, “determining,” of what is in a biological sample, though it is not even required that a biological sample is taken from a subject--- only that the level is determined.
Even if general measuring was claimed, or the nuclear magnetic resonance measuring which is in a dependent claim--- for general measuring and especially when recited at a high level of generality, there is no meaningful limitation, such as a particular machine or a transformation of a particular article, there is nothing that distinguishes it from conventional data gathering activity. Data gathering to be used in an abstract idea or with the claimed natural correlation, is insignificant extra-solution activity, and therefore not a particular practical application. See MPEP 2106.05(g).
Further, it is well established that the mere physical or tangible nature of additional elements such as the obtaining and detecting steps does not automatically confer eligibility on a claim directed to an abstract idea (or natural correlation) (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)).
Further—after data is gathered and a judicial exception of “comparing,” and the implicit diagnosis is performed, nothing further is done. Therefore- there is no practical application.
Step 2B: Do the claims recite any elements which are significantly more than the judicial exceptions?
Independent Claim 1 does not include additional elements that are sufficient to amount to significantly more than the judicial exception because there is no particularity or specificity of measurement, detection, treatment, or other limitations that makes the claims significantly more than the claimed judicial exceptions.
There are no additional steps claimed in addition to the judicial exception. Even if it was positively recited in the claims that a blood sample is obtained from a patient and that the level of biomarkers are determined by NMR, this would remain the case, especially if claimed at a low level of generality.
General measuring (even by NMR), and taking of a blood sample from a patient are things that are well-understood, routine and conventional activity (WURC) for those in the field of diagnostics. This is evidenced by the fact that prior art teaches of them, and is especially true at the level of generality claimed.
Further MPEP 2106.05 (d) II for examples of laboratory techniques that have been shown to be routine and conventional. “The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity…”
The dependent claims undergo a similar analysis.
Claim 2 does not change the matters above. It adds that two or more biomarkers are determined. These remain part of the judicial exception as shown for the one type of biomarker in Claim 1.
Claim 3 does not change the matters above. Claim 3 indicates that two specific kinds of biomarkers are determined and that they are compared to control values for determining risk. These remain part of the judicial exception as shown for the one type of biomarker in Claim 1.
Claim 4 does not change the matters above. Claim 4 indicates that two specific kinds of biomarkers are determined and that they are compared to control values for determining risk. These remain part of the judicial exception as shown for the one type of biomarker in Claim 1.
Claim 5 does not change the matters above. Claim 5 indicates what the metabolic condition is (iron deficiency, anemia…). The disease/correlation of the biomarker/disease remains part of the judicial exception as shown above.
Claim 6 does not change the matters above. Claim 6 indicates what the metabolic condition is (iron deficiency, B12 deficiency…). The disease/correlation of the biomarker/disease remains part of the judicial exception as shown above.
Claim 7 does not change the matters above. Claim 7 indicates what the metabolic condition is (iron deficiency, B12 deficiency…). The disease/correlation of the biomarker/disease remains part of the judicial exception as shown above.
Claim 8 does not change the matters above. Claim 8 indicates that the biomarkers are measured using NMR. NMR as generally claimed is still just used as a data pull to accomplish the judicial exception so does nothing to practically apply. Further NMR, especially at the level of generality claimed is WURC in the art so does not add significantly more.
Claim 9 does not change the matters above. It specifies that the disease or risk is determined by a few slightly more specific calculations using risk score, hazard ratio or absolute risk. As claimed as especially as generally claimed, the calculations are mental and mathematical processes and abstract ideas- so an abstract idea judicial exception itself. Also- these calculations are also WURC in the art.
Claim 10 does not change the matters above. It specifies that the disease or risk is determined by a few slightly more specific calculations using risk score, hazard ratio or absolute risk, and “based on a further measure,” which is unspecified as to what it is. As claimed as especially as generally claimed, the calculations are mental and mathematical processes and abstract ideas- so an abstract idea judicial exception itself. Also- these calculations are also WURC in the art.
Claim 11 does not change the matters above. It specifies that the characteristic (which is measured – though there is an antecedent basis issue with respect to this) is a characteristic of the subject which could include age, height, or BMI, and some other examples. The risk calculation is determined based on this characteristic and the measured/determined biomarkers. As claimed however, especially as generally claimed, the calculations are mental and mathematical processes and abstract ideas- so an abstract idea judicial exception itself. Also- these calculations are also WURC in the art.
Claim 12, it does not change the matters above. Claim 12 indicates that the amounts of a panel of biomarkers are determined and that they are compared to control values for determining risk. These remain part of the judicial exception as shown for the one type of biomarker in Claim 1.
Claim 13 does not change the matters above. Claim 13 indicates that three biomarkers are determined. This remains part of the judicial exception as shown for the one type of biomarker in Claim 1.
Claim 14 does not change the matters above. Claim 14 indicates that four biomarkers are determined. This remains part of the judicial exception as shown for the biomarkers in Claims 1 & 13.
Claim 15 does not change the matters above. Claim 15 indicates that five biomarkers are determined. This remains part of the judicial exception as shown for the biomarkers in Claims 1 & 14.
Claim 16 does not change the matters above. It specifies that are characteristic is a characteristic is measured in addition and (as disclosed the characteristic can include age, height, or BMI…). The risk calculation is determined based on this characteristic and the measured/determined biomarkers. As claimed however, especially as generally claimed, the risk calculations are mental and mathematical processes and abstract ideas- so an abstract idea judicial exception itself. Also- these calculations are also WURC in the art.
Claim 17 does not change the matters above. Claim 17 indicates what the metabolic condition is (iron deficiency, anemia…). The disease/correlation of the biomarker/disease remains part of the judicial exception as shown above.
Claim 18 does not change the matters above. Claim 18 indicates what the metabolic condition is (iron deficiency, B12 deficiency…). The disease/correlation of the biomarker/disease remains part of the judicial exception as shown above.
Claim 19 does not change the matters above. Claim 19 indicates what the metabolic condition is (iron deficiency, B12 deficiency…). The disease/correlation of the biomarker/disease remains part of the judicial exception as shown above.
Claim 20 does not change the matters above. It specifies that the disease or risk is determined by a few slightly more specific calculations using risk score, hazard ratio or absolute risk. As claimed as especially as generally claimed, the calculations are mental and mathematical processes and abstract ideas- so an abstract idea judicial exception itself. Also- these calculations are also WURC in the art.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 includes in the preamble, “the,” “nutritional state of the blood,” in the preamble. Though it is understood what is meant to ensure clarity, this should be rephrased, “a nutritional state of a blood sample from a patient,” or similar.
Further With respect to Claim 1, it is claimed, “wherein the at least one biomarker comprises or is glycoprotein acetyls,” which should instead read, “wherein the at least one biomarker comprises or is a glycoprotein acetyl/s.”
Appropriate correction is required.
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 1-20 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.
With respect to Claim 1, the preamble of the claim states, “the blood,” but the first wherein statement and throughout Claim 1, applicant refers to “a biological sample,” and later in the claim again “the blood.” From these things in the claim, it is unclear if applicant intends the sample to be a generalized biological sample, or a blood sample. If the sample is a generalized biological sample--- can any biological sample… for example urine or spit really indicate a nutritional state of blood? This is unclear and requires correction. “The biological sample,” is also used in dependent Claim 2-4, 12-15, and “the blood,” is used in Claims 3-4, 6-8 & 18-20, so dependent on which term applicant intends, it requires correction in all of these claims as well.
With respect to Claim 1, “increased,” in “increased risk,” is a relative term not defined by the claim. What is considered an increased risk would be different to different people and therefore this term is unclear. This also applies to claims 3-4, 12 and where this term is uses as well.
Further with respect to Claim 1, it claims the broad list of biomarkers being, “at least one biomarker of the following…” wherein the list in Claim 1 starts with glycoprotein acetyls and ends after a list of over 10 other possible biomarkers. Then- later in Claim 1, it is claimed that “the at least one biomarker comprises or is glycoprotein acetyls,” meaning the one of more biomarkers couldn’t be any of the other claimed broad group of biomarkers at the end of the claim if there is only one and it is glycoprotein acteyls. This is a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) and is considered indefinite as the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the instant claim there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Further for Claim 1, “glycoprotein acetyls,” reads as a plural, and only 1 biomarker is required in the claim, which is “glycoprotein acetyls.” Therefore this is confusing and unclear.
With respect to Claims 3-4, “glycoprotein acetyls,” was already required to be one of the biomarkers in Claim 1, however Claims 3-4 further recites it as a biomarker. Therefore, it is unclear if by using “glycoprotein acetyls,” is applicant intends more than one glycoprotein acetyl to be measured or not.
With respect to Claim 5, in Claim 5 it states that “the metabolic condition related to the nutritional state comprises or is iron deficiency anemia, vitamin deficiency, and/ or disorder of mineral metabolism.” Claim 1, from which Claim 5 depends only has the option being “comprises or is, “vitamin deficiency, and/or disorder of mineral metabolism.” Therefore--- the addition of “comprises or is,” “iron deficiency of anemia,” is broadening the claim in dependent Claim 5 from independent Claim 1. This makes the claims unclear and requires correction.
With respect to Claims 6-7, Claim 1 from which Claim 6 depends from requires “comprises or is, “vitamin deficiency, and/or disorder of mineral metabolism.” Therefore--- it is unclear if in Claims 6-7, by the list of vitamin deficiencies listed in Claim 6, if applicant intends to refer back to “the vitamin deficiency,” listed in Claim 1. Also, “deficiency of other nutrient elements,” reads broader than the two options of vitamins in Claim 1 and carbohydrates and things such as this can be considered “nutrient elements,” but are not vitamins or disorders of mineral metabolism. Correction is required.
With respect to Claims 6-7, 18-19, the parentheses in the claims make it unclear if what is within the parentheses is required or not. For example, D50 does not mean iron deficiency anemia, nor is it an abbreviation for iron deficiency anemia. From the instant specification what is within the parentheses of these claims seem to be labels for diagnoses data that is found within the specification. This makes it unclear what the claim requires and what is does not.
With respect to Claim 7, again applicant is broadening the claims by saying, “the metabolic condition related to the nutritional state and/or fluid balance of blood,” as “and/or fluid balance of blood,” was not mentioned in Claim 1 which Claim 7 depends therefrom. This makes the claims unclear, and requires correction.
Further with respect to Claim 7, it is unclear what “unspecified (E55.9),” is. Is it one of a, “vitamin deficiency, and/or disorder of mineral metabolism. This is unclear from the claims.
With respect to Claim 11, “the characteristic,” fails to have proper antecedent basis in the claims. Claim 11 depends on Claims 10, 9, and 1, and “as characteristic,” is not used in any of these claims either so it is unclear what “the,” characteristic refers to.
With respect to Claim 17, in Claim 17 it states that “the metabolic condition related to the nutritional state comprises or is iron deficiency anemia, vitamin deficiency, and/ or disorder of mineral metabolism.” Claims 12 & 1, from which Claim 17 depends only has the option being “comprises or is, “vitamin deficiency, and/or disorder of mineral metabolism.” Therefore--- the addition of “comprises or is,” “iron deficiency of anemia,” is broadening the claim in dependent Claim 17 from what is found in independent Claims 12 & 1. This makes the claims unclear and requires correction.
With respect to Claim 18, Claim 12 & 1 from which Claim 18 depends from requires “comprises or is, “vitamin deficiency, and/or disorder of mineral metabolism.” Therefore--- it is unclear if in Claims 18, by the list of vitamin deficiencies listed in Claim 18, if applicant intends to refer back to “the vitamin deficiency,” listed in Claim 1. Also, “deficiency of other nutrient elements,” reads broader than the two options of vitamins in Claim 1 and carbohydrates and things such as this can be considered “nutrient elements,” but are not vitamins or disorders of mineral metabolism. Correction is required.
With respect to Claim 19, again applicant is broadening the claims by saying, “the metabolic condition related to the nutritional state and/or fluid balance of blood,” as “and/or fluid balance of blood,” was not mentioned in Claim 12 and 1 which Claim 19depends therefrom. This makes the claims unclear, and requires correction.
With respect to Claim 19, it is unclear what “unspecified (E55.9),” and “(unspecified (D50.9),” is, of if it is one of a, “vitamin deficiency, and/or disorder of mineral metabolism. This is unclear from the claims.
Claims 2-20 are also rejected by virtue of being dependent on Claim 1.
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 non-obviousness.
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, 5-11, 13-14, 16 are rejected under 35 U.S.C. 103 as being obvious over OTVOS in US 20130328561 in view of PIERONI in A Novel Parameter for the Diagnosis of Iron Deficiency: The Transferrin/Albumin Ratio.
With respect to Claim 1, OTVOS teaches of a method for determining the risk of a patient having a clinical disease such a type II diabetes (which can be considered a metabolic condition related to the nutritional state of the blood—since diabetes is linked to how the body manages blood sugar from food or poor diet especially with high carbs, while good nutrition helps manage glucose spikes). OTVOS teaches that the method can also help detect coronary heart disease, or all-cause death, in addition to the type II diabetes by measuring GlycA by NMR signal measurements (abstract).
Specifically, OTVOS teaches of detecting glycoprotein acetyls, and that GlycA is detected, which is a signal that comes from glycoproteins containing N-acetylglucosamine (glycoprotein acetyls) (paragraph 0087), and that GlycB is also detected, which is a signal that comes from glycoproteins containing N-acetylneuraminic acid (so also a glycoprotein acetyl) (paragraph 0088), and of detection of other glycoprotein associated acetyls (paragraphs 0107-0108, 0111, 0131, 0144).
In addition, OTVOS teaches of detection of leucine and valine (paragraph 0138, 0206). OTVOS also teaches of detection of ratios of the measurements of the compounds to one another and specifically of ratios of valine and GlycA (paragraph 0034, 0036, 0100). All of the above biomarker detections read on the claimed “at least one biomarker,” from the claimed possible list of biomarkers.
OTVOS further teaches of comparing the measured values of the biomarkers to the values found in normal and at-risk populations (paragraph 0181, 0091, 0015). OTVOS even further teaches of determining if a patient has an increased risk relative to the normal population when the calculated quantitative values differ and wherein the person has an increased risk when the calculated values are in a first tertile, quartile or quintile of the population (paragraph 0036, 0139, 0141, 0144, 0151, 0179, 0182, 0185-0186, 0189).
OTVOS does not teach of the nutritional state of the blood being vitamin deficiency and/or a disorder of mineral metabolism.
PIERONI is used to remedy this and further teaches of a method for the diagnosis of iron deficiency. Iron deficiency can be considered a vitamin deficiency or disorder of mineral metabolism, since Iron can be ingested as a vitamin. (Also see applicant’s instant claim 19 to see that applicant considers iron deficiency to fall into these categories.) PIERONI further teaches that albumin is detected to determine if there is iron deficiency, which us one of the claimed biomarkers (abstract).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to use albumin to aid in detection of a mineral or vitamin deficiency as is done in PIERONI in the method of detection of metabolic diseases of OTVOS due to the need in the art for a better method of diagnosis of iron deficiency in patients with concomitant (accompanying or associated) pathologies and in chronic patients (such as those which have diabetes mellitus/type II diabetes, which is chronic)(abstract, lines 1-5).
With respect to Claim 2, OTVOS teaches of detecting glycoprotein acetyls, and that GlycA is detected, which is a signal that comes from glycoproteins containing N-acetylglucosamine (glycoprotein acetyls) (paragraph 0087), and that GlycB is also detected, which is a signal that comes from glycoproteins containing N-acetylneuraminic acid (so also a glycoprotein acetyl) (paragraph 0088), and of detection of other glycoprotein associated acetyls (paragraphs 0107-0108, 0111, 0131, 0144). In addition, OTVOS teaches of detection of leucine and valine (paragraph 0138, 0206). OTVOS also teaches of detection of ratios of the measurements of the compounds to one another and specifically of ratios of valine and GlycA (paragraph 0034, 0036, 0100). All of the above biomarker detections read on the claimed “two or more,” biomarkers as claimed from the claimed possible list of biomarkers.
With respect to Claim 3, OTVOS teaches of detecting glycoprotein acetyls, and that GlycA is detected, which is a signal that comes from glycoproteins containing N-acetylglucosamine (glycoprotein acetyls) (paragraph 0087), and that GlycB is also detected, which is a signal that comes from glycoproteins containing N-acetylneuraminic acid (so also a glycoprotein acetyl) (paragraph 0088), and of detection of other glycoprotein associated acetyls (paragraphs 0107-0108, 0111, 0131, 0144). OTVOS does not teach of the detection of albumin. OTVOS further teaches of comparing the measured values of the biomarkers to the values found in normal and at-risk populations (paragraph 0181, 0091, 0015). OTVOS even further teaches of determining if a patient has an increased risk relative to the normal population when the calculated quantitative values differ and wherein the person has an increased risk when the calculated values are in a first tertile, quartile or quintile of the population (paragraph 0036, 0139, 0141, 0144, 0151, 0179, 0182, 0185-0186, 0189).
OTVOS does not teach measuring albumin in comparison to a control.
PIERONI is used to remedy this and further teaches of a method for the diagnosis of iron deficiency. PIERONI further teaches that albumin is detected to determine if there is iron deficiency and albumin is one of the claimed biomarkers (abstract). PIERONI further teaches of comparison to cut-off values for the prediction of iron deficiency and that if a value falls outside the cutoff, it is predictive for iron deficiency (lines 3-4 from bottom).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to use albumin to aid in detection of a mineral or vitamin deficiency as is done in PIERONI in the method of detection of metabolic diseases of OTVOS due to the need in the art for a better method of diagnosis of iron deficiency in patients with concomitant (accompanying or associated) pathologies and in chronic patients (such as those which have diabetes mellitus/type II diabetes, which is chronic) (abstract, lines 1-5).
With respect to Claim 5, OTVOS teaches of a method for determining the risk of a patient having a clinical disease such a type II diabetes (which can be considered a metabolic condition related to the nutritional state of the blood—since diabetes is linked to how the body manages blood sugar from food or poor diet especially with high carbs, while good nutrition helps manage glucose spikes). OTVOS teaches that the method can also help detect coronary heart disease, or all-cause death, in addition to the type II diabetes by measuring GlycA by NMR signal measurements (abstract).
OTVOS does not teach of the nutritional state of the blood being vitamin deficiency and/or a disorder of mineral metabolism, and that specifically that it is an iron deficiency anemia.
PIERONI is used to remedy this and further teaches of a method for the diagnosis of iron deficiency, and specifically iron deficiency anemia (Page 1, abstract, last line). PIERONI further teaches that albumin is detected to determine if there is iron deficiency, which is one of the claimed biomarkers (abstract).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to use albumin to aid in detection of iron deficient anemia as is done in PIERONI in the method of detection of metabolic diseases of OTVOS due to the need in the art for a better method of diagnosis of iron deficiency in patients with concomitant (accompanying or associated) pathologies and in chronic patients (such as those which have diabetes mellitus/type II diabetes, which is chronic)(abstract, lines 1-5).
With respect to Claim 6, OTVOS teaches of a method for determining the risk of a patient having a clinical disease such a type II diabetes (which can be considered a metabolic condition related to the nutritional state of the blood—since diabetes is linked to how the body manages blood sugar from food or poor diet especially with high carbs, while good nutrition helps manage glucose spikes). OTVOS teaches that the method can also help detect coronary heart disease, or all-cause death, in addition to the type II diabetes by measuring GlycA by NMR signal measurements (abstract).
OTVOS does not teach of the nutritional state of the blood being vitamin deficiency and/or a disorder of mineral metabolism, and that specifically that it is an iron deficiency anemia.
PIERONI is used to remedy this and further teaches of a method for the diagnosis of iron deficiency, and specifically iron deficiency anemia (Page 1, abstract, last line). PIERONI further teaches that albumin is detected to determine if there is iron deficiency, which is one of the claimed biomarkers (abstract).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to use albumin to aid in detection of iron deficient anemia as is done in PIERONI in the method of detection of metabolic diseases of OTVOS due to the need in the art for a better method of diagnosis of iron deficiency in patients with concomitant (accompanying or associated) pathologies and in chronic patients (such as those which have diabetes mellitus/type II diabetes, which is chronic)(abstract, lines 1-5).
With respect to Claim 7, OTVOS teaches of a method for determining the risk of a patient having a clinical disease such a type II diabetes (which can be considered a metabolic condition related to the nutritional state of the blood—since diabetes is linked to how the body manages blood sugar from food or poor diet especially with high carbs, while good nutrition helps manage glucose spikes). OTVOS teaches that the method can also help detect coronary heart disease, or all-cause death, in addition to the type II diabetes by measuring GlycA by NMR signal measurements (abstract).
OTVOS does not teach of the nutritional state of the blood being vitamin deficiency and/or a disorder of mineral metabolism, and that specifically that it is an iron deficiency anemia.
PIERONI is used to remedy this and further teaches of a method for the diagnosis of iron deficiency, and specifically iron deficiency anemia (Page 1, abstract, last line). PIERONI further teaches that albumin is detected to determine if there is iron deficiency, which is one of the claimed biomarkers (abstract).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to use albumin to aid in detection of iron deficient anemia as is done in PIERONI in the method of detection of metabolic diseases of OTVOS due to the need in the art for a better method of diagnosis of iron deficiency in patients with concomitant (accompanying or associated) pathologies and in chronic patients (such as those which have diabetes mellitus/type II diabetes, which is chronic)(abstract, lines 1-5).
With respect to Claim 8, OTVOS teaches that the method uses NMR and NMR signal measurements/detections (abstract).
With respect to Claim 9, OTVOS teaches of using a hazard ratio detection/calculation for the biomarkers (paragraph 0074, paragraph 0179, 0185, 0194).
With respect to Claim 10, OTVOS teaches of the hazard ratio/prediction, being adjusted for another characteristic which can be age and gender (paragraphs 0194 & 0193).
With respect to Claim 11, OTVOS teaches of the hazard ratio/prediction, being adjusted for another characteristic which can be age and gender (paragraphs 0194 & 0193).
With respect to Claim 13, OTVOS teaches of detecting glycoprotein acetyls, and that GlycA is detected, which is a signal that comes from glycoproteins containing N-acetylglucosamine (glycoprotein acetyls) (paragraph 0087), and that GlycB is also detected, which is a signal that comes from glycoproteins containing N-acetylneuraminic acid (so also a glycoprotein acetyl) (paragraph 0088), and of detection of other glycoprotein associated acetyls (paragraphs 0107-0108, 0111, 0131, 0144). In addition, OTVOS teaches of detection of leucine and valine (paragraph 0138, 0206). OTVOS also teaches of detection of ratios of the measurements of the compounds to one another and specifically of ratios of valine and GlycA (paragraph 0034, 0036, 0100). All of the above biomarker detections read on the claimed “three or more,” biomarkers as claimed from the claimed possible list of biomarkers.
With respect to Claim 14, OTVOS teaches of detecting glycoprotein acetyls, and that GlycA is detected, which is a signal that comes from glycoproteins containing N-acetylglucosamine (glycoprotein acetyls) (paragraph 0087), and that GlycB is also detected, which is a signal that comes from glycoproteins containing N-acetylneuraminic acid (so also a glycoprotein acetyl) (paragraph 0088), and of detection of other glycoprotein associated acetyls (paragraphs 0107-0108, 0111, 0131, 0144). In addition, OTVOS teaches of detection of leucine and valine (paragraph 0138, 0206). OTVOS also teaches of detection of ratios of the measurements of the compounds to one another and specifically of ratios of valine and GlycA (paragraph 0034, 0036, 0100). All of the above biomarker detections read on the claimed “three or more,” biomarkers as claimed from the claimed possible list of biomarkers.
OTVOS does not teach of detection of 4 or more of the claimed biomarkers.
PIERONI is used to remedy this and further teaches of a method for the diagnosis of iron deficiency. Iron deficiency can be considered a vitamin deficiency or disorder of mineral metabolism, since Iron can be ingested as a vitamin. (Also see applicant’s instant claim 19 to see that applicant considers iron deficiency to fall into these categories.) PIERONI further teaches that albumin( which is a 4th biomarker) is detected to determine if there is iron deficiency, which us one of the claimed biomarkers (abstract).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to use albumin to aid in detection of a mineral or vitamin deficiency as is done in PIERONI in the method of detection of metabolic diseases of OTVOS due to the need in the art for a better method of diagnosis of iron deficiency in patients with concomitant (accompanying or associated) pathologies and in chronic patients (such as those which have diabetes mellitus/type II diabetes, which is chronic)(abstract, lines 1-5).
With respect to Claim 16, OTVOS teaches of the hazard ratio/prediction, being adjusted for another characteristic which can be age and gender (paragraphs 0194 & 0193).
Claims 4, 12, 15 & 17-20 are rejected under 35 U.S.C. 103 as being obvious over OTVOS in US 20130328561 in view of PIERONI in A Novel Parameter for the Diagnosis of Iron Deficiency: The Transferrin/Albumin Ratio and further in view of AHOLA-OLLI in Circulating metabolites and risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts (as cited on IDS dated 06/02/2023) .
With respect to Claim 4, OTVOS teaches of detecting glycoprotein acetyls, and that GlycA is detected, which is a signal that comes from glycoproteins containing N-acetylglucosamine (glycoprotein acetyls) (paragraph 0087), and that GlycB is also detected, which is a signal that comes from glycoproteins containing N-acetylneuraminic acid (so also a glycoprotein acetyl) (paragraph 0088), and of detection of other glycoprotein associated acetyls (paragraphs 0107-0108, 0111, 0131, 0144). In addition, OTVOS teaches of detection of leucine and valine (paragraph 0138, 0206). OTVOS also teaches of detection of ratios of the measurements of the compounds to one another and specifically of ratios of valine and GlycA (paragraph 0034, 0036, 0100). All of the above biomarker detections read on the claimed “three or more,” biomarkers as claimed from the claimed possible list of biomarkers.
OTVOS does not teach of detection of 5 or more of the claimed biomarkers.
With respect to Claim 15, OTVOS teaches of detecting glycoprotein acetyls, and that GlycA is detected, which is a signal that comes from glycoproteins containing N-acetylglucosamine (glycoprotein acetyls) (paragraph 0087), and that GlycB is also detected, which is a signal that comes from glycoproteins containing N-acetylneuraminic acid (so also a glycoprotein acetyl) (paragraph 0088), and of detection of other glycoprotein associated acetyls (paragraphs 0107-0108, 0111, 0131, 0144). In addition, OTVOS teaches of detection of leucine and valine (paragraph 0138, 0206). OTVOS also teaches of detection of ratios of the measurements of the compounds to one another and specifically of ratios of valine and GlycA (paragraph 0034, 0036, 0100). All of the above biomarker detections read on the claimed “three or more,” biomarkers as claimed from the claimed possible list of biomarkers.
OTVOS teaches the detection of 3 biomarkers, but not 4 of the claimed biomarkers.
PIERONI is used to remedy this and further teaches of a method for the diagnosis of iron deficiency. Iron deficiency can be considered a vitamin deficiency or disorder of mineral metabolism, since Iron can be ingested as a vitamin. (Also see applicant’s instant claim 19 to see that applicant considers iron deficiency to fall into these categories.) PIERONI further teaches that albumin (which is a 4th biomarker) is detected to determine if there is iron deficiency, which us one of the claimed biomarkers (abstract).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to use albumin to aid in detection of a mineral or vitamin deficiency as is done in PIERONI in the method of detection of metabolic diseases of OTVOS due to the need in the art for a better method of diagnosis of iron deficiency in patients with concomitant (accompanying or associated) pathologies and in chronic patients (such as those which have diabetes mellitus/type II diabetes, which is chronic)(abstract, lines 1-5).
OTVOS and PIERONI do not teach of detecting fatty acids.
AHOLA-OLLI is used to remedy this and teaches of a method of NMR detection of fatty acids (Page 2298, results).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of/to using fatty acids as biomarkers as is done in AHOLA-OLLI in the methods of OTVOS and PIERONI since they have shown to be robust predictive markers for future diabetes (disease related to a nutritional state of blood) (AHOLA-OLLI, Page 2300, column 1, paragraph 2).
With respect to Claim 12, OTVOS teaches of detecting glycoprotein acetyls, and that GlycA is detected, which is a signal that comes from glycoproteins containing N-acetylglucosamine (glycoprotein acetyls) (paragraph 0087), and that GlycB is also detected, which is a signal that comes from glycoproteins containing N-acetylneuraminic acid (so also a glycoprotein acetyl) (paragraph 0088), and of detection of other glycoprotein associated acetyls (paragraphs 0107-0108, 0111, 0131, 0144). In addition, OTVOS teaches of detection of leucine and valine (paragraph 0138, 0206). OTVOS also teaches of detection of ratios of the measurements of the compounds to one another and specifically of ratios of valine and GlycA (paragraph 0034, 0036, 0100). All of the above biomarker detections read on the claimed “three or more,” biomarkers as claimed from the claimed possible list of biomarkers.
OTVOS teaches the detection of 3 biomarkers, but not 4 of the claimed biomarkers.
PIERONI is used to remedy this and further teaches of a method for the diagnosis of iron deficiency. Iron deficiency can be considered a vitamin deficiency or disorder of mineral metabolism, since Iron can be ingested as a vitamin. (Also see applicant’s instant claim 19 to see that applicant considers iron deficiency to fall into these categories.) PIERONI further teaches that albumin (which is a 4th biomarker) is detected to determine if there is iron deficiency, which us one of the claimed biomarkers (abstract).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to use albumin to aid in detection of a mineral or vitamin deficiency as is done in PIERONI in the method of detection of metabolic diseases of OTVOS due to the need in the art for a better method of diagnosis of iron deficiency in patients with concomitant (accompanying or associated) pathologies and in chronic patients (such as those which have diabetes mellitus/type II diabetes, which is chronic)(abstract, lines 1-5).
Therefore, the combination of OTVOS in view of PIERONI teaches of detecting glycoprotein acetyls, leucine, valine, and albumin. OTVOS and PERONI do not teach of detecting the other claimed biomarkers including fatty acids.
AHOLA-OLLI is used to remedy this and teaches of a method of NMR detection of fatty acids (Page 2298, results). AHOLA-OLLI also teach of detection of total fatty acids, n-6 fatty acids, n-3 fatty acids (which are the omega 6 & 3 fatty acids), docosahexaenoic acid, linoleic acid, monounsaturated fatty acids, the degree of unsaturation, leucine, citrate, tyrosine, histidine, glutamine, alanine, phenylalanine, pyruvate (Figure 1), which reads on the claimed biomarkers, and also of detecting the ratio of the fatty acid compounds to one another (Page 2301, column 2, last paragraph & Figure 1). AHOLA-OLLI further teaches of comparison to baseline measurements (Page 2298, methods).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of/to using the biomarkers as is done in AHOLA-OLLI in the methods of OTVOS and PERONI to detect diseases and conditions due to nutritional, vitamin, or mineral metabolism or deficiency, since metabolite profiling as is claimed has been shown advantageous in identifying biochemical changes occurring before the onset of diseases (disease such as diabetes related to a nutritional state of blood) (AHOLA-OLLI, Page 2299, column 1, last paragraph).
With respect to Claim 15, OTVOS teaches of detecting glycoprotein acetyls, and that GlycA is detected, which is a signal that comes from glycoproteins containing N-acetylglucosamine (glycoprotein acetyls) (paragraph 0087), and that GlycB is also detected, which is a signal that comes from glycoproteins containing N-acetylneuraminic acid (so also a glycoprotein acetyl) (paragraph 0088), and of detection of other glycoprotein associated acetyls (paragraphs 0107-0108, 0111, 0131, 0144). In addition, OTVOS teaches of detection of leucine and valine (paragraph 0138, 0206). OTVOS also teaches of detection of ratios of the measurements of the compounds to one another and specifically of ratios of valine and GlycA (paragraph 0034, 0036, 0100). All of the above biomarker detections read on the claimed “three or more,” biomarkers as claimed from the claimed possible list of biomarkers.
OTVOS teaches the detection of 3 biomarkers, but not 4 of the claimed biomarkers.
PIERONI is used to remedy this and further teaches of a method for the diagnosis of iron deficiency. Iron deficiency can be considered a vitamin deficiency or disorder of mineral metabolism, since Iron can be ingested as a vitamin. (Also see applicant’s instant claim 19 to see that applicant considers iron deficiency to fall into these categories.) PIERONI further teaches that albumin (which is a 4th biomarker) is detected to determine if there is iron deficiency, which us one of the claimed biomarkers (abstract).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to use albumin to aid in detection of a mineral or vitamin deficiency as is done in PIERONI in the method of detection of metabolic diseases of OTVOS due to the need in the art for a better method of diagnosis of iron deficiency in patients with concomitant (accompanying or associated) pathologies and in chronic patients (such as those which have diabetes mellitus/type II diabetes, which is chronic)(abstract, lines 1-5).
This put the total at 4 biomarkers, but the combination does not teach of 5 biomarkers.
AHOLA-OLLI is used to remedy this and teaches of a method of NMR detection of fatty acids (Page 2298, results). AHOLA-OLLI also teach of detection of total fatty acids, n-6 fatty acids, n-3 fatty acids (which are the omega 6 & 3 fatty acids), docosahexaenoic acid, linoleic acid, monounsaturated fatty acids, the degree of unsaturation, leucine, citrate, tyrosine, histidine, glutamine, alanine, phenylalanine, pyruvate (Figure 1), which reads on the claimed biomarkers, and also of detecting the ratio of the fatty acid compounds to one another (Page 2301, column 2, last paragraph & Figure 1). AHOLA-OLLI further teaches of comparison to baseline measurements (Page 2298, methods).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention and one would have had reasonable expectation of/to using the biomarkers as is done in AHOLA-OLLI in the methods of OTVOS and PERONI to detect diseases and conditions due to nutritional, vitamin, or mineral metabolism or deficiency, since metabolite profiling as is claimed has been shown advantageous in identifying biochemical changes occurring before the onset of diseases (disease such as diabetes related to a nutritional state of blood) (AHOLA-OLLI, Page 2299, column 1, last paragraph).
With respect to Claim 17, OTVOS teaches of a method for determining the risk of a patient having a clinical disease such a type II diabetes (which can be considered a metabolic condition related to the nutritional state of the blood—since diabetes is linked to how the body manages blood sugar from food or poor diet especially with high carbs, while good nutrition helps manage glucose spikes). OTVOS teaches that the method can also help detect coronary heart disease, or all-cause death, in addition to the type II diabetes by measuring GlycA by NMR signal measurements (abstract).
OTVOS does not teach of the nutritional state of the blood being vitamin deficiency and/or a disorder of mineral metabolism, and that specifically that it is an iron deficiency anemia.
PIERONI is used to remedy this and further teaches of a method for the diagnosis of iron deficiency, and specifically iron deficiency anemia (Page 1, abstract, last line). PIERONI further teaches that albumin is detected to determine if there is iron deficiency, which is one of the claimed biomarkers (abstract).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention and one would have had reasonable expectation of success of/to use albumin to aid in detection of iron deficient anemia as is done in PIERONI in the method of detection of metabolic diseases of OTVOS due to the need in the art for a better method of diagnosis of iron deficiency in patients with concomitant (accompanying or associated) pathologies and in chronic patients (such as those which have diabetes mellitus/type II diabetes, which is chronic)(abstract, lines 1-5).
With respect to Claim 18, OTVOS teaches of a method for determining the risk of a patient having a clinical disease such a type II diabetes (which can be considered a metabolic condition related to the nutritional state of the blood—since diabetes is linked to how the body manages blood sugar from food or poor diet especially with high carbs, while good nutrition helps manage glucose spikes). OTVOS teaches that the method can also help detect coronary heart disease, or all-cause death, in addition to the type II diabetes by measuring GlycA by NMR signal measurements (abstract).
OTVOS does not teach of the nutritional state of the blood being vitamin deficiency and/or a disorder of mineral metabolism, and that specifically that it is an iron deficiency anemia.
PIERONI is used to remedy this and further teaches of a method fo