DETAILED ACTION
Claims 1-9 and 113-123 are pending.
Status of Claims
Claims 1-9 and 113-123 are pending. Claims 1 and 117 have been amended. Claims 1-9 and 113-123 are under examination.
This action is NON-FINAL.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 12/18/2025 has been considered by the examiner.
Withdrawn Claim Objections and/or Rejections
The arguments filed on 12/18/2025 have been considered by the examiner.
The rejection of claims 1-9 and 113-123 under 35 USC 112(a) for failing to comply with written description as set forth on pp. 2-3 of the previous office action (mailed on 09/30/2025) has been withdrawn.
The rejection of claims 1-9 and 113-123 under 35 USC 112(a) for failing to comply with the written description of a “classifier model” as set forth on p. 3 of the previous office action (mailed on 09/30/2025) has been withdrawn in view of the amendments (filed on 12/18/2025).
The rejection of claims 1-3, 8-9, and 113-116 under 35 USC 103 as being unpatentable over Wilcox, Hwang, Zhu, and Kar et al., as set forth on pp. 5-11 of the previous office action (mailed on 09/30/2025) has been withdrawn in view of the amendments and arguments (filed on 12/18/2025).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9 and 113-123 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether a disclosure enables one skilled in the
art to make and use the claimed invention in its full scope without resorting to undue
experimentation include: (1) the quantity of experimentation necessary; (2) the amount of
direction or guidance presented; (3) the presence or absence of working examples; (4) the
nature or complexity of the invention; (5) the state of the prior art; (6) the relative skill of those in
the art; (7) the predictability or unpredictability of the art; and (8) the breadth of the claims. See
In re Wands, 8 USPQ2d. 1400 (Fed. Cir. 1988).
All Wands factors listed above have been considered with regard to the instant claims, with the relevant factors discussed below.
Nature of the invention: The invention is a method of sample quality assessment comprising: a) measuring analyte levels of biomarkers; b) applying a random forest classifier model comprising multiple decision trees, wherein each decision tree comprises a series of nodes, wherein the nodes are based on the measurement analyte levels of the biomarkers measured, wherein a measured analyte level leads a node to a classification or to one or more nodes each comprising another measured analyte level, and wherein the classification decides if a sample is an analysis sample or a negative sample; and wherein the classification decision is based on a predetermined decision criteria based on analyte level patters; wherein the random forest classifier model identifies the sample as an analysis sample or a negative sample based on the collective classification of each decision tree; wherein the analyte sample is a sample that is used in one or more of the following: protein biomarker discovery analysis, protein expression level analysis, a diagnostic method or a prognostic method, and the negative sample is a sample that is not used as an analysis sample.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: The specification does not teach nor mention how a sample is determined to be an analysis sample or a negative sample. The classification determination would depend on the type of disease and sample being measured. The specification does not enable any person skilled in the art to which it pertains, or with which it is most connected, to use the invention commensurate in scope with these claims. Specifically, the method for classifying a sample as an “analysis” sample or a “negative” sample for every and all diseases is not well supported by the specification.
The working examples and guidance provided: The specification fails to provide any working examples on the criteria that needs to be met in order to determine if a sample is an analysis sample or a negative sample. The specification does not provide any examples that show how a sample is determined to be an analysis sample or a negative sample for any disease. While figure 4 shows a decision tree to predict time-to-spin timing of a sample of a sample based on analyte RFU levels, where each node of the tree predicts the possible time-to-spin, it does not enable classifying a sample as an analysis or negative sample for any and all diseases. The specification recites that samples having time-to-spin/time-to-decant below 2 hours is a “good” sample and samples sample with greater than 2 hours as “compromised/bad” samples (see [0091]). In the specification paragraphs [0091], [00101], and [00103] recite “good” sample and “bad” sample. However, “good” and “bad” samples do not correlate to an “analysis” sample and a “negative” sample, nor does it enable “analysis” or “negative” samples. Further paragraphs [0091], [00101], and [00103] are directed to determining the time-to-spin/time-to-decant, not the actual measurements of the biomarkers. However, the breadth of “good” and “bad” are unclear. While it’s understood that time is a factor in quality assessment, it is unclear what other factors are being measured to determine an “analysis” sample and a “negative” sample.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most connected, to use the invention commensurate in scope with these claims. Diseases are complex and thus the inventor needs to show how the method of the instant application will enable a skilled artisan to determine a sample being an analysis or negative sample in any and all diseases. The method for classifying a sample as an “analysis” sample or a “negative” sample for every and all diseases is not well supported by the specification.
Absent specific guidance, one skilled in the art before the effective filing date of the claimed invention would not know how to practice the claimed invention and would require undue experimentation to practice over the full scope of the invention claimed.
The state and unpredictable nature of the prior art: The state of the prior art for classifying a sample as an analysis or negative sample for any disease was unpredictable before the effective filing date of the claimed invention. The nature of this invention is complex and unpredictable, involving the effects of any and all diseases.
Furthermore, in re Vaeck, 947 F.2d 488,495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991), the Court ruled that a rejection under 35 U.S.C. 112, first paragraph for lack of enablement was appropriate given the relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. Such is the case here where there is a relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims of the instant application.
The level of one of ordinary skill:
Based on the complexity and unpredictability of diseases, the level of a person having ordinary skill in the art is not high enough to determine analysis or negative samples for any and all diseases.
The breadth of the claims: The claims are drawn to a method of sample quality assessment comprising: a) measuring analyte levels of biomarkers; b) applying a random forest classifier model comprising multiple decision trees, wherein each decision tree comprises a series of nodes, wherein the nodes are based on the measurement analyte levels of the biomarkers measured, wherein a measured analyte level leads a node to a classification or to one or more nodes each comprising another measured analyte level, and wherein the classification decides if a sample is an analysis sample or a negative sample; and wherein the classification decision is based on a predetermined decision criteria based on analyte level patters; wherein the random forest classifier model identifies the sample as an analysis sample or a negative sample based on the collective classification of each decision tree; wherein the analyte sample is a sample that is used in one or more of the following: protein biomarker discovery analysis, protein expression level analysis, a diagnostic method or a prognostic method, and the negative sample is a sample that is not used as an analysis sample.
Due to the large quantity of experimentation necessary to determine which is an analysis sample and negative sample for any and every disease, the lack of direction/guidance presented in the specification regarding an analysis sample and a negative sample, the complex nature of the invention, and the breadth of the claims, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
Response to Arguments
Applicant's arguments filed 12/18/2025 have been fully considered but they are not persuasive.
On pp. 7-10 applicant argues that the classification of analysis sample and/or negative sample is made based on the collective classification output of the decision trees within the random forest classifier model. Applicant argues that the classifier learns patterns of the measured protein levels associated with high-quality and low-quality samples, and once trained, evaluates new samples against these learned patterns.
However, the model is dependent on the type of disease that is being analyzed. Therefore, the analysis sample and then negative sample may be different depending on what disease is being assessed.
Further, it is unclear what the model is measuring. The independent claims recite measuring analyte levels and the applicant’s arguments teach that the time-to-spin/time-to-decant is being measured (see pages 9-10 of applicant arguments). However, the instant claims do not recite the time-to-spin/time-to-decant being measured and correlating the time to the quality of the sample. In fact, neither of the independent claims (1 and 117) mention time. Claims 1 and 117 do not recite what exactly is being measured.
Claims 8-9 and 122-123 recite predicting the length of time between the sample collection from the human subject and sample centrifugation and/or the length of time between sample centrifugation and sample decanting. There are other factors involved in the quality of a sample. It is unclear if the only criteria is the time-to-spin/time-to-decant. On p. 10 applicant argues that paragraphs [0091], [00101], and [00103] teaches “good” and “bad” sample classifications. However, “good” and “bad” do not directly correspond with “analysis” and “negative” samples. The instant claims do not recite a “good’ or “bad” sample.
On p. 10 applicant argues that Ostroff et al., (2012) teaches the use of a random classifier trained on patterns of expression across multiple protein biomarkers to determine malignant pleural mesothelioma diagnosis. However, Ostroff does not make mention of determining and classifying the quality of the sample. Further, Ostroff is direct towards a disease (malignant pleural mesothelioma), whereas, the instant invention is not directed to any specific disease.
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 1-9 and 113-123 are rejected under 35 U.S.C. 101 because the claimed method 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.
Step 1
This part of the eligibility analysis evaluates whether the claim falls within any statutory
category per MPEP 2106.03
Regarding instant claims 1-9 and 113-123, Example 43 of “2019 PEG” is particularly enlightening because the fact pattern of claim 1 of example 43 is most similar to the instant application claims1-9 and 113-123.
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 1, the claim is
directed to a process, which is one of the statutory categories of invention as the claim recites
“A treatment method comprising: (a) calculating a ratio of C11 to C13 levels measured in a
blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3)
to identify the patient as having a non-responder phenotype; (b) administering a treatment to the
patient having a non-responder phenotype.” (Step 1: YES).
Similarly instant claims 1-9 and 113-123 are directed to a statutory method that measures naturally occurring proteins and correlates the levels of the naturally occurring proteins with the quality of a sample (Step 1: YES).
Step 2A, Prong 1: Does the claim recite a judicial exception?
This part of the eligibility analysis evaluates whether the claim recites a judicial
exception. As explained in MPEP 2106.04(II) and the October 2019 Update, a claim “recites” a
judicial exception when the judicial exception is “set forth” or “described” in the claim.
Regarding instant claims 1-9 and 113-123, Example 43 of the “2019 PEG” shows a similar fact pattern.
Regarding claim 1 in Example 43 of the “2019 PEG” and per Step 2A, prong 1, the
claim recites the judicial exception of “calculating a ratio of C11 to C13 levels measured in a
blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3)
to identify the patient as having a non-responder phenotype,” and according to broadest
reasonable interpretation (BRI), an arithmetic calculation of a division is required to obtain the
ratio of C11 to C13 that can be used to identify whether the patient has the non-respondent
phenotype.
Specifically, limitation (a) in claim 1 of Example 43 of the “2019 PEG” recites “calculating
a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic
Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder
phenotype,” which has a BRI that requires performing an arithmetic calculation (division) in
order to obtain the ratio of C11 to C13 levels, and then using this ratio to identify whether the
patient has the non-responder phenotype (i.e., the patient has a calculated ratio of 3:1 or
greater and thus is not responding, or will not respond, to glucocorticoids). This limitation
therefore recites a mathematical calculation. The grouping of “mathematical concepts” in the
2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG
Section I, 84 Fed. Reg. at 52. Thus, limitation (a) falls into the “mathematical concept” grouping
of abstract ideas. In addition, this type of simple arithmetic calculation (division) can be
practically performed in the human mind, and is in fact performed in the human mind on a daily
basis, for instance by school-aged children studying mathematics. Note that even if most humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them
complete the recited calculation, the use of such physical aid does not negate the mental nature
of this limitation. Thus, limitation (a) also falls into the “mental process” groupings of abstract
ideas.
In addition, limitation (a) describes a naturally occurring relationship between the ratio
of C11 to C13 and the non-responder phenotype, and thus may also be considered to recite a
law of nature. Accordingly, limitation (a) recites a judicial exception (an abstract idea that falls
within the mathematical concept and mental process groupings in the “2019 PEG”, and a law of
nature), and the analysis must therefore proceed to Step 2A Prong Two.
Similarly, instant claims 1-9 and 113-123 recites “measuring analyte level” of proteins and using the measurements to assess the samples quality, which describes a naturally occurring relationship between the protein biomarker and the sample quality, and thus is considered a law of nature. Further, claims 1-9 and 113-123 recite “wherein the classification decides if a sample is an analysis sample or a negative sample and wherein the classification decision is based on a predetermined decision criteria based on analyte level patterns”, which is directed toward an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion). Comparing collected information to a predetermined threshold, which is an act of evaluating information that can be practically performed in the human mind. Consequently, claims 1-9 and 113-123 recite the judicial exception of applying and using a law of nature and an abstract idea.
Dependent instant claims 8 and 121 contain limitations that fall under a judicial exception. The instant claims 8 and 121 recite using the protein levels to “predict” the length of time between the sample collection from the human subject and sample centrifugation and/or the length of time between sample centrifugation and sample decanting. The language “predict” is directed to a judicial exception as it is an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion). Comparing collected information from a random forest model to a predetermined threshold which is an act of evaluating information that can be practically performed in the human mind. Further, claims 8 and 121 describes a naturally occurring relationship between nature-based products and correlating it to the prediction of length of time between sample collection from the human subject and sample centrifugation and/or the length of time between sample centrifugation and sample decanting, and thus is considered to recite a law of nature.
Accordingly, instant claims 1-9 and 113-123 recite a judicial exception (a law of nature and an abstract idea that falls within the mental process grouping) and the analysis must therefore proceed to Step 2A Prong Two.
Step 2A Prong 2: Does the claim recite additional elements that integrate the exception into a practical application?
Regarding instant claims 1-9 and 113-123, Example 43 of “2019 PEG” shows a similar fact pattern.
In claim 1 of example 43 of the “2019 PEG” and per Step 2A, prong 2, the claim as a whole does not integrate the recited judicial exception into a practical application of the
exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates
the exception into a practical application. Besides the abstract idea, the claim 1 of example 43
of the “2019 PEG” recites the additional element of “(b) administering a treatment to the patient
having a non-responder phenotype”. Although this limitation indicates that a treatment is to be
administered, it does not provide any information as to how the patient is to be treated, or what
the treatment is, but instead covers any possible treatment that a doctor decides to administer
to the patient. In fact, this limitation is recited at such a high level of generality that it does not
even require a doctor to take the calculation step’s outcome (the patient’s phenotype) into
account when deciding which treatment to administer, making the limitation’s inclusion in this
claim at best nominal. Thus, limitation (b) of example 43 of the “2019 PEG” fails to
meaningfully limit the claim because it does not require any particular application of the recited
calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial
exception. Accordingly, limitation (b) of example 43 of the “2019 PEG” does not integrate the
recited judicial exception into a practical application and the claim is therefore directed to the
judicial exception.
Similarly, instant claims 1-9 and 113-123 do not have additional elements that would integrate the judicial exception cited above into a practical application. In comparison to claim 43, Example 43 did not pass step 2A prong 2 with step of general treatment, instant claims 1-9 and 113-123 do not even recite a correlation to any disease. Instant claims 1-9 and 113-123 do note recite any additional elements other than the law of nature and the abstract idea. Example 43 failed with the step of a general treatment, instant claims 1-9 and 113-123 do not even recite a further active step, let alone a step for treatment.
Therefore, instant claims 1-9 and 113-123 do not integrate the judicial exception into a practical application.
Step 2B: Does the claim recite significantly more?
Regarding instant claims 1-9 and 113-123, this part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim does not recite any active steps. Instant claims 8 and 121 do recite “predicting”, however, that language is still directed to a judicial exception as it is an abstract idea that falls under the mental process grouping (i.e., concepts performed in the human mind (including an observation, evaluation, judgement, opinion). Comparing collected information to a predetermined threshold, which is an act of evaluating information that can be practically performed in the human mind. Further, claims 1-9 and 113-123 describes a naturally occurring relationship between a nature-based product and correlating it to the quality of the sample, and thus is considered to recite a law of nature. Accordingly, instant claims 1-9 and 113-123 are not eligible (STEP 2B: NO).
Thus, instant claims 1-9 and 113-123 are rejected under 35 USC 101.
Conclusion
No claim is allowed.
Claims 1-9 and 112-123 are free of the prior art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
The closest prior art for claims 1-9 and 112-123 is Wilcox et al. (US 2013/0116150 A1) (IDS filed on 10/07/2021). Wilcox teaches a method that includes sample quality assessment, comprising a) measuring levels of proteins, and the levels of at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve proteins in a sample from a human subject; and b) in order to assess sample quality, applying a forest decision tree, and based on the level of protein and the level of at least one, two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve proteins. Wilcox does not teach categorizing samples as “analysis sample” and “negative samples”. Wilcox does not teach measuring any combination of SHH, PTPN4, and the level of the one, two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve proteins chosen from PGAM1, PGAM2, C4A.C4B, TNFSF14, FAM49B, RBP7, IHH, DDX39B, S100A12, IL21R, TMEM9 and ADAM9, which are proteins. Because proteins are a composition of matter, the markers SHH, PTPN4, and the level of the one, two, three, four, five, six, seven, eight, nine, ten, eleven, or twelve proteins chosen from PGAM1, PGAM2, C4A.C4B, TNFSF14, FAM49B, RBP7, IHH, DDX39B, S100A12, IL21R, TMEM9 and ADAM9. Further, Wilcox does not teach wherein a measured analyte level leads a node to as classification or to one or more nodes each comprising another measured analyte level, and wherein the classification decides if a sample is an analysis sample or a negative sample, and wherein the classification decision is based on a predetermined decision criteria based on analyte level patters.
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/MCKENZIE A DUNN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678