DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 59-75, 77, and 78 in the reply filed on 23 December 2025 is acknowledged.
Information Disclosure Statement
The information disclosure statements filed 10 September 2025 and 2 August 2023 fail to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
Claim Objections
Claims 74 and 78 are objected to because of the following informalities:
Claim 74 must end with a period.
In claim 78, no capitalization must be used after the first word of the claim.
Regarding claim 78, the listing of both "Entrectinib" and "entrectinib" is redundant.
Appropriate correction is required.
Drawings
The drawings are objected to for the following reasons.
Regarding Fig. 1a, the key on the upper right associates a black circle with "Normal" and a gray circle with "Stage 1." The illustrated plot does not include any black circles, which implies that all the data are "Stage 1" data points, with no "Normal" data points. However, the specification teaches that Fig. 1a shows "the comparison between plasma metabolite data acquired for healthy controls (shown in shaded area on left) vs. stage I NSCLC patients (shown in shaded area on right)" (page 2). This description contracts the color key on the upper right of Fig. 1a. Figs. 2a, 5a, 8a, 8b, and 10 are objected to for analogous reasons.
Regarding Fig. 1b, the "High" versus "Low" color scale on the right of the figure cannot be distinguished from one another. Regarding Fig. 1b, the specification teaches that "The boxes indicate whether metabolite concentration is increased (circled) or decreased (not circled) in controls vs. cases" (pages 2-3). However, Fig. 1b does not illustrated circled boxes. Figs. 2b, 4b, 5b, 6b, 8c, and 11 are objected to for analogous reasons.
Regarding Figs. 4a and 6a, the data lines cannot be distinguished from one another.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: In Table 3 (page 13, last line), "Canitine" appears to be a misspelling of Carnitine.
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.
Claims 66, 69-75, 77, and 78 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Dependent claim 66 recites the limitation "wherein the group of metabolites comprises: β-hydroxybutyric acid, PC ae C40:6, LysoPC 20:3, tryptophan, glutamic acid, and carnitine." It is unclear whether the group of metabolites comprises fumaric acid or citric acid, as required by independent claim 59.
Claim 69 recites the limitation "wherein the early-stage NSCLC probability score further accounts for the subject's smoking history." There is insufficient antecedent basis for this limitation because neither claim 68 nor claim 69 previously set forth that the early-stage NSCLC probability score "accounts" for something.
Claims 70-75 and 77 recite the limitation "qualifying the blood sample as…" Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term "qualifying" in the claims is apparently used by the claims to mean "identifying," while the accepted meaning of the term is generally inconsistent with description of a blood sample. The term is indefinite because the specification does not clearly redefine the term. In fact, the specification does not use the term. For purposes of evaluating the claims under 35 USC 112(a), the term "qualifying" is interpreted as "identifying.
Claim 70 recites the limitation "wherein the threshold value is a stage I threshold or a stage I smoker threshold." It is unclear whether "stage I threshold" is a broader category than "stage I smoker threshold," or whether "stage I threshold" means "stage I non-smoker threshold," or a "stage I threshold that does not account for smoking." A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Claim 70 recites the limitation "wherein the threshold value is a stage I threshold or a stage I smoker threshold." It is unclear whether "stage I threshold" is a broader category than "stage I smoker threshold," or whether "stage I threshold" means "stage I non-smoker threshold," or a "stage I threshold that does not account for smoking." A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Claim 71 is indefinite for analogous reasons concerning the limitation "a stage II threshold or a stage II smoker threshold."
Claim 71 recites the limitation "[identifying] the blood sample as an early-stage NSCLC blood sample when the early-stage NSCLC probability score meets or exceeds the threshold value, wherein the early-stage NSCLC probability score is a stage I probability score or a stage II probability score, the threshold value is a stage II threshold or a stage II smoker threshold and the early-stage NSCLC is stage II non-small cell lung cancer." It is unclear how a stage I probability score is compared to a stage II threshold for a stage II cancer. Does this reflect a typographical error?
Claim 73 recites the limitation "the concentration of β-hydroxybutyric acid." There is insufficient antecedent basis for this limitation in the claim. This rejection can be overcome by specifying "the concentration of β-hydroxybutyric acid in the blood sample."
Claim 73 recites the limitation "the threshold value." There is insufficient antecedent basis for this limitation in the claim. Claim 73 is henceforth treated as depending from claim 68.
Claim 73 recites the limitation "when an increase in the concentration of β-hydroxybutyric acid [in the blood sample] when compared to the threshold value is detected." The meaning of comparing a concentration of β-hydroxybutyric acid to the threshold value is unclear. Claim 68 previously recites the following limitation: "using the group of metabolites [plural] to determine an early-stage NSCLC probability score [singular] for comparison to a threshold value [singular] indicative of the presence or absence of early-stage NSCLC in the subject." The group of metabolites introduced in claim 59 include β-hydroxybutyric acid as well as other metabolites. Accordingly, claim 68 suggests that the probability score and the threshold value are each a function of the plurality of metabolites. It is unclear how a concentration of β-hydroxybutyric acid can be compared to a value that is a function of the plurality of metabolites.
Claim 74 recites the limitation "the concentration of PC ae C40:6." There is insufficient antecedent basis for this limitation in the claim. This rejection can be overcome by specifying "the concentration of PC ae C40:6 in the blood sample."
Claim 74 recites the limitation "the threshold value." There is insufficient antecedent basis for this limitation in the claim. Claim 74 is henceforth treated as depending from claim 68.
Claim 74 recites the limitation "when a decrease in the concentration of PC ae C40:6 [in the blood sample] when compared to the threshold value is detected." The meaning of comparing a concentration of PC ae C40:6 to the threshold value is unclear. Claim 68 previously recites the following limitation: "using the group of metabolites [plural] to determine an early-stage NSCLC probability score [singular] for comparison to a threshold value [singular] indicative of the presence or absence of early-stage NSCLC in the subject." The group of metabolites introduced in claim 59 include PC ae C40:6 as well as other metabolites. Accordingly, claim 68 suggests that the probability score and the threshold value are each a function of the plurality of metabolites. It is unclear how a concentration of PC ae C40:6 can be compared to a value that is a function of the plurality of metabolites.
Claim 75 recites the limitations "the concentrations of LysoPC 20:3 and fumaric acid," "the concentration of citric acid," "the concentration of carnitine," and "the threshold value." There is insufficient antecedent basis for these limitations in the claim.
Claim 75 recites the limitation "(c1) an increase in the concentrations [plural] of LysoPC 20:3 and fumaric acid when compared to the threshold value [singular] is detected, and/or (c2) a decrease in the concentration of citric acid and an increase in the concentration of carnitine [two different concentrations] when compared to the threshold value [singular] is detected." It is unclear what is meant by comparing a plurality of concentrations of different metabolites to a singular threshold value. It is unclear how the same threshold value can be applied to the comparison of (c1) and (c2).
Claim 77 recites the following limitation:
(ii) qualifying the blood sample as an early-stage NSCLC blood sample when:
(a) an increase in the concentration of β-hydroxybutyric acid;
(b) a decrease in the concentration of PC ae C40:6; and
(cl) an increase in the concentrations of LysoPC 20:3 and fumaric acid, and/or (c2) a decrease in the concentration of citric acid and an increase in the concentration of carnitine;
relative to that of a corresponding non-lung cancer control value is detected;
It is unclear what is modified by the clause "relative to that of a corresponding non-lung cancer control value is detected." Only the immediately preceding limitation (c2)? Only (c1) and (c2)? Or all of (a) through (c2)? If this clause modifies "(cl) an increase in the concentrations of LysoPC 20:3 and fumaric acid," it is unclear how an increase of plural concentrations of different metabolites can be compared to a singular control value.
Claim 78 is rejected for depending from claim 77.
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.
Claims 70-75, 77, and 78 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention.
The examiner respectfully reminds the Applicant that according to MPEP §2163:
"2163.02. Standard for Determining Compliance with Written Description Requirement:
The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed.” In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon “reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter.” Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)). Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the University of California v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharmaceutical, 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by “whatever characteristics sufficiently distinguish it”).
Non-original independent claim 59 recites the following limitation:
quantifying a group of metabolites in the blood sample, the group of metabolites comprising:
(a) β-hydroxybutyric acid;
(b) PC ae C40:6; and
(c1) LysoPC 20:3 and fumaric acid, and/or (c2) citric acid and carnitine.
Intervening non-original claim 68 recites the limitation "using the group of metabolites to determine an early-stage NSCLC probability score for comparison to a threshold value indicative of the presence or absence of early-stage NSCLC in the subject." Claim 68 does not limit the group of metabolites recited in claim 59. Accordingly, the scope of the group of metabolites used to determine the early-stage NSCLC probability score is metabolites (a), (b), (c1) and/or (c2).
The original disclosure does not contain a general teaching regarding an early-stage NSCLC probability score for any group of metabolites. Instead, the specification discloses probability scores according to one of specific formulas 1-8:
Formula 1 - uses (a), (b), (c1) for stage I
Formula 2 - uses (a), (b), (c1), and smoking variable for stage I
Formula 3 - uses (a), (b), (c2) for stage II
Formula 4 - uses (a), (b), (c2), and smoking variable for stage II
Formula 5 - uses (a), (b), (c1), and citric acid for stage I/II
Formula 6 - uses (a), (b), (c1), citric acid, and smoking variable for stage I/II
Formula 7 - uses (a), (c1), and spermine for stage I
Formula 8 - uses (a), (c1), spermine, and smoking variable for stage I
Claim 68 for the group of metabolites comprising (a), (b), and (c1) is supported by the embodiments of formulas 1, 2, 5, and 6, while claim 68 for the group of metabolites comprising (a), (b), and (c2) is supported by the embodiments of formulas 3 and 4.
Non-original dependent claim 70 recites "[identifying] the blood sample as an early-stage NSCLC blood sample when the early-stage NSCLC probability score meets or exceeds the threshold value, wherein the threshold value is a stage I threshold or a stage I smoker threshold and the early-stage NSCLC is stage I non-small cell lung cancer."
The disclosure of the embodiments of formulas 1 and 2 support this stage I claim for the group of metabolites comprising (a), (b), and (c1). However, the claim also explicitly recites the option of the group of metabolites comprising (a), (b), and (c2) (because claim 70 depends from claim 59), and the original disclosure does not support using a group of metabolites comprising (a), (b), and (c2) without comprising (c1), as permitted by claim 59, to determine an early-stage NSCLC probability score for stage I non-small cell lung cancer. This is new matter.
Non-original dependent claim 71 recites "[identifying] the blood sample as an early-stage NSCLC blood sample when the early-stage NSCLC probability score meets or exceeds the threshold value, wherein the early-stage NSCLC probability score is a stage I probability score or a stage II probability score, the threshold value is a stage II threshold or a stage II smoker threshold and the early-stage NSCLC is stage II non-small cell lung cancer.
The specification in its description of formula 3 describes "determining a stage I probability score for the biological sample according to the formula 3" while also stating that "A probability score that meets or exceeds a stage II threshold indicates that the subject has stage II non-small cell lung cancer" ([0061], page 25). The specification's description of formula 4 is analogous ([0062], pages 25-26). However, original claim 29 recites "determining a stage II probability score for the biological sample according to the formula 3," and original claim 37 recites "determining a stage II probability score for the biological sample according to the formula 4." The original disclosure does not explain how a stage I probability score is compared to a stage II threshold for a stage II cancer. Accordingly, the disclosed determination of a stage I probability score for a stage II cancer appears to be a typographical error, and the recitation of "a stage I probability score" in claim 71 does not comply with the written description requirement.
The disclosure of the embodiments of formulas 3 and 4 support this stage II claim for the group of metabolites comprising (a), (b), and (c2). However, the claim also explicitly recites the option of the group of metabolites comprising (a), (b), and (c1) (because claim 71 depends from claim 59), and the original disclosure does not support using a group of metabolites comprising (a), (b), and (c1) without comprising (c2), as permitted by claim 59, to determine an early-stage NSCLC probability score for stage II non-small cell lung cancer. This is new matter.
Non-original dependent claim 72 recites "[identifying] the blood sample as an early-stage NSCLC blood sample when the early-stage NSCLC probability score meets or exceeds the threshold value, wherein the threshold value is a stage I/II probability threshold and the early-stage NSCLC is stage I non-small cell lung cancer or stage II non-small cell lung cancer."
The disclosure of the embodiments of formulas 5 and 6 support the combination of a stage I/II probability threshold with the group of metabolites comprising (a), (b), (c1), and citric acid. However, the claim also explicitly recites the option of the group of metabolites comprising (a), (b), and (c1) or (a), (b), and (c2) (because claim 72 depends from claim 59), and the original disclosure does not support using a group of metabolites other than metabolites comprising (c1) and citric acid, as permitted by the scope of claim 59, in combination with a stage I/II probability threshold. This is new matter.
Non-original dependent claim 73 recites "[identifying] the blood sample as an early-stage NSCLC blood sample when an increase in the concentration of β-hydroxybutyric acid when compared to the threshold value is detected."
The original disclosure does not teach identifying a blood sample as an early-stage NSCLC blood sample based on a change in concentration of a single metabolite when compared to a threshold value is detected. This is new matter. The only disclosure of a "threshold" in the original disclosure concerns the early-stage NSCLC probability scores of formulas 1-8, which each use a plurality of metabolites. The specification teaches that β-hydroxybutyric acid is "increased in NSCLC" ([0043], page 13) but does not teach identifying a blood sample as an early-stage NSCLC blood sample based solely on such an increase. Instead, the specification teaches that "Another advantage to our early stage lung cancer assay lies in the fact that it is a multi-component test…The ROC curve shape adjustment is not possible with a single biomarker panel" ([0078], page 32).
Non-original dependent claim 74 recites "[identifying] the blood sample as an early-stage NSCLC blood sample when a decrease in the concentration of PC ae C40:6 when compared to the threshold value is detected[.]"
The original disclosure does not teach identifying a blood sample as an early-stage NSCLC blood sample based on a change in concentration of a single metabolite when compared to a threshold value is detected. This is new matter. The only disclosure of a "threshold" in the original disclosure concerns the early-stage NSCLC probability scores of formulas 1-8, which each use a plurality of metabolites. Instead, the specification teaches that "Another advantage to our early stage lung cancer assay lies in the fact that it is a multi-component test…The ROC curve shape adjustment is not possible with a single biomarker panel" ([0078], page 32). Moreover, contrary to the specification's brief description of the drawings, the figures fail to illustrate with a particular metabolite concentration, including PC ae C40:6, is increased or decreased in controls vs. cases.
Non-original dependent claim 75 recites "[identifying] the blood sample as an early-stage NSCLC blood sample when (c1) an increase in the concentrations of LysoPC 20:3 and fumaric acid when compared to the threshold value is detected, and/or (c2) a decrease in the concentration of citric acid and an increase in the concentration of carnitine when compared to the threshold value is detected."
The original disclosure does not teach identifying a blood sample as an early-stage NSCLC blood sample based on a change in concentration of a single metabolite (or two metabolites) when compared to a threshold value is detected. This is new matter. The only disclosure of a "threshold" in the original disclosure concerns the early-stage NSCLC probability scores of formulas 1-8, which each use a plurality of metabolites as set forth above. Instead, the specification teaches that "Another advantage to our early stage lung cancer assay lies in the fact that it is a multi-component test…The ROC curve shape adjustment is not possible with a single biomarker panel" ([0078], page 32). The specification teaches that carnitines are "increased" and citrate is "decreased," and fumaric acid is "decreased" ([0043], page 13) but does not teach identifying a blood sample as an early-stage NSCLC blood sample based solely on such a changed. Moreover, contrary to the specification's brief description of the drawings, the figures fail to illustrate with a particular metabolite concentration, including LysoPC 20:3, is increased or decreased in controls vs. cases.
Non-original dependent claim 77 recites the following indefinite limitation:
(ii) qualifying the blood sample as an early-stage NSCLC blood sample when:
(a) an increase in the concentration of β-hydroxybutyric acid;
(b) a decrease in the concentration of PC ae C40:6; and
(cl) an increase in the concentrations of LysoPC 20:3 and fumaric acid, and/or (c2) a decrease in the concentration of citric acid and an increase in the concentration of carnitine;
relative to that of a corresponding non-lung cancer control value is detected;
As set forth above in the rejections under 35 USC 112(b), it is unclear what is modified by the clause "relative to that of a corresponding non-lung cancer control value is detected."
The original disclosure does not provide a verbatim disclosure of [identifying] the blood sample as an early-stage NSCLC blood sample when conditions (a), (b), (c1) and/or (c2) are met. The closest support is found in formulas 1 and 3:
logit(P)=log(P/(1−P))=0.258−1.341×PC ae C40:6+1.747×LysoPC 20:3+0.913×β-hydroxybutyric acid+0.939×fumaric acid (formula 1)
logit(P)=log(P/(1−P))=0.346+2.565×β-hydroxybutyric acid−2.219×citric acid+2.904×carnitine−1.599×PC ae C40:6 (formula 3).
Formula 1 is a narrower embodiment of conditions (a), (b), and (c1) of claim 77.
Formula 3 is a narrower embodiment of conditions (a), (b), and (c2) of claim 77.
The original disclosure does not provide written description support for diagnosing early-stage NSCLC based upon conditions (a), (b), (c1) and (c2) being true. This is new matter.
Claim 78 is rejected for depending from claim 77.
Therefore, the Applicants did not show possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention, by description of an actual reduction to practice, or by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention.
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 59-67 are directed to natural products and a law of nature without significantly more.
Claims 59-67 recite a method for processing a human clinical blood sample, comprising quantifying a group of metabolites in a blood sample, the blood sample being obtained from a subject clinically assessed as having or suspected of having early-stage non-small cell lung cancer (NSCLC).
The metabolites recited in claims 59-67 are natural products. The location and existence of these metabolites in "a blood sample from a subject clinically assessed as having or suspected of having early-stage non-small cell lung cancer (NSCLC)" is a natural phenomenon and thus identifying their presence is merely claiming the natural phenomena itself. See discussion of Ariosa Diagnostics, Inc. v. Sequenom regarding process claims in MPEP 2106.04(c), I, C.
By reciting a step of quantifying a group of metabolites in a blood sample obtained from a subject clinically assessed as having or suspected of having early-stage non-small cell lung cancer (NSCLC), the claimed steps investigate a correlation between the group of metabolites and early-stage non-small cell lung cancer (NSCLC). A natural relationship between quantities of metabolites in a blood sample and the presence of a disease such as early-stage NSCLC is a law of nature. MPEP 2106.04(b), I.
The natural product judicial exception of claims 59-67 is not integrated into a practical application because claims 59-67 do not recite any application of the metabolites or the quantities of the metabolites. The broadly recited "obtaining" and "quantifying" steps amount to merely identifying the presence and levels of the natural product itself. See discussion of Ariosa Diagnostics, Inc. v. Sequenom regarding process claims in MPEP 2106.04(c), I, C.
The natural law judicial exception of claims 59-67 is not integrated into a practical application because claims 59-67 do not recite any application of a natural relationship between quantities of metabolites in a blood sample and the presence of early-stage NSCLC.
Claims 59-67 do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions. The broadly recited "obtaining" and "quantifying" steps are in addition to the judicial exceptions but are mere data gathering steps that are insignificant extra-solution activity. See MPEP 2106.05(g). The courts have recognized the that determining the level of a biomarker in blood is well-understood, routine, conventional activity in the life science arts when it is claimed in a merely generic manner (e.g., at a high level of generality) or is insignificant extra-solution activity. See MPEP 2106.05(d), II and Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017).
Claims 68-75 are directed to a law of nature and an abstract idea without significantly more.
Dependent claims 68-75 further comprise using the group of metabolites to determine an early-stage NSCLC probability score for comparison to a threshold value indicative of the presence or absence of early-stage NSCLC in the subject.
By reciting a step of using the group of metabolites to determine an early-stage NSCLC probability score for comparison to a threshold value indicative of the presence or absence of early-stage NSCLC in the subject, the claimed steps recite a correlation between the group of metabolites and early-stage non-small cell lung cancer (NSCLC). A natural relationship between quantities of metabolites in a blood sample and the presence of a disease such as early-stage NSCLC is a law of nature. MPEP 2106.04(b), I. Claims 69-75 further limit the probability score and/or recite a further step of [identifying] the blood sample as an early-stage NSCLC blood sample based on a comparison. Accordingly, claims 69-75 further limit the natural correlation recited in claim 68 [consult the rejections under 35 USC 112(b) above regarding lack of antecedent basis and other indefinite limitations].
By reciting a step of using the group of metabolites to determine an early-stage NSCLC probability score for comparison to a threshold value indicative of the presence or absence of early-stage NSCLC in the subject, the claimed steps recite an abstract idea regarding a probability score for diagnosing early-stage NSCLC. A probability score, which is the result of mathematical calculations, is an abstract idea. A relationship between changes in metabolite levels relative to a threshold and identifying early-stage NSCLC is an abstract idea. Claims 69-75 further limit the probability score and/or recite a further step of [identifying] the blood sample as an early-stage NSCLC blood sample based on a comparison and changes in metabolite levels. Accordingly, claims 69-75 further limit the abstract recited in claim 68 [consult the rejections under 35 USC 112(b) above regarding lack of antecedent basis and other indefinite limitations].
The natural law judicial exception of claims 68-75 is not integrated into a practical application because claims 68-75 do not recite any application of a natural relationship between quantities of metabolites in a blood sample and the presence of early-stage NSCLC.
The abstract idea judicial exception of claims 68-75 is not integrated into a practical application because claims 68-75 do not recite any practical application of using a probability score and/or a change in metabolite levels relative to a threshold to identify the presence of early-stage NSCLC.
Claims 68-75 do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions. The broadly recited "obtaining" and "quantifying" steps are in addition to the judicial exceptions but are mere data gathering steps that are insignificant extra-solution activity. See MPEP 2106.05(g). The courts have recognized the that determining the level of a biomarker in blood is well-understood, routine, conventional activity in the life science arts when it is claimed in a merely generic manner (e.g., at a high level of generality) or is insignificant extra-solution activity. See MPEP 2106.05(d), II and Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017).
Claims 77 and 78 are directed to a law of nature and an abstract idea without significantly more.
Claim 77 recites a step of "(ii) [identifying] the blood sample as an early-stage NSCLC blood sample" when conditions (a), (b), (c1), and (c2) are met. These conditions each pertain to a change in a concentration of at least one metabolite relative to a corresponding non-long cancer control value.
By reciting a step of identifying early-stage NSCLC based upon levels of a group of metabolites, the claim recites a correlation between the group of metabolites and early-stage non-small cell lung cancer (NSCLC). A natural relationship between quantities of metabolites in a blood sample and the presence of a disease such as early-stage NSCLC is a law of nature. MPEP 2106.04(b), I.
Likewise, by reciting a step of identifying early-stage NSCLC based upon changes in metabolite levels relative to a corresponding non-long cancer control value, the claim recites recite an abstract idea.
The judicial exceptions of claims 77 and 78 are not integrated into a practical application. The treating step (iii) of claim 77 fails the integrate the natural law and abstract idea of conditional step (ii) into a practical application because treating step (iii) is performed regardless of whether the blood sample is identified as an early-stage NSCLC blood sample in contingent step (ii). The limitation "the subject" as recited in steps (i) and (iii) has antecedent basis in the preamble limitation "a subject having early-stage NSCLC." According, claim 77 requires that the subject is treated for lung cancer by administering a therapeutic agent independent of the judicial exceptions.
Moreover, because of the generality of the "therapeutic agent" of claim 77 and the large scope of conventional chemotherapies for a variety of different cancers recited in claim 78, treating step (iii) is not a "particular" treatment. For example, chemotherapy for endometrial cancer typically involves a combination of carboplatin and paclitaxel. Accordingly, the scope of the therapeutic agents recited in claim 78 is not particular to treating the subject for non-small cell lung cancer. The particularity or generality of a treatment is a relevant factor in determining whether the claim uses the recited judicial exception to effect a treatment. See discussion of Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d 1117, 126 USPQ2d 1266 (Fed. Cir. 2018) in MPEP 2106.04(d)(2).
Claims 77 and 78 do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions. The broadly recited "obtaining" and "quantifying" steps involved in processing step (i) are in addition to the judicial exceptions but are mere data gathering steps that are insignificant extra-solution activity. See MPEP 2106.05(g). The courts have recognized the that determining the level of a biomarker in blood is well-understood, routine, conventional activity in the life science arts when it is claimed in a merely generic manner (e.g., at a high level of generality) or is insignificant extra-solution activity. See MPEP 2106.05(d), II and Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). Treating step (iii) of claims 77 and 78 is also in addition to the judicial exceptions but is a well understood, routine, and convention step. The treating step (iii) by administering a "therapeutic agent" of claim 77 is highly generalized, and the wide scope of the conventional therapeutic agents for a variety of different cancers recited claim 78 together constitute a broad scope of conventional anti-cancer therapies that is not "particular."
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Bahado-Singh (US 2017/0003291) discloses a method for processing a human clinical blood sample, the method comprising obtaining a blood sample from a subject clinically assessed as having endometrial cancer ([0084]), and quantifying a group of metabolites in the blood sample, the group of metabolites comprising: (a) β-hydroxybutyric acid (3-hydroxybutyric acid, Table 4, page 12); (b) PC ae C40:6 (Table 5, page 14); and (c1) LysoPC 20:3 (Table 5, page 13), and (c2) citric acid (Table 4, page 12) and carnitine (Table 4, page 12). Bahado-Singh does not teach or suggest the subject is clinically assessed as having or suspected of having early-stage non-small cell lung cancer (NSCLC).
Holcapek (US 2020/0363419) discloses a method for processing a human clinical blood sample, the method comprising obtaining a blood sample from a subject clinically assessed as having or suspected of having lung cancer ([0032], [0033], Table 3 header), and quantifying a group of metabolites in the blood sample, the group of metabolites comprising: (b) PC ae C40:6 (PC O-40:6, Table 3, where "PC O-" is equivalent to PC alkyl-acyl, Table 1) and (c1) LysoPC 20:3 (LPC 20:3, Table 3, where "LPC" is equivalent to LysoPC, Table 1).
Puchades-Carrasco ("Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer," Oncotarget. 2016) discloses a method for processing a human clinical blood sample, the method comprising obtaining a blood sample from a subject clinically assessed as having or suspected of having early-stage non-small cell lung cancer (NSCLC) (abstract, Table 1B), and quantifying a group of metabolites in the blood sample, the group of metabolites comprising:(a) β-hydroxybutyric acid (3-hydroxybutyrate, Table 1B); and (c2) citric acid (citrate, Table 1B).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE ADAMS whose telephone number is (571)270-5043. The examiner can normally be reached M, T, Th, and F, 12-4 P.M.
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/MICHELLE ADAMS/ Examiner, Art Unit 1797
/JENNIFER WECKER/ Primary Examiner, Art Unit 1797