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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Status
Claims 1-18 are pending.
Claims 1, 3, 6, and 16 are objected to.
Claims 1-18 are rejected.
Priority
Applicant's claim for the benefit of a prior-filed application, PCT/JP2020/034198, filed Sep 9 2020, is acknowledged.
Accordingly, each of claims 1-18 are afforded the effective filing date of Sep 9 202.
Information Disclosure Statement
The information disclosure statement filed Feb 15 2023 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. It has been placed in the application file, but the information referred to therein, as indicated by strikethrough, has not been considered. All other references have been considered.
Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper.” Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The Drawings submitted Feb 10 2026 are accepted.
Claim Objections
The claims are objected to for the following informalities:
Claim 1, line 2, recites “preparing a database that has stored a marker panel”, which should be amended to recite “preparing a database storing a marker panel” to improve readability. Claim 16 is similarly objected to.
Claim 3 recites “according to three groups of the discrimination information”, which should be amended to recite “according to the three groups” because the three groups were previously recited in claim 1. Claim 6 is similarly objected to.
Claim Interpretation
35 U.S.C. 112(f)
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “an analysis unit that is configured to analyze, with respect to the measured values of the one or more cancer markers of the subject from the input unit, a correlation with the discrimination information in the database” and “an evaluation unit that is configured to evaluate cancer in the subject on a basis of an analysis result obtained by the analysis unit” in claim 16. The specification as published discloses an analysis unit and an evaluation unit for performing the claimed function at [0041-0042; 0132-0135; 0137-0139], but does not disclose adequate structure to perform the claimed function.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
35 U.S.C. 112(a)
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.
Claim 16 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 16 is rejected because, as outlined above under 35 USC 112(f), the disclosure does not contain adequate structure to perform the claimed functions of “an analysis unit that is configured to analyze, with respect to the measured values of the one or more cancer markers of the subject from the input unit, a correlation with the discrimination information in the database” and “an evaluation unit that is configured to evaluate cancer in the subject on a basis of an analysis result obtained by the analysis unit” because the invention is not described with sufficient detail such that one of ordinary skill in the art can reasonably conclude that the inventor had possession of the claimed invention. The specification as published discloses an analysis unit and an evaluation unit for performing the claimed function at [0041-0042; 0132-0135; 0137-0139], but does not disclose adequate structure to perform the claimed function.
With respect to the limitations, adequate written description for specific programming to carry out said functions in computer-related inventions requires disclosure of the algorithm by which to perform said function. Without the algorithm disclosed, it is unclear as to the exact structure that performs said function (see Finisar Corp. v. DirecTV Group Inc., 86 USPQ2d 1609, 1623 (Fed. Cir. 2008); Halliburton Energy Services v. M-I LLC 514 F.3d 1244, 1256 n.7 (Fed. Cir. 2008)). This raises issues under 112(a) because without the respective algorithms disclosed, one is not apprised of the inventor or joint inventor having possession of the claimed invention.
35 U.S.C. 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1-18 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.
Claim 1, first limitation, recites “preparing a database that has stored a marker panel on which information… is registered”. It is not clear whether “on which information… is registered” is intended to further limit the database or the marker panel. In other words, it is not clear whether the information is registered to the database or to the marker panel stored on the database. Thus, it is not clear whether registering the information is an active step which is required to be performed to prepare the database, or if the database merely comprises a marker panel which contains the recited information. For compact examination, it is assumed that the database merely comprises a marker panel which contains the recited information. Claim 16 is similarly rejected. Claims 2-15 and 17-18 are rejected based on their dependency from claim 1.
The claims recite the following parenthetical limitations: claims 1 and 16: “with a mean value of the healthy subjects ± X x standard deviation (wherein X is an arbitrary numerical value)”; claims 5 and 8: “the reference range comprises a reference range of the mean value of the healthy subjects ± X x the standard deviation (wherein X is 2)”; claim 7: “Formula I (wherein, gn denotes a relative value of importance calculated by machine learning, and a sign of gn is + if a measured value of a cancer marker of the subject has a same column value as that of the cancer patients and - if the measured value has a different column value; and Dn denotes a column value of + 1, 0, or - 1); and claim 10: “Formula II (wherein, gn denotes a relative value of importance calculated by machine learning; Dn denotes a row vector represented by a column value of + 1, 0, or - 1 with respect to each cancer marker of the cancer patients or the healthy subjects in the database; and Tn denotes a row vector represented by a column value of + 1, 0, or - 1 with respect to each cancer marker in the subject)”. It is not clear if the parenthetical statements intend to further limit the limitations, or if they are merely exemplary claim language. As set forth in MPEP 2173.05(d), exemplary claim language can make the scope of the claim unclear. For compact examination, it is assumed that the limitations are intended to be required and are not exemplary. The rejection may be overcome by amending the claims to include the limitations without the parentheses. Claims 2-15 and 17-18 are rejected based at least on their dependency from claim 1.
Claim 2 recites “wherein a marker panel of the subject is created…”. It is unclear whether the wherein clause is intended to require creating the marker panel of the subject within the metes and bounds of the claimed invention, or if it is only further limiting the method such that creating the marker panel of the subject is not required within the metes and bounds of the invention. As set forth in MPEP 2111.04.I, “wherein” clauses raise the question as to the limiting effect of the language in a claim. As the claims do not recite an active performance of creating the marker panel of the subject, the metes and bounds of the claims are unclear. For compact examination, it is assumed that creating the marker panel of the subject is required to be performed. The rejection may be overcome by clarifying what steps are required to be performed.
Claim 2 recites “the cancer markers of the subject”. However, claim 1 previously recites “one or more cancer markers of a subject”. It is therefore not clear whether claim 2 intends to remove the scope of claim 1 such that more than one cancer marker of the subject is required, or if claim 2 should recite “one or more of the cancer markers of the subject”, such that only one marker is still required. For compact examination, it is assumed that the claim should be amended as to recite “one or more of the cancer markers of the subject”.
Claim 3 recites “wherein, in the marker panel, columns of the cancer markers are displayed to be visually distinguishable…”. It is unclear whether the wherein clause is intended to require displaying columns of the cancer markers in the marker panel within the metes and bounds of the claimed invention, or if it is only further limiting the marker panel such that displaying columns of the cancer markers are not required within the metes and bounds of the invention. As set forth in MPEP 2111.04.I, “wherein” clauses raise the question as to the limiting effect of the language in a claim. As the claims do not recite an active performance of displaying columns of the cancer markers, the metes and bounds of the claims are unclear. For compact examination, it is assumed that displaying columns of the cancer markers are required to be performed. The rejection may be overcome by clarifying what steps are required to be performed.
Claim 4 recites “wherein, in the marker panel, the cancer markers are shown in order of importance…”. It is unclear whether the wherein clause is intended to require showing the cancer markers in order of importance within the metes and bounds of the claimed invention, or if it is only further limiting the marker panel such that showing the cancer markers is not required within the metes and bounds of the invention. As set forth in MPEP 2111.04.I, “wherein” clauses raise the question as to the limiting effect of the language in a claim. As the claims do not recite an active performance of showing the cancer markers, the metes and bounds of the claims are unclear. For compact examination, it is assumed that creating the marker panel of the subject is required to be performed. The rejection may be overcome by clarifying what steps are required to be performed.
Claim 6 recites “wherein, in accordance with three groups of the discrimination information, the measured values of the cancer markers are assigned a column value of…”. It is unclear whether the wherein clause is intended to require assigning a column value within the metes and bounds of the claimed invention, or if it is only further limiting the marker panel such that assigning a column value is not required within the metes and bounds of the invention. As set forth in MPEP 2111.04.I, “wherein” clauses raise the question as to the limiting effect of the language in a claim. As the claims do not recite an active performance of assigning a column value, the metes and bounds of the claims are unclear. For compact examination, it is assumed that assigning a column value is required to be performed. The rejection may be overcome by clarifying what steps are required to be performed. Claims 7-8 and 18 are rejected based on their dependency from claim 6.
Claim 8 recites “wherein the analyzing the correlation with the discrimination information is performed by calculating an evaluation function on a basis of the discrimination information…”. However, claim 7, from which claim 8 depends, previously recites “wherein the analyzing the correlation with the discrimination information is performed on a basis of a value of an evaluation function”. It is therefore not clear if claim 8 intends to refer to the same evaluation function or, as under the broadest reasonable interpretation by the term “an”, to a different evaluation function. Therefore, the relationship between the recitations of “an evaluation function” in claims 7 and 8 is not clear. For compact examination, it is assumed that claim 8 should recite “the evaluation function”.
Regarding the claim limitation that invokes 112(f): Claim limitations “an analysis unit that is configured to analyze, with respect to the measured values of the one or more cancer markers of the subject from the input unit, a correlation with the discrimination information in the database” and “an evaluation unit that is configured to evaluate cancer in the subject on a basis of an analysis result obtained by the analysis unit” in claim 16 invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
The specification as published indicates that the analysis unit and the evaluation unit are configured to perform the recited functions at [0041-0042; 0132-0135; 0137-0139]. However, the claim required “an analysis unit that is configured to analyze…” and “an evaluation unit that is configured to evaluate…”, and thus is programmed to perform the claimed function. This requires the disclosure of specific programming to carry out said function and in computer-related inventions said operation requires disclosure of the algorithm with which to perform said function. The limitation is indefinite as to the structure that performs said function. Without the algorithm disclosed, it is unclear as to the exact structure that performs said function (see Finisar Corp. v. DirecTV Group Inc., 86 USPQ2d 1609, 1623 (Fed. Cir. 2008); Halliburton Energy Services v. M-I LLC 514 F.3d 1244, 1256 n.7 (Fed. Cir. 2008)). This requires that the specification must disclose the specific way to perform the function and not what a skilled artisan would glean from the description, i.e. exemplary ways. Without the disclosed algorithm, the claim is unclear because there are no clear and definite boundaries to inform the public of the claim scope.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, the claims are directed to a method in claim 1 and systems claims 16-17, i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03].
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
The claims also recite a law of nature or a natural phenomenon. The MPEP at 2106.04(b) further explains that laws of nature and natural phenomena include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature.
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) as well as a law of nature or a natural phenomenon are as follows:
Independent claim 1: preparing a database that has stored a marker panel on which information of multiple cancer markers with respect to multiple healthy subjects and cancer patients is registered, the database comprising discrimination information that classifies a measured value of each cancer marker, with a mean value of the healthy subjects ± X x standard deviation (wherein X is an arbitrary numerical value) and/or the mean value of the healthy subjects ± the standard deviation as a reference range, into any of three groups: within the reference range, higher than the reference range, and lower than the reference range;
analyzing, with respect to measured values of one or more cancer markers of a subject, a correlation with the discrimination information in the database; and
evaluating cancer in the subject on a basis of a result of the analyzing.
Dependent claim 2: wherein a marker panel of the subject is created on a basis of the measured values of the cancer markers of the subject.
Dependent claims 9 and 18: with respect to the measured values of the one or more cancer markers of the subject, calculating differences from a pattern of the discrimination information of the cancer patients and a pattern of the discrimination information of the healthy subjects in the database; and
analyzing which of the patterns of the cancer patients and the healthy subjects the measured values of the subject are close to.
Independent claim 16: …analyze, with respect to the measured values of the one or more cancer markers of the subject from the input unit, a correlation with the discrimination information in the database; and
… evaluate cancer in the subject on a basis of an analysis result obtained by the analysis unit.
Dependent claims 3-8 and 10-15 recite further steps that limit the judicial exceptions in independent claim 1 and, as such, also are directed to those abstract ideas. For example, claims 3-4 further limit the display or showing of the marker panel; claim 5 further limits the reference range; claim 6 further limits the cancer markers in the database; claims 7-8 further limit analyzing the correlation to being based on a formula; claim 10 further limits calculating differences to being performed with a formula; claim 11 further limits the database which is prepared in claim 1 to comprising information of multiple cancer markers with respect to a specific stage or degree of severity; claim 12 further number of cancer markers in the prepared database; claim 13 further limits the cancers markers in the prepared database to urinary metabolites obtained by LC/MS; claim 14 further limits the prepared database to comprising different databased according to types of cancer; and claim 15 further limits evaluating cancer.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind and/or by mathematical operation because the method only requires a user to manually evaluate cancer in a subject based on a comparison of the cancer markers of the subject information about cancer markers in multiple healthy subjects and cancer patients. Without further detail as to the methodology involved in “preparing” a database, “analyzing” a correlation”, “evaluating” cancer, and “creating” a marker panel, under the BRI, one may simply, for example, use pen and paper to prepare a database comprising a marker panel of cancer markers from healthy subjects and cancer patients, include in the database discrimination information which is the mean and standard deviation of those markers, analyze a correlation between the cancer markers of a subject and the discrimination information in the database, evaluate cancer in the subject based on the correlation analysis (as in claims 1 and 16), and create a marker panel in the subject as in claim 2. Some of these steps and those recited in the dependent claims require mathematical techniques as the only supported embodiments, as is disclosed in the specification at: preparing a database to include a mean value and the standard deviation of the cancer markers, where preparing a database to include those values also embodies calculating the mean and standard deviation, which are inherently mathematical processes; analyzing a correlation is considered to inherently recite a comparison between the numerical discrimination information and the numerical values of the cancer markers of a subject, and is explicitly limited to a mathematical formula in claims 7-8; and claims 9-10 further include calculating differences in patterns of the discrimination information based on a mathematical formula; see the specification as published generally at [0013-0043].
The claims also recite the natural relationship between measured values of cancer markers and the state of cancer in the subject.
Therefore, claims 1 and 16 and those claims dependent therefrom recite an abstract idea and a law of nature/natural phenomenon [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Independent claim 16: a storage unit comprising a database that has stored a marker panel on which information of multiple cancer markers with respect to multiple healthy subjects and cancer patients is registered, the database comprising discrimination information that classifies a measured value of each cancer marker, with a mean value of the healthy subjects ± X x standard deviation (wherein X is an arbitrary numerical value) and/or the mean value of the healthy subjects ± the standard deviation as a reference range, into any of three groups: within the reference range, higher than the reference range, and lower than the reference range;
an input unit that is configured to receive inputs of measured values of one or more cancer markers of a subject;
an analysis unit…; and
an evaluation unit….
The claims also include non-abstract computing elements. For example, claims 16-17 include a system.
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to data gathering, such as “storing” a database and “receiving” data, perform functions of collecting the data needed to carry out the judicial exceptions. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
Further steps directed to additional non-abstract elements of the computer system and various units do not describe any specific computational steps by which the “computer parts” perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, and therefore the claim does not integrate that judicial exceptions into a practical application. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc.… are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (MPEP 2106.05(f)). Further, the computer system contains the recited units (i.e., software) that are used for storing and receiving data (which is a data gathering element that does not integrate the judicial exceptions) and for performing the judicial exception (which does not integrate the judicial exceptions because the operations are generically recited and/or include nothing but mathematical operations). Thus, the limitations only generically link the use of the judicial exceptions to the technological environment of a computer.
The specification discloses that the method and system of the invention are excellent in sensitivity and specificity, and therefore reduces false positives and false negatives and helps in precise diagnosis, and that the present invention may be useful in the fields of cancer diagnosis, examination, treatment evaluation, and the like at [0044], but does not provide a clear explanation for how the additional elements provide these improvements. Therefore, the additional elements do not clearly improve the functioning of a computer, or comprise an improvement to any other technical field. Further, the additional elements do not clearly affect a particular treatment; they do not clearly require or set forth a particular machine; they do not clearly effect a transformation of matter; nor do they clearly provide a nonconventional or unconventional step (MPEP2106.04(d)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, the courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(II)(i)). As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
With respect to claims 16-17, the computer-related elements or the general purpose computer do not rise to the level of significantly more than the judicial exception. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (Alice Corp., 573 U.S. at 225-26, 110 USPQ2d at 1984; see MPEP 2106.05(A)). Further, the specification provides no description of a specialized computer system for performing the method. The additional elements are set forth at such a high level of generality that they can be met by a general purpose computer. Therefore, the computer components constitute no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the judicial exceptions (see MPEP 2106.05(b)I-III).
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, the instant claims are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
A. Claims 1-4, 6-7, 9, 11-12, and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Bagaev et al. (US 2018/0358118; newly cited) in view of Bevilacqua et al. (Clinical Chemistry, 60(12):1532-1542; newly cited).
Claim 1 discloses a method. Claim 16 discloses a system comprising a storage unit, an input unit that is configured to receive inputs of measured values of one or more cancer markers of a subject, an analysis unit, and an evaluation unit. Claim 17 discloses a system configured to implement the method according to claim 1.
Bagaev discloses techniques for determining therapy scores, using sequencing data for the subject and information indicating distribution of biomarker values across one or more reference populations, sets of normalized biomarker scores for sets of biomarkers associated with sets of therapies (abstract). Bagaev discloses systems and methods, where the system comprises at least one computer hardware processor; at least one database that stores biomarker information; and at least one non-transitory computer-readable storage medium storing processor-executable instructions that, when executed by the at least one computer hardware processor, cause the at least one computer hardware processor to perform the method [0017-0018; 0182]. Bagaev teaches a system comprising a database which stores biomarker information (i.e., a storage unit as in claim 16) [0018]. Bagaev teaches a system with instructions for obtaining sequencing data about at least one biological sample of a subject (i.e., an input unit that is configured to receive inputs of measured values of one or more cancer markers of a subject as in claim 16) (claim 1) The instructions taught by Bagaev are considered to read on the analysis unit and evaluation unit in claim 16, because those units are considered to merely recite instructions for performing the method steps.
The method of claim 1 and the database stored in claim 16 and the steps performed by the units of claim 16 comprise:
preparing (in claim 1 only) a database that has stored a marker panel on which information of multiple cancer markers with respect to multiple healthy subjects and cancer patients is registered, the database comprising discrimination information that classifies a measured value of each cancer marker, with a mean value of the healthy subjects ± X x standard deviation (wherein X is an arbitrary numerical value) and/or the mean value of the healthy subjects ± the standard deviation as a reference range, into any of three groups: within the reference range, higher than the reference range, and lower than the reference range;
Bagaev teaches a database that stores biomarker information indicating a distribution of values for each biomarker (i.e., a marker panel), across a respective group of people, in at least a reference subset of the plurality of biomarkers (claim 1). Bagaev teaches determining positive and negative biomarkers from multiple datasets (i.e., preparing a database) [0279-0281]. Bagaev teaches a method for normalizing the values of biomarkers relative to their variation in reference populations (i.e., discrimination information) to place them on a common scale [0064; 0098-0107; 0185; 0285]. Bagaev teaches that the biological sample may be any sample from a subject known or suspected of having cancerous cells or pre-cancerous cells [0109]. Bagaev teaches comparing the expression level of a biomarker in a sample obtained from a subject to a reference (or control) to determine whether the subject has an altered expression level (e.g., increased or decreased) as compared to the reference (or control) [0090]. Bagaev teaches normalizing biomarker values in terms of “high,” (i.e., higher than the reference range) “medium” (i.e., within the reference range), and “low,” (i.e., lower than the reference range) where mathematically high values correspond to 1 and mathematically low values correspond to −1 ([0283]; FIG. 3), where a zero value of the parameter fell in the middle of the distribution, and the highest values were assigned to parameters at the extreme upper end of the distribution [0287] with threshold values to determine high and low parameter values [0289]. Bagaev teaches calculating the mean and standard deviation from the distribution of parameter values for the large patient cohort to which the patient belonged (i.e., the mean value of the reference subjects ± the standard deviation as a reference range) [0286].
See below for teachings by Bevilacqua regarding information of multiple cancer markers with respect to healthy subjects.
analyzing, with respect to measured values of one or more cancer markers of a subject (from the input unit – claim 16 only), a correlation with the discrimination information in the database; and
Bagaev teaches determining biomarkers which are statistically significantly correlated with treatment response or survival [0074; 0281]. Bagaev teaches determining normalized biomarker scores for a subject using a reference subset of biomarkers (i.e., analyzing a correlation) [0186; 0294].
evaluating cancer in the subject on a basis of a result of the analyzing (obtained by the analysis unit – claim 16 only).
Bagaev teaches determining a therapy score for a patient for a particular therapy using multiple normalized biomarkers by calculating a sum, a weighted sum, or by using a linear model or statistical model by taking the normalized biomarker scores for the patient as input and producing an output indicative of a patient’s predicted response (i.e., evaluating cancer) ([0141; 0187; 0295-0299]; FIG. 4) . Bagaev teaches using normalized biomarker scores derived from a patient for various clinical purposes, including identifying subjects suitable for a particular treatment or for predicting therapy efficacy or adverse reactions [0140].
While Bagaev teaches teach a database that has stored a marker panel on which information of multiple cancer markers with respect to cancer patients is registered and a reference range based on a mean value of the reference subjects, Bagaev does not teach a database that has stored a marker panel on which information of multiple cancer markers with respect to multiple healthy subjects and cancer patients is registered or a reference range based on a mean value of the healthy subjects.
However, the prior art to Bevilacqua discloses a pediatric database of covariate-stratified reference value distributions for 11 key circulating tumor markers used to assess cancer (abstract background). Bevilacqua teaches analyzing serum levels of the tumor markers in healthy children to establish reference intervals (abstract methods; p. 1534, col. 2, par. 1 through p. 1535, col. 1; Fig. 1)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, Bagaev and Bevilacqua because both references disclose methods for determining reference intervals for cancer markers. The motivation to include the data from the healthy subjects in the database would have been to use those data to determine reference intervals of biomarkers for the subsequent diagnosis of cancer, prediction of cancer patient outcomes, and treatment monitoring, as taught by Bevilacqua (abstract background; p. 1532, col. 2, par. 1-2; p. 1533, col. 1, par. 2; p. 1541, col. 2, par. 1). Therefore, it would have been obvious to one of skill in the art to include healthy samples as taught by Bevilacqua in the reference database and method of Bagaev to assess an individual for cancer in comparison to a reference range of healthy samples.
Regarding claim 2, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 2 further adds that a marker panel of the subject is created on a basis of the measured values of the cancer markers of the subject.
Bagaev teaches obtaining and analyzing biomarker panels from published datasets, which included measured values of the biomarkers (Table 2), for therapy responses in subject based on the biomarker values of the subject (i.e., a marker panel of the subject) (abstract).
Regarding claim 3, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 3 further adds that in the marker panel, columns of the cancer markers are displayed to be visually distinguishable according to three groups of the discrimination information.
Bagaev teaches shading normalized biomarker values in a gradient from -1 to 1 for high positive, medium, and high negative biomarker values or high, low, and neutral (i.e., three groups of discrimination information) [0219; 0222]. Bagaev teaches displaying the normalized biomarkers for patients, where each biomarker for each patient is shaded based on whether the biomarker was normalized to be high or low (lighter crosshatching or dark solid shading) or neutral (white) (i.e., displayed to be visually distinguishable) (FIG. 4; 6A-C).
Regarding claim 4, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 4 further adds that in the marker panel, the cancer markers are shown in order of importance calculated by machine learning.
Bagaev teaches that a therapy score is calculated using one or more normalized biomarker values which may be weighted by one or more respective weights as part of the calculation, where the weights may be determined, for example, using a machine learning technique [0143]. Bagaev teaches a graphical representation of biomarker importance in terms of feature importance calculated with forest regression algorithms ([0053]; FIG. 8C).
Regarding claim 6, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 6 further adds that in accordance with three groups of the discrimination information, the measured values of the cancer markers are assigned a column value of 0 if it is within the reference range, a column value of + 1 if it is higher than the reference range, or a column value of -1 if it is lower than the reference range.
Bagaev teaches normalizing biomarker values in terms of “high,” (i.e., higher than the reference range) “medium” (i.e., within the reference range), and “low,” (i.e., lower than the reference range) where mathematically high values correspond to 1 and mathematically low values correspond to −1 ([0283]; FIG. 3), where a zero value of the parameter fell in the middle of the distribution, and the highest values were assigned to parameters at the extreme upper end of the distribution [0287]. As Bagaev teaches displaying the data in tables shaded by the low, medium, and high values (see at least FIG. 4), it is considered that Bagaev fairly teaches assigning these values as column values as instantly claimed.
Regarding claim 7, Bagaev in view of Bevilacqua teaches claims 1 and 6 as described above. Claim 7 further adds that the analyzing the correlation with the discrimination information is performed on a basis of a value of an evaluation function represented by Formula I:
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, wherein, gn denotes a relative value of importance calculated by machine learning, and a sign of gn is + if a measured value of a cancer marker of the subject has a same column value as that of the cancer patients and - if the measured value has a different column value; and Dn denotes a column value of + 1, 0, or – 1.
Bagaev teaches that therapy scores are calculated as a weighted sum [0141], where biomarkers are multiplied by their weight (i.e., gn) and summed [0299]. Bagaev teaches normalizing biomarker values in terms of “high”, “medium”, and “low,” where mathematically high values correspond to 1 and mathematically low values correspond to −1 (i.e., Dn) ([0283]; FIG. 3), where a zero value of the parameter fell in the middle of the distribution, and the highest values were assigned to parameters at the extreme upper end of the distribution [0287]. Bagaev teaches that the weights may be determined, for example, using a machine learning technique [0143]. Although Bagaev does not explicitly teach Formula 1 as claimed, it is considered that the formula taught by Bagaev for summing weighted biomarkers is equivalent to Formula 1. For example: if the weight, or gn, is 2, a positive biomarker as evaluated by Bagaev would result in 2 x 1 = 2, and Formula 1 would result in positive 2 multiplied by the square root of 1 squared, which equals 2; if : if the weight, or gn, is 2, a neutral/medium biomarker as evaluated by Bagaev would result in 2 x 0 = 0, and Formula 1 would result in 2 multiplied by the square root of 0 squared, which equals 0; and if the weight, or gn, is 2, a negative biomarker as evaluated by Bagaev would result in 2 x -1 = -2, and Formula 1 would result in negative 2 multiplied by the square root of -1 squared, which equals -2. Therefore, Bagaev teaches an equivalent, alternative formula for calculating a weighted sum of biomarkers as that which is instantly claimed.
Regarding claim 9, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 9 further adds, with respect to the measured values of the one or more cancer markers of the subject, calculating differences from a pattern of the discrimination information of the cancer patients and a pattern of the discrimination information of the healthy subjects in the database; and analyzing which of the patterns of the cancer patients and the healthy subjects the measured values of the subject are close to.
Bagaev teaches calculating a therapy score using a sum of normalized biomarker values, where different the numbers of positive and negative biomarkers of the patients (i.e., a pattern of the discrimination information) were compared to reference patients to determine which patients are more similar to each other ([0299]; FIG. 4).
Regarding claim 11, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 11 further adds that the database comprises a marker panel on which information of multiple cancer markers with respect to a cancer patient in a specific stage or with a specific degree of severity is registered.
Bagaev teaches that biomarkers used in the method can be disease-state biomarkers that are indicative of metastasis status (e.g., absence or presence of metastasis), remission status (e.g., number of previous remissions, current remission), disease progression (e.g., low, moderate, or high disease progression) (i.e., severity), and cancer stage (e.g., stage 1, stage 2, stage 3, or stage 4) [0093].
Regarding claim 12, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 12 further adds that the cancer markers comprise 3 or more, 5 or more, 10 or more, or 20 or more cancer markers.
Bagaev teaches a group or subset of biomarkers that may include at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 200, at least 300, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, or at least 1000 biomarkers [0078]. As Bagaev teaches a range of at least 3 to at least 20 or more biomarkers, it is considered that this range anticipates the instantly claimed range of 3 or more, 5 or more, 10 or more, or 20 or more cancer markers.
Regarding claim 14, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 14 further adds that the database comprises different databases according to types of cancers.
Bagaev teaches that biomarkers may be associated with multiple cancers [0080]. Bagaev also teaches that biomarker information may be obtained from one or more databases and/or any other suitable electronic repository of data including databases regarding large scale cancer studies [0125].
Regarding claim 15, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 15 further adds that the evaluating cancer comprises determination of cancer in the subject, prediction of a risk of cancer in the subject, determination of a stage or severity of cancer in the subject, prognostication of cancer in the subject, monitoring of cancer in the subject, monitoring of efficacy in the treatment of cancer present in the subject, or aid in diagnosis of cancer.
Bagaev at least teaches techniques for predicting the efficacy of therapies for a subject [0064].
Regarding claim 18, Bagaev in view of Bevilacqua teaches claims 1 and 6-7 as described above. Claim 18 further adds, with respect to the measured values of the one or more cancer markers of the subject, calculating differences from a pattern of the discrimination information of the cancer patients and a pattern of the discrimination information of the healthy subjects in the database; and analyzing which of the patterns of the cancer patients and the healthy subjects the measured values of the subject are close to.
Bagaev teaches calculating a therapy score using a sum of normalized biomarker values, where different the numbers of positive and negative biomarkers of the patients (i.e., a pattern of the discrimination information) were compared to reference patients to determine which patients are more similar to each other ([0299]; FIG. 4).
B. Claims 5 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Bagaev in view of Bevilacqua, as applied to claims 1 as above, and in further view of Abe et al. (Respiratory Investigation, 2016, 54:148-155; newly cited).
Regarding claim 5, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 5 further adds that in the database, the reference range comprises a reference range of the mean value of the healthy subjects ± X x the standard deviation (wherein X is 2) and a reference range of the mean value of the healthy subjects ± the standard deviation, and a measured value of each cancer marker has different discrimination information for the two reference ranges.
Bagaev teaches calculating the mean and standard deviation from the distribution of parameter values for the large patient cohort to which the patient belonged (i.e., the mean value of the reference subjects ± the standard deviation as a reference range) [0286], but does not teach that the reference range comprises a second reference range of the mean value of the healthy subjects ± X x the standard deviation (wherein X is 2) with different discrimination information.
However, the prior art to Abe discloses an establishment of reference values for respiration biomarkers (abstract). Abe teaches calculating values representing both one and two standard deviations from the mean (abstract; p. 150, col. 2, par. 3; Tables 4-5). Table 4 shows that the 1SD and 2SD values indicate different values (i.e., different discrimination information).
Regarding claim 8, Bagaev in view of Bevilacqua teaches claims 1 and 6-7 as described above. Claim 8 further adds that the analyzing the correlation with the discrimination information is performed by calculating an evaluation function on a basis of the discrimination information with the mean value of the healthy subjects ± X x the standard deviation (wherein X is 2) as the reference range, and then calculating an evaluation function on a basis of the discrimination information with the mean value of the healthy subjects ± the standard deviation as the reference range.
Bagaev teaches calculating the mean and standard deviation from the distribution of parameter values for the large patient cohort to which the patient belonged (i.e., the mean value of the reference subjects ± the standard deviation as a reference range) [0286], but does not teach first calculating an evaluation function on a basis of the discrimination information with the mean value of the healthy subjects ± X x the standard deviation (wherein X is 2) as the reference range.
However, Abe teaches calculating values representing both one and two standard deviations from the mean (abstract; p. 150, col. 2, par. 3; Tables 4-5). Table 4 shows that the 1SD and 2SD values indicate different values (i.e., different discrimination information).
Regarding claims 5 and 8, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, Bagaev in view of Bevilacqua and Abe because each reference discloses methods for analyzing statistical distributions of biomarker reference values. The motivation to calculate the mean ± the standard deviation and the 2 x the standard deviation would have been to use both values to evaluate the statistical normal ranges of transformed data, as taught by Abe (p. 150, col. 2, par. 2). Therefore, it would have been obvious to one of ordinary skill in the art to calculate known values, as taught by Abe, and to use both of those values to evaluate the biomarkers of a subject because such a modification would have yielded no more than the predictable outcome of evaluating cancer based on biomarkers using two different threshold values.
C. Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Bagaev in view of Bevilacqua, as applied to claims 1 and 9 as above, and in further view of Greenacre et al. (Journal of Classification, 2016, 33:442-459; newly cited).
Regarding claim 10, Bagaev in view of Bevilacqua teaches claims 1 and 9 as described above. Claim 10 further adds that calculating the differences from the patterns is performed with a distance function represented by Formula II:
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, wherein, gn denotes a relative value of importance calculated by machine learning; Dn denotes a row vector represented by a column value of + 1, 0, or - 1 with respect to each cancer marker of the cancer patients or the healthy subjects in the database; and Tn denotes a row vector represented by a column value of + 1, 0, or - 1 with respect to each cancer marker in the subject.
Bagaev does not teach this Formula II.
However, the prior art to Greenacre discloses a weighted Euclidean distance that approximates any distance or dissimilarity measure between individuals that is based on a rectangular cases-by-variables data matrix (abstract). Greenacre teaches an equation
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, where Dw is a diagonal matrix of squared weights w2 k, k =1,2,...,m, for the m variables, xi and xj are vectors denoting the i-th and j-th rows of X and Ds is the diagonal matrix of standard deviations sk, k =1,2,...,m. (p. 444, par. 3-4). As “d” in equation 2 is squared, taking the square root of “
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” results in an equivalent equation to Formula II in the instant claims.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, Bagaev in view of Bevilacqua and Greenacre because Bagaev and Greenacre both teach methods for determining the similarity between data. The motivation to use the method of Greenacre to determine the similarity between vectors of normalized biomarker values as taught by Bagaev in view of Bevilacqua would have been to use an approach which leads to biplots of individuals and variables while preserving all the good properties of dimension-reduction methods that are based on the singular-value decomposition and to balance out the contributions of variables to the distances between cases, as taught by Greenacre (abstract; p. 444, par. 4).
D. Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Bagaev in view of Bevilacqua, as applied to claim 1 as above, and in further view of Sakairi et al. (Bull. Chem. Soc. Jpn. 2018, 91:1351-1356; newly cited).
Regarding claim 13, Bagaev in view of Bevilacqua teaches claim 1 as described above. Claim 13 further adds that the cancer markers are urinary metabolites, and the marker panel on which the information of the cancer markers is registered is a metabolite list on which information of ion intensities of metabolites obtained by liquid chromatography mass spectrometry (LC/MS) is registered.
Bagaev teaches that the biological sample may be urine [0074; 0110]. Bagaev teaches that the biomarkers may be any biomolecule, including a metabolite [0081]. Bagaev does not teach a metabolite list on which information of ion intensities of metabolites obtained by liquid chromatography mass spectrometry (LC/MS) is registered.
However, Sakairi discloses a method using liquid chromatography/mass spectrometry (LC/MS) for analysis of urinary metabolites and identification of substances that show fluctuations in cancer patients compared with healthy individuals (i.e., cancer markers) (abstract). Sakairi teaches that the LC/MS data of the urinary metabolites includes ion intensities (p. 1352, col. 2, par. 1; p. 1353, col. 1, par 1 and 7; p. 1355, col. 1 through col. 1, par. 1; Figure 6).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, Bagaev in view of Bevilacqua and Sakairi because each reference discloses methods for analyzing biomarkers. The motivation to use LC/MS to analyze urinary metabolites as biomarkers would have been to examine markers which have been established for cancer testing, as taught by Sakairi (p. 1352, col. 1, par. 3).
Conclusion
No claims are allowed.
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/JANNA NICOLE SCHULTZHAUS/Examiner, Art Unit 1685
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