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 1-7 are pending.
Claims 1-7 are under examination.
Claims 1-7 are rejected.
Priority
Applicant's claim for the benefit of a prior-filed application, PCT/KR2022/012341, filed 08/18/2022, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 12/28/2022, 03/22/2024, and 12/18/2024 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action.
Drawings
The Drawings submitted 03/30/2023 are accepted.
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 following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
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.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
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: “a signal acquisition unit” in claims 1 and 4.
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.
The three-prong test: (A) “unit” is a substitute for “means” that is a generic placeholder; (B) unit is modified by the functional language “configured to”; (C) unit is modified by “signal acquisition”, which does not provide sufficient structure for performing the step of generating a trace for a biological sample. The specification does not disclose a trace generator. See below regarding issues under 112(a) and 112(b) arising from this claim interpretation.
The three-prong test: (A) “unit” is a substitute for “means” that is a generic placeholder; (B) unit is modified by the functional language “configured”; (C) segmenter is not modified and therefore does not provide sufficient structure for performing the steps to drop exosomes acquired from a measurement target person on a chip to acquire a plurality of the exosome surface enhanced Raman spectroscopy (SERS) signals from the chip. The specification discloses a signal acquisition unit at [39], but does not disclose adequate structure to perform the claimed function. The specification describes the method of acquiring the SERS but not the structure to perform it [49-52]. See below regarding issues under 112(a) and 112(b) arising from this claim interpretation.
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(s) 1-6 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the 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.
Claims 1 and 4 and those dependent therefrom is/are rejected because, as outlined above under 35 USC 112(f), the disclosure does not contain adequate structure for “a signal acquisition unit” to perform the claimed functions. The specification as published does not mention a signal acquisition unit coupled to a Raman spectroscopy device to generating to acquire a plurality of the exosome surface enhanced Raman spectroscopy (SERS) signals. Therefore, there is insufficient disclosure as to necessary structure, steps explained in prose, or any mathematical expression necessary to carry out the above recited function.
With respect to the above 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 1-7 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.
Claims 1 and those dependent therefrom (claims 2-6) limitation “a signal acquisition unit”, 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. (i) the disclosure is devoid of any structure that performs the function in the claim. Therefore, the claims are indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Claim 5 is indefinite because the terms “close to 0” and “close to 1” are each relative terms which render the claim indefinite. The above terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While paragraphs 12 and 79 of the specification use each term in the same context as recited in the claim, the disclosure does not provide sufficient information to determine what would constitute “close to 0” or “close to 1.” Claim(s) 6 is/are rejected for the same reason because they depend from claims 5, respectively, and do not resolve the indefiniteness issue in those claims.
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 1-7 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 process and method, 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).
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) are as follows:
Independent claim 1:
a cancer diagnosis unit configured to acquire signal values of 0 or 1 for each of the plurality of exosome SERS signals by inputting the plurality of acquired exosome SERS signals to a trained cancer classification algorithm
diagnose cancer or normality by using an average of the acquired signal values
a cancer information providing unit configured to acquire the signal values of 0 or 1 for each of the plurality of exosome SERS signals by inputting the plurality of exosome SERS signals to a plurality of tissue of origin (TOO) determination algorithms when diagnosed as the cancer
to predict a cancer type by using the average of the acquired signal values,
Dependent claim 2:
a first learning unit configured to input the plurality of labeled first exosome SERS signals and the plurality of labeled second exosome SERS signals to a cancer classification algorithm to train the cancer classification algorithm to classify each of the plurality of input first and second exosome SERS signals as 0 or 1.
Dependent claim 3:
a second learning unit configured to input the second exosome SERS signal acquired from a cancer patient having a preset cancer type among the plurality of cancer types and the second exosome SERS signals acquired from the other cancer patients excluding the cancer patient having the preset cancer type to the plurality of tissue of origin (TOO) determination algorithms to train each of the plurality of TOO determination algorithms to determine whether the second exosome SESR signals correspond to the preset cancer type.
Dependent claim 5:
classifies as normality when an average of the output signal values is close to 0 and classifies as cancer when the average of the output signal values is close to 1
Dependent claim 6:
the cancer information providing unit compares an average of the output signal values with a classification reference value for each cancer type to determine each cancer type.
Independent claim 7:
acquire signal values of 0 or 1 for each of the plurality of exosome SERS signals by inputting the plurality of acquired exosome SERS signals to a trained cancer classification algorithm and configured to diagnose cancer or normality by using an average of the acquired signal values
acquire the signal values of 0 or 1 for each of the plurality of exosome SERS signals by inputting the plurality of exosome SERS signals to a plurality of tissue of origin (TOO) determination algorithms when diagnosed as the cancer
Under the BRI, the instant claims recite judicial exceptions that are an abstract idea of the type is in the grouping of a “mathematical concept”, such as mathematical relationships and mathematical equations.
The claims recite mathematical concepts of trained cancer classification algorithm, using an average, tissue of origin (TOO) determination algorithms, cancer classification algorithm, classifies as normality when an average of the output signal values is close to 0 and classifies as cancer when the average of the output signal values is close to 1, and compares an average.
Therefore, claims 1 and 7 and those claims dependent therefrom recite an abstract idea [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 1:
a signal acquisition unit configured to drop exosomes acquired from a measurement target person on a chip to acquire a plurality of the exosome surface enhanced Raman spectroscopy (SERS) signals from the chip
provides information on the predicted cancer type.
Dependent claim 2:
acquire a plurality of first exosome SERS signals from exosomes acquired from a normal person, configured to acquire a plurality of second exosome SERS signals from exosomes acquired from cancer patients having a plurality of cancer types, configured to label the plurality of first exosomes SERS signals as 0, and configured to label the plurality of second exosome SERS signals as 1.
Independent claim 7:
dropping exosomes acquired from a measurement target person on a chip to acquire a plurality of exosome surface enhanced Raman spectroscopy (SERS) signals from the chip
providing information on the predicted cancer type.
Dependent claims 4 recite steps that further limit the recited additional elements in the claims. For example, claim 4 further limits signal acquisition unit of claim 1;
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 “acquire”, and to data outputting, such as “provide information”, 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)).
The steps directed to a signal acquisition unit configured to drop exosomes acquired from a measurement target person on a chip to acquire a plurality of the exosome surface enhanced Raman spectroscopy (SERS) signals from the chip perform functions of collecting the data needed to carry out the judicial exceptions. Mere data gathering such as performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989); are found to be insignificant extra-solution activity and do not integrate the judicial exception into a practical application (MPEP 2106.05(g)).
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 1 and 7 and those claims dependent therefrom, a signal acquisition unit configured to drop exosomes acquired from a measurement target person on a chip to acquire a plurality of the exosome surface enhanced Raman spectroscopy (SERS) signals from the chip do not rise to the level of significantly more than the judicial exception. The use of enhanced Raman spectroscopy (SERS) to acquire a plurality of the exosome surface enhanced Raman spectroscopy (SERS) signals is well-understood, routine, and conventional in the art. In a review by Yang et al. (Yang L, Jia J and Li S (2022) Advances in the Application of Exosomes Identification Using Surface-Enhanced Raman Spectroscopy for the Early Detection of Cancers. Front. Bioeng. Biotechnol, 2022, newly cited), surface-enhanced Raman Spectroscopy (SERS) uses light to interact with nanostructured materials such as gold and silver to produce a strong surface plasmon resonance effect, which can significantly enhance the Raman signal of molecules adsorbed on the surface of nanostructures to obtain a rich fingerprint of the sample itself or Raman probe molecules with ultra-sensitivity [abstract].
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 § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3 and 7 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Banaei et al (Banaei, Nariman, et al. "Machine learning algorithms enhance the specificity of cancer biomarker detection using SERS-based immunoassays in microfluidic chips." RSC advances 9.4 (2019): 1859-1868, newly cited).
Claim 1 is directed to a multi-cancer simultaneous diagnosis system which is based on artificial intelligence and uses exosome SERS signals, the multi-cancer simultaneous diagnosis system comprising:
Banaei discloses a SERS-based protein biomarker detection platform in a microfluidic chip and two machine learning algorithms (K-nearest neighbor and classification tree) are used to improve the reproducibility and specificity of the SERS-based liquid biopsy assay [abstract]. Banaei further discloses applying machine learning algorithms to the analysis of the expression level data of 5 protein biomarkers (CA19-9, HE4, MUC4, MMP7, and mesothelin) in pancreatic cancer patients, ovarian cancer patients, pancreatitis patients, and healthy individuals improves the chance of recognition for one specific disorder among the aforementioned diseases with overlapping protein biomarker changes [abstract].
a signal acquisition unit configured to drop exosomes acquired from a measurement target person on a chip to acquire a plurality of the exosome surface enhanced Raman spectroscopy (SERS) signals from the chip;
Banaei discloses collecting the SERS dataset and test sample by a microfluidic SERS-based immunoassay approach for the multiplex detection of CA19-9, HE4, mesothelin, MMP7 and MUC4 levels in serum samples [p. 1861, fig. 2]. Banaei further discloses a SERS-based protein biomarker detection platform in a microfluidic chip and two machine learning algorithms (K-nearest neighbor and classification tree) are used to improve the reproducibility and specificity of the SERS-based liquid biopsy assay [abstract].
a cancer diagnosis unit configured to acquire signal values of 0 or 1 for each of the plurality of exosome SERS signals by inputting the plurality of acquired exosome SERS signals to a trained cancer classification algorithm and configured to diagnose cancer or normality by using an average of the acquired signal values; and
Banaei discloses the sensitivity and specificity for each panel of patients using classification trees with 5-fold cross-validation with depth ¼ 2 for increasing number of biomarkers [p. 1865, table 2.]. Banaei further discloses a SERS-based protein biomarker detection platform in a microfluidic chip and two machine learning algorithms (K-nearest neighbor and classification tree) are used to improve the reproducibility and specificity of the SERS-based liquid biopsy assay [abstract]. Banaei also discloses the classification tree trained with whole dataset of peak-value Raman shifts with depth [p. 1865, fig. 6]. Banaei further discloses the average over the measurements for each biomarker is computed and used as the features of the input dataset [p. 1863, col. 2, par. 2].
a cancer information providing unit configured to acquire the signal values of 0 or 1 for each of the plurality of exosome SERS signals by inputting the plurality of exosome SERS signals to a plurality of tissue of origin (TOO) determination algorithms when diagnosed as the cancer, configured to predict a cancer type by using the average of the acquired signal values, and configured to provides information on the predicted cancer type.
Banaei discloses methods disclosing a multi-cancer simultaneous diagnosis system with determination of the tissue of origin from exosome SERS signals and outputting the cancer type [abstract, pg. 1865, fig. 6].
Claim 2 is directed to the multi-cancer simultaneous diagnosis system of claim 1, further comprising: a SERS signal collection unit configured to acquire a plurality of first exosome SERS signals from exosomes acquired from a normal person, configured to acquire a plurality of second exosome SERS signals from exosomes acquired from cancer patients having a plurality of cancer types, configured to label the plurality of first exosomes SERS signals as 0, and configured to label the plurality of second exosome SERS signals as 1; and a first learning unit configured to input the plurality of labeled first exosome SERS signals and the plurality of labeled second exosome SERS signals to a cancer classification algorithm to train the cancer classification algorithm to classify each of the plurality of input first and second exosome SERS signals as 0 or 1.
Banaei discloses the K-NN algorithm is a supervised learning method for classifying data points based on the proximity or similarity of them to the previously observed data [p. 1863, col. 2, par. 3]. Banaei further discloses the algorithm accepts a new patient's data and compares it with a training set of previously classified patients with various medical conditions [p. 1863, col. 2, par. 3]. Banaei also discloses the algorithm then utilizes the K-NN technique to classify patients as having or not having a specific condition [p. 1863, col. 2, par. 3].
Claim 3 is directed to the multi-cancer simultaneous diagnosis system of claim 2, further comprising: a second learning unit configured to input the second exosome SERS signal acquired from a cancer patient having a preset cancer type among the plurality of cancer types and the second exosome SERS signals acquired from the other cancer patients excluding the cancer patient having the preset cancer type to the plurality of tissue of origin (TOO) determination algorithms to train each of the plurality of TOO determination algorithms to determine whether the second exosome SESR signals correspond to the preset cancer type.
Banaei discloses the next step in the algorithms follows by sorting this list of distances and choosing the k shortest distances from the list [p. 1864, col. 2, par. 1]. Banaei further discloses these k instances correspond to k pre-classified samples in the training set [p. 1864, col. 2, par. 1]. Banaei also discloses the final stage of the algorithm is performed by taking a majority vote over the classes corresponding to these k samples and determining the diagnosis for the unknown test sample [p. 1864, col. 2, par. 1]. Banaei further discloses the classification between 3 cancers [p. 1865, fig. 6].
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. Claim(s) 4-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Banaei in view of Shin et al (Shin, Hyunku, Dongkwon Seo, and Yeonho Choi. "Extracellular vesicle identification using label-free surface-enhanced raman spectroscopy: detection and signal analysis strategies." Molecules 25.21 (2020), newly cited).
Claim 4 is directed to the multi-cancer simultaneous diagnosis system of claim 1, wherein the signal acquisition unit acquires an exosome SERS signal map including n*m exosome SERS signals from the chip including n*m (where n and m are identical or different natural numbers) dot arrays.
Banaei discloses collecting the SERS dataset and test sample by a microfluidic SERS-based immunoassay approach for the multiplex detection of CA19-9, HE4, mesothelin, MMP7 and MUC4 levels in serum samples [p. 1861, fig. 2]. Banaei further discloses a SERS-based protein biomarker detection platform in a microfluidic chip and two machine learning algorithms (K-nearest neighbor and classification tree) are used to improve the reproducibility and specificity of the SERS-based liquid biopsy assay [abstract] but is silent on SERS signal map including n*m exosome SERS signals from the chip including n*m (where n and m are identical or different natural numbers) dot arrays.
However, Shin discloses extracellular vesicle identification using label-free surface-enhanced Raman spectroscopy: detection and signal analysis strategies [title]. Shin further discloses mapping result using SERS peak of EVs [p. 6, fig. 4].
Claim 5 is directed to the multi-cancer simultaneous diagnosis system of claim 4, wherein the cancer diagnosis unit inputs the n*m exosome SERS signals to the cancer classification algorithm and outputs signal values of 0 or 1 respectively corresponding to the n*m exosome SERS signals, and classifies as normality when an average of the output signal values is close to 0 and classifies as cancer when the average of the output signal values is close to 1.
Banaei discloses the K-NN algorithm is a supervised learning method for classifying data points based on the proximity or similarity of them to the previously observed data [p. 1863, col. 2, par. 3]. Banaei further discloses the algorithm accepts a new patient's data and compares it with a training set of previously classified patients with various medical conditions [p. 1863, col. 2, par. 3]. Banaei also discloses the algorithm then utilizes the K-NN technique to classify patients as having or not having a specific condition [p. 1863, col. 2, par. 3], but is silent on the average.
However, Shin discloses it was possible to form clusters expected to contain TRPP2, a specific biomarker of the HN2 cell line, and a clear difference was observed between the averages of the signals from different clusters [p. 14, par. 1]. Shin further discloses by applying the multiple instance learning (MIL) concepts, an individual spectrum was collectively labeled with 0 for the control group and 1 for the patient group (Fig. 3a), then the average of predicted output derived from an individual sample was used as a single numerical value for diagnostic criteria [p. 3, col. 2, par. 2].
Claim 6 is directed to the multi-cancer simultaneous diagnosis system of claim 5, wherein the cancer information providing unit inputs the n*m exosome SERS signals to the plurality of TOO determination algorithms, and the plurality of TOO determination algorithms output signal values of 0 or 1 for each of the input n*m exosome SERS signals, and the cancer information providing unit compares an average of the output signal values with a classification reference value for each cancer type to determine each cancer type.
Banaei discloses the next step in the algorithms follows by sorting this list of distances and choosing the k shortest distances from the list [p. 1864, col. 2, par. 1]. Banaei further discloses these k instances correspond to k pre-classified samples in the training set [p. 1864, col. 2, par. 1]. Banaei also discloses the final stage of the algorithm is performed by taking a majority vote over the classes corresponding to these k samples and determining the diagnosis for the unknown test sample [p. 1864, col. 2, par. 1]. Banaei further discloses the classification between 3 cancers [p. 1865, fig. 6], but is silent on plurality of TOO determination algorithms.
However, Shin discloses a single process directed to lung cancer [title]. It would be obvious to perform an ensemble of those methods and algorithms with known cancer types in the same manner.
In regards to claim(s) 4-6, 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 Banaei with Shin as they both discloses cancer diagnosis by deep learning-based spectroscopic analysis of circulating exosomes using SERS. The motivation would have been to include an extension to a plurality of cancer types would be straightforwardly conducted by a skilled artisan, seeking to determine tissue of origin of a diagnosed cancer. One could have therefore combined the elements as claimed by the known methods of Banaei and Shin, and that in combination, each element merely would have performed the same function as it did separately for a predictable result.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Shin et al, Extracellular Vesicle Identification Using Label-Free Surface-Enhanced Raman Spectroscopy: Detection and Signal Analysis Strategies;
Shin et al, Correlation between Cancerous Exosomes and Protein Markers Based on Surface-Enhanced Raman Spectroscopy (SERS) and Principal Component Analysis (PCA);
Hassantabar et al (US Patent Application Publication 2025/0078998);
Choi et al (US Patent Application Publication 2021/0247382);
Lee et al (US Patent Application Publication 2020/0080151).
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/D.M.B./Examiner, Art Unit 1685
/Soren Harward/Primary Examiner, TC 1600
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