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 .
Status of the Claims
Claims 1-10 are pending and examined herein.
No claims are canceled.
Priority
As detailed on the 17 February 2023 filing receipt, the application claims priority as early as 02 February 2022 to Italian patent 102022000001817. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Information Disclosure Statement
Information disclosure statements (IDS) were filed on 11 January 2023 and 30 November 2023 and date. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the references are being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: the term “disease” is misspelled as “desease” (title; pg. 1, line 10; pg. 3, lines 25, 26, 30, and 33; and pg. 14, line 9).
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (pg. 8, line 21). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: the steps included under “generating a training dataset” including the determining of respective feature sets and indices should be further indented to clarify their relationship compared to the other steps (MPEP 608.01(i)).
Appropriate correction is required.
Claim Interpretation Under 35 USC § 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: the device of claim 9.
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 specification discloses a corresponding device and a computer for executing instructions and a processing system (pg. 3, second paragraph; pg. 8, second and third paragraphs). Therefore, the device is interpreted as a general purpose computer.
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(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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation “the respective mapping rules.” There is insufficient antecedent basis for this limitation in the claim. Mapping rules are not previously instantiated in the claim. Therefore, the term is unclear. The specification discloses mapping rules in relation to an RPCA (pg. 10, lines 24-28) but it remains unclear what these rules are. Claims 2-8 are rejected on similar grounds as claim 1 for not remedying this lack of clarity. Claims 9-10 are machine-manufacture claims that recite the limitations of claim 1 and so are also rejected as claim 1.
35 USC § 101
Matter Belonging to No Statutory Category
Claim 10 is rejected under 35 USC 101 because the claimed invention is directed to non-statutory subject matter.
Claim 10 is to "a computer-program product," which is not, in all embodiments within a broadest reasonable interpretation, interpreted as belonging to any category listed in 101. In a broadest reasonable interpretation, the claim reads on data and/or software comprising no structure other than data and/or software. The claim is not recited as a process, and the claim is not limited to any particular structure as a 101 machine or manufacture. The claim reads on transitory propagating signals which are not proper patentable subject matter because it does not fit within any of the four statutory categories of invention (In re Nuijten, Federal. Circuit, 2006).
In a broadest reasonable interpretation, the recited program product can be loaded into memory to be run on a computer and a computer as means for executing instructions (pg. 3, second paragraph). The specification does not limit the program product to non-transitory embodiments.
A claim drawn to a computer readable medium that covers both transitory and non-transitory embodiments may be amended to narrow the claim to cover only statutory embodiments to avoid a rejection under 35 USC § 101 by adding the limitation "non-transitory" to the claim. Cf Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (suggesting that applicants add the limitation "non-human" to a claim covering a multicellular organism to avoid a rejection under 35 USC § 101). Such an amendment would typically not raise the issue of new matter, even when the specification is silent because the broadest reasonable interpretation relies on the ordinary and customary meaning that includes signals per se.
Therefore, this rejection can be overcome by, for example, amending to "a non-transitory computer-program product." For compact examination, it is assumed that such an amendment or equivalent will be entered.
Patent Eligibility
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 1-10 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements individually and in combination, are directed to a judicial exception at Step 2A, Prong 2, and the additional elements of the claims, considered individually and in combination, do not provide significantly more at Step 2B than the abstract idea of disease prognosis.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
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 (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to a method (claims 1-8) and a computer system (claim 9), each of which falls within one of the categories of statutory subject matter. The computer-program product (claim 10) is not instantly recited as non-transitory and thus does not fall within a statutory category. [Step 1: Claims 1-9: Yes; Claim 10: No]
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 (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in independent claims 1 and 9-10 include generating preprocessed data by principal components analysis; determining a distance measure between references; determining a longer disease-free survival time, which may be interpreted as a numerical evaluation; training a classifier, which is interpreted as being a mathematical concept given a broadest reasonable interpretation in light of the specification, which discloses mathematical concepts such as k-nearest neighbor, Gaussian, and regression methods (pg. 4, third paragraph); generating pre-processed data for the patient based on said rules; generating a verification dataset, which is based on calculated distance measures and thus mathematical differences; estimating an index, where estimating an index is recited as based on using the classifier; calculating probabilities; and estimating disease-free survival time based on a position, which is considered to be data interpretation and evaluation; and estimating disease-free survival time based on a position, which is based on determination of a numerical value.
Mental processes, defined as concepts practically performed in the human mind such as steps of observing, evaluating, or judging information, recited in the independent claims include generating data pairs; determining the longer disease-free survival time, which may be interpreted as data evaluation; generating pre-processed data for the patient based on said rules; generating a verification dataset; generating a sorted list of estimated indices, where generating a list sorted by a value is a step practically performed mentally; selecting the position for a parameter with the highest probability; and estimating disease-free survival time based on a position, which is considered to be data interpretation and evaluation.
Claim 2 recites setting an index, where setting an index is considered to be a mental step of data selection.
Claim 3 recites generating indices by selection, where selection is a mental step, and obtaining a patter and calculating a parameter based on a similarity or distance metric, which are verbal descriptions of mathematical concepts.
Claim 4 recites sorting data, where sorting is a step practically performed by the human mind.
Claim 5 recites normalizing and/or scaling data by a non-linear function, which is a verbal description of a mathematical concept.
Claim 7 recites selecting data by a feature selection method such as LASSO and training a classifier to estimate an index based on the subset. LASSO is a mathematical concept.
Claim 8 recites classifiers include k-nearest neighbor, decision trees, random forest, discriminant analyses, and Gaussian classifiers, which are mathematical concepts.
Thus, the claims do not recite elements in addition to the abstract ideas which integrate the judicial exception into a practical application and so the claims are interpreted as directed to one or more judicial exceptions. [Step 2A Prong One: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Because the claims 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)).
Claim 1 recites receiving a dataset of reference patients and receiving omics data of a patient, and storing those data. Claim 6 recites the received omics data is transcriptomic data obtained by next generation sequencing. Claim 9 recites a device, interpreted as a general purpose computer. Claim 10 recites a computer-program product, which will be assumed to be amended to be non-transitory, in memory and executed by a processor.
Receiving data on which the abstract steps are subsequently performed is considered to be data gathering. Data gathering is considered to be insignificant extra-solution activity, which does not integrate the abstract ideas into a practical application (MPEP 2106.05(g)).
The recited general purpose computer and components such as a memory and a processor are interpreted as instructions to apply the judicial exceptions using a computer. Mere instructions to implement an abstract idea on a computer does not integrate the abstract ideas into a practical application (MPEP 2106.05(f)). [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself. Step 2B of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
The claims recite receiving a dataset of reference patients and receiving omics data of a patient (claim 1); the received omics data is transcriptomic data obtained by next generation sequencing (claim 6); a device, interpreted as a general purpose computer (claim 9); and a computer-program product, which will be assumed to be amended to be non-transitory, in memory and executed by a processor (claim 10).
Receiving or obtaining data does not amount to an inventive concept (MPEP 2106.05(g)). The claims recite a computer, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions, which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)). Storing data on a computer is a conventional computer function (Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93; MPEP 2106.05(d)).
Specifically receiving transcriptomic data for analysis for differential gene expression related to treatment is taught at least by: Bouquet (mBio 7(1): 11 pgs., 2016; newly cited) as differential gene expression in patients after treatment for Acute Lyme Disease (abstract); Rajan (BMC Cancer 14(977): 10 pgs., 2014; newly cited) as differential expression following chemotherapy (Abstract: Results); and Mello-Grand (Breast Cancer Research and Treatment 121: 399-411, 2010; newly cited) as differential expression related to treatment (pg. 400, col. 1, last paragraph; pg. 401, col. 1, last paragraph).
Therefore, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claims 1-2 and 5-10 are rejected under 35 U.S.C. 103 as being unpatentable over Tong (BMC Medical Informatics and Decision Making 20(225): 12 pgs., 2020; previously cited on the 30 November 2023 IDS form) in view of Kumar (Plos One 14(11): 30 pgs., 2019; newly cited).
Claim 1 recites receiving a dataset comprising a plurality of reference patients having performed a therapeutic treatment of said given disease, wherein said dataset comprises for each reference patient of said plurality of reference patients respective omics data and data indicating a disease-free survival time of the respective reference patient after the respective therapeutic treatment of said given disease.
Tong teaches paired cancer and normal samples with omics data, including transcriptomic data, and survival information (pg. 3, col. 2, second paragraph).
Claim 1 recites generating for each reference patient respective pre-processed data via a principal
component analysis of the respective omics data, and storing the respective mapping rules used to generate said pre-processed data as a function of the respective omics data.
Tong teaches PCA for survival analysis (pg. 5, col. 1, first paragraph).
Claim 1 recites generating a training dataset by forming reference patient pairs between a respective first reference patient and a respective second reference patient and determining for each
reference patient pair: a respective feature set calculated via a distance measure between the pre-processed data of the respective two reference patients, and a respective index indicating which of the respective two reference patients has a longer disease-free survival time.
Tong teaches survival time, interpreted as the index, between comparable pairs, interpreted as reference patients (pg. 5, col. 2, last paragraph).
Claim 1 recites training a classifier configured to estimate said index as a function of the respective feature set calculated for the pre-processed data of two patients by using said training dataset.
Tong teaches training the feature selection or dimension reduction step and survival networks (Fig. 2, caption).
Claim 1 recites receiving omics data of a patient and generating for said patient respective pre-processed data by using said mapping rules.
Tong teaches a testing set (Fig. 2, caption), where testing data is data wherein the training parameters are applied.
Claim 1 recites generating a verification dataset by forming pairs of patients by combining said patient with a plurality of reference patients and determining for each pair of patients a respective feature set calculated by said distance measure between the pre-processed data of said patient and the pre-processed data of the respective reference patient.
Tong teaches comparing any two comparable pairs (pg. 5, col. 2, last paragraph), which includes the test sample and other samples.
Claim 1 recites estimating for each pair of patients a respective index by providing the feature set of the respective pair of patients to said classifier.
Tong teaches determining the C-index between any two pairs (pg. 5, col. 2, last paragraph), which includes the test sample and other samples.
Claim 1 recites generating a list of said estimated indices, wherein said list is sorted according to the disease-free survival time of the reference patients of the pairs of patients and calculating for each position of a plurality of positions of said list a respective parameter indicating the probability that said patient has a disease-free survival time being greater than the disease-free survival time of the reference patient in said position, but smaller than the disease-free survival time of the reference patient in the next position.
Tong teaches determining the C-index of any two pairs (pg. 5, col. 2, last paragraph) but does not teach comparing the query patient to each reference patient in the dataset and generating an index for every pair.
Claim 1 recites selecting the position for which the respective parameter indicates the highest
probability, and estimating the disease-free survival time of said patient with a value between the disease-free survival time of the reference patient in said selected position and the disease-free survival time of the reference patient in the position following said selected position.
Tong teaches estimating survival prediction directly (abstract) and not based on multiple comparison within a list.
Kumar teaches using survival times to rank the patients to compute the partial likelihood for all patients where the death times are used to rank in ascending order (pg. 24, third and fourth paragraphs).
Claim 2 recites setting said index to a first value to indicate that the respective first reference patient has a disease-free survival time being greater than the disease-free survival time of the respective second reference patient, and to a second value to indicate that the respective first reference patient has a disease-free survival time being smaller than the disease-free survival time of the respective second reference patient.
This claim is interpreted as ranking by disease free survival time, which is taught by Kumar as ranking patient death times (pg. 24, fourth paragraph).
Claim 5 recites said generating for each reference patient respective pre-processed data comprises normalizing said omics data, and/or scaling said omics data via a non-linear function.
Tong teaches normalizing the data modalities (pg. 3, col. 2, last paragraph), where the omic data types are the modalities.
Claim 6 recites said omics data comprises transcriptomic data obtained via Next Generation Sequencing.
Tong teaches next generation sequencing for omic data generation, including gene expression data, which is transcriptomic (abstract).
Claim 7 recites said training a classifier comprises selecting a subset of said features via a feature selection method, such as LASSO, and training a classifier configured to estimate said index as a function of the respective subset of features calculated for the pre-processed data of two patients using said training dataset.
Kumar teaches Lasso (pg. 24, last paragraph), where Lasso regression is a method for automatic feature selection and thus selects a subset from the possible features.
Claim 8 recites said classifier comprises at least one of: a k-nearest neighbor classifier, an artificial neural network, such as a multi-layer perceptron type network, a support vector machine, a gaussian process classifier, decision trees, random forests, quadratic discriminant analysis, and/or Naive Bayes gaussian classifiers.
Tong teaches implementation using random forest, artificial neural network, and support vector machine methods, noting similar accuracy levels between them (pg. 2, col. 1, last paragraph).
Claim 9 recites a device configured to implement the method according to claim 1.
Tong and Kumar teach steps performed in a computational environment, with Kumar in particular teaches requiring a memory and processor (pg. 13, fifth paragraph).
Claim 10 recites a computer-program product that can be loaded into the memory of at least one processor and comprises portions of software code for implementing the steps of the method according to claim 1.
Tong and Kumar teach steps performed in a computational environment, with Kumar in particular teaches requiring a memory and processor, and comparison of their program with another program (pg. 13, fifth paragraph).
Combining Tong and Kumar
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the ranking method of determining survival time of Kumar with the work of Tong because Kumar teaches “the partial likelihood only uses the patient’s death times to rank them in the ascending order to find the risk sets and does not use the exact times explicitly” and therefore “the coefficients estimated by maximizing the partial likelihood depend only on the ordering of the patient’s death times and the covariates, allowing for an implicit optimization for good concordance of the risk score” (pg. 24, Section A.5). Therefore, ranking in determining survival analysis as taught by Tong would be advantageous. Both Tong and Kumar are directed to using gene expression to determine survival estimates and their combination would be expected to succeed. Therefore, the invention is prima facie obvious.
Claims 3-4 and 5-10 are rejected under 35 U.S.C. 103 as being unpatentable over Tong in view of Kumar as applied to claims 1-2 and 5-10 above and further in view of Huang (Frontiers in Genetics 10(166): 13 pgs., 2019; newly cited).
Claim 3 recites said calculating for each position a respective parameter comprises generating for each position a respective pattern to be verified by selecting the index of said list at said position, and a first number of indexes of said list before said position and/or a second number of indexes of said list after said position, obtaining for each pattern to be verified a respective reference pattern, wherein said reference pattern corresponds to a pattern of indices in case said position corresponds to the position at which occurs the switching between a sequence of said first number of said first value and a sequence of said second number of said second value takes place, and calculating the value of said parameter associated with said position by means of a similarity measure or a distance measure between the respective pattern to be verified and the respective reference pattern.
The parameters of the classifier are interpreted as the gene expression values informing the disease free survival classification.
Tong teaches genes are selected as part of a survival prediction (pg. 10, col. 1, second paragraph) and consensus among features as similarity of features determined by Euclidean distance (pg. 8, col. 2, second paragraph).
Kumar teaches retaining genes with the most prognostic ability as part of feature reduction (pg. 20, first paragraph) and retaining a subset of genes (pg. 23, Section A.4).
The previously applied art does not clearly teach evaluating patterns of expression.
Huang teaches co-expression of genes as part of feature selection (abstract), where patterns are interpreted as subsets of co-expressed genes.
Claim 4 recites each pattern to be verified corresponds to the sequence of said estimated indices of said list, and the reference pattern associated with said position has set all indices up to said position to said first value, and all indices after said position to said second value.
This claim is interpreted as evaluating gene expression with respect to survival time.
Huang teaches evaluating co-expression modules (pg. 2, col. 1, last paragraph), where genes which contributed highly to the index were further evaluated (pg. 2, col. 2, first paragraph), and the modules were ranked (pg. 5, col. 2, second paragraph), where ranking is interpreted as evaluating based on survival ratio, taught by Huang as hazard.
Combining Tong, Kumar, and Huang
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine Huang’s co-expression modules with the previously combined works because Huang teaches genes may be densely connected across patients and samples, and can be used to revel latent interactions (pg. 3, col. 1, second paragraph), and can be used for survival prognosis. Huang teaches reduced dimensionality in feature space by analyzing a reduced suite of co-expressed genes helps address the curse of dimensionality (pg. 2, col. 2, last paragraph). Both Huang and the previously combined art are directed to using gene expression to determine survival estimates and their combination would be expected to succeed. Therefore, the invention is prima facie obvious.
Conclusion
The following prior art is made of record and not relied upon is considered pertinent to applicant's disclosure.
Raykar (Advances in Neural Information Processing Systems 20, 8 pgs., 2007; newly cited) teaches ranking the data points, interpreted as the patients, based on survival times, then using these ranks to determine a survival time rather than predict actual survival times (pg. 1, first paragraph). The times ranked lower is one is smaller than the other (pg. 3, Section 3).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia M. Wise can be reached at (571) 272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Robert J. Kallal/Examiner, Art Unit 1685
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