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 .
Applicant’s amendment and response, filed 1/07/2025 have been entered and carefully considered, but are not completely persuasive.
The amendment to the specification has been entered, and obviates the objection to the specification.
Claims 1-20 are pending in this application. Claims 15-20 stand withdrawn from consideration as being drawn to a non-elected invention. Claims 1-14 are under examination.
The rejections under 35 USC 102 and 35 USC 103 have been withdrawn.
Claim Interpretation
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.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
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 1-14 remain 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.
Applicant’s amendments have removed parts of this rejection; however, some indefiniteness remains, or was introduced by amendment.
In claim 1, the metes and bounds of the phrase “performing a mutation analysis” are unclear. Claim 1 fails to particularly point out and distinctly claim the type of analysis which can provide the required “set of mutations” from which a “mutational spectrum” can be determined. Claim 1 fails to identify what aspect of the genetic data is to be analyzed for “mutations.” Applicant has amended this limitation to recite “performing a mutation analysis… by a panel analysis of a panel of known mutations.” The term “known” in claim 1 is a relative term which renders the claim indefinite. The term “known mutations” is 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. This term is indefinite, as what is known to one individual is not necessarily known to another. A "known panel" implies a set whose membership is known (i.e. the list of members, in any order). But an individual known mutation (or a small set of mutations) might be in a lot of different sets, each having a different list of members (unordered). Applicant appears to intend to include pre-determined panels, such as the 96 mutation panel of SNP in MSK-IMPACT, but as the claim is written any two or more mutations known in some context are encompassed (as a single mutation is generally not considered a panel). The claim fails to particularly point out what pre-determined panels are to be used or can be used in the method of classifying a tumor of a patient.
While breadth of a claim is not the same as indefiniteness, the claim lacks vital information and processing steps required to achieve the desired goal, and one of skill would not be apprised of the particular mutations to be identified and analyzed in carrying out the claimed method.
Further in claim 1, the metes and bounds of the phrase “determining a sample mutational spectrum of a number of known mutations of the panel in the set of mutations” are unclear. Claim 1 fails to particularly point out and distinctly claim how a mutational spectrum is determined from the indefinite “panel of known mutations” identified above. The specification indicates that MSK-IMPACT panels “computes a vector of 96 triplets for a set of genomes and deconvolves the observed mutational spectra into independent components” [0004], however the claim is not limited to this pre-determined panel. It is unclear what form or value the “spectra” represents with respect to the patient tumor genome (i.e. whether it is a total count of mutations, a count of a subset of mutations, a calculated allele distribution, an independent vector value…). While breadth of a claim is not the same as indefiniteness, the claim lacks vital information and processing steps required to achieve the desired goal, and one of skill would not be apprised of the particular mutations to be identified and analyzed in carrying out the claimed method.
Further in claim 1 the metes and bounds of the term “an indication of a mutational signature of the sample based on the matching cluster” are unclear. The claim fails to particularly point out and distinctly claim what makes up the mutational signature of the patient’s sample, as opposed to the mutational spectrum of the patient’s sample, and how this relates to the patient’s tumor. No details are provided as to what the clusters are to match, whether they are clusters linked to a definable tumor type, class, stage, or treatment aspect, or whether they represent control clusters. These clusters do not clearly have any relationship to a classification of a tumor, as required by the preamble, as they are not clearly linked or clearly classified into tumor types, or stages, or other types of classes. It is entirely unclear how the indication of a mutational signature is the classification of the tumor of the patient, as the signature, or spectrum are not linked to any particular tumor classes. While breadth of a claim is not the same as indefiniteness, the claim lacks vital information and processing steps required to achieve the desired goal, and one of skill would not be apprised of the particular clusters to be identified and analyzed in carrying out the claimed method.
Applicant’s arguments:
Applicant’s arguments and amendments with respect to this rejection have been considered, and are mostly persuasive, however some indefiniteness remains, or was introduced by the amendments.
MPEP 2173: “To comply with 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, applicants are required to make the terms that are used to define the invention clear and precise, so that the metes and bounds of the subject matter that will be protected by the patent grant can be ascertained. See MPEP § 2173.05(a), subsection I. It is important that a person of ordinary skill in the art be able to interpret the metes and bounds of the claims so as to understand how to avoid infringement of the patent that ultimately issues from the application being examined. See MPEP § 2173.02, subsection II (citing Morton Int ’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470, 28 USPQ2d 1190, 1195 (Fed. Cir. 1993)); see also Halliburton Energy Servs., 514 F.3d at 1249, 85 USPQ2d at 1658 ("Otherwise, competitors cannot avoid infringement, defeating the public notice function of patent claims."). Examiners should bear in mind that "[a]n essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process." Zletz, 893 F.2d at 322, 13 USPQ2d at 1322.
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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 1-14 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental steps, mathematic concepts, organizing human activity, or a natural law without significantly more.
Applicant is directed to MPEP 2106 and the recent Federal Register notice (FR89, no 137 (7/17/2024) p 58128-58138) for the most current and complete guidelines in the analysis of patent- eligible subject matter. The current MPEP (9th Edition, Rev. 07.2022), published in February 2023 is the primary source for the USPTO’s patent eligibility guidance.
With respect to step (1): yes, the claims are drawn to a statutory category and recite methods.
With respect to step (2A) (1): yes, the claims recite an abstract idea, law of nature and/or natural phenomenon. The claims recite an abstract idea of obtaining mutation analysis data from a sample of a patient’s tumor tissue, analyzing the mutations to determine a sample mutational spectrum, comparing that spectrum to a set of clusters, and outputting an indication of a mutational signature of the sample based on the matching cluster. The claims also embrace the natural law describing the naturally occurring correlations between naturally occurring genomic mutations, and a phenotype of cancer or tumor type, a genotype/phenotype relationship.
Claim 1 is independent.
Mathematic concepts, Mental Processes or Elements in Addition (EIA) in independent claim 1 include:
1. (Currently Amended) A method of classifying a tumor of a patient, the method comprising:
obtaining a sample of a patient's tumor tissue;
(EIA- Data gathering step, no limitations as to the tumor tissue, or how to obtain it.)
performing DNA sequencing on the sample to output a set of sequenced genetic data via a processor;
(EIA- Data Gathering steps: DNA sequencing is a laboratory process, and “outputting a set of sequenced genetic data” represents the data gathered. The “processor” at all recitations in the claims is a part of a general-purpose computer, an EIA)
performing a mutation analysis on the set of genetic data by a panel analysis of a panel of known mutations to output a set of mutations of the known mutations of the set of sequenced genetic data via the processor;
(Mental Process of observing the presence of mutations in the received data, by any process, of “known” mutations)
determining a sample mutational spectrum of a number of known mutations of the panel in the set of mutations;
(Mental Process of observing the subset of all possible known mutations present in the sample, and a Mathematic Concept of calculating a parameter for the subset, representing the sample mutational spectrum, See Specification [0004]: this analysis computes a vector of 96 triplets (6 substitution subtypes, C>A, C>G, C>T, T>A, T>C, and T>G; each flanked by 4 types on the 5' and 3' sides) for a set of genomes and deconvolves the observed mutational spectra into independent components”)
comparing the sample mutational spectrum to a set of clusters comprising different mutational spectrums to determine a matching cluster of the set of clusters by determining a likelihood similarity feature of the sample mutational spectrum with each of the clusters in the set of clusters, wherein the likelihood similarity feature is generated from a probability distribution defined by the mutational profiles of each of the clusters in relation to the sample mutational spectrum via the processor; and
(Mathematic Concept of calculating likelihood similarity features between the sample mutational spectrum, and each of a set of pre-identified clusters. Specification [0039-0040])
outputting an indication of a mutational signature of the sample based on the likelihood of similarity feature of the determined matching cluster via the processor.
(EIA- routine output of a calculated result, without specific limitations)
The Examiner has included the below analysis of claim 2, which was heavily amended:
2. (Currently Amended) The method of claim 1, wherein comparing the set of clusters to determine a matching cluster further comprises:
performing a cosine similarity measure on each of the set of clusters and the sample mutational spectrum to output a cosine similarity feature of the sample mutational spectrum with each of the clusters in the set of clusters;
(Mathematic Concept of calculating a cosine similarity feature, as defined in the specification “additional matching scores such as cosine similarity can be calculated to a signature in the catalog and the magnitude of a signature can be calculated with linear decomposition (NNLS) to find magnitude of several signatures simultaneously 851.” [0042])
performing a non-negative least squares measure on each of the set of clusters and the mutational spectrum to output a non-negative least squares feature of the sample mutational spectrum with each of the clusters in the set of clusters; and
(Mathematic Concept of calculating a non-negative least squares feature as set forth in the specification at [0042-0046])
inputting the likelihood similarity feature, non-negative least squares feature and the cosine similarity feature for each of the set of clusters into a gradient boosted machine learning model executed by a processor, the gradient boosted machine learning model trained for determining a specific tumor type using whole genome sequencing (WGS) data from a training set of likelihood similarity features, non-negative least square features, and cosine similarity features and a corresponding mutation signature of the specific tumor type to output a matching score for the determined matching cluster based on the likelihood similarity features, the cosine similarity features and the non-negative least square features.
(Mathematic Concept of applying the calculated features to a trained machine learning model, trained on features specific to a tumor type, to output a matching score representing the classification of the patient’s tumor.)
Natural law embraced by independent claim 1:
Claim 1 embraces the natural law correlating naturally occurring genomic mutations in a patient tumor sample to a naturally occurring phenotype of a type of cancer or type of tumor, a genotype/phenotype relationship that exists whether or not it is measured.
Therefore, the claims explicitly recite elements that, individually and in combination, constitute one or more judicial exceptions (JE).
With respect to step 2A (2): NO. The claims must therefore be examined further to determine whether they integrate that JE into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone or in combination to determine if the JE is integrated into a practical application (MPEP 2106.04(d)(I.); MPEP 2106.05(a-c, e, f and h)).
Independent claims 1 recite the additional non-abstract element of:
obtaining a sample of a patient's tumor tissue;
performing DNA sequencing on the sample to output a set of sequenced genetic data via a processor;
which are each a data gathering step, or a description of the data gathered as noted above. No limitations are present as to how the sample is obtained, or how the sequencing is performed. The sequencing step is defined by the output of “a set of sequenced genetic data.”
Data gathering steps are not an abstract idea, they are extra-solution activity, as they collect the data needed to carry out the JE. Data gathering does not impose any meaningful limitation on the JE, or how the JE is performed. Data gathering steps are not sufficient to integrate a JE into a practical application. The additional limitation must have more than a nominal or insignificant relationship to the identified judicial exception. (MPEP 2106.04/.05, citing Intellectual Ventures LLC v. Symantec Corp, McRO, TLI communications, OIP Techs. Inc. v. Amason.com Inc., Electric Power Group LLC v. Alstrom S.A.).
Independent claim 1 recites “via a processor” implying the presence of a general-purpose computer system. The processor has no specific attributes, and is recited at a high level of generality, i.e., as a generic computer performing generic computer functions.
The independent claim does not describe any specific computational steps by which the claimed computer elements perform or carry out the JE, nor does it provide any details of how specific structures of the computer elements are used to implement the JE. The claims require nothing more than a general-purpose computer to perform the functions that constitute the judicial exceptions. The computer elements of the claims do not provide improvements to the functioning of a computer (as in DDR Holdings, LLC v. Hotels.com LP); they do not provide improvements to any other technology or technical field (as in Diamond v. Diehr); nor do they utilize a particular machine (as in Eibel Process Co. v. Minn. & Ont. Paper Co.). Hence, these are mere instructions to apply the JE using a computer, and therefore the claim does not recite integrate that JE into a practical application.
Dependent claims 2-14 have been analyzed with respect to 2A-2.
Dependent claims 2, 5, 12-14 each add an abstract limitation to the JE requiring additional mathematic concepts, or mental processes. Additional abstract limitations cannot provide a practical application of the JE as they are a part of that JE.
Dependent claims 3, 4, 6-11 each add non-abstract limitations (EIA) which are directed to the data gathering, aspects of the data gathered, or to the output of results. Data gathering is pre-solution insignificant activity (MPEP 2106.05(g) citing OIP Tech Inc v. Amazon.com, Inc.) Describing aspects of the data gathered are similarly considered pre-solution insignificant activity. The output of results is post-solution insignificant activity (MPEP 2106.05(g) citing Apple v. Ameranth Inc.) Collectively they are extra-solution activity.
In combination, the limitations of data gathering, for the purpose of carrying out the JE, using a general-purpose computer merely provide extra-solution activity, and fail to integrate the JE into a practical application.
With respect to step 2B: NO. Because the claims recite a JE, and do not integrate that JE into a practical application, the claims are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the JE amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception. (MPEP 2106.05.A i-vi).
With respect to independent claim 1: The additional element of data gathering does not rise to the level of significantly more than the judicial exception.
GRAIL (Written Opinion) discloses obtaining a sample of a patient’s tumor tissue [0082,0089]; performing DNA sequencing on the sample [0081, 0098], to output a set of sequenced genetic data via a processor [0061-0062, 0081, 0098].
GRL ‘068 (Written Opinion) discloses obtaining a sample of a patient’s tumor tissue (p7); performing DNA sequencing on the sample (p7) to output a set of sequenced genetic data via a processor (p7).
COLUMBIA (Written Opinion) discloses obtaining a sample of a patient’s tumor tissue [003, 007], performing DNA sequencing on the sample [003, 007] to output a set of sequenced genetic data via a processor [007, 0073].
KIM (Of record) discloses obtaining a sample of a patient’s tumor tissue, performing DNA sequencing on the sample to output a set of sequenced genetic data via a processor. (Fig. 1a and Supplementary Table 1) The TCGA data is genetic data, comprising sequence read data which can comprise various types of mutations, including SNV. See Online Methods p607, Datasets.
These elements meet the broadest reasonable interpretation of the claimed data gathering steps, and the prior art recognizes that these data gathering steps and elements are routine, well-understood and conventional in the art of bioinformatics. (Alice Corp., CyberSource v. Retail Decisions, Parker v. Flook)
The specification at [0036] notes that prior art known MSK-IMPACT data from tumor samples is useful in carrying out the invention.
In the specification at [0031] it is disclosed that the steps identified as data gathering can be met using the commercially available machines and protocols of MiSeqTM, NextSeqTM, NovaSeqTM, Oxford NanoporeTM and PacBioTM sequencers.
This underscores the finding that the steps identified as data gathering represent routine, well-understood and conventional steps in the related art.
Activities such as data gathering do not improve the functioning of a computer, or comprise an improvement to any other technical field. The limitations do not require or set forth a particular machine, they do not effect a transformation of matter, nor do they provide an unconventional step (citing McRO and Trading Technologies Int’l v. IBG). Data gathering steps constitute a general link to a technological environment. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception are insufficient to provide significantly more (as discussed in Alice Corp.,).
With respect to independent claim 1: the implied computer related elements or the general-purpose computer systems do not rise to the level of significantly more than the judicial exception.
GRAIL (Written Opinion) discloses general purpose computer elements throughout.
GRL ‘068 (Written Opinion) discloses general purpose computer elements throughout.
COLUMBIA (Written Opinion) discloses general purpose computer elements throughout.
KIM (Of record) discloses general purpose computer elements throughout.
Each of the above disclose computer systems or computing elements which meet the broadest reasonable interpretation of the claimed computer system or computer system elements, comprising input, output/ display, a processor, and memory. As such, the prior art recognizes that these computing elements are routine, well understood and conventional in the art.
The specification at [0032-0033] sets forth that the “computing device may be any suitable computing device including a desktop computer…”
This underscores the finding that the processor as claimed is a part of a general-purpose computer system, and represents routine, well-understood and conventional activity.
These elements do not improve the functioning of a computer, or comprise an improvement to any other technical field (Trading Technologies Int’l v IBG, TLI Communications). They do not require or set forth a particular machine (Ultramercial v. Hulu, LLC., Alice Corp. Pty. Ltd v. CLS Bank Int’l), they do not effect a transformation of matter, nor do they provide an unconventional step. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception are insufficient to provide significantly more (as discussed in Alice Corp., CyberSource v. Retail Decisions, Parker v. Flook, Versata Development Group v. SAP America).
Dependent claims 2-14 have been analyzed with respect to step 2B.
Dependent claims 2, 5, 12-14 each add an abstract limitation requiring additional mathematic calculations or mental processes. Additional abstract limitations cannot provide significantly more than the JE as they are a part of that JE.
As set forth above, dependent claims 3, 4, 6-11 add non-abstract limitations (EIA) which are directed to the data gathering, aspects of the data gathered, or routine output steps which are insufficient to provide significantly more than the JE (citing McRO, Alice Corp. and Trading Technologies Int’l v. IBG).
In combination, the data gathering steps providing the information required, to be acted upon by the JE, performed in a generic computer or generic computing environment fail to rise to the level of significantly more. The data gathering steps provide the data for the JE, which is carried out by the general-purpose computers. No non-routine step or element has clearly been identified.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. For these reasons, the claims, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Applicant’s Arguments:
Applicant’s arguments have been carefully considered, but are not persuasive.
Applicant argues the categorization or identification of abstract ideas, and/or a natural law in the claims. The Examiner has specifically identified each limitation in the claim, and what category of judicial exception is encompassed. The abstract ideas identified in the independent claims are the same as those identified as mathematic correlations, mathematic calculations, and mathematical relationships or as mental processes: concepts performed in the human mind including observations, evaluations, judgements and opinions, in MPEP 2106.04.
The examiner acknowledges Applicant’s arguments which set forth that the claims lead to an improvement in the accuracy of the indication of a mutational signature of the sample. However, according to the guidance set forth in MPEP 2106, this is an improvement to the judicial exception itself, and is not reflected back into a specific technological environment or practically applied process.
An improvement in the judicial exception itself is not an improvement in the technology. For example, in In re Board of Trustees of Leland Stanford Junior University, 989 F.3d 1367, 1370, 1373 (Fed. Cir. 2021) (Stanford I), … applicant argued that the claimed process was an improvement over prior processes because it ‘‘yields a greater number of haplotype phase predictions,’’ but the court found it was not ‘‘an improved technological process’’ and instead was an improved ‘‘mathematical process.’’ The court explained that such claims were directed to an abstract idea because they describe ‘‘mathematically calculating alleles’ haplotype phase,’’ like the ‘‘mathematical algorithms for performing calculations’’ in prior cases. Notably, the Federal Circuit found that the claims did not reflect an improvement to a technological process, which would render the claims eligible (FR89 no.137, p58137, 7/17/2024).
With respect to the arguments regarding example 47 and the July 2024 Guidance, initially, it is noted that in the arguments, Applicant appears to imply that the limitations of claim 2 are required to achieve the improvement. In consideration of the improvement, the independent claim must contain the necessary and sufficient limitations to achieve that improvement. Applicant may wish to amend claim 1 to include the limitations of amended claim 2, to ensure all necessary and sufficient limitations are present to achieve the alleged improvement. It is further noted that claim 1 fails to classify a tumor, as no classification of a tumor takes place, merely the indication of a mutational signature. No analysis or comparison with known tumor information is present, and again it is noted that some of these elements are present in amended claim 2.
With respect to example 47 and the claimed gradient boosted machine learning model, it is noted that machine learning, and artificial neural networks are not commensurate in scope. The trained machine learning model is a set of algorithms that have had training data applied to adjust the weights of the parameters to achieve a particular goal, and is completely a mathematic process. When given their BRI in light of the specification, the cosine similarity measure, the non-negative least squares measure, and the likelihood similarity measure are calculated features, and the gradient boosted machine learning model trained for determining a specific tumor type is a set of mathematical calculations. The plain meaning of these terms are optimization algorithms, which compute machine learning model parameters using a series of mathematical calculations. The ML model of claim 2 is a multivariate machine learning model as set forth in [0042-0046]. The specification notes that other ML models can me employed such as random forest, naiive Bayesian, elastic net, SVM, lasso, and generalized linear regression at [0045].
Claim 2 does not provide details about how the trained ML model operates, beyond combining the listed features, nor how the classification to a type of tumor is made, beyond indicating the ML is trained on tumor-specific features.
In claim 2, the limitations using the “trained machine learning model” provide nothing more than mere instructions to implement an abstract idea on a generic computer. See MPEP 2106.05(f). The trained ML model is used to generally apply the JE without placing limits on how the trained ML functions. These limitations recite the desired outcome of “to output a matching score for the matching cluster based on the…features” and do not include details about how the determining or outputting are accomplished. The recitation of using a trained ML model also merely indicates a field of use or technological environment in which the JE is performed. This type of limitation merely confines the use of the abstract idea to the particular technological environment (machine learning) and thus fails to provide an inventive concept. MPEP 2106.05(h).
With respect to example 47, and particularly claim 3 of that example, the instant claims fail to provide the elements which led to the finding of patent-eligibility. The limitations of claim 1 (and claims 2-14) do not provide an improvement in the functioning of the computer itself. The claims do not reflect an improvement in the technological field of network intrusion detection. The claims do not “detect network intrusions and take real-time remedial actions…” Claim 1 does not set forth all the limitations required to reflect the improvement, including the limitations of claim 2.
The improvement in the indication of a mutational signature of the sample (carried out by the judicial exception) does not provide an improvement in the technology of obtaining a sample of a tumor of a patient, or the technology of DNA sequencing to output a set of sequenced genetic data. The data gathering steps are carried out, unchanged, whether or not the judicial exception is applied. (Cleveland Clinic Foundation: using well-known or standard laboratory techniques is not sufficient to show an improvement (MPEP2106.05(a)) Both obtaining samples from a tumor, and performing DNA sequencing are routine, well-known and standard laboratory techniques.
The improvement in the indication of a mutational signature of the sample (achieved by the judicial exception) does not require a non-conventional interaction with a specific element of a computer as was required in Enfish. The improvement in the indication of a mutational signature of the sample (carried out by the judicial exception) does not improve the functionality of the computer itself. It does not improve a technology by enabling the automation of a task which previously could not be performed, as in McRo.
The elements in addition to the abstract idea are data gathering steps which provide or generate the data which are then acted upon by the abstract idea. Adding data gathering steps, which are extra-solution activity, has been determined not to integrate a judicial exception into a practical application. MPEP2106.05(g). “The term "extra-solution activity” can be understood as activities incidental to the primary process or product that are merely a nominal or tangential addition to the claim...”
In the claims, the data gathering steps do not affect how the steps of the abstract idea are performed, they provide the data which is acted upon by the limitations of the JE. The JE idea can act on any dataset which comprises a set of sequenced genetic data from a sample of a tumor of a patient. These data gathering steps do not apply, rely on, or use the steps identified as making up the JE. Rather, the mental process steps avail themselves of the data gathered. The data gathering in the claims constitutes insignificant pre-solution activity. See MPEP § 2106.05(g):
“An example of pre-solution activity is a step of gathering data for use in a claimed process, e.g., a step of obtaining information about credit card transactions, which is recited as part of a claimed process of analyzing and manipulating the gathered information by a series of steps in order to detect whether the transactions were fraudulent.”
See also CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372 (Fed. Cir. 2011) ("[E]ven if some physical steps are required to obtain information from the database ... such data-gathering steps cannot alone confer patentability.").
The listed claims set forth the element in addition to the JE of a computing system. The computing system of these claims is recited at such a high level of generality, it can be met by a general-purpose computer system and is not considered a particular machine or manufacture integral to the claim (MPEP 2106.05(b)). Any routine, commercially available generic computing system would be adequate to carry out the abstract limitations and routine computer elements acting upon the data in a manner consistent to and according to their design are not considered to be sufficient to provide eligibility. (MPEP 2106.04(d): Gottschalk v. Benson “‘held that simply implementing a mathematical principle on a physical machine, namely a computer, was not a patentable application of that principle.”)
The processor is recited generically as simply a "processor" and the activity performed by that generic processor is normal computer functionality. The requirement of using a computer processor is not sufficient to establish integration of the abstract idea into a practical application.
One of the "examples in which a judicial exception has not been integrated into a practical application" is when "[a]n additional element ... merely includes instructions to implement an abstract idea on a computer, or merely uses a computer as a tool to perform an abstract idea." Guidance 84 Fed. Reg. at 55 (emphasis added); FairWarning, 839 F.3d at 1096 ("[T]he use of generic computer elements like a microprocessor or user interface do not alone transform an otherwise abstract idea into patent-eligible subject matter.").
That the claimed system may result in faster and more accurate identifications in large data sets does not take the claim out of the realm of the abstract.
"[R]elying on a computer to perform routine tasks more quickly or more accurately is insufficient to render a claim patent eligible." OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015); see also Intellectual Ventures I LLC v. Erie Indemnity Co., 711 F. App'x 1012, 1017 (Fed. Cir. 2017) (unpublished) ("Though the claims purport to accelerate the process of finding errant files and to reduce error, we have held that speed and accuracy increases stemming from the ordinary capabilities of a general-purpose computer 'do[] not materially alter the patent eligibility of the claimed subject matter."'); see also Bancorp Servs., L.L.C. v. Sun Life Assurance Co. of Can. (US.), 687 F.3d 1266, 1278 (Fed. Cir. 2012) ("[T]he fact that the required calculations could be performed more efficiently via a computer does not materially alter the patent eligibility of the claimed subject matter.").
Step 2B requires that we look to whether the claim "adds a specific limitation beyond the judicial exception that [is] not 'well-understood, routine, conventional' in the field." Guidance 89 Fed. Reg. at 58133 (emphasis added); MPEP § 2106.05(d); see BSG TechLLCv. BuySeasons, Inc., 899 F.3d 1281, 1290 (Fed. Cir. 2018) (explaining that the Supreme Court in Alice "only assessed whether the claim limitations other than the invention's use of the ineligible concept to which it was directed were well-understood, routine and conventional").
With respect to the arguments regarding the alleged improvement and the prior art "Even assuming [the claimed invention is novel], it does not avoid the problem of abstractness." Affinity Labs of Tex., LLC v. DIRECTV, LLC, 838 F.3d 1253, 1263 (Fed. Cir. 2016). That is because the inventive concept must be significantly more than the abstract idea itself. Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1151 (Fed. Cir. 2016) ("[A] claim for a new abstract idea is still an abstract idea.")
As discussed above, the additional elements recited in claim 1, beyond the abstract idea to which it is directed, are the data-gathering step of obtaining a sample of a tumor of a patient, performing DNA sequencing to output a set of sequenced genetic data and the use of a generic computer. The examiner provided multiple prior art citations reciting the same steps for the same purpose, indicating that each of the data gathering steps, and the general-purpose computer were routine, well understood and conventional in the art of bioinformatics. Applicant's Specification supports the Examiner's conclusion that these additional elements are well-understood, routine, and conventional, because it describes them at a high level of generality and in a manner that indicates that they are sufficiently well-known.
In light of the foregoing, we conclude that claims 1-14 are directed to no more than judicial exceptions to Section 101 and does not recite the "significantly more" requisite to transform the nature of the claim into a patent-eligible application.
With respect to the finding of a natural law, the claim involves a naturally occurring correlation, i.e., the characterization of a tumor sample based on the presence of sequence data that, after statistical manipulation, correlates with sequence data linked to a tumor type. The sequence information of the sample is a natural phenomenon and the relationship of that information to a phenotypic trait is simply put a natural law. Nothing more than this observation is required by the claims. In Mayo, the discovery underlying the claims was that when blood levels were above a certain level harmful effects were more likely and when they were below another level the drug's beneficial effects were lost. Mayo, 566 U.S. at 74--76. The claims provided that particular levels of measured metabolite indicated a need to increase or decrease the amount of drug subsequently administered to the subject. Id. at 75. However, the claims did not require any actual action be taken based on the measured level of metabolite. Id. at 75-76. Thus, the claims which required only the observation of a natural law were deemed patent-ineligible. Similarly, here, the claim requires only the observation of the natural law, and for this reason too are properly deemed patent-ineligible.
The naturally occurring relationship between genotypes and other characteristics of an organism is a recognized, naturally occurring correlation which exists whether or not it is measured. The claims clearly obtain genetic data of the tumor cells in the sample, analyzes them, statistically manipulates them and compares them to known characteristics, to make the identification of a phenotype- a type of tumor. These correlate to at least the following examples provided in MPEP 2106.04b:
“iii. a correlation between variations in non-coding regions of DNA and allele presence in coding regions of DNA, Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1375, 118 USPQ2d 1541, 1545 (Fed. Cir. 2016);
iv. a correlation that is the consequence of how a certain compound is metabolized by the body, Mayo Collaborative Servs. v. Prometheus Labs., 566 U.S. 66, 75-77, 101 USPQ2d 1961, 1967-68 (2012);
vii. qualities of bacteria such as their ability to create a state of inhibition or non-inhibition in other bacteria, Funk Bros., 333 U.S. at 130, 76 USPQ at 281; and
xi. the natural relationship between a patient’s CYP2D6 metabolizer genotype and the risk that the patient will suffer QTc prolongation after administration of a medication called iloperidone, Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F.3d 1117, 1135-36, 126 USPQ2d 1266, 1281 (Fed. Cir. 2018).”
Further, with respect to the arguments regarding the alleged improvement, it is unclear that the independent claims recite all the necessary and sufficient steps required to achieve that improvement. MPEP 2106.05(a): “An important consideration in determining whether a claim improves technology is the extent to which the claim covers a particular solution to a problem or a particular way to achieve a desired outcome, as opposed to merely claiming the idea of a solution or outcome. McRO, 837 F.3d at 1314-15, 120 USPQ2d at 1102- 03; DDR Holdings, 773F.3d at 1259, 113 USPQ2d at 1107.”
The MPEP sets forth that “if the examiner concludes the disclosed invention does not improve technology, the burden shifts to applicant to provide persuasive arguments supported by any necessary evidence to demonstrate that one of ordinary skill in the art would understand that the disclosed invention improves technology. Any such evidence submitted under 37 CFR 1.132 must establish what the specification would convey to one of ordinary skill in the art and cannot be used to supplement the specification.” Applicant’s arguments cannot take the place of evidence.
New Grounds of Rejection
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.
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.
Claim(s) 1, 3-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al in view of Castro et al.
Kim, J. et al. (2016) Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors. Nature Genetics, Vol 48, no 6, p600-610 and some supplemental information.
Castro, R, et al. (2004) Likelihood Based Hierarchical Clustering. IEEE Transactions on signal processing, vol 52, no 8, Aug 2004, p2308-2321.
Kim is directed to: “… the mutational processes operating in urothelial cancer, a tumor type in which the core NER gene ERCC2 is significantly mutated. Analysis of three independent urothelial tumor cohorts demonstrates a strong association between somatic ERCC2 mutations and the activity of a mutational signature characterized by a broad spectrum of base changes. In addition, we note an association between the activity of this signature and smoking that is independent of ERCC2 mutation status, providing genomic evidence of tobacco-related mutagenesis in urothelial cancer. Together, these analyses identify an NER-related mutational signature and highlight the related roles of DNA damage and subsequent DNA repair in shaping tumor mutational landscape.” (Abstract).
With respect to claim 1, Kim discloses: “1. (Original) A method of classifying a tumor of a patient, the method comprising: obtaining a sample of a patient's tumor tissue;” and “performing DNA sequencing on the sample to output a set of sequenced genetic data via a processor”; at p601, Results.
“To understand the DNA damage and repair processes operating in urothelial tumors, we performed mutational signature analysis of 130 muscle-invasive urothelial tumors from the TCGA-130 cohort (Fig. 1a and Supplementary Table 1).”
TCGA provides data wherein tumor tissue is obtained from a patient, and then amplified and sequenced according to standard protocols. The TCGA data is genetic data, comprising sequence read data which can comprise various types of mutations, including SNV. See Online Methods p607, Datasets.
Kim discloses: “performing a mutation analysis on the set of genetic data by a panel analysis of a panel of known mutations to output a set of mutations of the known mutations of the set of sequenced genetic data via the processor;” at p607, Online Methods, Mutation Signature Analysis.
Kim notes in the introduction, p600, that “dozens of mutational signatures have been identified, including several that have been linked to specific DNA-damaging agents or DNA repair defects…” The gene at issue in Kim has known “recurrent somatic ERCC2 mutations” identified in 6-18% of urothelial tumors in TCGA’s databases. These represent “a panel of known mutations” as now required.
The known mutations also include those of the COSMIC database (Suppl Reference 1), which is a catalog of somatic mutations known to be present in cancer. The COSMIC database contains known cancer-associated mutation signatures, which are subsets of the set of all known mutations.
“Mutation signature analysis. Methods and algorithms. Mutational signature discovery is a process of deconvoluting cancer somatic mutation counts, strati-fied by mutation context or biologically meaningful subgroup, into a set of characteristic patterns (signatures) and inferring the activity of each of the discovered signatures across samples… The common classification of SNVs is based on six base substitutions within the trinucleotide sequence context including the bases immediately 5′ and 3′ to the mutated base. Six base substitutions (C>A, C>G, C>T, T>A, T>C, and T>G) each with 16 possible combinations of neighboring bases yield 96 pos-sible mutation types (or contexts). Thus, the input data for mutation signature discovery comprise a 96 × M matrix X, where M is the number of samples and each element xij represents the number of observed mutations of context i in sample j.”
Kim discloses: “determining a sample mutational spectrum of a number of known mutations of the panel in the set of mutations;” at p601, p607, Online Methods, Signature Selection.
The mutation signatures were analyzed by Kim to generate a mutational spectrum, where each mutation in the count matrix is analyzed. Four independent signatures were identified, which correlated to known signatures in the COSMIC database, underscoring the assertion that the mutations were known mutations.
“We applied a Bayesian variant of the NMF algorithm to mutation counts, stratified by 96 trinucleotide mutational contexts, to infer (i) the number of operating mutational processes, (ii) their signatures (96 normalized weights per process), and (iii) the activity of each signature in every tumor (the estimated number of mutations associated with each signature) (Online Methods)”
“Our analysis identified four independent mutational signatures in the TCGA-130 cohort (Fig. 1b and Supplementary Tables 2 and 3), and although our analysis methods are not identical to those applied by the Sanger Institute our signatures matched four of the previously identified Sanger signatures (cosine similarities between 0.86 and 0.95), which are described in the Catalogue of Somatic Mutations in Cancer (COSMIC) database (Supplementary Fig. 1 and Supplementary Table 4)4. Two of the signatures, characterized by C>T transitions and C>G transversions at TC[A/T] motifs (where the mutated C is preceded by T and followed by A or T), occur in multiple tumor types and are attributed to APOBEC-mediated mutagenesis (denoted as APOBEC1 and APOBEC2 in Fig. 1b and corresponding to COSMIC signatures 13 and 2, respectively)4,23,24. A third signature, characterized by C>T transitions at CpG dinucleotides, is found in all tumor types and is thought to result from age-related accumulation of 5-methylcytosine deamination events (C>T CpG in Fig. 1b; COSMIC signature 1). Finally, a fourth signature was identified that closely resembles COSMIC signature 5 (cosine similarity of 0.90; denoted as signature 5* in Fig. 1b and Supplementary Fig. 1). COSMIC signature 5 is characterized by a broad spectrum of base changes and is present in all tumor types; an etiology has