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 6, 9-10, 12, and 16 are pending and examined herein.
Claims 1-5, 7-8, 11, and 13-15 are canceled.
Priority
As detailed on the 11 August 2022 filing receipt, the application claims priority as early as 10 July 2019. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Withdrawn Rejection(s)
The rejection under 35 USC 103 is withdrawn in view of amendment and argument. It is agreed that the specific requirements of simulating knockdown of all genes in a matched tumor-normal cell pair in a patient using gene regulatory networks and determining updated expression values, which are then fed into an algorithm to determine gene essentiality based on cell death probability, is not taught by the previously applied combination of Kim, Plaimas, Cao, and Gelman. Furthermore, Paull (Bioinformatics 29(21): 2757-2764, 2013; newly cited) teaches potentially simulating the effect of knockdown using regulation networks (pg. 2763, col. 2, first paragraph) and identifying essential cancer genes as drug targets (pg. 2760, col. 1, second paragraph) but not tumor-normal matches where expression of all genes is input to determine death probabilities. Therefore, the instant claims are considered free of the prior art.
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 6, 9-10, 12, and 16 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 essential gene identification.
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 methods (claims 6 and 9-10) and a computer system (claims 12 and 16), each of which falls within one of the categories of statutory subject matter. [Step 1: Yes]
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)).
Claim 6 recites generating a pattern based on simulating knock down of each gene in a tumor cell using a first gene regulation network and simulating knock down of each gene in a normal cell using a second gene regulation network. This step is considered to be a mental processes because it involves determining a pattern of expression based on known regulation networks, which can be logically followed by the human mind. The pattern information is interpreted as up- and down-regulation resulting in differential expression, which is determinable based on the given networks. This may also be understood as a mathematical concept in view of, for example, Figure. 4A, wherein knockdown of specific genes (Ref. 100) results in a value for expression (Ref. 710 and 712) and a resulting number suggests a mathematical relationship. This is further supported in light of the specification, which recites a loss function (Fig. 5C) and backpropagation (Fig. 6C), which are mathematical concepts.
Claim 6 recites a machine learning model, which, under a broadest reasonable interpretation, includes mathematical concepts.
Claim 6 recites generating death probabilities, where determining a probability is a verbal description of a mathematical concept.
Claim 6 recites generating a list based on the evaluation of the death probability information, where making such a list is a step practically performed in the human mind.
Claim 6 recites the expression values are updated for each gene upon a target’s simulated knockdown according to the regulation network. This is considered to be further description of the operation of a regulation network work regulation of one gene affects another.
These elements are also recited in claim 12.
Claims 9-10 recite additional information about the training, where the training data is input values of the expression and survival label.
Claim 16 converting expression data into a vector for the machine learning model and information about the vector, where converting data into a vector is a mathematical concept.
Hence, the claims explicitly recite numerous elements that, individually and in combination, constitute abstract ideas. The claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A: 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 recite elements in addition to the abstract ideas which 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 6 recites receiving expression data and inputting data into an algorithm. Claim 12 recites these elements as well as an input device, storage device, and processor as part of an analysis apparatus, interpreted as a general purpose computer. These additional elements are interpreted as data collection steps, which are insignificant extra solution activity (MPEP 2106.05(g)) and performing the steps by invoking a general purpose computer (MPEP 2106.05(f)), further explained below.
Steps reciting receiving or inputting data are interpreted as data collecting steps for use in the abstract determination of essential genes step using a machine learning model. Data collecting is insignificant extra solution activity and does not integrate the abstract idea into a practical application (MPEP 2106.05(g)).
The analysis apparatus and constituent components are interpreted as a generic computer. The claims do not describe any specific computational steps by which the computer performs or carries out the abstract idea, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than that a generic computer performs the functions that constitute the abstract idea.
Thus, the claims recite elements in addition to the abstract ideas which do not integrate the abstract ideas into a practical application, and must be examined further to determine whether elements in addition to the abstract ideas provide significantly more (MPEP 2106.05). [Step 2A Prong Two: Yes]
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 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)).
Additional elements beyond the abstract ideas are recites receiving expression data and inputting data into an algorithm (claims 6 and 12), an input device, storage device, and processor (claim 12) as part of an analysis apparatus (claims 6 and 12), together interpreted as a general purpose computer.
Storing data on a computer in memory 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)).
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 (storing and retrieving information in memory), as discussed in MPEP 2106.05(d)(II)(i)).
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.
Response to the 29 June 2026 Applicant Remarks
Applicant remarks state use of the gene regulatory network is not a mental process because it allows for changes in expression levels of downstream genes in a network (pg. 12, third paragraph). The gene regulation network is a map of relationships among genes and how one gene’s expression affects another. Using such a framework to follow from one gene’s expression to another does not seem to be beyond what the human mind can perform. Furthermore, the calculation of expression values, for instance in Refs. 710 and 712, indicates a mathematical relationship. Repeating this for every gene in a transcriptome may take a long time but would remain within the realm of being performable by the human mind. While it is acknowledged that such computations performed mentally, or with paper and pencil, would take considerable time and effort, the singular purpose of computers and computer networks, to perform large numbers of calculations via algorithms, rapidly, and without error (assuming no error in user input). Although a general-purpose computer can perform calculations at a rate and accuracy that can far outstrip the mental performance of a skilled artisan, the nature of the activity is essentially the same and constitutes an abstract idea. See Bancorp Serves., L.L.C. v. Sun life Assur. Co. of Canada (U.S.), 687 F.3d 1266, 1278 (Fed. Cir. 2012) (holding that "the 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"); see also SiRF Tech., Inc. v. lnt'I Trade Comm'n, 601 F.3d 1319,1333 (Fed. Cir. 2010) (holding that: In order for the addition of a machine to impose a meaningful limit on the scope of a claim, it must play a significant part in permitting the claimed method to be performed, rather than function solely as an obvious mechanism for permitting a solution to be achieved more quickly, i.e., through the utilization of a computer for performing calculations).
It is further asserted that the relationships are determined simultaneously (pg. 12, third paragraph), but this requirement is found neither in the claims nor in the specification, and thus is considered not commensurate with the metes and bounds of the claims.
It is asserted the operation is “in-silico CRISPR” and thus requires a specific computer system (pg. 12, last paragraph to pg. 13, first paragraph). Regardless of what it is named, simulating knockdown on a computer is materially different than CRISPR, and the recited computer, which is the element in addition to the abstract ideas – is invoked to perform abstract steps.
Applicant remarks state the alleged improvement, similar to McRO, is a result of the specific steps completed by the computer, resulting essential gene identification in a short time and at low cost (pg. 13, third paragraph). However, it is unclear what technological result is being achieved by using the gene regulation networks and determining probabilities of cell death. Applicant remarks state generating the candidate list for screening is not a mental process because it enables personalized therapy and appropriate targets, and thus is a real-world use analogous to Vanda (pg. 14, first paragraph). Applicant remarks appear to analogize making a list of genes to treating a patient. The instant claims do not recite a treatment; they recite making a list. What the list of candidate genes is used for is not claimed. The claims are therefore considered to be directed to constructing a list, which is not a technological improvement.
At Step 2B, applicant remarks state the elements in addition to the abstract ideas are not conventional alone or in combination, and the results are more accurate than those in CRISPR analyses (pg. 14, third paragraph). However, the elements in addition to the abstract ideas – here, an input device, storage device, and processor which receive data – are conventional and thus do not provide significantly more than the abstract ideas.
Therefore, the rejection under 35 USC 101 is maintained.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/R.J.K./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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