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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03 February 2026 has been entered.
Status of the Claims
Claims 1-23 are pending and examined herein. No claims are canceled.
Priority
As detailed on 15 March 2021 filing receipt, the application claims priority as early as 17 December 2019. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Withdrawn Rejections
The objection to the specification is withdrawn in view of removal of the reference to tumoroids.
The objection to claim 23 is withdrawn in view of amendment to remove the second period ending the sentence.
The rejection under 35 USC 112(a) to claims 1-23 regarding application to tumoroids is withdrawn in view of amendment to remove reference to tumoroids.
The following rejections and/or objections are either maintained or newly applied. They constitute the complete set applied to the instant application.
Claim Interpretation
Claim 1 recites electing one or more models "when" the cancer models comprise scores above a certain threshold, and then using the models to investigate cancer biology. Since there is an embodiment in which the models comprise scores which do not reach a certain threshold, the using of the models is not required. A similar interpretation applies to claim 14.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims recite “determining a therapeutic response of the selected cancer model to at least one cancer therapy.” The claims do not appear to disclose a “therapeutic response.” The background found in the specification discloses these models are used to explore patient specific response (pg. 1, paragraph [3]) and a major goal of the field being enabling therapeutic discoveries (pg. 35, paragraph [110]), but not such a determination based on a therapy based on the recited method. Claims 14-15 recite similar limitations. Claims 2-13 and 16-23 are similarly rejected as they are dependent on claim 1 or 14-15.
Furthermore, claim 15 recites a system comprising a controller comprising a computer readable medium and processor which determines a response in the cancer model after a cancer therapy based on the recommendation from the classification. However, the specification does not appear to disclose the physical hardware that allows response determination from a cancer model to which a therapy has been applied. Therefore, this claim elements lack written description support from the specification and is rejected along with dependent claims 16-20 and 23.
Response to the 03 February 2026 Applicant Remarks
Applicant remarks state, regarding the lack of written description for determining a therapeutic response, that the specification need not recite the claim language verbatim nor must it describe every implementation detail, particularly where the missing detail would be well-understood in the art (pg. 49) and experimental discovery of a response using, for instance, tumor growth inhibition, cell viability or proliferation changes, biomarker modulation, and survival or regression metrics (for in vivo models), are conventional (pg. 50). This argument is unpersuasive. Applicant remarks state exploring patient response in the introduction (paragraph [3]). Importantly, this is disclosed in the background of the disclosure and is not disclosed as based on the abstract steps required in the claims. Similarly, disclosure that developing models is a major goal (paragraph [110]) does not disclose determining a response in a physical model. Applicant remarks state the application of selected cancer models for therapeutic evaluation (paragraphs [55-56]). Paragraph [55] discloses the subject but not the model. Paragraph [56] discloses identifying and selecting cancer models, but not performing a physical test on a model to validate the selection. Neither the text nor drawings show possession of the idea of validating or experimentally determining a therapeutic response based on the model selection. For instance, Figure 1, disclosed as exemplary, ends with a selection step. While a specification need not disclose what is well known in the art, as determined in Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366, 42 USPQ2d 1001, 1005 (Fed. Cir. 1997), determining a response based on a real world model following selection of that model based on the recited abstract steps is not disclosed at all. Therefore, the written description support for determining a therapeutic response is considered not found in the specification (MPEP 2163) and this rejection is maintained under 35 USC 112(a).
Applicant remarks state, regarding the lack of written description for a computer comprising a controller, computer-readable media, and at least one processor being able to carry out the above discussed therapeutic response, that a generic computer need not be described in detail (pg. 51) and that the claims recite computational identification and analysis but not measuring tumors, which can be performed by receiving and analyzing experimental data (pg. 52). These statements appear to contradict prior statements which stress that the models – CCL, GEMM, and PDX – are used to physically determine a real-world response: “The claims do not end with a score or recommendation. They require use of the selected physical cancer models to identify therapeutics” (pg. 55, seventh bullet). A preclinical therapeutic evaluation using one of the models is interpreted as actually using the model based on the data generated by the abstract steps. However, the instant remarks emphasize a therapy or tumor measurement is not required, only data analysis, which would not integrate the abstract ideas into a practical application at Step 2A Prong Two of analysis in the 101 framework. If the data is being generated outside of the computer system comprising the controller, media, and processor and the system is invoked for analyzing the results, then method steps not performed by the system are claimed, which would render the claims indefinite. MPEP 2173.05(p)(II) pertains. Therefore, this rejection under 35 USC 112(a) is also maintained.
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 1-23 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 "evaluating cancer model fidelity."
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prone 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 1-10, 12-14, and 21-22), a non-transitory computer-readable medium (claim 11), and a computer system (claims 15-20 and 23), 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);
• certain methods of organizing human activity (fundamental economic practices or
principles, managing personal behavior or relationships or interactions between people);
and/or
• mental processes (procedures for observing, evaluating, analyzing/ judging and
organizing information).
Mathematical concepts recited in the independent claims include: "pair-transforming… the gene pairs to produce one or more binarized training data sets," "generating… one or more random gene-pair profiles through random permutations of the training data sets," "selecting… one or more gene-pairs as features to produce a random forest classifier," and "producing one or more classification scores." It is important to note that a mathematical concept need not be expressed in mathematical symbols, because words used in a claim operating on data to solve a problem can serve the same purpose as a formula (MPEP 2106.04(a)(2)), and these steps involve using math (e.g., "utilizing" a "model," "pair-transforming" to "binarize," "producing one or more classification scores"). A mathematical relationship may be expressed in words and there is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, a claim does not have to recite the word "calculating" in order to be considered a mathematical calculation. For example, a step of "determining" a variable or number using mathematical methods or "performing" a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation (MPEP 2106.04(a)(2)).
Mental processes, defined as concepts practically performed in the human mind such as steps of evaluating, analyzing or organizing information, recited in the independent claims include: "generating… one or more training data sets," "identifying… intersecting genes," "partitioning… the intersecting genes," "generating… one or more read-pairs," and "selecting… one or more discriminatory gene-pairs," "classifying a biological sample… using the classification score," "evaluating one or more cancer models," and "selecting a cancer model… using the classification score." Generating a dataset is interpreted as creating a list of data, which the human mind is practically equipped to do. Identifying intersecting genes is interpreted as data comparison, which the human mind is practically equipped to perform. Partitioning data and generating pairs is interpreted as subsetting the data, which the human mind can perform. The human mind is practically equipped to perform a selection.
Dependent claim 2 recites details about the input data. Dependent claim 3 recites further details of the abstract step of partitioning. Dependent claim 4 recites further details of the abstract step of evaluating. Dependent claims 5, 8, and 17 recite further details of the step of generating a classifier. Dependent claims 6, 9-10, 13, 16, 18, and 20 recite further details of the genes to be selected and thus an abstract step. Dependent claims 7, 12, and 19 recite further details the abstract step of producing classifiers.
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 2 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))?
The following are additional elements that are not abstract ideas: a "computer" (claims 1, 14, and 15), "a non-transitory computer-readable media" (claim 11), "a controller" (claim 15), "non-transitory computer executable instruction" (claim 15), "processor" (claim 15), "outputting a recommendation" (claim 15), “determining a therapeutic response of the selected cancer models” following a therapy (claims 1 and 14-15) and additional information regarding the therapy (claims 21-23).
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. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)). The step of outputting a recommendation is interpreted as necessary data outputting and thus insignificant extra solution activity (MPEP 2106.05(g)).
The step of determining a therapeutic response to a therapy is interpreted as applying the determination of the model. The therapy, whether a therapeutic or potential therapeutic – is non-specific, and appears to be validating the selection of the model. Therefore, this step is interpreted as instructions to apply the exception, which does not integrate the abstract idea into a practical application (MPEP 2106.05(f)).
Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are directed to that abstract idea. [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 following are additional elements that are not abstract ideas: a "computer" (claims 1, 14, and 15), "a non-transitory computer-readable media" (claim 11), "a controller" (claim 15), "non-transitory computer executable instruction" (claim 15), "processor" (claim 15), "outputting a recommendation" (claim 15), “determining a response of the selected cancer models” following a therapy (claims 1 and 14-15) and additional information regarding the therapy (claims 21-23).
Use of conventional computer elements is interpreted as instructions to apply the abstract idea using a computer, and applying the abstract ideas cannot provide an inventive concept. Outputting a recommendation is interpreted as sending information over a network, which is a conventional computer task (buySAFE Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) ). Mere instructions to apply the abstract idea are, when considered individually, insufficient to constitute an inventive concept that would render the claims significantly more than an abstract idea (see MPEP 2106.05(f)). Trastulla (Molecular Systems Biology 18(11017): 24 pgs., 2022; previously cited on the 11 November 2025 PTO-892 form) teaches computational methods of evaluating suitability of cancer models and determining the best patient representative, and subsequently investigating oncological therapies (abstract). Finally, as described above in the “Claim Interpretation” section, the claims recite selecting a model when the score is above a threshold, then determining a response based on the selected model. However, there is a possibility that a model does not have a classification score above a threshold and thus a model is not selected, and therefore response in a model is not determined. A similar interpretation applies to claim 14. [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 03 February 2025 Applicant Remarks
Applicant remarks state, with respect to Step 2A Prong One in the 101 analysis framework, that the claims do not recite abstract ideas (pg. 53). First, applicant remarks assert that generating expression datasets, pair-transforming gene pairs, producing binarized datasets, generating random permutations, producing a random forest classifier, and producing scores are not mental steps. This is agreed to, with the exception that generating a dataset can be practically performed by the human mind and/or with pen and paper. Applicant remarks go on to assert these list elements are not to be interpreted as mathematical concepts because they are part of a larger process (pg. 54). Whether the elements are directed to a practical application is determined at Step 2A Prong Two. Because mathematical concepts and mental processes are claimed, analysis in the 101 framework continues at Step 2A Prong Two.
Applicant remarks state, with respect to Step 2A Prong Two in the 101 analysis framework, that the claims are directed to a practical application because they require selecting a model based on scores and determining a response to identify a potential therapy, which further asserted to be a real-world application and not instructions to apply the abstract idea (pg. 55). The claim recites determining a therapeutic response in the model to identify therapeutics. While selection of a model is based on the abstract steps, what the therapy is and how a response is determined is not recited nor clearly disclosed in the specification. Therefore, this step is interpreted as broadly reciting using the determined model. Applicant remarks analogize the instant claims to Diamond v. Diehr, where calculations are used to automatically process reagents produce rubber, transforming it into a different state or thing, but no such similar steps are performed in the instant claims. Applicant remarks analogize the instant claims to Rapid Litig. Mgmt. v. Cellzdirect, Inc., where an improved process for preserved cells is disclosed based on laws of nature. The only non-abstract steps recited are collecting data, outputting data, and use of a computer, and so the claims are not interpreted as analogous. Applicant remarks assert outputting a recommendation is not merely outputting information because the output is a cancer model. It is unclear why the data being output by the computer based on the abstract steps changes the outputting from data outputting to a practical application. Employing the model – interpreted as physically using the model to determine a therapy in the real-world – is not part of the data outputting step. Therefore, the additional elements are not interpreted as integrating the abstract ideas into a practical application at Step 2A Prong Two.
Applicant remarks state, with respect to Step 2B in the 101 analysis framework, that a gene-pair transformation, binarization, random permutation, and classification using a model provides significantly more than the abstract ideas because they are non-conventional steps, as evidenced by not being taught by cited art Trastulla (pg. 56). The steps found in the list are all abstract steps. An inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05). The conventionality, alone and in combination, of elements in addition to the abstract ideas is determined at Step 2B, and steps such as binarization, permutation, and classification are abstract steps. The following are elements in addition to the abstract ideas which are evaluated at Step 2B: a "computer" (claims 1, 14, and 15), "a non-transitory computer-readable media" (claim 11), "a controller" (claim 15), "non-transitory computer executable instruction" (claim 15), "processor" (claim 15), "outputting a recommendation" (claim 15), “determining a response of the selected cancer models” following a therapy (claims 1 and 14-15) and additional information regarding the therapy (claims 21-23). The review by Trastulla teaches these elements, namely computational methods of evaluating suitability of cancer models and determining the best patient representative, and subsequently investigating oncological therapies (abstract). The “architecture” comprises abstract steps and are not required to be evaluated for conventionality. Finally, it is noted that eligibility and novelty are not being conflated at Step 2B (pg. 56). Evidence of conventionality of the additional elements being taught by Trastulla is a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional elements (MPEP 2106.05(d)(I)(2)(c)). The claims are considered free of the prior art because the abstract steps are considered novel alone or in combination with the additional elements.
Finally, as explained in the Clams Interpretation section above, it is remarked that the last claim element recites outputting a selected cancer model recommendation only when they are scored above a threshold and then determining a response based on the selected model. Because there is interpreted to be a situation in which classification scores do not score above a given threshold, the step determining a response is contingent and only happens under the stated circumstance. Amendment to recite selecting a model with classification scores above a threshold then outputting the recommendation of the model with such a classification score may overcome this interpretation.
For these reasons, 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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/Robert J. Kallal/Examiner, Art Unit 1685