DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-23 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Withdrawn Rejections
The rejection of claim 15 and claims dependent on claim 15 under 35 USC 112(a) is withdrawn in view of persuasive argument and amendment regarding what the computer system is able to perform.
The following rejections and/or objections are either maintained or newly applied. They constitute the complete set applied to the instant application.
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 1-14 and 21-22 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.
Claim 1 recites “testing at least one cancer therapy on the one or more selected cancer models in vitro or in vivo.” The specification does not disclose testing at least one cancer therapy determined by the required steps on the one or more selected cancer models in vitro or in vivo. Claim 1 recites “determining a therapeutic response of the selected cancer models to the at least one cancer therapy to evaluate or identify the one or more potential therapeutics.” The specification discloses “PDXs to explore patient-specific response to therapy in a physiologically relevant context” (pg. 1, paragraph [3]) but not determining a therapeutic response from the selected model. Claim 14 recites similar elements. Claims 2-13 and 21-22 are similarly rejected as they are dependent on claim 1 or 14.
Response to the 27 August 2026 Applicant Remarks
Applicant remarks state there is support in the specification for having classification scores that are above a classification score at paragraph [11] of the specification, pointing to "selecting one or more of the cancer models ... when the cancer models comprise classification scores that are above a classification threshold score" and paragraph [55]). The phrase “above a classification threshold score” does not appear in the specification. Paragraph [11] discloses expression profiles comprise RNA-seq and/or microarray profiles and paragraph [55] discloses information about the subject. Therefore written description support is lacking. Applicant remarks state the claimed "testing at least one cancer therapy on the one or more selected cancer models in vitro or in vivo” is supported in paragraph [0003] as "evaluating candidate therapeutics across preclinical models") and paragraph [0055] as "the selected cancer models can be used to evaluate or identify potential therapeutics ... tested in vitro or in vivo"), and paragraph [0110]. The quoted text does not appear in paragraphs [3], [55], or elsewhere in the specification. Paragraph [110] discloses major goal of the field being enabling therapeutic discoveries (pg. 35, paragraph [110]), but not testing the selected model. Applicant remarks state paragraph [14] recites “outputting a recommendation” but outputting is not disclosed except outputting a classification in paragraph [52]. Applicant remarks state a computational controller outputting actionable model selection metrics to guide laboratory preclinical studies is supported at paragraph [139]), but these are not supported; paragraph [63] recites a program to facilitate “a guided search application.” Therefore, written description support for the claims where indicated by the applicant is not found.
Applicant remarks state paragraphs [3], [55], and [110] disclose using the selected models to test candidate drugs. 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. Applicant remarks state paragraph [55] “explicitly states that once high-fidelity models are selected, candidate therapies are tested in vitro or in vivo to measure therapeutic responses” but paragraph [55] describes the subjects which are used for the training set. As explained above, paragraph [110] discloses comparing models but not therapeutic response.
Therefore, the paragraphs indicated in the specification do not provide written description support for the amendments.
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," "selecting a cancer model… using the classification score," and “determining a therapeutic response.” 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. Determining a therapeutic response is an evaluation step following the application of a cancer therapy, where evaluating if a response is a mental process.
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))?
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)).
The following are additional elements that are not abstract ideas: a "computer" (claims 1, 14, and 15), “testing at least one cancer therapy” (claims 1 and 14), "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), 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)). It is also construed as further data collection to perform the final step of determining a response, where determination is an abstract step.
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. Claims that are directed to abstract ideas must be examined further to determine whether the additional elements besides the abstract idea render the claims significantly more than the abstract idea. Claims that are directed to abstract ideas and that raise a concern of preemption of those abstract ideas must be examined to determine what elements, if any, they recite besides the abstract idea, and whether these additional elements constitute inventive concepts that are sufficient to render the claims significantly more than the abstract idea (MPEP 2106.05). [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), “testing at least one cancer therapy” (claims 1 and 14), "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), 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), which is considered to include testing therapies. 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 27 August 2026 Applicant Remarks
Applicant remarks state, with respect to Step 2A Prong Two in the 101 analysis framework, “claims 1 and 14 do not end in abstract calculations, classification scores, or mere data analysis” (pg. 48). This is not persuasive because claim 1 ends with “determining a therapeutic response,” where determining a response is an evaluation step following the testing step and thus an abstract step in the form of a mental process. Applicant remarks state claims 11 and 15 recite improvements to a computational system in the form of generating binarized gene-pair permutations to generate selection recommendations (pg. 48), but the improvement lies in the abstract ideas and the selection is an abstract step.
Applicant remarks state, with respect to Step 2B of the 101 framework, that Trastulla, as Berkheimer evidence, fails to teach pair transforming gene sets into binarized data sets, generating gen-pair profiles, and construction random forest classifiers (pg. 49). However, all of these are abstract ideas. 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 criterion for overcoming the rejection under 35 USC 101 as compared to those for art rejections under 35 USC 102 and 103 is different. If the prior art does not teach or fairly suggest all aspects of the claims, then the art rejection is overcome, but at Step 2B, elements in addition to the abstract ideas are evaluated for conventionality such that, alone or in combination, they suggest significantly more if not found in the prior art. Elements in addition to the abstract ideas are not considered at Step 2B, and so pointing to steps such as binarization is not persuasive..
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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/R.J.K./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
