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 Claims
Applicant' s amendment filed 06/10/2026 is acknowledged. Claims 1-2, 4, 8-9, 11, 13, and 16 have been amended. Claims 3, 5-7, 10, and 12 have been cancelled. Claims 1-2, 4, 8-9, 11, and 13-17 are pending in the instant application and the subject of this final office action.
All of the amendments and arguments have been reviewed and considered. Any rejections or objections not reiterated herein have been withdrawn in light of amendments to the claims or as discussed in this office action.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Non-Compliant Amendment
Applicant’s amendments filed 06/10/2026 fail to comply with 37 CFR 1.121 for the following reason(s): Claim 4 has deleted text (“and/or mRNA expression.”) relative to the previous version dated 12/16/2025 that is not shown with a strike-through.
It is emphasized that Applicant’s response filed 06/10/2026 has been considered in the
interest of customer service and compact prosecution. However, for the response to this Office Action to be complete, Applicant is required to file amendments that are fully compliant with 37 CFR 1.121. Failure to comply with this requirement will be considered nonresponsive.
Previous Rejection
Status of Prior Rejections/Objections:
The objection to claim 1 is withdrawn in view of the claim amendments.
The 112(a) enablement and written description rejections are withdrawn in view of the amendments and arguments. See Response to Arguments.
The 101 rejection is maintained and clarified/updated in view of the amendments.
New Ground(s) of Rejections
The new ground(s) of rejections were necessitated by applicant’s amendment of the claims.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Objections
Claim 4 is objected to because of the following informalities:
Claim 4: The claim is missing a period.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
Claims 1-2, 4, 6-11, and 13-17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception(s) without significantly more. The claim(s) recite(s) abstract ideas. This judicial exception is not integrated into a practical application. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The following three inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter?
Yes, the claims are directed to a process/method.
Step 2A, prong 1. Does the claim recite a law of nature, a natural phenomenon, or an abstract idea (recognized judicial exceptions)?
Claim 1 recites an in vitro cell-based screening method to identify compounds effective in the treatment of cancer, comprising determining an expression level for a cell or plurality of cells; and assigning to a test compound a score wherein said score is high and indicating identification of a compound effective in the treatment of cancer if said expression level is below a predetermined threshold; said score is low if said expression level is equal to or above said predetermined threshold corresponding to an expression level in a control cell.
The steps of determining an expression level and assigning said score encompass abstract ideas. Namely, the determining an expression level encompasses an abstract idea, e.g., mental processes (e.g., observations, evaluations, judgements), for example, direct visualization of an image of stained protein/in situ hybridized of mRNA (see, for example, instant specification pg. 7, para 1). Likewise, assigning the test score to the compound encompasses an abstract idea, including mental processes (e.g., observations, evaluations, judgements) and/or mathematical calculations (including those that may be performed by the human mind), including basic comparisons of two numbers or visual evaluations.
In claim 2 where the expression level is limited to the average expression level, the claims further reiterate the abstract ideas as performing an average calculation is a mathematical calculation, including one that may be performed by the human mind.
Step 2A, prong 2. Is the judicial exception(s) integrated into a practical application?
Regarding claims 1-2, the claim further recites contacting a cell or plurality of cells with an inhibitor of a signaling pathway and a test compound and that the cell/plurality of cells comprises an activating mutation in a gene encoding a protein comprised in said signaling pathway or an amplification in a gene encoding a protein comprised in said signaling pathway.
The step of contacting is a matter of mere data gathering that is necessary for all such instances of the abstract ideas. See MPEP 2106.05(g). The determining of an expression level may also be considered such data gathering, see, e.g., Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968.
The limitation that the expression level be an average maintains the abstract nature of those steps of the claim, as an average is a mathematical calculation.
Regarding claim 4, the claim, as amended, requires that the determining is by analyzing protein expression. The claim does not require steps of analyzing, but merely a determination by analyzing the types of expression. Thus, the step still encompasses an abstract idea of a mental process as this limitation merely recites the particular data utilized in the determining (e.g., visual image of protein/mRNA expression or data in a table representing protein/mRNA expression).
Regarding claims 9, 11, and 15-17, the claims represent limitations directed to the selection of cells (e.g., via the signaling pathway and mutations therein) and/or of particular inhibitors. Such represents essential data gathering for the judicial exception(s) and is insufficient to integrate the claims into a practical application. See MPEP 2106.04(d)(I) and 2106.05(g).
Regarding claims 8 and 13-14, the limitations are directed to the cancer. The cancer is recited in the preamble, wherein it imposes the structure of the “over-activated signaling pathway” that the mutation in the cell/plurality of cells and the inhibitor corresponds to and in the score assignment. The cancer in “the treatment of cancer” is also recited in the assignment of the test compound score as what the compound is effective in treating. Accordingly, the limitations are directed to selecting a particular data source to be manipulated in the judicial exceptions and are a part of the abstract “indication” being asserted in step (c). Neither is sufficient to integrate the claims into a practical application. See MPEP 2106.04(d)(I) and 2106.05(g).
The activating mutation/amplification in claim 13 is directed to a selection of data and is insufficient to integrate the claims for the same reasons.
Step 2B. Does the claim amount to significantly more?
The analysis from Step 2A Prong 2 is reiterated.
As above, the score assignment and determination of an efficacious treatment encompasses an abstract idea. Even if the scoring system were novel, MPEP 2105.06(I) recites that the inventive concept cannot be furnished by the judicial exception and the “novelty” of any element or steps in a process is of no relevance to determining whether the subject matter itself falls within the 101 categories of patentable subject matter.
The courts have found that adding insignificant extra solution-activity to the judicial exception is not sufficient to represent significantly more. Thus, even if the determination of an expression level were narrowed beyond an abstract idea to any of the well-known and conventional means of assessing expression level, such contacting and determining of expression in steps (a) and (b) represent essential data gathering that is also well-known and routine (i.e., insignificant extra-solution activity). For example, Sun (Sun X, et al. High-throughput methods for combinatorial drug discovery. Sci Transl Med. 2013 Oct 2;5(205):205rv1) teaches that combination drug treatments have been used for over 30 years and that high-dimensional data capture technologies, such as transcriptome sequencing, expression and protein microarrays, and drug screening are being applied to evaluate drug combinations (pg. 1, col 2, para 1). Roller (Roller, 2015, e.g., pg. 2741, col 2, para 2; Supplementary Table 2) more specifically, teaches the contacting of cells with an activating mutation with an inhibitor and a test compound and determining an expression level for the cell both subsequent to contacting with both drugs and with only the inhibitor, wherein such is applied over an average of cells for proteins and mRNA (entire document, e.g., Supplementary Table 2).
In claim 4, where the amended claim is directed to methods of determining protein expression, Roller also teaches determination of protein expression following a combination of an inhibitor and a “test compound” (Fig. 4 C-H). See also above where Sun recites that methods of protein microarrays in combination drug screens are used to evaluate combination drug treatments. While the expression of the instant genes was not determined, the limitation remains directed to insignificant extra-solution activity where the choice of genes represents merely a particular type of data to be manipulated, essential to perform the abstract idea of step (c). See MPEP 2106.05(g).
The remaining claim limitations are directed to the abstract idea and/or choices of cells/signaling pathways/inhibitors that amount to selecting a particular type of data to be manipulated in the judicial exception, i.e., insignificant extra solution activity.
Thus, taken as a whole, the claims do not represent significantly more than the judicial exception.
Response to Arguments
Applicant’s arguments, see pg. 6-10, filed 6/10/2026, with respect to the 112(a) written description and enablement rejections of claims 1-2, 4, 6-11, and 13-17 have been fully considered and are persuasive. In particular, Applicant argues that the amended claims are now directed to the top deregulated genes (e.g., Fig. 1C) and that the variability in the expression levels across different cell lines does not undermine written description or enablement as the claim recites assigning a score based on whether expression is above or below a threshold and do not require any particular magnitude of expression change.
Therefore, the 112(a) rejections of claims 1-2, 4, 8-9, 11, and 13-17 have been withdrawn.
Applicant's arguments regarding the 101 rejections, filed 6/10/2026, have been fully considered but they are not persuasive.
Applicant argues, on pg. 11-12, that even if the claims recite a judicial exception, the claims recite steps that are not well-known and conventional. Applicant alleges that it was the inventors who found that compounds that prevent the development of resistance to inhibitors of the MAPK and EDGR pathway can be found by an in vitro cell-based screening by determining expression level of SOX2 and/or the expression of a gene under transcriptional control of SOX. Applicant argues that contrary to the Office Action, Roller does not suggest using expression levels as a readout in a screening assay; rather Roller relates to cytotoxic synergy screens measuring cell viability and refers to Supplementary Table 2 in the context of gaining potential mechanistic insights. Applicant argues that the claims recite additional elements that amount to significantly more than the alleged judicial exception.
While it is appreciated that the scoring and read out of the inventors may be novel, such represents a judicial exception, as analyzed above. MPEP 2106.05(I) recites that:
An inventive concept "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself." Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016). See also Alice Corp., 573 U.S. at 21-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 78, 101 USPQ2d at 1968 (after determining that a claim is directed to a judicial exception, "we then ask, ‘[w]hat else is there in the claims before us?") (emphasis added)); RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"). Instead, an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).
Roller recites this analysis as a “analysis of drug-induced adaptive changes in cell signaling … profil[ing] the transcriptional responses in five lines to treatment for 8 hours with PLX4720, lapatinib, masitinib or the combinations using Illumina HT12 v4 arrays” (pg. 2741, col 2, para 2; see also Supplementary Table 2 for the lines comprising such activating pathways as claimed), which may be broadly interpreted as a “in vitro cell-based screening method to identify compounds effective in the screening of cancer”. See, for example, Abstract: ”In this communication we ask whether BRAFV600E melanomas share common adaptive responses to BRAF inhibition that can provide clinically relevant targets for drug combinations” and Fig. 8: Heat Map of adaptive transcriptional changes in response to drug treatment. Respectfully, that Roller also utilizes cytotoxicity as a read out in a larger screen is immaterial. First, Roller is determining expression for at least at one claimed gene under the control of SOX2 after contacting a cell with a BRAFi and a TKI (i.e., test compound) or an EGFRi and a TKI and it is in an in vitro cell-based screen context, broadly interpreted, where the intention is to find clinically relevant targets for drug combinations. Second, the claims recite “comprising”.
Applicant may consider, if sufficiently supported by the disclosure, a particular treatment step as in the example in MPEP 2106.04(d)(2)(c); see also 2105.06(e) discussing Classen Immunotherapies Inc. v. Biogen IDEC. Alternatively, Applicant may consider specific steps in the methods, as supported by the disclosure, of contacting and/or determining expression that is not recited at the generic level of insignificant extra-solution activity (i.e., data gathering/selecting a particular data source) such that it would integrate the claim into a practical application.
Conclusion
No claims are allowed.
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 Emma R Hoppe whose telephone number is (703)756-5550. The examiner can normally be reached Mon - Fri 11:00 am - 7:00 pm.
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/EMMA R HOPPE/Examiner, Art Unit 1683
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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