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 amendments and remarks, filed on 12/10/2025, are acknowledged. Applicant’s arguments have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn.
Status of Claims
Claims 1, 2-4, 7, 9, 10, and 12-19 are under examination.
Claims 5-6, 8, 11, 20, 21 have been cancelled.
Priority
Applicant’s claim for the benefit of priority under 35 U.S.C. 119(a)-(d) is acknowledged. This application is a U.S. National Stage Patent Application under 35 U.S.C. § 371 of International Application No. PCT/US2015/030118, filed on May 11, 2015, which claims priority to US Provisional Application Nos. 61/991,005, filed on May 9, 2014, and 62/027,045, filed on July 21, 2014. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
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, 2-4, 7, 9, 10, and 12-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
The United States Patent and Trademark Office published revised guidance on the application of 35 U.S.C. § 101. USPTO’s 2019 Revised Patent Subject Matter Eligibility Guidance (“Guidance”). Under the Guidance, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes) (Guidance Step 2A, Prong 1); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)) (Guidance Step 2A, Prong 2).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that are not “well-understood, routine and conventional in the field” (see MPEP § 2106.05(d)); or 2019 Revised Patent Subject Matter Eligibility Guidance, 84 Fed. Reg. 50-57 (January 7, 2019).
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.(Guidance Step 2B). See Guidance, 84 Fed. Reg. at 54-56.
After careful consideration of the two-part analysis, it is the examiner’s position that the claimed invention encompasses an abstract idea for the following reasons.
Guidance Step 1:
The instantly claimed invention is directed to a method/system for identifying a mechanism of action of a compound using network dysregulation. Thus, the claim is directed to one of the statutory categories of invention. MPEP 2106.03.
A. Guidance Step 2A, Prong 1:
As discussed in the MPEP, abstract ideas include mathematical concepts (mathematical relationships, mathematical formulas or equations, mathematical calculations; see MPEP § 2106.04(a)(2), subsection I); certain methods of organizing human activity (see MPEP § 2106.04(a)(2), subsection II); and mental processes (concepts performed in the human mind including an observation, evaluation, judgment, opinion; see MPEP § 2106.04(a)(2), subsection III). In this case, the claimed steps that are part of the abstract idea are as follows:
Claim 1
(b) determine, using Gaussian kernel smoothing and a gene expression profile… a two-dimensional probability density of gene expression levels for each of the interactions in a control state of the regulatory network…;
(c) determine, using Gaussian kernel smoothing and a gene expression profile…a two-dimensional probability density of gene expression levels for each of the interactions in at least one compound-perturbed state…;
(d) estimate, for each of the interactions, differences between the control probability density and the compound-perturbed probability density…;
(e) determine…a set of statistically significant dysregulated interactions, based only on the gene expression data;
(f) rank the statistically significant dysregulated interactions, to provide a set of candidate mechanism of action (MoA) genes.
(g) determine a MoA of the therapeutic compound within the tissue-specific regulatory network, by selecting the set of candidate MoA genes and assessing the MoA in the context of the established regulatory network, wherein at least one of the MoA genes used in determining and included in the MoA was not differentially expressed between the control and compound-perturbed state.
Claim 13
(b) determine, using Gaussian kernel smoothing and a gene expression profile…a first n-dimensional probability density of gene expression levels for the first gene and one or more genes in a control state of the regulatory network;
(c) determine, using Gaussian kernel smoothing and a gene expression profile…a second n-dimensional probability density of gene expression levels for the first gene and the one or more genes in a first compound-perturbed state…;
(d) estimate changes between the first probability density and the second probability density;
(e) determine whether the estimated changes are statistically significant;
(f) determine, where the estimated changes are statistically significant, whether the interaction is dysregulated;
(g) repeat (a)-(f) for each of m interactions wherein the m interactions comprise every interaction ending in the first gene in a regulatory network;
(h) determine whether the first gene is dysregulated based at least in part on the significance of each interaction; (i) repeat (a)-(h) for a plurality of genes;
j) identify a mechanism of action (MoA) of the first compound by selecting genes that are dysregulated, and assessing the MoA in the context of the established regulatory network, wherein at least one of the MoA genes used in determining and included in the MoA was not differentially expressed between the control and compound-perturbed state;
(k) repeat (a)-(j) for a plurality of compound treatments using a plurality of compounds; and (l) identify two or more compounds with similar pharmacological effect, based on similar MoA.
Mental Processes
Regarding claim(s) 1 and 13, the above steps encompass analyzing gene expression data (using mathematical techniques) and making determinations/decisions based on said analysis. As such, the above steps can all be reasonably performed by the human mind of a scientist. Applicant is reminded that the Office's eligibility guidance does not set limit on the number of calculations that can or cannot be performed mentally. MPEP § 2106.04(a)(2)III. It is also well settled that mere computer-based efficiency does not save an otherwise abstract method. Bancorp Servs. L.L.C. v. Sun Life Assur. Co. of Canada (US.), 687 F.3d 1266, 1277-78 (Fed. Cir. 2012) (explaining that performance by computer of operations that previously were performed manually or mentally, albeit less efficiently, does not convert a known abstract idea into eligible subject matter). For these reasons, the above steps also fall within the “mental processes” grouping of abstract idea set forth in the 2019 PEG (Section I, 84 Fed. Reg. at 52). With regards to the recitation of a processor and output device in the claims, this does not negate the mental nature of these limitations because the claims here merely use them as a tool to perform the otherwise mental processes. See also Intellectual Ventures I LLC v. Capital One Fin. Corp., 850 F.3d 1332, 1340 (Fed. Cir. 2017) (“[A]n invention directed to collection, manipulation, and display of data was an abstract process”). Therefore, the claims recite the judicial exception of a mental processes within the abstract-idea category [Step 2A, Prong 1: YES].
Mathematical Concept
Regarding claim(s) 1 and 13, the above steps for “determining” and “estimating” steps require determining probability densities and differences based on said probability densities. In addition, a review of the specification teaches mathematical algorithms for performing the claimed calculations [pages 9-11]. Therefore, under the BRI and in light of the specification, these steps amount to mathematical calculations. Applicant is reminded that there is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, claims are evaluated in light of the specification, and a claim does not have to recite the word "calculating" in order to be considered a mathematical calculation. Therefore, the claims also recite the judicial exceptions of mathematical concepts within the abstract-idea category [Step 2A, Prong 1: YES].
B. Guidance Step 2A, Prong 2
This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. In this case, the claimed steps that are not part of the abstract idea are as follows:
Claim 1
select a tissue-specific regulatory network having a plurality of molecular interactions , including both protein-DNA interactions and protein-protein interactions, each connecting a pair of genes;
(h) validating the MoA by confirming, by assessing direct compound binding targets in cells or a tissue having the tissue-specific regulatory network, a direct primary target interaction and/or an indirect effector interaction between the compound and the candidate MoA genes.
Claim 13
select a tissue-specific regulatory network having a plurality of molecular interactions each connecting a pair of genes, and having a first interaction involving at least a first gene;
(k) validating the MoA by confirming, in cells or a tissue having the tissue-specific regulatory network, a direct primary target interaction and/or an indirect effector/modulatory interaction between the compound and the candidate MoA genes;
With regards the claimed “selecting” steps, under the BRI, these limitations broadly encompass selecting data a particular data source for use by the abstract idea. Therefore, these steps amount to nothing more than insignificant extra-solution activity and are not indicative of an integration into a practical application. See MPEP 2106.05(g).
With regards to the validating steps, this limitation is nominally recited without any specific acts or operations for achieving the claimed result. Accordingly, these steps amount to generally linking the use of a judicial exception to a particular technological environment or field of use. See MPEP § 2106.05(h). It is notable that mere physicality or tangibility of an additional element or elements is not a relevant consideration in Step 2A Prong Two. As the Supreme Court explained in Alice Corp., mere physical or tangible implementation of an exception does not guarantee eligibility. Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 573 U.S. 208, 224, 110 USPQ2d 1976, 1983-84 (2014).
With regard to the generically processor, memory, and computer readable medium, applicant is reminded that “generic computer components such as a computer and database do not satisfy the inventive concept requirement.” See MPEP 2106.05(h). Accordingly, the claim as a whole does not integrate the recited judicial exception into a practical application and the claim is directed to the judicial exception. [Step 2A, Prong 2: NO]
C. Guidance Step 2B:
Under the 2019 PEG, a conclusion that an additional element is insignificant extra-solution activity in Step 2A should be re-evaluated in Step 2B. In this case, the claims do not include additional steps and/or elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s) for the following reasons:
As discussed above, the non-abstract steps (including the full limitations and not just the verbs) amount to nothing more than insignificant extra-solution activity. Therefore, these limitations remain nothing more than insignificant extra-solution activity even upon reconsideration, and does not amount to significantly more. In addition, Zhu et al. (PLoS Biology, April 2012, Volume 10, Issue 4, e1001301, p.1-19) teaches selecting a transcription network for identifying mechanisms of action of a compound [abstract, page 2, col 2, para 2] and validating target interactions [Abstract and page 2, col. 2, page 9, col. 2, and page 11]. Moreover, Zhu teaches their network combines six different types of data including DNA–protein binding, protein–metabolite interaction, and protein–protein interaction data [Abstract]. Therefore, the examiner maintains that there is nothing unconventional with regards to “selecting” a regulatory network as claimed or the nature of the data being used for analysis. With regards to the generically recited processor and computer readable medium, as explained above, these limitations at best are the equivalent of merely adding the words “apply it” to the judicial exception. Mere instructions to apply an exception cannot provide an inventive concept, and the courts have also explained that the use of generic computer elements do not alone transform an otherwise abstract idea into patent-eligible subject matter. See DDR Holdings (Fed. Cir. 2014). Even when considered in combination, these additional steps/elements do not provide an inventive concept [Step 2B: NO].
Dependent Claims
Dependent claims 2-4, 7, 9, 10, 12, 14-19 have also been considered under the two-part analysis but do not include additional steps/elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s) for the following reasons. In particular, claims 2-4, 7, 9, 10, 12, 14-19 all further limit the specificity of the abstract idea or the data used by the abstract idea and therefore are also directed to an abstract idea for reasons discussed above (Step 2A, prong 1 analysis). Therefore, based on the two-part analysis, the instantly rejected claims as a whole are not drawn to eligible subject matter as they are directed to an abstract idea (and/or natural correlation) without significantly more.
Response to Arguments
Applicant’s arguments, filed 12/10/2025, have been fully considered but are not persuasive for the following reasons.
Applicant argues that the step (e), as amended, is non-abstract and provides an improvement to the technology (by limiting the data used in step e) to ONLY gene expression data and requiring that at least one of the selected MOA genes is not differentially expression). In response, steps (b) through (g) have been interpreted as part of the abstract idea for reasons set forth above (Step 2A, prong 1 analysis) and analyzing a particular type of data (or data set) does not take step (e) out of the realm of being abstract. That being said, applicant is reminded that judicial exceptions themselves cannot show improvement to technology or integration into a practical application, because judicial exceptions themselves are neither technology nor practical applications. In other words, Applicant is essentially arguing that the abstract idea is the inventive concept. However, the claimed invention’s use of the ineligible concept to which it is directed (i.e. the abstract idea) cannot supply the inventive concept that renders the invention ‘significantly more’ than that ineligible concept.” See also BSG Tech LLC v. BuySeasons, Inc., 899 F.3d 1281, 1290 (Fed. Cir. 2018). In this case, the claim relies upon routine and conventional steps in combination with the abstract idea. That is not the kind of “technological” improvement that suffices for patent eligibility. See also Amdocs Ltd. v. Openet Telecom, Inc., 841 F.3d 1288, 1300, 1302 (Fed. Cir. 2016) (the claim “entail[ed] an unconventional technological solution (enhancing data in a distributed fashion) to a technological problem (massive record flows [that] previously required massive databases)” that “improve[d] the performance of the system itself.”) The novelty of the abstract idea is not sufficient to establish a practical application.
Applicant additionally argues that the claimed invention provides an improvement to the technology, namely by allowing for identification of MOA proteins that are not differentially expressed (citing pages 15-16 of the specification). In response, applicant still appears to be asserting that abstract idea (i.e. the algorithmic process steps) is what is providing the improvement and Applicant is reminded that the claimed invention’s use of the ineligible concept to which it is directed (i.e. the abstract idea) cannot supply the inventive concept that renders the invention ‘significantly more’ than that ineligible concept”, as set forth above. Indeed, the courts have instructed that “[t]he different use of a mathematical calculation, even one that yields different or better results, does not render patent eligible subject matter.” Board Of Trustees Of Leland Stanford Junior University, 991 F.3d 1245, 1251 (Fed. Cir. 2021). In addition, Applicant is reminded that it is improper to conflate 35 USC 101 analysis with prior art analysis under 35 USC 102/103, i.e. it is true that claims can be free of the prior art and yet still rejected under 35 USC 101.
Finally, applicant argues that the claims recite elements (i.e., limiting the data used in step (e) to only gene expression data; and requiring that at least one of the selected candidate MOA genes is not differentially expressed between the control and compound-perturbed state) that are not part of the alleged abstract ideas and were not "well understood, routine, conventional activity in the field" at the time the application was filed. In response, this argument is not persuasive because step (e) has been reasonably interpreted as part of the abstract idea, as set forth above, and therefore is not analyzed under the “Step 2A, prong 2” or “Step 2B” analysis. For these reasons, and absent any evidence to the contrary, the rejection is maintained.
Claim rejections - 35 USC § 112, 2nd Paragraph
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, 2-4, 7, 9, 10, and 12-19 are 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 pre-AIA the applicant regards as the invention. Claims that depend directly or indirectly from claim(s) 1 and 13 is/are also rejected due to said dependency.
Claim 1 recites “(g) determine a MoA of the compound within the tissue-specific regulatory network, by selecting the set of candidate MoA genes and assessing the MoA using the molecular interactions of the established regulatory network...”. It remains unclear as to the metes and bounds of the claimed “assessing” step such that the artisan would recognize the boundaries of the mathematical/computational step(s) intended, i.e. in what way is the claim “using” molecular interactions. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. See MPEP § 2173.05(q). In this case, the claim does not set forth any steps involved in the method/process of use and the specification does not describe in what way “molecular interactions” are used for “assessing” MoA that would serve to clarity the scope of this step. As such, it is unclear what method/process applicant is intending to encompass by said “assessing”. By claiming a method for performing such a specialized function in a computer system without disclosing the internal structure of that system/processor in the form of an algorithm, the claim is indefinite. Clarification is requested via amendment. This rejection is maintained as applicant has not provided any illuminating or clarifying amendments with regards to this issue.
Claims 1 and 13 recite “(h) validating the MoA by confirming, by assessing direct compound binding targets in cells or a tissue having the tissue-specific regulatory network, a direct primary target interaction and/or an indirect effector interaction between the compound and the candidate MoA genes.” In this case, the above phrase recites two different “by” phrases, e.g. “by confirming, by assessing direct compound binding targets”. Accordingly, it is unclear what positive process limitation(s) are encompassed by the above “validating” step such that the artisan would recognize the boundaries of the mathematical/computational step(s) intended. Clarification is requested via amendment.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PABLO S WHALEY whose telephone number is (571)272-4425. The examiner can normally be reached between 1pm-9pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anita Coope can be reached at 571-270-3614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PABLO S WHALEY/Primary Examiner, Art Unit 3619