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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/25/2026 has been entered.
Applicant's amendments and remarks, filed on 01/14/2026, 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 Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn.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 1-15 are presently under examination.
Priority
Applicant’s claim for the benefit of priority under 35 U.S.C. 119(a)-(d) is acknowledged. this application is the U.S. National Phase application under 35 U.S.C. §371 of International Application No. PCT/EP2020/052522, filed on February 2, 2020, which claims the benefit of European Patent Application No. 19155911.1, filed on February 7, 2019. 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 1-15 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.
Step 1
The instantly claimed invention (claims 1 and 14 being representative) is directed to a method and system for performing a series of process steps. As such, the claims fall into one of the four statutory categories.
A. Guidance Step 2A, Prong 1
The Revised Guidance instructs us first to determine whether any judicial exception to patent eligibility is recited in the claim. The Revised Guidance identifies three judicially-excepted groupings identified by the courts as abstract ideas: (1) mathematical concepts, (2) certain methods of organizing human behavior such as fundamental economic practices, and (3) mental processes. In this case, the following limitations constitute the abstract idea for the following reasons:
processing the image or sequencing data to determine values for biomarkers in the cancerous lesion; wherein the biomarkers comprise: (i) a measurement of three prime repair exonuclease 1 (TREXI) in the cancerous lesion compared to a measurement of TREX1 from a first control…;
calculating, for the respective determined values of the biomarkers, a responsiveness score, wherein the responsiveness score indicates a predicted treatment outcome to each of a plurality of treatment modalities; wherein the treatment modalities comprise at least one of a defined radiation dose and/or fractionation in combination with immunotherapy…;
ranking the treatment modalities based on the calculated responsiveness score in order to identify a specified treatment modality for treating the cancerous lesion in the subject;
providing output comprising the ranking for the treatment modalities to a user on a display for decision support for choosing the treatment modality for the cancerous lesion.
Mental Processes
In this case, the italicized steps are all nominally recited in result-oriented fashion without any details specifying how these functions are being performed. As such, the claimed steps generally encompass performing analysis and/or calculations, and making decisions based on said analysis. In addition, the specification provides sufficient evidence that the claims are directed to an abstract idea since the specific descriptions provided for accomplishing these tasks include algorithms for performing data analysis [see, e.g. pages 12-14]. Accordingly, but for the recitation of a computer processor (in claim 14), the above steps clearly fall within the mental process groupings of abstract ideas because they cover concepts performed in the human mind, including observation, evaluation, judgment, and opinion. See MPEP 2106.04(a)(2), subsection III [Step 2A, Prong 1: YES].
Natural Correlation
Under the broadest reasonable interpretation, the above claims also recite a natural correlation. In particular, the instant claims require generating scores associated with biomarkers from cancerous lesions. Therefore, the claims require determining a naturally occurring relationship between a subject’s data and disease. See MPEP 2106.04(b). It is noted that even if a claim does recite a law of nature or natural phenomenon, it may still be eligible. For example, claims reciting a naturally occurring relationship between a patient’s genotype and the risk of QTc prolongation (a law of nature) were held eligible as not “directed to” that relationship because they also recited a step of treating the patient with an amount of a particular medication that was tailored to the patient’s genotype. Vanda Pharms., 887 F.3d at 1134-36, 126 USPQ2d at 1279-81. This particular treatment step applied the natural relationship in a manner that integrated it into a practical application. The court’s analysis in Vanda is equivalent to a finding of eligibility at Step 2A Prong Two (Pathway B).
B. Guidance Step 2A, Prong 2
This part of the eligibility analysis evaluates whether the claim includes any additional steps/elements that integrate the recited judicial exception into a practical application of the exception. In this case, the additional steps/elements that are not part of the abstract idea are as follows:
receiving image or sequencing data associated with a cancerous lesion in the subject;
providing output comprising the ranking for the treatment modalities to a user on a display for decision support for choosing the treatment modality for the cancerous lesion;
administering a treatment of the cancerous lesion to the subject, based on the treatment modality chosen for the cancerous lesion.
In this case, under the BRI, the receiving step is generically recited and broadly requires obtaining data for use by the abstract idea. Accordingly, this step amounts to insignificant extra-solution activity and is not indicative of an integration into a practical application. See MPEP 2106.05(g). Similarly, the providing step is generically recited and amounts to outputting/displaying information. Accordingly, this step also amounts to insignificant extra-solution activity and is not indicative of an integration into a practical application. See MPEP 2106.05(g). It is additionally noted that providing output “for choosing” a treatment modality does not amount to a positive process limitation of administering a particular treatment. See MPEP 2106.04(d)(2).
With regards to the administering step, this step is not limited to any particular treatment modality other than a generically recited “radiation dose or fractionation in combination with immunotherapy” (which is notably recited in the “wherein” clause of the “calculating” step and not positive recited). Applicant is reminded that the treatment or prophylaxis limitation must be particular, i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). See MPEP 2106.04(d)(2). For example, consider a claim that recites “administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype.” This administration step recites a particular dosage and type of medication and it integrates the mental analysis step into a practical application. The Federal Circuit also has rejected the premise that “claims drafted to include treatment steps are automatically patent eligible.” INO Therapeutics LLC v. Praxair Distribution Inc., 782 F. App’x 1001, 1007 (Fed Cir. 2019). Therefore, after careful consideration, this limitation amounts to mere instructions to “apply” the exception in a generic way and does not integrate the mental analysis step into a practical application. Consequently, the claimed invention does not integrate the abstract idea into a “practical application.”
With regards to the recited display (claim 14), this is recited at a high level of generality and thus can be viewed as nothing more than a generic element for outputting data. With regards to the recited interface, memory, display, and processor (claim 14), these are also recited at a high level of generality and generally link the use of the judicial exception to the technological environment of a computer. Accordingly, these elements do not satisfy the inventive concept requirement. See MPEP 2106.05(f) and 2106.05(h). [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/elements amount to nothing more than insignificant extra-solution activity or field of use. Moreover, a review of applicant’s own specification teaches the use of routine and conventional elements for receiving image and sequence data [page 10] and outputting data to a user, e.g. a display, interface, and I/O device [pages 4, 10, 11]. Accordingly, it is the examiner’s position that the additionally recited steps/elements appended to the judicial exception were well understood, routine, and conventional in the art. See MPEP 2106.05(d)(Part II). Thus, the independent claims as a whole do not amount to significantly more than the exception itself. Therefore, the claim(s) is/are not patent eligible.
Dependent Claims
Dependent claims 2-13, and 15 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. Regarding claim(s) 2-13 these claims further limit the abstract idea (by adding additional functional limitations) or the nature of the data being used by the abstract idea. Accordingly, these claims are also abstract ideas that are not patent eligible for reasons discussed above (Step 2A, analysis). Regarding claim(s) 15, this claim is directed to a computer program product performing the method of claim 1. Accordingly, this claim is also directed to an abstract idea and is not patent eligible for reasons set forth above (Step 2A, Step 2B analysis). Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea without significantly more.
Response to Arguments
Applicant’s arguments, filed 01/14/2026, have been fully considered but are not persuasive for the following reasons.
Applicant argues that the claimed invention does not recite any mental steps because the claims involve “applied technology and specialized computer operations” that are needed to process imaging and sequence data and perform the claimed calculations which are beyond the capability of the human mind. In response, the instantly claimed processing and calculating steps are recited in generic in result-oriented fashion without any details specifying how these functions are being performed. As such, absent any evidence to the contrary, the claimed steps clearly fall within the mental process groupings of abstract ideas because they cover concepts performed in the human mind, including observation, evaluation, judgment, and opinion. See MPEP 2106.04(a)(2), subsection III.
Applicant argues that the claims do not recite a natural correlation since the output and selection of a particular modality for treatment is not a law of nature. In response, the instant claims require generating scores associated with biomarkers from cancerous lesions. Therefore, the claims require determining a naturally occurring relationship between a subject’s data and disease. See MPEP 2106.04(b). As set forth above, the claims do not recite a step for administering a particular treatment to a patient as in Vanda Pharms., 887 F.3d at 1134-36, 126 USPQ2d at 1279-81. Accordingly, the examiner maintains that the claims indeed recite a natural correlation since the treatment is not particular and thus does not apply the natural relationship in a manner that integrated it into a practical application.
Applicant additionally argues that the newly added administering steps amounts to an integration of the abstract idea into a practical application. In response, this argument is not persuasive for reasons set forth above. Applicant is reminded that the treatment or prophylaxis limitation must be particular, i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). See MPEP 2106.04(d)(2). For example, consider a claim that recites “administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype.” This administration step recites a particular dosage and type of medication and it integrates the mental analysis step into a practical application. The Federal Circuit also has rejected the premise that “claims drafted to include treatment steps are automatically patent eligible.” INO Therapeutics LLC v. Praxair Distribution Inc., 782 F. App’x 1001, 1007 (Fed Cir. 2019). Therefore, after careful consideration, this limitation amounts to mere instructions to “apply” the exception in a generic way and does not integrate the mental analysis step into a practical application. Consequently, the claimed invention does not integrate the abstract idea into a “practical application.” For at least these reasons, the rejection is maintained.
Claim Rejections - 35 USC § 112 - Written Description
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
This is a written description rejection.
Claims 1-15 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”). Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include: A) Partial structure; B) Physical and/or chemical properties; C) Functional characteristics; D) Known or disclosed correlation between structure and function; E) Method of making; and F) Combinations of A-E. See also MPEP 2163 and the 2011 Supplementary Guidelines to analysis under 35 USC 112 (Computer-Implemented Functional Claim Limitations).
Based on a consideration of the above factors, the level of skill and knowledge in the art, and the specification, the instant claims fail to meet the written description requirement for the following reasons:
Regarding claim(s) 1 and 14 are directed to a method and system for identifying responsiveness to therapy for a subject suffering from cancer based on, inter alia, “calculating…a responsiveness score…wherein the responsiveness score is calculated for each of the treatment modalities using rules dependent on: (i) whether the measurement of TREX1 is increased or decreased in the cancerous lesion relative to the first control value; (ii) whether the measurement of PD-L1 is increased or decreased in the cancerous lesion relative to the second control value; and iii) whether the measurement of the number of infiltrating immune cells is increased or decreased in the cancerous lesion relative to the third control value”.
With regards to the claimed calculating step, the instant claims are not limited to comprise any particular acts or equations for performing the claimed functions. A review of the specification does not describe any algorithms, equations, or prose equivalent for calculating “responsiveness scores” as claimed. At best, Tables 1 and 2 provide nothing more than a decision support rubric for preferred treatment type. However, this is not commensurate in scope with what is being claimed and does not provide any specificity with regards to how the “responsiveness scores” are actually being calculated. As such, the examiner maintains that the instant specification fails to provide evidence of a mathematical techniques (e.g. model, equations, prose equivalent) for calculating scores predictive of treatment responsiveness for the full scope of what is being claimed, i.e. the calculating steps as claimed are essentially a black box. In addition, one of ordinary skill in the art would recognize that methods for calculating responsiveness scores are not trivial. For example, Gibney et al. (Lancet Oncol., 2016 December; 17(12): e542–e551, pp.1-19) teaches methods for determining predictive markers associated with PD-L1 expression for checkpoint inhibitor-based immunotherapy using sequence data. Unlike the instant claims, Gibney teaches determining predictive scores associated with specific biomarker sequences, positivity thresholds, mutational load, patient survival, ROC curves, and responsiveness (to treatments) [see pages 3, 7, 8, 9, 10, ¶1, page 11, ¶3] and predictive statistical methods for calculating scores associated with treatment outcomes (e.g. ROC scores, survival scores, probability scoring). As such, the instant specification fails to provide evidence of a mathematical techniques (e.g. model, equations, prose equivalent) for calculating scores predictive of treatment responsiveness for the full scope of what is being claimed, i.e. the calculating steps as claimed are essentially a black box.
Moreover, the claims broadly encompass “image or sequencing data” associated with a cancerous lesion. There is no evidence that applicant has provided a sufficient disclosure for the claimed “values” or “responsiveness scores” associated with the full scope of “image or sequencing data” that would be necessary for achieving the intended result (ranking treatment modalities) for the full scope of scope of what is being claimed. One of ordinary skill in the art would recognize that such values are not trivial or universal and are, in fact, highly variable depending on the type of data (image or sequence), cancer, stage of cancer, and type of treatment modality. This position is supported by applicant’s own specification [page 8], as well as the cited prior art of Gong et al. (Journal for Immuno Therapy of Cancer (2018) 6:46, pp.1-17), which reviews the complexities with combination radiation therapy and PD-1/PD-L1 treatments as well as TREX1 (see entire). In addition, Goitein (Seminars in Radiation Oncology, 1992, Vol. 2, Issue 4, Abstract, pp.1-4) teaches that comparing RT treatments is a sophisticated process that must account for a variety of different parameters including: dose distributions, dose statistics, and biophysical models associated with normal and tumor probability (Abstract). Accordingly, the specification does not provide a sufficient disclosure of the computer and necessary algorithms to demonstrate to one of ordinary skill in the art that the inventor possessed the invention including how to program the disclosed computer to perform the claimed functions, at the time the application was filed. Therefore, the specification fails to support a “broad genus” claim that covers all ways of performing the claimed function when there is no evidence that a more generic way is contemplated.” See also LizardTech, Inc. v. Earth Res. Mapping, Inc., 424 F.3d 1336, 76 USPQ2d 1724 (Fed. Cir. 2005).
For the reasons discussed above, the specification does not satisfy the written description requirement with respect to the full scope of what is being claimed. For more information regarding the written description requirement, see MPEP §2161.01- §2163.07(b).
Response to Arguments
Applicant’s arguments, filed 01/14/2026, have been fully considered but are not persuasive for the following reasons.
Applicant argues that the rejection is rendered moot in view of the claim amendments. In response, this argument is not persuasive for reasons set forth above. Accordingly, absent any evidence to the contrary, the rejection is maintained.
Claim rejections - 35 USC § 112 – Indefiniteness
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 1-15 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, 13, 15 is/are also rejected due to said dependency.
Claims 1 and 14 recite “processing the imaging or sequencing data to determine values….wherein the determined values…comprise: (i) a measurement of three prime repair exonuclease 1 (TREX1) in the cancerous lesion compared to a measurement of TREX1 from a first control…”. In this case, it is unclear what is meant by “a measurement” of TREX1, PD-L1, and infiltrating immune cells, respectively. The claim sets forth that the determined values are indicative of a “level of a corresponding biomarker”. However, there are no previous active method steps for “measuring” anything---only receiving imaging or sequence data. Accordingly, there is lack of antecedent basis for said “measurements”. Applicant is reminded that claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed. MPEP 2111.04. Clarification is requested via amendment.
Claims 1 and 14 recite “calculating…a responsiveness score…wherein the responsiveness score is calculated for each of the treatment modalities using rules dependent on: (i) whether the measurement of TREX1 is increased or decreased in the cancerous lesion relative to the first control value; (ii) whether the measurement of PD-L1 is increased or decreased in the cancerous lesion relative to the second control value; and iii) whether the measurement of the number of infiltrating immune cells is increased or decreased in the cancerous lesion relative to the third control value”. This limitation is problematic for the following reasons.
Firstly, the term “predicted” implies that a treatment is being predicted, but there is nothing in the claims that requires or even suggests such a step. The claims are literally “identifying responsiveness to therapy” (not predicted therapy outcomes), as set forth in the preamble. Accordingly, it remains unclear what is meant by a “predicted treatment outcome”. Clarification is requested via amendment.
Secondly, it is unclear what limiting effect is intended by the above conditional “whether” clauses such that the artisan would recognize what computational operations are intended, i.e. in what way is the responsiveness score “using rules dependent on” the subsequent “whether” statements. Applicant is reminded that claim scope is not limited by “conditional” limitations that suggests or makes optional but does not require steps to be performed. See MPEP 2111.04. A review of the Table 1 in the specification provides a chart that indicates preferred treatment type based on different quantitative scenarios (e.g. up-regulation, down-regulation, positive, negative). However, this is not commensurate in scope with what is claimed and does not provide a discernable boundary on what operations are required to generate responsiveness scores based on the various conditional statements. Moreover, 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). Stated differently, applicant has chosen to claim a black box ‘calculating’ step as a critical aspect of the invention (without defining it). Therefore, the “calculating” step remains indefinite 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. Clarification is again requested via amendment.
Cited Prior Art
The following prior art made of record and not relied upon is considered pertinent to applicant' s disclosure.
EP 3693974 A1 (common inventor), which teaches a method for identifying responsiveness to radio-immunotherapy for subject suffering from cancer, involves processing values of biomarkers to obtain score indicative of responsiveness of cancerous lesion to multiple treatment modalities.
Conclusion
No claims are allowed.
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
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