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 07/29/2025, 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 Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn.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 1-15 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) three prime repair exonuclease 1 (TREXI) in the cancerous lesion; (ii) programmed death-ligand 1 (PD-L1) on tumor cells in the cancerous lesion; and (iii) infiltration of immune cells in the cancerous lesion;
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 without any details specifying how these functions are being performed and 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.
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 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 07/29/2025, 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 amended claims involve imaging/sequencing techniques that are beyond the capability of the human mind. In response, this argument is not persuasive as the receiving step has not been interpreted as part of the abstract idea. As discussed above (Step 2A, prong 2), the receiving step is generically recited and broadly requires obtaining data for use by the abstract idea. Similarly, the providing step amounts to outputting/displaying information. Accordingly, these steps amount to insignificant extra-solution activity and are not indicative of an integration into a practical application. See MPEP 2106.05(g). Applicant is directed to MPEP 2106.04(d)(1), which lists the following considerations for evaluating whether additional elements integrate a judicial exception into a practical application:
An improvement in the functioning of a computer, or an improvement to other technology or technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to affect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
Applicant additionally argues that the claimed invention provides a practical application because it results in predicting treatment outcomes and is not a natural correlation. In response, this argument is not persuasive for reasons set forth above. In particular, the providing step amounts to outputting/displaying information. Accordingly, these steps amount to insignificant extra-solution activity and are 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). In summary, the claims fail to recite any limitations that purport to improve the functioning of a specific claimed device, effect an improvement to the technology or technical field, or provide meaningful limitations beyond generally linking the use of an abstract idea to a particular technological environment. See Enfish LLC v. Microsoft Corp., 822 F.3d 1327, 1335—6 (Fed. Cir. 2016). Notably, the instant claims do not recite any steps for using the information produced by the abstract idea to generate an effect outside of a computer (i.e. a real-world practical application). Consequently, the examiner maintains that the claimed invention does not integrate the abstract idea into a “practical application.” [Step 2A, Prong 2: NO]. 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, 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;
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, i.e. they generically encompass critical thinking and doing math. “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005))(emphasis added). A review of the specification does not describe any algorithms, equations, or prose equivalent for calculating “responsiveness scores” as claimed. At best, the specification generally recites that the “processor 104 may analyze the obtained responsiveness scores in order to identify a treatment modality (e.g. dose and fractionation of radiotherapy for use in combination with immunotherapy) having a score indicative of highest responsiveness” [page 12], which fails to provide significant details of how the claimed processor is achieving the claimed function. The specification does teach that a “responsiveness score” may be calculated in different ways [page 16], e.g. via inverse proportionality, proportionality, etc. However, such limitations are not commensurate in scope with what is being claimed and applicant is reminded that it is improper to import narrowing limitations into the claims. MPEP 2111.01. 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. Unlike the instant claims, Gibney teaches determining predictive scores associated with specific biomarkers, 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.
In addition, there is no evidence that applicant has provided a sufficient disclosure for the claimed “values for respective biomarkers”, “responsiveness scores”, “control values” and “infiltration” 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 07/29/2025, have been fully considered but are not persuasive for the following reasons.
Applicant argues that the specification provides sufficient written description calculating responsiveness scores in [0066-0067]. In response, as discussed above, this section does nothing more than assert there are various ways that the claimed score can be calculated. In addition, a review of Tables 1 and 2 provides nothing more than qualitative information associated with different types of treatment. 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. 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 “wherein biomarkers comprise…(iii) infiltration of immune cells”. It is unclear limiting effect is intended by the italicized phrase such that the artisan would know how to avoid infringement, i.e. in what way does a biomarker (which is reasonably interpreted as a physical structure) comprise “infiltration” (which is reasonably interpreted as a physical act). A review of the specification teaches that variability between tumours can lead to differences in the TREX1, Tumour Infiltrating Lymphocytes (TILs) and checkpoint expression (e.g. PD-L1) [page 8] and a processor that quantifies the level of staining and/or the number of infiltrating immune cells in order to determine a value for the expression level [page 13]. However, these are not commensurate in scope with what is claimed and it is improper to import narrowing limitations into the claims. MPEP 2111.01. Accordingly, the claims are indefinite as it fails to provide a discernable boundary on what structural and/or functional limitation is intended. Clarification is requested via amendment.
Claims 1 and 14 recite “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.” Firstly, it is unclear what is meant by a “predicted treatment”, which suggests a treatment is being predicted. In other words, the artisan would understand calculating a score that is indicative of a treatment outcome (i.e. predicting a treatment outcome) but there is nothing in the claim to suggest that a treatment is being “predicted”. Secondly, with regards to said “calculating”, such generic functional claim language amounts to descriptions of problems to be solved and covers all means or methods of performing the claimed function. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. Accordingly, the claim is indefinite because it does not provide a discernable boundary on what operations are required to perform the specialized function. 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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PABLO S WHALEY/Primary Examiner, Art Unit 3619