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 04/30/2026, are acknowledged. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Status of Claims
Claims 1, 2, 5, 7, 8, 10, 11, 12, 16, 30 are under examination.
Claims 3, 4, 6, 9, 13-15, 17, 18, 20, 25, 26, 28, 29, 31-42 are cancelled.
Claims 19, 21-24, 27 are withdrawn.
Priority
Applicant’s claim for the benefit of priority under 35 U.S.C. 119(a)-(d) is acknowledged. This application is the National Stage filing under 35 USC 371 of PCT/US2022/015275, filed 02/04/2022 and claims priority to earlier filed Provisional Application No. 63/146,392, filed 02/05/2021. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
Information Disclosure Statement(s)
The information disclosure statement (IDS) document(s) submitted on 04/30/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS document(s) has/have been fully considered by the examiner.
Withdrawn Rejections
The rejection of claims 1, 2, 5, 7, 8, 10, 11, 12, 16, 30, and 34 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of applicant’s amendments and arguments.
The rejection of claims 1, 2, 7, 30, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Nicosia et al. (WO 2020099614 A1; Pub. Date: 2020-05-22) in view of Biskbup et al. (WO 2020/043805; File Date: 08/28/2019; Pub. Date: 03/05/2020) is withdrawn in view of applicant’s amendments and arguments.
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.
This rejection is modified in view of applicant’s amendments.
Claims 1, 2, 5, 7, 8, 10, 11, 12, 16, 30 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.
Guidance Step 1:
The instant invention (claim 1 being representative) is directed to a method for ranking tumor-specific neoantigens that performs a series of processes. Thus, the claims are directed to one of the statutory categories of invention. MPEP 2106.03.
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. Regarding claim(s) 1, the claimed steps that are part of the abstract idea are as follows:
b) for each individual somatic mutation in the plurality of somatic mutations:
i) determining a best short neoantigen from an initial plurality of short neoantigens based at least in part on a short neoantigen immunogenicity score of the best short neoantigen, wherein the short neoantigen immunogenicity score is computed for each short neoantigen by one or more trained machine-learning models using subject-specific HLA data and peptide sequence of each short neoantigen to predict presentation, and wherein the best short neoantigen comprises a highest short neoantigen immunogenicity score among the initial plurality of short neoantigens;
ii) determining a best long neoantigen from an initial plurality of long neoantigens based at least in part on a long neoantigen immunogenicity score of the best long neoantigen, wherein the long neoantigen immunogenicity score is computed for each long neoantigen by one or more trained machine-learning models using subject-specific HLA data and peptide sequence of each long neoantigen to predict presentation, and wherein the best long neoantigen is a highest long neoantigen immunogenicity score among the initial plurality of long neoantigens;
iii) adding the best short neoantigen to a list of short neoantigen candidates, wherein the list of short neoantigen candidates when completed includes the respective best short neoantigens for the plurality of somatic mutations;
iv) adding the best long neoantigen to a list of long neoantigen candidates, wherein the list of long neoantigen candidates when completed includes the respective best long neoantigens for the plurality of somatic mutations;
Mental Processes
With regards to said determining, a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim. MPEP 2106.04, subsection II. In this case, under the BRI, the claim recites determining a best short neoantigen (based at least in part on a short…immunogenicity score…computed…by one or more trained machine learning models using HLA data). Notably, the model is recited at a high level of generality (without any technological details directed to how it is trained and without any specificity with regards to the type of model being used). In addition, scientists routinely observe and analyze data to select data with optimal scores. As such, this step recites a mental process of observing data and/or making a decision. MPEP 2106.04(a)(2), section III.
With regards to said determining, a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim. MPEP 2106.04, subsection II. In this case, under the BRI, the claim recites determining a best long neoantigen (based at least in part on a long…immunogenicity score…computed…by one or more trained machine learning models using HLA data). Notably, the model is recited at a high level of generality (without any technological details directed to how it is trained and without any specificity with regards to the type of model being used). In addition, scientists routinely observe and analyze data to select data with optimal scores. As such, this step recites a mental process of observing data and/or making a decision. MPEP 2106.04(a)(2), section III.
With regards to said adding (the best short and long neoantigen), a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim. MPEP 2106.04, subsection II. In this case, under the BRI, the claim recites adding the best data to a list of additional candidates. As such, this step recites a mental process of observing data and/or manipulating data to generate additional data. MPEP 2106.04(a)(2), section III.
With regards to said ranking(the best short and long neoantigen), a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim. MPEP 2106.04, subsection II. In this case, under the BRI, the claim recites ranking data based on descending scores. As such, this step recites a mental process of observing data and/or making a decision. MPEP 2106.04(a)(2), section III [Step 2A, Prong 1: YES].
Mathematical Concept
With regards to said determining, a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim. MPEP 2106.04, subsection II. In this case, under the BRI, the claims recite the act of determining numerical scores and selecting the best score and therefore sets forth or describes a mathematical calculation and/or mathematical relationship. As such, these steps recite a mathematical concept. MPEP 2106.04(a)(2) Section I.
With regards to said ranking(the best short and long neoantigen), a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim. MPEP 2106.04, subsection II. In this case, under the BRI, the claim recites ranking data based on descending scores and therefore sets forth or describes a mathematical calculation and/or mathematical relationship. As such, these steps recite a mathematical concept. MPEP 2106.04(a)(2) Section I.
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 or whether the claim is “directed to” the judicial exception. This evaluation is performed by (1) identifying whether there are any additional steps/elements recited in the claim beyond the judicial exception, and (2) evaluating those additional steps/elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. See MPEP 2106.04(d).
The additional steps/elements recited in the claim beyond the judicial exception are as follows: a) identifying a plurality of somatic mutations present in the tumor;
In this case, this step is recited at a high of generality (without any details regarding how it is being performed) and results in nothing more than collecting 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). See MPEP 2106.04(d)(1) for a list of considerations when evaluating whether additional elements integrate a judicial exception into a practical application. [Step 2A, Prong 2: NO].
C. Guidance Step 2B:
This part of the eligibility analysis evaluates whether the claim as a whole amount to significantly more than the recited exception i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP 2106.05. In addition, a review of the specification teaches routine and conventional sequencing method for determining mutations [0023-0026, 0063-0065]. Therefore, even upon reconsideration, there is nothing unconventional with regards to the above non-abstract step. See MPEP 2106.05(d)(Part II). Thus, the independent claim(s) as a whole do not amount to significantly more than the exception itself. Therefore, the claim(s) is/are not patent eligible. [Step 2B: NO].
D. Dependent Claims
Dependent claims 2, 5, 7, 8, 10, 11, 12, 16, 30 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, 5, 7, 8, 10, 11, 12, 16, 30 are entirely directed to limitations that further limit the specificity of the abstract idea or the type of data being used by the abstract idea. Accordingly, these claims are also directed to an abstract idea for the reasons set forth above (Step 2A, prong 1, 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 04/30/2026, have been fully considered but are not persuasive for the following reasons.
Applicant argues that claim 1 is integrated into a practical application by improving personalized cancer treatment by selecting neoantigens likely to be immunogenic and citing the instant specification [0039, 0017]. In response, contrary to applicant’s assertion, the claims do not recite any limitations directed to forming a composition or administering a particular drug to a patient and it is improper to import narrowing limitations from the specification into the claims. MPEP 2111.01. In other words, the claims result in analyzing data and generating additional data without using the data in the real world. In addition, the MPEP is clear that the word "improvements" in the context of this consideration is limited to improvements to the functioning of a computer or any other technology/technical field, whether in Step 2A Prong Two or in Step 2B. MPEP 2106.04(d)(1). In this case, applicant has not provided any objective evidence to support the case that the claims result in an improvement to the functioning of a computer and no such evidence is provided in the specification. To evaluate an improvement to a computer or technical field, the specification must set forth an improvement in technology and the claim itself must reflect the disclosed improvement. See MPEP 2106.04(d)(1) and 2106.05(a). Applicant has failed to identify any steps/elements appended to the abstract idea that provide for a new technology (Step 2A, prong 2 or Step 2B) or provided any evidence of an unconventional combination of steps. Therefore, applicant is essentially arguing that the improvement is entirely in the realm of abstract ideas and that abstract idea is providing the improvement (by providing “better data”). However, 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.” BSG Tech LLC v. BuySeasons, Inc., 899 F.3d 1281, 1290 (Fed. Cir. 2018). Similarly, the courts have also 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).
As such, the claims do not recite an improvement to computer functionality and do not delineate steps through which the machine learning technology achieves an improvement. See, e.g. Ex Parte Desjardins. For example, "Ex parte Desjardins had claims drawn to the use of a machine learning model, trained on one task with a first set of data, and set parameter weights, then trained again using differing data on a different task, adjusting parameters and weights, while protecting performance of the first task. Further, in Desjardins, the retraining of the particular ML changed the structure of that ML in a way that provided "'[a]n improvement in the functioning of a computer, or an improvement to other technology or technical field,' as discussed in MPEP §§ 2106.04(d)(l) and 2106.05(a). Moreover, the independent claim in Ex parte Desjardins contained specific limitations as to how at least some aspects of the asserted improvements are achieved: "When evaluating the claim as a whole, we discern at least the following limitation of independent claim 1 that reflects the improvement: "adjust the first values of the plurality of parameters to optimize performance of the machine learning model on the second machine learning task while protecting performance of the machine learning model on the first machine learning task." We are persuaded that constitutes an improvement to how the machine learning model itself operates, and not, for example, the identified mathematical calculation." Ex parte Desjardins, p9. In contrast, the instant claims do not clearly set forth the link between the data gathered, the initial training of the ML models, the structure of the models, and how training affects the structure to obtain the desired results or asserted improvement. For at least these reasons, 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, 5, 7, 8, 10, 11, 12, 16, 30 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 are also rejected due to said dependency.
Claim 1 recites “determining a best short neoantigen from an initial plurality of short neoantigens based at least in part on a short neoantigen immunogenicity score of the best short neoantigen, wherein the short neoantigen immunogenicity score is computed for each short neoantigen by one or more trained machine-learning models using subject-specific HLA data and peptide sequence of each short neoantigen to predict presentation.” In this case, it is unclear what positive process limitation(s) is/are intended by the above “wherein” clause. More specifically, this clause suggests a functional limitation, e.g. computing scores “by one or more trained machine learning models”, and predicting a presentation (suggested by the intended use “to predict presentation”). Applicant is reminded that intended use recitations are not given patentable weight and claim scope is not limited by claim language that “suggests” but does not limit a claim to a particular structure. See MPEP 2111.04. Clarification is requested via amendment.
Claim 1 recites “determining a best long neoantigen from an initial plurality of long neoantigens based at least in part on a long neoantigen immunogenicity score of the best long neoantigen, wherein the long neoantigen immunogenicity score is computed for each long neoantigen by one or more trained machine-learning models using subject-specific HLA data and peptide sequence of each long neoantigen to predict presentation. In this case, it is unclear what positive process limitation(s) is/are intended by the above “wherein” clause and what type of “presentation” is being predicted. More specifically, this clause suggests a functional limitation, e.g. computing scores “by one or more trained machine learning models”, and predicting a presentation (suggested by the intended use “to predict presentation”). Applicant is reminded that intended use recitations are not given patentable weight and claim scope is not limited by claim language that “suggests” but does not limit a claim to a particular structure. See MPEP 2111.04. Clarification is requested via amendment.
Claim 1 recites the terms “short neoantigen” and “long neoantigen”. It remains unclear as to the metes and bounds of these terms such that the artisan would know how to avoid infringement. In particular, the terms “long” and “short” are subjective terms that are not defined by the claim and the specification does not provide a standard or criteria such that one of ordinary skill in the art would know the metes and bounds of these terms, i.e. how short is short and how long is long. Clarification is requested via amendment.
Claim 5 still recites “wherein the probability is determined at least in part based on data from an MHC Class I machine learning model trained to determine a probability that a given allele in the plurality of HLA class I alleles presents a certain antigen”. In this case, there is still lack of antecedent basis for “an MHC Class I machine learning model” since this feature has not been previously introduced (e.g. for generating data) and is not inherent to the process of determining a probability score. As a result, it is also unclear what limiting effect is intended by the above clause, i.e. in what way is the probability “based on data from an MHC Class I machine learning model” such that the artisan would recognize what computational operations are intended. A review of the specification [0041] merely reiterates the claim language and does not provide any additional guidance. Applicant is reminded that limitations directed to the nature of the data, per se, do not impose any actual boundaries on the scope of the claim. Clarification is requested via amendment. This rejection is maintained as applicant has not provided any illuminating arguments or clarifying amendments.
Citation of Relevant Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant' s disclosure.
Bulik-Sullivan et al. (Nature Biotechnology, 2019, volume 37, pages 55–63) teaches deep learning methods using tumor HLA peptide mass spectrometry datasets to improve neoantigen identification.
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
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