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 .
Election/Restrictions
Applicant's election with traverse of invention Group I (Claims 1-29) in the reply filed on 06/22/2026 is acknowledged. The traversal is on the grounds that Group II (claims 30-32) are dependent on claims 1-29, and the search and examination of claims do not present an undue burden to the Examiner (remarks pg 2). This is not found persuasive because this is a National Stage entry (PCT application) – for this type of application the burden to the examiner is not a factor considered. Rather, there is a requirement of “unity of invention,”, which was addressed in the previous office action. Group I (claims 1-20) is directed to methods and systems to implement the methods, and Group II (claims 30-32) is directed to a diagnostic assay. While the diagnostic assay may comprise elements identified using the method of claim 1, it is a separate invention with a separate classification and search requirements (methods steps vs assay components), and would also require additional separate rejections. The inventions do not share the same/corresponding technical features, and do not relate to a single general inventive concept under PCT Rule 13.1.
Therefore the requirement is still deemed proper and is therefore made FINAL.
Claims 30-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 06/22/2026.
Priority
This application filed 10/19/2022 is a National Stage entry of PCT/EP2021/060259, with an International Filing Date of 04/20/2021, and claims foreign priority to 20187765.1, filed 07/24/2020, and also claims foreign priority to 20170484.8, filed 04/20/2020. The claims are therefore examined as filed on 04/20/2020, the effective filing date. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further review of the priority application(s).
Claim Status
Claims 1-32 are pending.
Claims 30-32 are withdrawn.
Claims 1-29 are directed to the elected invention.
Claims 1-29 are examined.
Claims 1-29 are rejected.
Information Disclosure Statement
The Information Disclosure Statements are in compliance with the provisions of 37 CFR 1.97. Accordingly, all references have been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see pages 8 and 14). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112
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 4, 9-10, 14, 16, and 23 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 4 recites the broad recitation “wherein the candidate epitopes have a length of at least 8 amino acids”, and the claim also then recites “preferably wherein the candidate epitopes have a length of 8, 9, 10, 11, 12 or 15 amino acids”. which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The above also applies to claims 9-10, 14, 16, and 23:
Claim 9 has the broader limitation “wherein the set of HLA types comprises HLA types representative of at least one human population group” followed by the narrower limitation “preferably where the set of HLA types is representative of the human population”.
Claim 10 has the broader limitation “wherein the set of HLA types comprises the top N most frequent HLA types within the human population or a human population group” followed by the narrower limitation “preferably wherein N is at least 5, more preferably at least 50 and even more preferably at least 100”.
Claim 14 has the broader limitation “further comprising applying a false discovery rate, FDR, procedure to the results of the statistical model” followed by the narrower limitation “preferably wherein the FDR procedure is a Benjamini-Hochberg or Benjamini-Yekutieli procedure”.
Claim 16 has the broader limitation “wherein each amino acid sub-sequence comprises at least 8 amino acids” followed by the narrower limitation “preferably between 20 and 50 amino acids, more preferably between 50 and 150 amino acids”.
Claim 23 has the broader limitation “wherein the one or more source proteins are one or more proteins of a coronavirus” followed by the narrower limitation “preferably the SARS-CoV-2 virus”.
Therefore claims 4, 9-10, 14, 16, and 23 are indefinite due to lack of clarity.
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 1-25 and 27-29 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental processes and mathematical concepts, without significantly more.
The MPEP at MPEP 2106 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of matter?
(2A)(1) Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea?
(2A)(2) Do the claims recite additional elements that integrate the judicial exception into a practical application?
(2B) If the claims recite a judicial exception and do not integrate the judicial exception, do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception?
With regard to step (1) (Are the claims directed to a process, machine, manufacture or composition of matter?): Claims 1- 25, 27 and 29 are directed to one of the statutory classes. Claims 1-25 are directed to a process (computer implemented method), claim 27 is directed to a product (a system comprising a processor and memory device), and claim 29 is also directed to a process (method).
Claim 28 is not directed to one of the statutory classes, as it is direct to a “computer readable medium” without specifying that the medium is non-transitory. The broadest reasonable interpretation of machine readable media can encompass non-statutory transitory forms of signal transmission, such as a propagating electrical or electromagnetic signal per se. See In re Nuijten, 500 F.3d 1346, 84 USPQ2d 1495 (Fed. Cir. 2007). When the broadest reasonable interpretation encompasses transitory forms of signal transmission, a rejection under 35 U.S.C. 101 as failing to claim statutory subject matter would be appropriate (see MPEP 2106.03 section II). The Examiner recommends amending claim 28 to read “a non-transitory computer readable medium” instead, and this claim will continue to be examined with the others below as if this amendment had been made, for the sake of compact prosecution.
With regard to step (2A)(1) (Do the claims recite a judicially recognized exception?): Yes. The claims recite the abstract ideas of processing data using mental steps and mathematical concepts. Claims that recite nothing more than abstract ideas, natural phenomena, or laws of nature are not eligible for patent protection (see MPEP 2106.04).
Abstract ideas include mathematical concepts, (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (including procedures for collecting, observing, evaluating, and organizing information (See MPEP 2106.04(a)(2)). In particular, these abstract ideas include but are not limited to:
Dividing the amino acid sequence into a plurality of amino acid sub-sequences (mental process; the human mind is capable of dividing a sequence into sub sequences; claims 1, 27-29)
Generating a region metric that is indicative of a predicted ability of the amino acid sub-sequence to instigate an immunogenic response across the set of HLA types, wherein the region metrics are based on the predicted immunogenic potentials of the plurality of candidate epitopes (mental process/mathematical concept; the human mind is capable of generating a metric based on data and/or predicted parameters, and determining a metric from data is equivalent to performing a calculation; claims 1, 27-29)
Applying a statistical model to identify whether any of the generated region metrics are statistically significant (mental process/mathematical concept; the human mind is capable of applying a statistical model to data, and doing so is equivalent to performing a calculation/a mathematical process; claims 1, 27-29)
Assigning, for each of the set of HLA types, an epitope score to each amino acid, wherein the epitope score is based on the predicted immunogenic potentials of one or more of the candidate epitopes comprising that amino acid (mental process/mathematical concept; the human mind is capable of assigning scores based on data, and determining a score based on a parameter is equivalent to performing a calculation; claim 2)
Identifying a first plurality of candidate epitopes having a first length, across the amino acid sequence and identifying a second plurality of candidate epitopes having a second length, across the amino acid sequence (mental process; the human mind is capable of identifying sequence segments of various lengths; claim 3
Generating, for each of the set of HLA types, an epitope score for each of the first and second plurality of candidate epitopes that is indicative of the predicted immunogenic potential of the respective candidate epitope for that HLA type (mental process/mathematical concept; the human mind is capable of determining a score based on a parameter/data, and doing so is equivalent to performing a calculation; claim 3)
Assigning, for each amino acid of the amino acid sequence, the epitope score of the candidate epitope that is predicted to have the best immunogenic potential of all of the first and second candidate epitopes comprising that amino acid, for that HLA type (mental process, the human mind is capable of assigning a score for an HLA type based on a ranking of that score; claim 3)
Dependent claims 4-25 further limit the abstract ideas recited in the independent claims, and do not change their characterization as abstract ideas.
Therefore, the claims recite elements that constitute one or more judicial exceptions.
With regard to step (2A)(2) (Do the claims recite additional elements that integrate the judicial exception into a practical application?): No. Claim 1 and its dependents recite the additional element of the methods being computer implemented, and the additional elements of accessing the amino acid sequence of one or more source proteins and a set of HLA types. Claim 27 similarly recites a system for performing the method of claim 1, comprising at least one processor and memory device, and claim 28 recites a computer readable medium.
While the claims recite the additional element of receiving or accessing data, such steps that only amount to necessary data gathering, without any technical details of how the data is obtained that integrate the judicial exception, are insignificant extrasolution activities that do not add a meaningful limitation to the claims (see MPEP 2106.05(g)). As a result, the judicial exception is not integrated into a practical application. In addition, while the claims recite additional elements related to the use of computers, they do not provide any specific details by which the computer/system, processor, or readable medium performs or carries out the judicial exception listed in step (2A)(1), nor do they provide any details of how specific structures of the computer are used to implement these functions. The judicial exception is therefore not integrated into a practical application because the generically recited computer elements do not add a meaningful limitation to the abstract idea, as they amount to simply implementing the abstract idea on a computer (see MPEP 2106.05(f)). Because the claims do not recite any additional elements that integrate the judicial exception into a practical application, the claims as a whole are directed to an abstract idea.
With regard to step (2B) (Do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception?): No. The claims recite an abstract idea with additional elements; however, these additional elements are general computer elements added to abstract ideas, and non-particular instructions to apply the abstract idea by linking it to a field of use or extrasolution activity (see MPEP 2106.05(f-h)). General computer elements used to perform an abstract idea do not provide an inventive concept, and similarly, non-particular instructions to gather or produce data do not provide an inventive concept. Non-particular instructions to gather or output data using general computer elements are also considered well-understood, routine and conventional activities (see MPEP 2106.05(d), which indicates that limitations such as “Receiving or transmitting data over a network” from Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362, and “Storing and retrieving information in memory” from Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, are recognized as conventional activities). The claims therefore do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As a result, the claims as a whole do not provide an inventive concept.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim Rejection
Claims 1-5, 7-11, 16-19, and 21-29 are rejected under 35 U.S.C. 103 as being unpatentable over BREMEL 2013 (US 20130330335 A1, as cited on the IDS filed 06/22/2023) in view of SANCHEZ-TRINCADO 2017 “Fundamentals and Methods for T- and B-Cell Epitope Prediction.”
Claim Interpretation and Scope and Contents of Prior Art
Claim 1 recites a computer-implemented method of identifying one or more candidate regions of one or more source proteins that are predicted to instigate an adaptive immunogenic response across a plurality of human leukocyte antigen, HLA, types, wherein the one or more source proteins has an amino acid sequence, the method comprising: accessing the amino acid sequence of the one or more source proteins; accessing a set of HLA types; predicting an immunogenic potential of a plurality of candidate epitopes within the amino acid sequence for each of the set of HLA types.
With respect to these limitations, BREMEL 2013 teaches a computer implemented method and systems for identifying candidate peptides that bind to different MHC binding regions and are immunogenic for multiple HLA types [028, 47, 296], wherein the source proteins have an amino acid sequence [0014], and where the method involves accessing the amino acid sequence and a set of HLA types, and identifying candidate peptides/epitopes that are immunogenic for the HLA types [0167-169, 280, 0296-299]. While BREMEL 2013 teaches identifying candidate binding affinity and identifying whether candidates are immunogenic or have useful immunological characteristics [0181], it does not teach determining a specific immunogenic potential of each of the candidate epitopes. However, SANCHEZ-TRINCADO teaches immunogenicity/immunogenic potential can be determined from antigen processing prediction and binding prediction (pg 5-6) and also teaches several publicly available epitope prediction tools for determining immunogenic potential (Table 1) that can be combined with the methods of BREMEL.
Claim 1 further recites dividing the amino acid sequence into a plurality of amino acid sub-sequences; for each of the plurality of amino acid sub-sequences, generating a region metric that is indicative of a predicted ability of the amino acid sub-sequence to instigate an immunogenic response across the set of HLA types, wherein the region metrics are based on the predicted immunogenic potentials of the plurality of candidate epitopes, for each of the set of HLA types. With respect to these limitations, BREMEL 2013 teaches dividing amino acids into sub-sequences and generating a region metric indicative of binding affinity of the sub sequence to an MHC region or other binding partner in the different HLA types [014-15, 0175-176, 0185, 297-299, claim 1] which can then further be used to determined immunogenic potential using the methods of SANCHEZ-TRINCADO (pg 5-6, Table 1).
Claim 1 further recites applying a statistical model to identify whether any of the generated region metrics are statistically significant, whereby an amino acid sub-sequence identified as having a statistically significant region metric corresponds to a candidate region of the amino acid sequence that is predicted to instigate an immunogenic response across at least a subset of the set of HLA types. With respect to these limitations, BREMEL 2013 teaches applying a statistical model to determine if the region metrics are statistically significant, wherein the region metrics correspond to a candidate region predicted to instigate an immunogenic response in a subset of HLA types [0079, 0296], and SANCHEZ-TRINCADO also teaches various statistical methods to identify statistically significant epitopes (Table 1, pg 5).
Claims 27 and 28 recite a system comprising a processor and memory, and a computer readable medium, respectively, for performing the methods of claim 1. These are similarly taught be the art cited above.
Claim 2 recites the limitation of assigning, for each of the set of HLA types, an epitope score to each amino acid, wherein the epitope score is based on the predicted immunogenic potentials of one or more of the candidate epitopes comprising that amino acid, for that HLA type; and wherein each of the region metrics is generated based on the epitope scores for the amino acids within the respective amino acid sub-sequence, across the set of HLA types. With respect to this limitation, BREMEL 2013 teaches determining physical characteristics for each amino acid within a sub sequence predictive of binding affinity (used to determine immunogenicity), and using these to determine the binding affinity region metrics for each HLA type [016-19, 50, 0169, 0187-191, 204-211, 226].
Claim 3 recites the limitation wherein at least a subset of the epitope scores are assigned by: identifying a first plurality of candidate epitopes having a first length, across the amino acid sequence; generating, for each of the set of HLA types, an epitope score for each of the first plurality of candidate epitopes that is indicative of the predicted immunogenic potential of the respective candidate epitope for that HLA type; identifying a second plurality of candidate epitopes having a second length, across the amino acid sequence; generating, for each of the set of HLA types, an epitope score for each of the second plurality of candidate epitopes that is indicative of the predicted immunogenic potential of the respective candidate epitope for that HLA type; and for each of the set of HLA types, assigning, for each amino acid of the amino acid sequence, the epitope score of the candidate epitope that is predicted to have the best immunogenic potential of all of the first and second candidate epitopes comprising that amino acid, for that HLA type.
With respect to this limitation, BREMEL 2013 teaches identifying candidate epitopes of varying lengths, and determining the binding affinity of the candidate epitopes for each HLA type [51, 70, 169-171, 0260-269, 296-299]. SANCHEZ-TRINCADO teaches immunogenicity/immunogenic potential can then be determined using binding affinity (pg 5-6) and also teaches several publicly available epitope prediction tools for determining immunogenic potential for epitopes and rank them based on the best immunogenic potential to determine which is best (Table 1).
Claim 4 recites the limitation wherein the candidate epitopes have a length of at least 8 amino acids, preferably wherein the candidate epitopes have a length of 8, 9, 10, 11, 12 or 15 amino acids. With respect to this limitation, BREMEL 2013 teaches that candidate epitopes are at least 4 amino acids in length, and can be 9 or 15 amino acids in length [0262].
Claim 5 recites the limitation wherein the predicted immunogenic potential of a candidate epitope for a particular HLA type is based on one or more of a predicted binding affinity and a predicted processing of the identified candidate epitope. With respect to this limitation, SANCHEZ-TRINCADO teaches that immunogenicity/immunogenic potential prediction for an epitope is based on antigen processing prediction and binding prediction (pg 5-6).
Claim 7 recites the limitation of digitizing the assigned epitope scores, wherein each epitope score meeting a predetermined criterion is transformed to a "1" and each epitope score not meeting the predetermined criterion is transformed to a "0". With respect to this limitation, BREMEL 2013 teaches applying thresholds to the epitope scores to determine if they meet criteria [0215] but does not specifically mention transforming the score into a 1 or 0. However indicating a score as a 0 or 1 based on its meeting a threshold is a well-known and obvious method for digitization/recording of a metric.
Claim 8 recites the limitation wherein the set of HLA types includes HLA types of Major Histocompatibility Complex, MHC, Class I and HLA types of MHC Class II. With respect to this limitation, BREMEL 2013 teaches that the HLA types include HLA types of Major Histocompatibility Complex/MHC, MHC Class I and MHC Class II [106-107].
Claim 9 recites the limitation wherein the set of HLA types comprises HLA types representative of at least one human population group, preferably where the set of HLA types is representative of the human population. With respect to this limitation, BREMEL 2013 teaches that the HLA types are representative of a human population [0041].
Claim 10 recites the limitation wherein the set of HLA types comprises the top N most frequent HLA types within the human population or a human population group, preferably wherein N is at least 5, more preferably at least 50 and even more preferably at least 100. With respect to this limitation, BREMEL 2013 teaches that the HLA types include the most frequent HLA types for humans [0107-108].
Claim 11 recites the limitation wherein the set of HLA types is representative of a given individual. With respect to this limitation, BREMEL 2013 teaches that the HLA type can be representative of an individual patient [0028].
Claim 16 recites the limitation wherein each amino acid sub-sequence comprises at least 8 amino acids, preferably between 20 and 50 amino acids, more preferably between 50 and 150 amino acids. With respect to this limitation, BREMEL 2013 teaches that the amino acid subsets can be from about 4 to about 50, about 4 to about 30, about 4 to about 20, about 5 to about 15, or 9 or 15 amino acids in length [0015].
Claim 17 recites the limitation wherein each of the region metrics is further indicative of a predicted B-cell response potential of the respective amino acid sub-sequence. With respect to this limitation, BREMEL 2013 teaches that the region metrics can be indicative of a B-cell response potential [0021-22].
Claim 18 recites the limitation wherein each assigned epitope score is further based on the predicted B cell response potential of the respective amino acid. With respect to this limitation, BREMEL 2013 teaches that the epitope score can be based on the B-cell response potential [0181, 209-211].
Claim 19 recites the limitation of analyzing each candidate region of the one or more source proteins for the presence of B cell epitopes. With respect to this limitation, BREMEL 2013 teaches analyzing the candidate for B-cell epitopes [0021].
Claim 21 recites the limitation of adjusting a candidate region based on one or more adjacent amino acid sub-sequences. With respect to this limitation, BREMEL 2013 teaches that the window around the region can be adjusted based on upstream or downstream amino acids [0223].
Claim 22 recites the limitation wherein the one or more source proteins are one or more proteins of a virus, tumor, bacterium or parasite, or fragments thereof, including neoantigens. With respect to this limitation, BREMEL 2013 teaches that the source protein can be from a virus, tumor, bacterium or parasites [0231-233].
Claim 23 recites the limitation wherein the one or more source proteins are one or more proteins of a coronavirus, preferably the SARS-CoV-2 virus. With respect to this limitation, BREMEL 2013 teaches that the source protein can be from a human coronavirus [0233] including a SARS coronavirus [0249].
Claim 24 recites the limitation wherein the one or more source proteins comprise a plurality of variations of one or more proteins. With respect to this limitation, BREMEL 2013 teaches that source proteins can include variations of the protein [0034, 0269].
Claim 25 recites the limitation of filtering the one or more candidate regions so as to select one or more candidate regions in conserved areas. With respect to this limitation, BREMEL 2013 teaches identifying and selecting candidates that are conserved across organism strains [0008, 21].
Claim 26 recites a method of creating a vaccine by identifying at least one candidate region of at least one source protein by a method according to claim 1, and synthesizing a candidate region or predicted epitope within the candidate region, or encoding the at least one candidate region and/or predicted epitope within the candidate region, into a corresponding DNA or RNA sequence. With respect to this limitation, BREMEL 2013 teaches creation of vaccines that involve synthesizing the candidate epitope [0280].
Claim 29 recites a method of creating a diagnostic assay to determine whether a patient has or has had prior infection with a pathogen, wherein the diagnostic assay is carried out on a biological sample obtained from a subject, comprising identifying at least one candidate region of at least one source protein of the pathogen using a method according to claim 1; wherein the diagnostic assay comprises the utilization or identification within the biological sample of the candidate region and/or predicted epitope within the at least one candidate region. With respect to this limitation, BREMEL 2013 teaches creation of diagnostic assays carried out on a biological sample from a subject to identify an epitope, which can be used to determine prior infection [026-27, 155, 0266, 0294].
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in epitope prediction would have been motivated to combine the methods of BREMEL 2013 with the teachings of SANCHEZ-TRINCADO, in order to achieve the claimed invention, because determining immunogenicity potential is necessary for understanding disease etiology, immune monitoring, developing diagnosis assays, and designing epitope-based vaccines and because binding affinity is used with other factors to determine immunogenic potential (Abstract, pg 2 col 2),. A person of ordinary skill would reasonably expect success from combining these teachings, as both BREMEL 2013 and SANCHEZ-TRINCADO teach overlapping methods for identifying and selecting epitopes for vaccines and diagnostic assays. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
Claim Rejection
Claims 6 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over BREMEL 2013 in view of SANCHEZ-TRINCADO as applied to claims 1-5, 7-11, 16-19, and 21-29 above, and further in view of RICHMAN 2019 “Neoantigen dissimilarity to the self-proteome predicts immunogenicity and response to immune checkpoint blockade.”
Claim Interpretation and Scope and Contents of Prior Art
BREMEL 2013 in view of SANCHEZ-TRINCADO teaches the limitations of claims 1-5, 7-11, 16-19, and 21-29 above.
Claim 6 recites the limitation wherein the immunogenic potential of a candidate epitope is further based on a similarity of the candidate epitope to a human protein.
BREMEL 2013 in view of SANCHEZ-TRINCADO does not specifically teach this limitation, however, RICHMAN teaches that immunogenic potential in a neoantigen can be predicted based on similarity to the human proteome (Abstract, pg 2).
Claim 20 recites the limitation of comparing each identified candidate region with at least one human protein sequence in order to determine a degree of similarity, and ranking or discarding the candidate regions based on the degree of similarity with at least one of the human proteins being greater than a predetermined threshold.
With respect to this limitation, RICHMAN teaches determining similarity/dissimilarity to the human proteome and analyzing neoantigens with dissimilarity above a threshold (pg 4 par 4).
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in epitope prediction would have been motivated to combine the methods of BREMEL 2013 and SANCHEZ-TRINCADO with the teachings of RICHMAN, in order to achieve the claimed invention, because the level of similarity of an epitope to a human proteome can be used to help predict it’s immunogenicity and therefore its usefulness as a treatment (Abstract, pg 2). A person of ordinary skill would reasonably expect success from combining these teachings, as BREMEL 2013 in view of SANCHEZ-TRINCADO and RICHMAN teach methods for identifying and selecting epitopes/immunogenic peptides for vaccines or immunotherapy treatments. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
Claim Rejection
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over BREMEL 2013 in view of SANCHEZ-TRINCADO as applied to claims 1-5, 7-11, 16-19, and 21-29 above, and further in view of BREMEL 2017 “Immune Recognition Motifs” (US 20170161430 A1, as cited on the IDS filed 6/22/2023).
Claim Interpretation and Scope and Contents of Prior Art
BREMEL 2013 in view of SANCHEZ-TRINCADO teaches the limitations of claims 1-5, 7-11, 16-19, and 21-29 above.
Claim 12 recites the limitation wherein applying the statistical model comprises applying a Monte Carlo simulation to estimate a p-value for each of the generated region metrics. BREMEL 2013 in view of SANCHEZ-TRINCADO does not teach this limitation, however BREMEL 2017 teaches applying a Monte Carlo simulation to generate peptides with different region metrics to determine significance [0123, 397].
Claim 13 recites the limitation wherein applying the Monte Carlo simulation includes: for each HLA type, arranging the epitope scores into a plurality of epitope segments and epitope gaps based on the distribution of the epitope scores; and for each HLA type, iteratively generating a random arrangement of the epitope. With respect to this limitation, BREMEL 2017 teaches applying a Monte Carlo simulation to generate peptides with modified/random sequences [0397] which would be obvious to apply to each HLA type described in BREMEL 2013.
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in epitope prediction would have been motivated to combine the methods of BREMEL 2013 and SANCHEZ-TRINCADO with the teachings of BREMEL 2017, in order to achieve the claimed invention, because Monte Carlo is a well-known and obvious statistical method for generating random samples and calculating probabilities/significance. A person of ordinary skill would reasonably expect success from combining these teachings, as BREMEL 2013 in view of SANCHEZ-TRINCADO and BREMEL 2017 teach methods for identifying and selecting epitopes for vaccines or diagnostic assays. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
Claim Rejection
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over BREMEL 2013 in view of SANCHEZ-TRINCADO as applied to claims 1-5, 7-11, 16-19, and 21-29 above, and further in view of SMITH 2019 “Machine-Learning Prediction of Tumor Antigen Immunogenicity in the Selection of Therapeutic Epitopes”.
Claim Interpretation and Scope and Contents of Prior Art
BREMEL 2013 in view of SANCHEZ-TRINCADO teaches the limitations of claims 1-5, 7-11, 16-19, and 21-29 above.
Claim 14 recites the limitation of further comprising applying a false discovery rate, FDR, procedure to the results of the statistical model, preferably wherein the FDR procedure is a Benjamini-Hochberg or Benjamini-Yekutieli procedure.
BREMEL 2013 in view of SANCHEZ-TRINCADO does not teach this limitation, however SMITH 2019 teaches applying a false discovery rate procedure to the results of an immunogenicity prediction model (pg 1594 col 1).
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in epitope prediction would have been motivated to combine the methods of BREMEL 2013 and SANCHEZ-TRINCADO with the teachings of SMITH, in order to achieve the claimed invention, because FDR is a well-known and obvious statistical method in to determining significance and controlling for errors. A person of ordinary skill would reasonably expect success from combining these teachings, as BREMEL 2013 in view of SANCHEZ-TRINCADO and SMITH teach methods for identifying and selecting epitopes for vaccines or other clinical applications. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
Claim Rejection
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over BREMEL 2013 in view of SANCHEZ-TRINCADO as applied to claims 1-5, 7-11, 16-19, and 21-29 above, and further in view of RECHE 2013 “PEPVAC: a web server for multi-epitope vaccine development based on the prediction of supertypic MHC ligands.”
Claim Interpretation and Scope and Contents of Prior Art
BREMEL 2013 in view of SANCHEZ-TRINCADO teaches the limitations of claims 1-5, 7-11, 16-19, and 21-29 above.
Claim 15 recites the limitation of weighting the epitope scores dependent upon the human population frequency of the respective HLA type within the set of HLA types.
BREMEL 2013 in view of SANCHEZ-TRINCADO does not teach this limitation, however RECHE teaches a method of multi-epitope vaccine development that weights epitope scores based on human population frequency of HLA types (pg 139).
Resolving Ordinary Skill in the Art and Obviousness Rationale
A teaching, suggestion, or motivation in the prior art would have led one of ordinary skill in the art to modify or combine the prior art to arrive at the claimed invention. Specifically, a person of ordinary skill in epitope prediction would have been motivated to combine the methods of BREMEL 2013 and SANCHEZ-TRINCADO with the teachings of RECHE, in order to achieve the claimed invention, because favoring epitopes that bind to several common/frequent HLA types results in a limited number of potential epitopes without compromising the population coverage required for practical vaccine design considerations (Abstract, pg 139 col 1). A person of ordinary skill would reasonably expect success from combining these teachings, as BREMEL 2013 in view of SANCHEZ-TRINCADO and RECHE teach methods for identifying and selecting epitopes for vaccines development. Therefore, the claims at issue would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention as there is both a reason to modify or combine the prior art, and a reasonable expectation of success (see MPEP 2143.02 (I)).
Conclusion
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/MARY C LEVERETT/Examiner, Art Unit 1687
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