DETAILED ACTION
Applicant's response, filed 07/16/2026, has been fully considered.
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 .
Priority
This application filed 12/20/2022 claims priority from Provisional Application 63292205, filed 12/21/2021. The claims are therefore examined as filed on 12/21/2021, 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).
Election/Restrictions
Applicant’s cancellation of nonelected claims 11-18 and 87-89 is acknowledged. Election was made without traverse in the reply filed on 07/16/2026.
Applicant’s election without traverse of invention Group I, claims 3-10 and 86 in the reply filed on 07/16/2026 is acknowledged.
Claim Status
Claims 3-10, 86, and 90-92 are pending.
Claim 7 is objected to.
Claims 11-85 and 87-89 are cancelled.
Claims 90-92 are newly added.
Claims 3-10, 86, and 90-92 are examined.
Claims 3-10, 86, and 90-92 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.
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.
Claim 6 is 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.
The term “low expression” in claim 6 is a relative term which renders the claim indefinite. The term “low expression” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The claim is therefore indefinite because it is unclear what would be considered “low expression,” or in what range or under what threshold the level of expression must be to meet the claim limitation.
Claim Objections
Claim 7 is objected to because of the following informalities:
Claim 7 should read “the DoS score being based at least in part on a number of amino acids identical to amino acids at corresponding positions of the target peptide, in which the amino acids of the target peptide are available to interact with the antigen-recognition molecule…”
Appropriate correction is required.
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 3-10, 86, and 90-92 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?): Yes. The claims are directed to one of the statutory classes. The claims are directed to a machine product (a non-transitory computer readable medium).
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:
Predicting amino acid positions within a target peptide that are available to interact with an antigen-recognition molecule that recognizes the MHC-target peptide complex (mental process; the human mind is capable of forming a prediction based on data; claim 3)
Generating a working list of peptides, within a total pool of predicted or detected peptides of suitable length, such that peptides listed in the working list each include at least two amino acids that are located at positions corresponding to positions within the target peptide that are available to interact with the antigen-recognition molecule and are identical to the corresponding amino acids of the target peptide (mental process; the human mind is capable of making a list based on set criteria; claim 3)
Determining binding affinity, of each of the peptides listed in the working list, to the MHC molecule (mental process/mathematical concept; additional claim limitations and specification indicate that the binding affinity is calculated through mathematical processes, and the human mind is capable of making a determination based on a calculation; claim 3)
Filtering the working list based on calculated binding affinity to the MHC molecule, thereby generating a working list of off-target peptide (mental process; the human mind is capable of filtering data based on a parameter/data; claim 3)
Estimating the number of peptides in the working list of off-target peptides which are expressed in essential, normal tissues (mental process/mathematical process; the human mind is capable of estimating a number, and doing so is a mathematical concept; claim 4)
Determining, for each peptide in the working list of peptides, whether such peptide is expressed in essential, normal tissues; and filtering the working list to include only peptides which are expressed in essential, normal tissues (mental process; the human mind is capable of making a determination based on data and filtering the data based on a parameter; claim 5)
Generating a list of potential secondary target peptides comprising peptides having a calculated binding affinity to the MHC molecule having low expression in essential, normal tissues (mental process; the human mind is capable of generating a list based on a calculated parameter or set of parameters; claim 6)
Calculating a Degree of Similarity (DoS) score for the peptide(s) in the working list of peptides based at least in part on a number of amino acids identical to amino acids at corresponding positions of the target peptide and filtering the working list to include only peptides having a DoS score greater than a second threshold value (mental process/mathematical concept; the human mind is capable of calculating a degree of similarity based on matching amino acids and filtering data based on the calculation; performing a calculation is a mathematical concept; claim 7)
Determining binding affinity of the antigen-recognition molecule to a plurality of MHC- peptide complexes each including a respective likely off-target peptide from the working list and the MHC molecule; and filtering the working list to include only likely off-target peptides which comprise a binding motif for the antigen-recognition molecule (mental process/mathematical concept; additional claim limitations and specification indicate that the binding affinity is calculated through mathematical processes, and the human mind is capable of making a determination based on a calculation and filtering based on a parameter; claim 9)
Determine binding affinity of the target peptide to the MHC molecule; generating sequences of a plurality of mutated peptides each associated with a mutation at a respective amino acid position of the target peptide; determining binding affinity of each mutated peptide of the plurality of mutated peptides to the MHC molecule; and predicting the amino acid position(s) available to interact with an antigen-recognition molecule that recognizes said MHC-target peptide complex based at least in part on a comparison of the binding affinity for each mutated peptide to the binding affinity of the target peptide (mental process/mathematical concept; the human mind is capable of making determinations and predictions based on data or data comparisons, and additional claim limitations and specification indicate that the binding affinity is calculated through mathematical processes; claim 86)
Dependent claims 8 and 90-92 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 3 and its dependents recite the additional elements of a non-transitory computer-readable medium configured to communicate with one or more processors of a computational device, and the additional elements of receiving data as inputs and providing data as an outputs. Claims 9-10 further describe data inputs/outputs.
While the claims recite the additional element of receiving and outputting data, such steps that only amount to necessary data gathering and outputting, without any technical details of how the data is obtained/output 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-readable medium, processors, or computational device 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 as inputs/outputs do not provide an inventive concept. Non-particular instructions to gather or output data 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 § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim Rejection
Claims 3-4, 9-10, 86, and 90-92 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by KARAPETYAN 2019 “TCR Fingerprinting and Off-Target Peptide Identification” (cited on the IDS filed 02/26/2025).
Claim Interpretation and Scope and Contents of Prior Art
Claim 3 recites a non-transitory computer-readable medium configured to communicate with one or more processors of a computational device, the non-transitory computer-readable medium including instructions thereon, that when executed by the processors, cause the computational device to receive, as an input, a computational representation of a target peptide presented in a complex with a major histocompatibility complex (MHC) molecule (MHC-target peptide complex) and predict all amino acid positions within the target peptide that are available to interact with an antigen-recognition molecule that recognizes the MHC-target peptide complex.
With respect to this limitation, KARAPETYAN teaches computer implemented methods for determining off target peptides presented on MHC molecules (Abstract) involving using a representation of peptide epitope SLLMWITQC presented by HLA-A∗02:01 (Abstract, Fig 2) and predicting all amino acid positions within the target available to interact with the molecular/TCR that recognizes the MHC target peptide complex (pg 2 col 2, pg 4 col 2).
Claim 3 further recites the limitations of generating a working list of peptides, within a total pool of predicted or detected peptides of suitable length, such that peptides listed in the working list each include at least two amino acids that (i) are located at positions corresponding to positions within the target peptide that are available to interact with the antigen-recognition molecule and (ii) are identical to the corresponding amino acids of the target peptide.
With respect to this limitation, KARAPETYAN teaches generating a list of 9-mer peptides that include amino acids located at positions corresponding to positions within the target peptide available to interact with the antigen molecule, where two of the amino acids are identical to those of the target peptide (pg 2 col 2, 4 col 2).
Claim 3 further recites the limitation of determining binding affinity, of each of the peptides listed in the working list, to the MHC molecule; filtering the working list based on calculated binding affinity to the MHC molecule, thereby generating a working list of off-target peptides; and providing, as an output, the working list of off-target peptides and/or the number of the off-target peptides in the working list.
With respect to these limitations, KARAPETYAN also teaches determining binding affinity of all of the peptides to the MHC molecule and discarding those with low binding affinity (filter) to produce and output a final list of 9-mer peptide sequences with intermediate and high binding affinity toward HLA-A∗02:01 (pg 8 col 2).
Claim 4 recites the limitation of estimating the number of peptides in the working list of off-target peptides which are expressed in essential, normal tissues; and provide, as an output, the number of off-target peptides which are expressed in essential, normal tissues.
With respect to this limitation, KARAPETYAN teaches estimating and outputting which peptides of the list are expressed in normal human tissue (Fig 5, pg 10 col 2, pg 11 par 1).
Claim 9 recites the limitation of providing, as an input, a computational representation of the antigen-recognition molecule, the antigen-recognition molecule being capable of binding to the MHC-target peptide complex; determining binding affinity of the antigen-recognition molecule to a plurality of MHC- peptide complexes each including a respective likely off-target peptide from the working list and the MHC molecule; and filtering the working list to include only likely off-target peptides which comprise a binding motif for the antigen-recognition molecule.
With respect to these limitations, KARAPETYAN teaches using a representation of the T-cell receptor (TCR), an antigen recognition molecule capable of binding to the HLA-A∗02:01-peptide complex in an algorithm to determine binding affinity of TCR to MHC-peptide complexes that include off-targets, and filtering the list of peptides to those above a threshold of a predicted score indicative of the TCR NY-ESO recognition motif (Abstract, pg 6 col 1, Fig 3).
Claim 10 recites the limitation of providing, as an input, off-target peptide expression in essential, normal tissues of a specific patient; and providing, as an output, an indication of the off-target effects for said patient.
With respect to these limitations, KARAPETYAN teaches computationally predicting and experimentally validating off-target peptide expression in normal human tissues and providing an indication of off target effects in a human (pg 10 last par, Fig 5).
Claim 86 recites the limitation wherein predicting all amino acid positions within the target peptide that are available to interact with the antigen-recognition molecule, comprises the steps of : i) determining binding affinity of the target peptide to the MHC molecule; ii) generating sequences of a plurality of mutated peptides each associated with a mutation at a respective amino acid position of the target peptide; iii) determining binding affinity of each mutated peptide of the plurality of mutated peptides to the MHC molecule; and iv) predicting the amino acid positions available to interact with an antigen-recognition molecule that recognizes the MHC-target peptide complex based on a comparison of the binding affinity for each mutated peptide to the binding affinity of the target peptide.
With respect to these limitations, KARAPETYAN teaches that predicting amino acid sequences available to interact with TCR comprises determining binding affinity of the target peptide to the MHC molecule, generating sequences of mutated peptides associated with a mutation at an amino acid position of the target peptide, determining binding affinity of the mutated peptides to the MHC molecule, and predicting the amino acid positions available to interact with TCR that recognizes the MHC-target peptide complex based on a comparison of the binding affinity for each mutated peptide to the binding affinity of the target peptide (pg 2 col 2, pg 4 col 2, pg 6 col 2, pg 8 col 1, Fig 3).
Claim 90 recites the limitation of filtering the working list to include only peptide(s) having a calculated binding affinity to the MHC molecule greater than a first threshold value.
With respect to this limitation, KARAPETYAN teaches discarding peptides with low binding affinity (IC50 > 500nM) to the HLA-A∗02:01 to obtain the final list (pg 8 col 1).
Claim 91 recites the limitation of verifying that amino acid positions predicted as available to interact with the antigen- recognition molecule are not involved in interacting with the MHC molecule based on a known structure of the MHC-target peptide complex.
With respect to these limitations, KARAPETYAN teaches verifying that amino acid positions predicted to interact with the TCR are not involved in interacting with the MHC molecule based on known structure (pg 6).
Claim 92 recites the limitation wherein the total pool of predicted or detected peptides comprises peptides of 8-12 amino acids in length. With respect to this limitation, KARAPETYAN teaches that the peptides are 9 amino acids in length (pg 8 col 2).
Claim Rejections - 35 USC § 103
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 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over KARAPETYAN as applied to claims 3-4, 9-10, 86, and 90-92 above.
Claim Interpretation and Scope and Contents of Prior Art
KARAPETYAN teaches the limitations of claims 3-4, 9-10, 86, and 90-92 above.
Claim 5 recites the limitation of determining, for each peptide in the working list of peptides, whether such peptide is expressed in essential, normal tissues; and filtering the working list to include only peptides which are expressed in essential, normal tissues.
Claim 6 recites the limitation of generating a list of potential secondary target peptides comprising peptides having a calculated binding affinity to the MHC molecule having low expression in essential, normal tissues.
With respect to these limitations, KARAPETYAN teaches determining which peptides of the list are expressed in normal human tissue and determining the level of expression in different tissues for each peptide (Fig 5, pg 10 col 2, pg 11 par 1), but does not teach filtering the list to include only peptides expressed in these tissues or only peptides having low expression in these tissues. However, it would be obvious to one of ordinary skill in the art to further filter the list based on expression of the peptides for the purpose of producing an off-target list or a low risk list, as KARAPETYAN teaches that the risk of on and off target toxicity is a concern with engineered TCRs (pg 11 par 2-3).
Claim Rejection
Claims 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over KARAPETYAN as applied to claims 3-4, 9-10, 86, and 90-92 above, and further in view of DHANIK 2016 “In-silico discovery of cancer-specific peptide-HLA complexes for targeted therapy” (as cited on the IDS filed 06/05/2023).
Claim Interpretation and Scope and Contents of Prior Art
KARAPETYAN teaches the limitations of claims 3-4, 9-10, 86, and 90-92 above.
Claim 7 recites the limitation of calculating a Degree of Similarity (DoS) score for the peptides in the working list of peptides, the DoS score being based at least in part on a number of amino acids identical to amino acids at corresponding positions of the target peptide, which amino acids of the target peptide are available to interact with the antigen-recognition molecule; and filter the working list to include only peptides having a DoS score greater than a second threshold value.
With respect to this limitation, KARAPETYAN teaches determining scores for the peptides based on predicted binding, activation, and killing efficiency and determining a cutoff value for the scores (pg 6 col 2, pg 8), but does not teach that the score is specifically a Degree of Similarity (DoS) score. However, DHANIK teaches a computational method to identify cancer specific HLA targets and prioritize them based on potential cross-reactivity, and calculates the degree of similarity (DoS) score to do so (pg 3 par 1). It would be obvious to one of ordinary skill in the art that a DoS score could be calculated and used in place of or in addition to the scores of KARAPETYAN.
Claim 8 recites the limitation wherein only positions of the target peptide identified as being unbound to the MHC molecule are considered in calculating the DoS score. With respect to this limitation, DHANIK takes into account which positions of the peptide are important vs non-important for binding interactions with a therapeutic molecule in determining DoS and off-target toxicity (Fig 1, pg 4-5), and one of ordinary skill in the art would understand that a position available for binding to a therapeutic molecule would be unbound to the MHC molecule.
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 analysis of peptide-MHC complexes for off-target identification would have been motivated to combine the teachings of KARAPETYAN with the teachings of DHANIK, in order to achieve the claimed invention, because determining a Degree of Similarity score is a well-known method of quantifying similarity which can be used in determining the likelihood of off target effects (pg 4). A person of ordinary skill would reasonably expect success from combining these teachings, as both KARAPETYAN and DHANIK teach methods of determining peptide-MHC complexes that produce off-target effects. 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
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY C LEVERETT whose telephone number is (571)272-5494. The examiner can normally be reached 8:00am - 5:00pm M-Th.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz R. Skowronek can be reached at (571) 272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY C LEVERETT/Examiner, Art Unit 1687
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