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 .
Restriction/Election of Species
Applicant’s election without traverse of Group I, claims 1-7, set forth in the Reply filed 07 June 2026, is acknowledged.
Status of the Claims
Claims 1-20 are currently pending. Claims 8-20 are withdrawn. Claims 1-7 are the subject of this Office Action. This is the first Office Action on the merits of the claims.
IDS
The references cited on the information disclosure statement(s) were considered and have been made of record.
Please note that the listing of references in the specification or claims is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a). If copies of the individual references cited on the document(s) noted above are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
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 1-7 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
The claims recite “judicial exceptions” as a limiting element or step without reciting additional elements/steps that integrate the judicial exceptions into the claimed inventions such that the judicial exceptions are practically applied and are sufficient to ensure that the claims amount to significantly more than the judicial exceptions themselves. In the instant case, the “judicial exceptions” include the abstract idea (e.g., a mathematical concept), “acquiring information about synthetic long peptides for treating carcinoma… outputting an immunogenicity score…” which is not eligible for patent protection without significantly more recited in the claims.
A claim that focuses on use of judicial exceptions must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966. Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas).
The Mayo framework provides that first whether the claims at issue are directed to a patent-ineligible concept is determined. If the answer is yes, then the elements of each claim both individually and “as an ordered combination” are considered to determine whether additional elements “transform the nature of the claim” into a patent-eligible application. The second step—known as the “inventive concept”—requires that claims include elements which would render the method both new and useful.
The PTO’s revised guidance on the application of § 101. (USPTO's January 7, 2019, Memorandum, 2019 Revised Patent Subject Matter Eligibility Guidance indicates that 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 fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)). 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:
(3) adds a specific limitation beyond the judicial exception that is not "well-understood, routine, conventional" in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
Step 2A Prong One: are the present claims directed to judicial exception(s)? The claims recite judicial exceptions as limiting elements, the abstract ideas (i.e., mathematical concepts) being “acquiring information about synthetic long peptides for treating carcinoma… outputting an immunogenicity score…”. These limitations could be carried out by merely reviewing the data mentally and mentally comparing and determining.
Step 2A Prong Two: do the claim(s) recite additional elements that integrate the exception into practical application, in the present case, are there other limitations in the claim that show a patent-eligible application of the abstract idea, e.g., more than a mere instruction to apply the abstract idea? If there are no meaningful limitations in the claim that transform the exception into a patent eligible application such that the claim amounts to significantly more than the exception itself, the claim should be rejected under 35 U.S.C. § 101 as being directed to non-statutory subject matter. The present claims, as a whole, do not integrate the judicial exception into a practical application. As recited in claim 1, “acquiring information”, “inputting” information, and “outputting” information, are mere data gathering and output recited at a high level of generality, and thus are insignificant extra-solution activity. Furthermore, the limitations, “embedding”, “encoding”, “BLOSUM”), are recited as being performed by a computer (see instant specification, e.g., at para. 15 on p. 5; para. 25 on p. 7; para. 20 on p. 28), which is recited at a high level of generality and amounts to no more than mere instructions to apply/implement the mathematical calculations using a generic computer. Moreover, there are no active method steps that transform the process into a practical application of the comparing and determining steps, e.g., using the immunogenicity score in treatment of a subject having carcinoma. Even if there were active treatment (e.g., administration of the synthetic long peptides) steps, there would not be an administration step if the subject was identified as not being a candidate for carcinoma treatment using synthetic long peptides.
Step 2B: do the claim(s) provide an inventive concept, i.e., do the claims recite additional element(s) that amount to significantly more than the exception? The present claims do not provide an inventive concept significantly more than the abstract idea, and thus, the claims are ineligible. As discussed above, the limitations (e.g., “acquiring”, “inputting”, “outputting”), were considered insignificant extra solution activity, and are also well-understood, routine, and conventional (see, e.g., Wu1). Even when considered in combination, these additional elements represent mere instructions to apply an exception and insignificant extra-solution activity, which cannot provide an inventive concept.
In sum, when the relevant factors are analyzed, they weigh against the present claims amounting to significantly more than the judicial exceptions themselves. Accordingly, the claims do not qualify as eligible subject matter. See MPEP 2106.03-2106.06.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-7 are rejected under 35 U.S.C. 112(b) as failing to set forth the subject matter which the inventor or a joint inventor the applicant regards as the invention.
Claim 1 is indefinite in the recitation of the step of "processing the synthetic long peptides by one processing method of embedding, one-hot encoding, and BLOSUM through the immunogenicity prediction device". This expression is unclear, as it suggests that the physical peptides are processed by the device using one of the methods listed. These methods, however, typically apply to sequence information and not the peptide itself. In general, the method of claim 1 appears to relate to sequence information of peptides (which seems to be acquired in the first step of the method), which is further supported by the expression "positions of the ... peptides" in step 3.
Claim 1, from which claims 2-7 depend, is indefinite in the recitation of "the cleavage probability vector" for lacking antecedent basis.
Claim 1 is indefinite in the recitation of “inputting a neoantigen peptide sequence, an HLA class I sequence, an HLA class II sequence within the”. This expression is unclear, as it appears to be missing an "and', or an "or", before "an HLA class II sequence".
Claim 1 is indefinite in the recitation of “outputting an immunogenicity score of the neoantigen peptide through the immunogenicity prediction device in consideration of…” as it is unclear how this score is generated.
Claim 2 is indefinite in the recitation of “the cleavage probability vector for each position of the neoantigen peptide is a cleavage probability vector for each position, when” as it is unclear what the cleavage probability vector for each position of the neoantigen peptide is when cleavage does not occur.
Claim 3 is indefinite in the recitation of “outputting a first… second… third neoantigen feature value…” as it is unclear how these values are generated.
Claim 4 is indefinite in the recitation of “outputting a first… second… third antigen using a model learned from data…” as it is unclear what the model is.
Claim 6 is indefinite in the recitation of “positioned at the center” as it is unclear what the center is relative to.
Claim 7 is indefinite in the recitation of “determining the synthetic long peptide with the highest immunogenicity score” as it is unclear how this score is generated.
Priority
The effective filing date of the claims is deemed the filing date of foreign application, KR10-2022-010565, namely August 23, 2022.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Wu (supra) in view of Chen2 and Yang3.
Wu teaches: An immunogenicity prediction method (see, e.g., Title, "Neoantigen Prediction"; Abstract, "deep learning techniques to predict neoantigens considering both the possibility of HLA-peptide binding (binding model) and the potential immunogenicity (immunogenicity model)") comprising the steps of: acquiring information about synthetic long peptides for treating carcinoma in a subject through an immunogenicity prediction device (see, e.g., Fig. 1, blocks "Input" and "Encoding"; Section "HLA-Peptide Binding and lmmunogenicity Data"); processing the synthetic long peptides by one processing method of embedding, one-hot encoding, and BLOSUM through the immunogenicity prediction device, and outputting one or more antigen feature values based on the processed data (see, e.g., Fig. 1, block "Encoding", "One-hot and "Embedding"; section "Model Training", page 4, "The one-hot method was used for amino acid representation"); inputting a neoantigen peptide sequence, an HLA class I sequence, an HLA class II sequence within the synthetic long peptides through the immunogenicity prediction device (see, e.g., Fig. 1, block "Encoding", "HLA pseudo sequence" and "Peptide sequence"; reads on claims 1, 4) to output one or more neoantigen feature values related to the immunity and binding affinity to the neoantigen peptide sequence (see, e.g., Fig. 1, block "Output", "Binding score" and "lmmunogenicity score"); and outputting an immunogenicity score of the neoantigen peptide through the immunogenicity prediction device in consideration of the one or more antigen feature values, and the one or more neoantigen feature values (see, e.g., Fig. 1, block "Output", “Binding Score”, "lmmunogenicity score"; Introduction, last paragraph, "combining the binding model and the immunogenicity model'; reads on claims 1, 2-3, 7). Wu further teaches that the synthetic long peptides have a length of less than 40mers (see, e.g., Materials and Methods, section "CDS+ T-Cell Epitopes; reads on claim 5).
The prior art of Wu differs from the instantly claimed invention as follows: Wu does not expressly teach that cleavage feature values are calculated, which are considered for the final immunogenicity prediction.
Chen teaches a method of predicting antigen presentation through deep learning based on binding scores and cleavage scores (see, e.g., Abstract; last para. Introduction, last paragraph in particular; Discussion, last paragraph in particular; Methods, sections "Amino acid representation" and "Cleavage score estimation"; Fig. 1-2).
Yang teaches a machine learning approach in which binding and immunogenicity information are combined in a model to predict neo-epitopes (see, e.g., abstract).
Obviousness Analysis: It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the presently claimed invention in view of the prior art because it amounts to no more than: combining the prior art elements of the cited references according to known methods to yield predictable results e.g., incorporating the disclosures of Chen and Yang into the known method of Wu, as immunogenicity prediction is known to incorporate the factors set forth in the references, i.e., binding activity, neoantigen expression, and cleavage signatures (see MPEP 2143(I)(A),(G); renders obvious instant claims 1-7).
Furthermore, it is prima facie obvious to combine equivalents, e.g., factors contributing to immunogenicity including binding activity, neoantigen expression, and cleavage signature, each of which is taught by the prior art to be useful for the same purpose, as “[T]he idea of combining them flows logically from there having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980.
Additionally, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Thus, a skilled artisan could predictably and reasonably produce the methods of the instant invention, as the prior art references cited above provide support and motivation for doing so, as discussed above.
Accordingly, claims 1-7 are rejected.
Conclusion
Claims 1-7 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEA S O'BRIEN whose telephone number is (703)756-4793. The examiner can normally be reached Monday - Thursday 9:00 AM to 6:00 PM PT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch, can be reached on (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LEA S O'BRIEN/Examiner, Art Unit 1646
/MARK HALVORSON/Primary Examiner, Art Unit 1646
1 JINGCHENG WU ET AL: "DeepHLApan: A Deep Learning Approach for Neoantigen Prediction Considering Both HLA-Peptide Binding and lmmunogenicity", FRONTIERS IN IMMUNOLOGY, vol. 10, 1 January 2019 (2019-01-01), page 2559, XP055682961, DOI: 10.3389/fimmu.2019.02559; as cited on the IDS filed 08/26/2024. Wu teaches:
An immunogenicity prediction method (Title, "Neoantigen Prediction"; Abstract, "deep learning techniques to predict neoantigens considering both the possibility of HLA-peptide binding (binding model) and the potential immunogenicity (immunogenicity model)") comprising the steps of: acquiring information about synthetic long peptides for treating carcinoma in a subject through an immunogenicity prediction device (Fig. 1, blocks "Input" and "Encoding"; Section "HLA-Peptide Binding and lmmunogenicity Data"); processing the synthetic long peptides by one processing method of embedding, one-hot encoding, and BLOSUM through the immunogenicity prediction device, and outputting one or more antigen feature values based on the processed data (Fig. 1, block "Encoding", "One-hot and "Embedding"; section "Model Training", page 4, "The one-hot method was used for amino acid representation"); inputting a neoantigen peptide sequence, an HLA class I sequence, an HLA class II sequence within the synthetic long peptides through the immunogenicity prediction device (Fig. 1, block "Encoding", "HLA pseudo sequence" and "Peptide sequence") to output one or more neoantigen feature values related to the immunity and binding affinity to the neoantigen peptide sequence (Fig. 1, block "Output", "Binding score" and "lmmunogenicity score"); and outputting an immunogenicity score of the neoantigen peptide through the immunogenicity prediction device in consideration of the one or more antigen feature values, and the one or more neoantigen feature values (Fig. 1, block "Output", "lmmunogenicity score"; Introduction, last paragraph, "combining the binding model and the immunogenicity model').
2 CHEN BINBIN ET AL: "Predicting HLA class II antigen presentation through integrated deep learning", NATURE BIOTECHNOLOGY, NATURE PUBLISHING GROUP US, NEW YORK, vol. 37, no. 11, 14 October 2019 (2019-10-14), pages 1332-1343, XP036920809, ISSN: 1087-0156, DOI: 10.1038/S41587-019-0280-2; as cited on the IDS filed 08/26/2024
3 XIAOYUN YANG ET AL: "DeepNetBim: deep learning model for predicting HLA-epitope interactions based on network analysis by harnessing binding and immunogenicity information", BMC BIOINFORMATICS, BIOMED CENTRAL LTD, LONDON, UK, vol. 22, no. 1, 5 May 2021 (2021-05-05), pages 1-16, XP021290448, DOI: 10.1186/S12859-021-04155-Y; as cited on the IDS filed 08/26/2024
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