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 .
Claim Status
Claims 1-2, 4-6, 8, 10-11, 13, and 23 are pending and under examination.
Claims 1-2, 4-6, 8, 10-11, 13, and 23 are rejected.
Claim 1 is independent.
Claims 1-2, 4, 6, 8, 10, 13, and 23 are amended.
Claim 13 is objected to.
Claims 3, 7, 9, 12, 14-22, and 24-27 are canceled.
No claims are new or withdrawn.
Office Action Outline
Rejections applied
Abbreviations
x
112/b Indefiniteness
PHOSITA
"a Person Having Ordinary Skill In The Art before the effective filing date of the claimed invention"
112/b "Means for"
BRI
Broadest Reasonable Interpretation
x
112/a Enablement,
Written description
CRM
"Computer-Readable Media" and equivalent language
112 Other
IDS
Information Disclosure Statement
x
102, 103
JE
Judicial Exception
101 JE(s)
112/a
35 USC 112/a and similarly for 112/b, etc.
101 Other
N:N
page:line
Double Patenting
MM/DD/YYYY
date format
Priority
As detailed in the 10/28/2022 filing receipt, this application is a 371 of PCT/KR2021/000116, filed 01/06/2021. Additionally, this application claims priority to Korean application KR10-2020-0002260, filed 01/07/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. See paper entered 07/07/2022.
Overview of Withdrawal/Revision of Objections/Rejections
In view of the amendment and remarks received 07/09/2026:
• The objection to the drawings is withdrawn.
• The objection to the abstract of the disclosure is withdrawn.
• The objection to the specification for embedded hyperlinks is withdrawn.
• The objection to the specification for illegibility of Table 2 at [0136] and Table 3 at [0151] is maintained.
• The claim objection is withdrawn.
• The previous 112b rejections are withdrawn, except as maintained below, and new 112b rejections are applied.
• A new 112a rejection is applied below.
• The 101 rejection is withdrawn. Independent claim 1 recites a transformation in preparing an anticancer vaccine comprising synthesized peptides derived from identified neoantigens. A nexus occurs in that both the preparing of the vaccine, as well as the synthesizing of neoantigen derived peptides which comprise the vaccine, are informed by the output of the judicial exception (abstract ideas) of identifying and selecting neoantigens derived from genes essential for cancer cell survival. Therefore, claims 1-2, 4-6, 8, 10-11, 13, and 23 recite a practical application of a transformation at Step 2A Prong Two of the 101 analysis. Applicant's 07/09/2026 remarks at p.17-18 support withdrawal of the 101 rejection.
• Three 103 rejections (designated 103-1, 103-2, and 103-3) were applied previously; 103-1 and 103-2 are maintained with revision; 103-3 is moot as claim 25 and 26 have been canceled.
Specification
The specification is objected to for not complying with 37 CFR 1.58(b) and 37 CFR 1.52(a)(1)(iv-v) because Table 2 at [0136] and Table 3 at [0151] are illegible. The font appears to have a blurry, dot-matrix quality which is insufficient to support automated character recognition. A more legible font is requested. 37 CFR l.52(a)(l )(iv) requires all papers, other than drawings, that are submitted on paper or by facsimile transmission and are to become a part of the permanent United States Patent and Trademark Office records in the file of a patent application must be plainly and legibly written. Additionally, 37 CFR l.58(b) asserts tables must be presented in compliance with 37 CFR l .52(a) and (b ), and should have the lines and columns of data closely spaced to conserve space, consistent with a high degree of legibility. See MPEP § 608.01, 37 CFR l.58(b), l.52(a) and (b), and 1.125. Appropriate correction is required.
Claim Objections
Claim 13 is objected to because of the following informalities: Claim 13 recites "when a CNN-MHC value between the neoantigen and the HLA of the antigen-presenting cell is> 0.5" which should be corrected to "when a CNN-MHC value between each of the selected neoantigens and the HLA of the antigen-presenting cell is> 0.5." Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 4-6, 8, 10-11, 13, and 23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims depending from rejected claims are rejected similarly, unless otherwise noted, and any amendments in response to the following rejections should be applied throughout the claims, as appropriate.
Claim 1 recites the term "personalized" twice; once in the preamble, which recites "A method of preparing a personalized anti-cancer vaccine, the method comprising," and once in the last element, which recites "preparing the personalized anti-cancer vaccine comprising the synthesized peptides." (Emphasis added.) However, the claim seems inconsistent with the Specification, as the claims do not prepare a vaccine based on personalized neoantigens because there is no connection between the sequencing data of the patient and the selected neoantigens from which the personalized anti-cancer vaccine is ultimately based on. Specifically, in claim 1 nothing further is recited regarding the comparison after the "(i) comparing..." step. For compact prosecution, the claims will be examined as if the connection is present, with an assumption that claim 1will be amended to be consistent with the Specification in describing preparation of a personalized anti-cancer vaccine.
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.
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, 4-6, 8, 10-11, 13, 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. Claims depending from rejected claims are rejected similarly, unless otherwise noted, and any amendments in response to the following rejections should be applied throughout the claims, as appropriate.
In the claim 1 element beginning with "(i) comparing a sequence of a cancer cell," the connection is unclear between "a sequence of a cancer cell" and "a sequence of a normal cell from the cancer patient." While it is clear that "a sequence of a normal cell" is from the cancer patient, it is uncertain if "a sequence of a cancer cell" is also from the cancer patient. Possibly amending to "(i) comparing a sequence of a cancer cell from the cancer patient and a sequence of a normal cell from the cancer patient" would help overcome the rejection. The claim will be interpreted as suggested to amend.
In an issue that relates to the rejection directly above, in the claim 1 element beginning with "(i) comparing a sequence of a cancer cell," it is also unclear in what way the comparing of sequence data between normal cells and cancer cells would be performed when the "obtaining" element of claim 1 is interpreted to obtain sequencing data on only one exome, transcriptome, single cell transcriptome, peptidome, or entire genome from a cancer patient. Possibly amending to obtain sequencing data of (an exome, etc.) for both normal cell(s) from the cancer patient and cancer cell(s) from the cancer patient would help overcome the rejection. The claim will be interpreted as suggested to amend.
Claim 1 recites the term "personalized" twice; once in the preamble, which recites "A method of preparing a personalized anti-cancer vaccine, the method comprising," and once in the last element, which recites "preparing the personalized anti-cancer vaccine comprising the synthesized peptides." However, the vaccine ultimately prepared in the claim does not appear to meet the interpretation of a "personalized vaccine" in that there is no connection between the sequencing data of the patient and the selected neoantigens from which the personalized anti-cancer vaccine is ultimately based on, leaving the claim indefinite. Specifically, in claim 1 nothing further is recited regarding the comparison after the "(i) comparing..." step. For compact prosecution, the claims will be examined as if the connection is present, with the expectation that Applicant will amend appropriately. (Emphasis added.)
In claim 10, the connection is unclear between recited "sequence" and "the neoantigens," in that it is not clear that one sequence corresponds to the plural "the neoantigens." Possibly amending "sequence" in claim 10 to recites the plural "sequences" would help overcome the rejection. The claim will be interpreted as suggested to amend.
The recitation of "the neoantigens," recited in claims 10, is unclear as to if the neoantigens refers to "the selected neoantigens" (recited in claims 2 and 10) or if the neoantigens refers to the neoantigens in "identifying neoantigens derived..." (recited in claim 1). Possibly amending the instances of "the neoantigens" in claim 10 to "the selected neoantigens" would help overcome the rejection. The claim will be interpreted as suggested to amend.
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.
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.
103 (1 of 2):
Claims 1-2, 4-6, 8, 10-11, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Bulik-Sullivan (WO 2018/227030 A1; cited on the attached PTO Form 892) in view of Wang (EBioMedicine, vol. 50, pp.67-80 (2019); cited on the attached PTO Form 892).
Regarding the claim 1 elements for obtaining sequencing data of a cancer patient, and comparing a sequence from a cancer sell and a normal cell, and selecting neoantigens, Bulik-Sullivan discloses an optimized approach for identifying and selecting neoantigens for personalized cancer vaccines [0009]. Bulik-Sullivan shows exome, transcriptome, and/or whole genome tumor nucleotide sequencing data from tumor cells and normal cells of each patient are obtained. The tumor nucleotide sequencing data is used to obtain peptide sequences of each of a set of neoantigens identified by comparing the nucleotide sequencing data from the tumor cells and the nucleotide sequencing data from the normal cells. The peptide sequence of each neoantigen for the patient includes at least one alteration that makes it distinct from a corresponding wild-type parental peptide sequence identified from the normal cells of the patient [0010].
Regarding the claim 1 element for a model for predicting ...dependency, Bulik-Sullivan shows generating a dependency score (Bulik-Sullivan, [0095-0102]), and discusses immune tolerance escape features (Bulik-Sullivan, [0091]).
Regarding the claim 1 elements for preparing an anticancer vaccine comprising synthesizing neoantigen peptide sequences of 9-30 amino acids, the claim 10 element for predicting binding affinity of a peptide by learning data regarding interactions between amino acids of a peptide and of an HLA, the HLA being class I or II, and the claim 13 element for CNN-MHC, Bulik-Sullivan shows the training data set may further include data associated with peptide-MHC binding affinity measurements for at least one of the isolated peptides [00116]. Bulik-Sullivan shows obtaining a tumor vaccine comprising the set of selected neoantigens [00143] and at least one of neoantigens in the set of selected neoantigens, when in polypeptide form, may include at least one of: a binding affinity with MHC with an IC50 value of less than l000nM, for MHC Class I polypeptides a length of 8-15, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids, for MHC Class II polypeptides a length of 6-30, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids [00144]. Bulik-Sullivan shows peptide synthesis procedures [00213]. Bulik-Sullivan shows convolutional neural networks (CNN) [00370], and each MHC allele is associated with a separate network model, and NNh(·) denotes the output(s) from a network model associated with MHC allele h [00371].
Regarding the claim 2 elements for determining and modeling binding affinity of the neoantigens to HLA of an antigen-presenting cell, and the claim 11 element of the APC is a dendritic cell, macrophage, or B cell, Bulik-Sullivan shows a method for selecting neoantigens that have an increased likelihood of being capable of being presented to naïve T cells by professional antigen presenting cells (APCs) relative to unselected neoantigens based on the presentation model, optionally wherein the APC is a dendritic cell (DC) [00134]. Bulik-Sullivan shows measurements or predictions of binding affinity between a given MHC allele and a given peptide [00273].
Regarding the claim 8 element for non-synonymous mutations, Bulik-Sullivan shows a (neoantigen) vaccine can be compiled so that the selection, number and/or amount of neoantigens present in the composition is/are tissue, cancer, and/or patient-specific [00241]. Bulik-Sullivan shows number of non-synonymous mutations in each patient, and the proportion of sample patients that have the given number of non-synonymous mutations [00464]
Bulik-Sullivan does not show the claim 1 elements for identifying genes essential for cancer cell survival using a model for predicting cell survival dependency generated by learning a relationship between gene expression and apoptosis, and identifying the gene essential for cancer cell survival as a gene for which expression reduction or removal of the gene causes cell apoptosis, the claim 4 element for apoptosis when expression is decreased or removed, the claim 5 element for cancer cell line data, and the claim 6 element for homogeneous expression. These elements are taught below by Wang.
Regarding the claim 1 element for identifying genes essential for cancer cell survival using a model for predicting cell survival dependency generated by learning a relationship between gene expression and apoptosis, and identifying the gene essential for cancer cell survival as a gene for which expression reduction or removal of the gene causes cell apoptosis, the claim 4 element for apoptosis when expression is decreased or removed, the claim 5 element for cancer cell line data, and the claim 6 element for homogeneous expression, Wang shows a study using systematic comparison for CRISPR- and shRNA-based gene essentiality profiles across a larger collection of cancer cell lines, and development of a computational approach called combined gene essentiality score (CES) that provides an effective data integration strategy to allow improved estimation of cancer dependency maps (p.68, col.2, ¶ 3). Wang shows GAPDH is a constitutively expressed gene that encodes the enzyme for regulating cell energy metabolism, the inhibition of which leads to apoptosis (p.72, bridging cols.1-2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the neoantigen screening and neoantigen vaccine methods of Bulik-Sullivan with the identification of essential cancer genes of Wang to come to a methods for neoantigen discovery, and neoantigen vaccine preparation, using essential cancer genes. This is because Wang states to improve the estimation of true essentiality, a computational approach was developed called combined gene essentiality score (CES) which significantly improved the performance of gene essentiality prediction...for therapeutic targets that are selective for a specific cancer cell line (Wang, p. 68, col.1, ¶ 3), while Bulik-Sullivan presents a high accuracy neoantigen discovery method. One would have had a reasonable expectation of success in modifying Bulik-Sullivan with Wang, because Bulik-Sullivan and Wang are generally drawn to related teaching concerning cancer genes and tumor progression, and one of ordinary skill in the art would have understood how to and would have been motivated to apply the teaching of Wang to the related teachings of Bulik-Sullivan, and as such, the combination would have been obvious.
103 (2 of 2):
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Bulik-Sullivan in view of Wang as applied to claims 1-2, 4-6, 8, 10-11, and 13 above, and in further view of Parvizpour (BioImpacts: BI, vol. 9(1), pp.45-56 (2019); cited on the attached PTO Form 892).
Neither Bulik-Sullivan or Wang, alone or in combination, show a peptide sequence with Kyte-Doolittle GRAVY< 0 and InstaIndex < 40 of claim 23.
Regarding the claim 23 element of a peptide sequence with Kyte-Doolittle GRAVY< 0 and InstaIndex < 40, Parvizpour shows a vaccine peptide targeting cancer antigens with an instability index (i.e., InstaIndex) of 35.89, indicating stability of the protein; and the grand average of hydropathicity (GRAVY) was found to be -0.062 (p.49, col.2, ¶ 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of screening neoantigens and preparing anti-cancer vaccines of Bulik-Sullivan and Wang with the InstaIndex and GRAVY scoring of Parvizpour, because the InstaIndex and GRAVY values provide useful information regarding peptide stability and hydrophobicity.
Response to Applicant Arguments - 35 USC § 103
Applicant's arguments filed 07/09/2026 have been fully considered but they are not yet persuasive.
Applicant asserts:
• "The distinct technical feature of the present application is the use of neoantigens derived from genes essential for cancer cell survival.... (Remarks, p.19, ¶ 6.)
• ..."neither Bulik-Sullivan nor Wang discloses or suggests neoantigens derived from genes essential for cancer cell survival..." (Remarks, p.20, ¶ 2.)
• "Bulik-Sullivan only discloses selection of neoantigens having high PPV ...of being presented by one or more MHC alleles on the surface of the tumor cells of a patient... without any disclosure or suggestion that gene essentiality may be used as a criterion for selecting neoantigens." (Remarks, p.20, ¶ 3.)
• "Wang is silent on neoantigens derived from genes essential for cancer cell survival... Wang neither recognizes nor suggests that essential genes may serve as a source of neoantigens for personalized cancer vaccines, much less that selecting neoantigens derived from such genes could reduce the likelihood of tumor immune escape." (Remarks, p.20, ¶ 4.)
• "Wang does not include any description of neoantigens or its relevance to immune evasion." (Remarks, p.21, ¶ 1.)
The arguments are not persuasive for the following reasons:
In the 103 rejections, Bulik-Sullivan has been relied upon for teaching selecting of neoantigens and preparation of personalized neoantigen vaccines, while Wang has been relied upon for teaching determining genes essential for cancer cell survival.
Bulik-Sullivan shows generating a dependency score (Bulik-Sullivan, [0095-0102]), and discusses immune tolerance escape features (Bulik-Sullivan, [0091], while Wang shows a method for dependency mapping in analyzing essentiality of cancer genes to come to a combined gene essentiality score (CES) (Wang, entire document). Wang shows CES significantly improved the performance of gene essentiality prediction...for therapeutic targets that are selective for a specific cancer cell line (Wang, p.68, col.1, ¶ 3). As such, Wang provides a connection (and therefore motivation to modify Bulik-Sullivan with Wang) between therapeutic targets (which would include neoantigens for neoantigen vaccines) and essential genes. Therefore the 103 rejections are maintained with revision in view of the 07/09/2026 amendment.
Additionally, it is noted that the claims do not specifically recite "immune evasion" or "immune escape," which are terms used in the 103 arguments (remarks, p.19-21). The broader terms "apoptosis" and "cancer cell survival" are recited in the claims.
Conclusion
No claims area 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/M.A.V./Examiner, Art Unit 1687
/G. STEVEN VANNI/Primary patents examiner, Art Unit 1686
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