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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on Nov. 7, 2025 has been entered.
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Nov. 7, 2025. Claims 1-2, 14, 16 and 21-30 are pending and currently examined.
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 of this title, 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.
(Previous Rejection – Maintained) Claims 1-2, 14, 16, 21-25 and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Johnston et al. (US 2013/0072660 A1, published Mar. 21, 2013; submitted in IDS filed on Aug. 4, 2021), as applied in a withdrawn rejection above, in view of Bannen et al. (US 2017/0234868 A1, published on Aug. 17, 2017).
Base claim 1 is drawn to a method of producing a vaccine for a cancer and/or tumor and stage of interest, comprising:
identifying a first population of peptides that are immunoreactive with a set of biological samples obtained from a set of test subjects that have been identified as having the cancer and/or tumor and stage of interest,
wherein the first population of peptides comprises peptides encoded by a frameshifted mRNA expressed by a cancer cell, wherein the frameshifted mRNA is created in a splicing error or a transcription insertion or deletion error,
wherein identifying the first population of peptides comprises determining immunoreactivity of the first population of peptides to the set of biological samples obtained from the set test subjects by measuring antibody reactivity to a high density array comprising the first populations of peptides; and
preparing a cancer vaccine composition specific for the cancer and/or tumor and stage of interest, wherein the cancer vaccine composition comprises a second population of peptides comprising one or more peptides in the first population or a nucleic acid sequence encoding the one or more peptides, thereby producing the vaccine for the cancer and/or tumor and stage of interest.
Johnston teaches compositions relating to novopeptides identified by the presence of frameshift mutations in tumor genes previously not identified as being oncogenic as well as methods for the treatment of cancer using the novopeptides. See Abstract.
Johnston teaches that a "novopeptide associated mutation or variation" means one or a combination of any one or more point mutations, frame shift mutations, in-frame insertions or deletions, translocations, improper splicing, post-transcriptional events, variations, or other alterations in a nucleic acid sequence from a non-cancerous reference sequence, regardless of whether heritable or not, the effect of which is to cause the amino acid sequence or composition of a polypeptide encoded thereby to differ from that of the non-cancerous reference sequence; "novopeptide associated mutation or variation" expressly includes, without limitation, deviations from non-cancerous reference sequences occurring as a result of mis-translation, mis-splicing, or other events occurring at the RNA level. See [0025].
“Summary” of Johnston is presented below:
Disclosed are methods for identifying and immunologically screening candidate antigens for inclusion in a prophylactic and/or therapeutic cancer vaccine. Further disclosed is a general class of antigens, referred to herein as novopeptides, as well as two specific subsets thereof, non-MS novopeptides and FS-novopeptides. Disclosed are methods and compositions related to novopeptides, unique nonsense proteins specific to a tumor, for use in diagnosing, preventing and treating cancer. Also disclosed is a method of using novopeptides to induce an immune response against cancer. Disclosed are vaccines having one or more novopeptide components, which are used prophylactically, or as a therapeutic treatment against existing cancerous cells.
FIG. 8 of Johnston shows that protective or therapeutic antibodies may be generated to FS (peptides) after vaccination, serum taken from patients with different tumor types was assayed for reactivity with predicted novopeptides by standard ELISA techniques. The bar graph in FIG. 8 shows one cancer patient in 23 with antibody reactivity in sera to FS novopeptide sequences (novopeptide 6-21). Reactive sera is shown by the arrow.
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FIG. 9 shows that the probable immunoprotectiveness of a predicted novopeptide can be assayed by immunological screening via a CTL assay, and discloses one method for doing so. CTLs activated against novopeptide 6-21, described above were able to kill MHC-matched tumor cells pulsed with 6-21 novopeptide, but not unpulsed SW480 tumor cells as shown by the square symbol. Since SW480 tumor cells do not express 6-21 novopeptide endogenously, the cells required peptide pulsing.
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Accordingly, Johnston teaches a method of identifying a peptide tumor antigen to be used in vaccine compositions for cancer treatment or prophylaxis by screening candidate novopeptides, generated by various frameshift mutations to tumor related antigens, using samples from tumor patients. However, Johnston is silent on if a “population of peptides” can be determined for immunoreactivity by measuring antibody reactivity to a high-density array with a set of biological samples obtained from a set test subjects, even though Johnston teaches that specific sequences can be identified by using antibody or other probes with ELISA or microarray (see [0047]).
Bannen teaches an invention relating to a method of identifying a neoantigen in a subject comprising contacting an antibody-comprising composition derived from a subject to a microarray having addressable features, wherein each feature comprises a wild-type or a mutant peptide and the mutant position in the mutant peptide is placed near the C-terminus of the peptide, detecting binding of an antibody to one or more features on a microarray, identifying features containing a mutant peptide where the binding has occurred while the binding has not occurred in features containing a corresponding wild-type peptide, detecting the identified mutant peptides as neoantigens. The antibody-comprising composition can be a blood serum. See [0009].
Bannen teaches that methods of forming a peptide microarray are known in the art. Certain methods of producing peptide arrays comprise spotting prefabricated peptides or in-situ synthesis by spotting reagents on membranes see U.S. Pat. No. 6,375,903. Other known methods used for generating peptide arrays of higher density involve photolithographic techniques, where the synthetic design of the desired biopolymers is controlled by suitable photolabile protecting groups (PLPG) releasing the linkage site for the respective next amino acid upon exposure to electromagnetic radiation, such as light (Fodor et al., (1993) Nature 364:555-556; Fodor et al., (1991) Science 251:767-773). See [0049].
Accordingly, Bannen teaches the concept and practice of using peptide microarrays, including high density ones, in the identification of neoantigen peptides using antibody-containing samples (e.g., blood serum) from subjects of interest.
It would have been prima facie obvious for one of ordinary skill in the art at the time of invention to combine the teachings of Johnston and Bannen to arrive at the invention as claimed. One would have been motivated to do so to screen a large number of peptides for neoantigens by using peptide microarrays, as well as to do the screening with samples from multiple subjects with various clinical conditions (e.g., different cancer patients).
(Previous Rejection – Maintained) Claims 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Johnston et al. (US 2013/0072660 A1, published Mar. 21, 2013; submitted in IDS filed on Aug. 4, 2021) in view of Bannen et al. (US 2017/0234868 A1, published on Aug. 17, 2017), as applied above, further in view of Nicosia et al. (US 2020/0222519 A1, published on Jul 16, 2020; PCT filed on Jul. 12, 2018), Plasterk (US 2021/0238244 A1, published on Aug. 5, 2021; foreign priority date Jul. 26, 2018 and Jan. 24, 2019; “Plasterk’224”), and/or Plasterk (US 2022/0349010 A1, published on Nov. 3, 2022; foreign priority date Jul. 26, 2018 and Jan. 24, 2019; “Plasterk’010”).
These claims specify that the population of peptides comprises an amino acid sequence selected from SEQ ID NOs: 1-20, 41-60 and 81-100.
Relevance of Johnston and Bannen is set forth in the rejection above. However, they are silent on the recited sequences.
Nicosia and the two Plasterk references teach inventions relating to tumor-related neoantigens and their application in the treatment of cancer. See Abstracts of the references.
Among many neoantigen peptides disclosed in the references, Nicosia discloses SEQ ID NO: 149 of 78 amino acid in length comprising the amino acid sequence of SEQ ID NO: 9 of instant claim 26; Plasterk’224 discloses three neoantigen peptides with sequences SEQ ID NO: 1787, 1022 or 146, which respectively comprise SEQ ID NOs: 17, 20, and 92 recited in claims 26 and 28; and Plasterk’010 discloses a neoantigen peptide with SEQ ID NO: 3662 comprising SEQ ID NO: 59 of claim 27. See alignments below:
SEQ9 1 LTPRTSAATKALPRQ 15
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SEQ149 44 LTPRTSAATKALPRQ 58
SEQ17 1 LGSTLCTSSVTMRTS 15
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SEQ1787 70 LGSTLCTSSVTMRTS 84
SEQ20 1 NPTSVTAARPPSATR 15
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SEQ1022 90 NPTSVTAARPPSATR 104
SEQ59 1 GGRSALGTFAAATPP 15
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SEQ3662 43 GGRSALGTFAAATPP 57
SEQ92 1 LLLLLLSLDPNLNPK 15
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SEQ146 40 LLLLLLSLDPNLNPK 54
Accordingly, neoantigen peptides comprising SEQ ID NO: 9, 17, 20, 59 or 92 recited in claims 26-28 are known at the time of invention.
It would have been prima facie obvious for one of ordinary skill in the art at the time of invention to combine the teachings of Johnston, Bannen, Nicosia, and the two Plasterk references to arrive at the invention as claimed. One would have been motivated to do so to include the neoantigen peptides disclosed in Nicosia and/or the Plasterk references in the studies.
Response to Applicant’s Arguments
Applicant’s arguments filed on Nov. 7, 2025 have been fully considered and are addressed as follows.
Applicant argues that Johnston does not teach or reasonably suggest, among other things, the step of "wherein identifying the first population of peptides comprises determining immunoreactivity of the first population of peptides to the set of biological samples obtained from the set test subjects by measuring antibody reactivity to a high density array of the first populations of peptides." Applicant argues that Johnston and the present application share the same first inventor, Stephen Johnston, that the inventor of the present application had not yet invented the high density peptide array technology at the time of filing of Johnston, and that, in addition, it was subsequently discovered that traditional immunological methods discussed in Johnston, such as ELISA, were not sensitive enough to detect the anti-frameshift antibodies, as described in Zhang, (2018) 8:17366 I DOI:10.1038/s41598-018-35673-0) (cite no. 8 in IDS filed August 4, 2021). Applicant argues that Bannen, Nicosia, and the two Plasterk references do not cure the deficiencies of Johnston.
Applicant’s arguments are not persuasive. The current rejections do not require that the Johnson reference teach or suggest explicitly the application of high density peptide array technology in the screening of neoantigens. Bannen cures this deficiency of Johnston. Additionally, since introduction of the microarray technology disclosed in Bannen into the study of Johnston would lead to the invention as claimed, the same functions as the claimed invention are expected, including the sensitivity of detecting neoantigens as shown in Zhang (2018). Applicant may be arguing that the claimed invention produces unexpected results. If this is the case, Applicant may refer to MPEP 716.02(b)-(e) for how unexpected results can be established.
Allowable Subject Matter
SEQ ID NOs: 1-8, 10-16, 18-19, 41-58, 60, 81-91, and 93-100 recited in claims 26-28 are free of prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/Primary Examiner, Art Unit 1671