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 .
Priority
Acknowledgement is made of Applicants’ claim for benefit to prior filed US Provisional application 63/144,250 (filed on 02/01/2021).
Election/Restriction
Applicant’s election without traverse of Group I, corresponding to claims 1-12, in the reply filed 13 February 2026 is acknowledged. Claims 13-15 and 19-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 13 February 2026.
Specification
The Specification is objected to because the drawings are indicated by “Fig.” rather than “FIG.” as required by 37 C.F.R. § 1.84 (u)(1) (see also MPEP §608.02 (V)).
The Specification is objected to because of the following informalities: “MALDI-ToF” should read “MALDI-TOF” in paragraphs 0012, 0015, 0093, 00101, 00217, and 00220. Appropriate correction is required.
The listing of references in the specification 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.
Claim Objections
Claim 6 is objected to because of the following informalities: “SARS-CoV2” should read “SARS-CoV-2”.
Claim 9 is objected to because of the following informalities: “MALDI-ToF” should read “MALDI-TOF”.
Appropriate correction is required.
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 1-12 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.
The term “about” in claim 1 is a relative term which renders the claim indefinite. The term “about” 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 size of peptides that are pre-treated by denaturation is rendered indefinite by the term “about”. The dependent claims do not add additional clarity, and therefore, are also indefinite.
The term “about” in claim 7 is a relative term which renders the claim indefinite. The term “about” 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 size of peptides is rendered indefinite by the term “about”. The dependent claims do not add additional clarity, and therefore, are also indefinite.
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.
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.
1. Claims 1-3, 5, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Dick, et al. (Cell. 1996 Jul 26;86(2):253-62., NPL-IDS, filed, 07/07/2023, hereinafter “Dick”) and further in view of Zhen, et al. (J Am Soc Mass Spectrom. 2004 Jun;15(6):803-22., hereinafter “Zhen”), Altin, et al. (US 2019/0383813, US-IDS, filed, 07/07/2023, hereinafter “Altin”), and ThermoFisher (Overview of the Immunoprecipitation (IP) Technique, available at https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/immunoprecipitation-ip.html and https://web.archive.org/web/20151005002151/http://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/immunoprecipitation-ip.html on 15 October 2015)
Regarding claim 1, Dick teaches identifying peptide sequences from polypeptides of interest that are presented on Class I MHC proteins (Abstract and pg. 261 column 2). Dick further teaches that the polypeptide of interest was incubated with purified 20S immunoproteasome (pg. 261 column 1) and 5-fold molar excess of PA28 to digest the polypeptide (pg. 261 column 2), the peptides are then isolated with RP-HPLC , and the eluent was analyzed and identified for molecular weight by mass spectrometry (pg. 261 column 2). The Specification defines de novo sequencing as matching the peptides of intertest against a database (¶0013). Dick does not teach pre-treating large polypeptides before digesting. However, Zhen teaches that it is usually necessary to denature proteins before digestion to render them accessible, denaturation prevents incomplete digestion which can cause larger fragments which are harder to fragment in tandem mass spectrometry (pg. 808 column 1).
It would have been prima facie obvious before the effective filing date of the invention to one of ordinary skill in the art to have combined the teachings of Dick for a method of identifying peptide sequences from polypeptides of interest and the teachings of Zhen for denaturing large proteins. Zhen provides motivation by teaching that denaturation prevents incomplete digestion which can cause larger fragments which are harder to fragment in tandem mass spectrometry (pg. 808 column 1). One of ordinary skill would have had a reasonable expectation of success in combining Dick and Zhen because they both teach using MS to identify peptides.
Dick and Zhen do not teach immunoprecipitating the proteasome digest by incubation with immobilized HLA peptides, washing the substrate, and eluting the bound peptides. However, Altin teaches immunoprecipitating peptides by incubating the peptides with immobilized HLA proteins (¶0106), washing the peptide/HLA complex free of unbound peptides and then eluting the bound peptides before analysis to detect the binding of a peptide to an MHC molecule (¶0019).
It would have been prima facie obvious before the effective filing date of the invention to one of ordinary skill in the art to have combined the teachings of Dick and Zhen for a method of identifying peptide sequences from polypeptides of interest and the teachings of Altin for a way to isolate peptides. ThermoFisher provides motivation by teaching that immunoprecipitation is used to isolate and eventually detect and measure specific proteins (Immunoprecipitation Methodology ¶1). One of ordinary skill would have had a reasonable expectation of success in combining Dick, Zhen, Altin, and ThermoFisher because they both teach protein detection.
Regarding claims 2-3 and 5, Altin teaches that the peptide is an infectious, autoimmunity, allergy, or cancer antigen (¶0016).
Regarding claim 7, Dick teaches that the 20s proteasome processes antigens including viral antigen and self-protein and these peptides are identified by their molecular mass (pg. 261 column 2).
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
2. Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Dick, Zhen, Altin, and ThermoFisher as applied to claims 1-3, 5, and 7 above, and further in view of Shen, et al. (J Hematol Oncol. 2013 May 9;6:33., NPL-IDS, filed, 07/07/2023, hereinafter “Shen”).
As discussed above, claims 1-3, 5, and 7 were rendered prima facie obvious over Dick, Zhen, Altin, and ThermoFisher.
Regarding claim 4, Altin teaches that the peptide can be a cancer antigen (¶0016). Dick, Zhen, Altin, and ThermoFisher do not teach that the cancer antigen is EGFRvIII. However, Shen teaches CAR-modified T cells are a promising immunotherapeutic strategy against cancer and that EGFRvIII is an attractive therapeutic target because it is frequently expressed by multiple types of cancer (Abstract).
It would have been prima facie obvious before the effective filing date of the invention to one of ordinary skill in the art to have combined the teachings of Dick, Zhen, Altin, and ThermoFisher for a method of identifying peptide sequences from polypeptides of interest and the teachings of Shen for a cancer polypeptide of interest. Shen provides motivation by teaching that CAR-modified T cells are a promising immunotherapeutic strategy against cancer and that EGFRvIII is an attractive therapeutic target because it is frequently expressed by multiple types of cancer (Abstract). One of ordinary skill would have had a reasonable expectation of success in combining Dick, Zhen, Altin, ThermoFisher, and Shen because they all teach identifying peptides of interest.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
3. Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Dick, Zhen, Altin, and ThermoFisher as applied to claims 1-3, 5, and 7 above, and further in view of Grifoni, et al. (Cell. 2020 Jun 25;181(7):1489-1501.e15., NPL-IDS, filed, 07/07/2023, hereinafter “Grifoni”).
As discussed above, claims 1-3, 5, and 7 were rendered prima facie obvious over Dick, Zhen, Altin, and ThermoFisher
Regarding claim 6, Altin teaches that the peptide can be a viral antigen (¶0016). Dick, Zhen, Altin, and ThermoFisher do not teach that the viral antigen is the SARS-CoV-2 spike or nucleocapsid protein. However, Grifoni teaches that the spike and nucleocapsid proteins account for a majority of the epitopes that cause a CD8+ and CD4+ T cell response (pg. 1495).
It would have been prima facie obvious before the effective filing date of the invention to one of ordinary skill in the art to have combined the teachings of Dick, Zhen, Altin, and ThermoFisher for a method of identifying peptide sequences from polypeptides of interest and the teachings of Grifoni for a SARS-CoV-2 polypeptide of interest. Grifoni provides motivation by teaching that the spike and nucleocapsid proteins account for a majority of the epitopes that cause a CD8+ and CD4+ T cell response (pg. 1495). One of ordinary skill would have had a reasonable expectation of success in combining Dick, Zhen, Altin, ThermoFisher, and Grifoni because they all teach identifying peptides of interest.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
4. Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Dick, Zhen, Altin, and ThermoFisher as applied to claims 1-3, 5, and 7 above, and further in view of Charité Universitätsmedizin Berlin (EP 2362225 A1, FOR-IDS, filed, 07/07/2023, hereinafter “CUB”).
As discussed above, claims 1-3, 5, and 7 were rendered prima facie obvious over Dick, Zhen, Altin, and ThermoFisher.
Regarding claim 8, Dick, Zhen, Altin, and ThermoFisher do not teach that molecular weights observed through MALDI-TOF are aggregated; and each linear and PCPS-derived arrangement of the parental sequence that matches the original weight is calculated, restricted to peptides of lengths between about 8 and about 11 amino acid residues in length to generate a FASTA database of co-linear and PCPS spliced peptides. However, CUB teaches that peptides from a 20S proteasome digest were analyzed by MALDI-TOF to identify the combinatorial amino acid member (PSP) (¶0034), all arrangement of the parental sequence that matched the original weight were calculated (¶0042) and only the peptides 8-10 amino acids long (¶0024) are used to generate a database of all peptides (¶0042 and FASTA file listing).
It would have been prima facie obvious before the effective filing date of the invention to one of ordinary skill in the art to have combined the teachings of Dick, Zhen, Altin, and ThermoFisher for producing MHC class I ligands by the proteasome and the teachings of CUB for investigating 20s proteasome digests by LC-ESI-MS/MS and generating a FASTA database. CUB provides motivation by teaching that generating a database od PCPS peptides helps identify peptides of interest (¶0042). One of ordinary skill would have had a reasonable expectation of success in combining Dick, Zhen, Altin, ThermoFisher, and CUB because they all teach identifying peptides of interest.
Regarding claims 9-10, Dick, Zhen, Altin, ThermoFisher do not teach that molecular weight data from MALDI-TOF is used to generate a database of co-linear fragments in a digest, an algorithm is used to assemble a database where 2-10 or 2-12 aa fragments across any given 50 aa window are used in combinatorial fashion to make hypothetical PCPS sequences of between 8-12 aa, containing no more than 3 fragments. However, CUB teaches that the molecular weight data from MALDI-TOF is used to generate a database from the peptides of the proteasome digest (¶0042) and all hypothetical PCPS sequences are calculated (Figure 4), these fragments are preferably no larger than 20 aa to be presented of MHC Class I (¶0024).
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
5. Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Dick, Zhen, Altin, and ThermoFisher as applied to claims 1-3, 5, and 7 above, and further in view of Ross, et al. (Vet Immunol Immunopathol. 2012 Dec 15;150(3-4):206-12., hereinafter “Ross”).
As discussed above, claims 1-3, 5, and 7 were rendered prima facie obvious over Dick, Zhen, Altin, ThermoFisher.
Regarding claim 11, Dick, Zhen, Altin, and ThermoFisher do not teach confirming the peptide for binding to an appropriate class I MHC in an MHC stabilization assay. However, Ross teaches that one of the simplest, most cost-effective means of testing peptide binding to class I alleles is the peptide-induced MHC stabilization assay (pg. 2 ¶2).
It would have been prima facie obvious before the effective filing date of the invention to one of ordinary skill in the art to have combined the teachings of Dick, Zhen, Altin, and ThermoFisher for a method of identifying peptide sequences from polypeptides of interest and the teachings of Ross for an MHC stabilization assay. Ross provides motivation by teaching one of the simplest, most cost-effective means of testing peptide binding to class I alleles is the peptide-induced MHC stabilization assay (pg. 2 ¶2). One of ordinary skill would have had a reasonable expectation of success in combining Dick, Zhen, Altin, ThermoFisher, and Ross because they all teach identifying peptides of interest.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
6. Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Dick, Zhen, Altin, and ThermoFisher as applied to claims 1-3, 5, and 7 above, and further in view of Ji, et al. (Methods Mol Biol. 2016;1304:63-71., hereinafter “Ji”).
As discussed above, claims 1-3, 5, and 7 were rendered prima facie obvious over Dick, Zhen, Altin, and ThermoFisher.
Regarding claim 12, Dick, Zhen, Altin, and ThermoFisher do not teach confirming the peptides with functional assays. However, Ji teaches using ELISpot to test the ability of a peptide to bind and stimulate T cells by measuring the amount of cytokines release by stimulated T cells (Fig. 1)
It would have been prima facie obvious before the effective filing date of the invention to one of ordinary skill in the art to have combined the teachings of Dick, Zhen Altin, and ThermoFisher for a method of identifying peptide sequences from polypeptides of interest and the teachings of Ji for ELISpot. Ji provides motivation by teaching that the ELISpot assay tests the ability of an antigen to stimulate T cells (Fig. 1). One of ordinary skill would have had a reasonable expectation of success in combining Dick, Zhen, Altin, ThermoFisher, and Ji because they all teach identifying peptides of interest.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Cassandra Senn Grizer whose telephone number is (571)272-2292. The examiner can normally be reached M-Th 0630 - 1700 ET.
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/CASSANDRA SENN GRIZER/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
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