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 .
Election/Restrictions
Applicant's reply to the Restriction Requirement, dated July 21, 2026, has been received. By way of this submission, Applicant has elected, with traverse, the species of administering a peptide.
Applicant's election with traverse of species of a peptide in the reply filed on July 21, 2026, is acknowledged. The traversal is on the grounds that the Restriction Requirement does not map the pending claims to the alleged species, identify a unique special technical feature for each alleged group, or explain why the corresponding peptide-directed limitations of claims 1, 23, and 33 fail to provide the required technical relationship. This is not found persuasive for reasons stated in the previous Restriction Requirement, dated May 21, 2026. As stated in the Requirement, the claims lack unity of invention because even though the inventions of these groups require the technical feature of detecting a plurality of patient-specific tumor mutations in the tumor cells with a genomic analysis of tumor DNA and/or RNA and normal DNA and/or RNA from the patient, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Richters (Genome Med. 2019 Aug 28;11(1):56, cited in IDS). Richters teaches a method of bioinformatic characterization of neoantigens, comprising analyzing DNA from tumor cells by next-generation sequencing to detect somatic mutations, analyzing corresponding peptide sequences for prediction of MHC binding, and selecting candidates for vaccine design (Figure 1).
Should Applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, Applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the Examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-2, 4-5, 8, 11, 16, 23-27, 30, 33-35, 41, 43, 47 and 50 are pending in the application. Claims 23-27, 30, 33-35, 41, 43, 47 and 50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on July 21, 2026.
Claims 1-2, 4-5, 8, 11, and 16 are under examination before the Office.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at page 21. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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.
Claim Rejections - 35 USC § 102
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.
Claims 1, 2, 4, and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Richters (Genome Med. 2019 Aug 28;11(1):56, cited in IDS).
Richters teaches a method, comprising extracting cells from a patient's tumor (Figure 1, upper left), detecting patient-specific somatic mutations compared to normal DNA (Figure 1, upper right), analyzing corresponding peptide sequences with respect to their predicted expression, processing, and ability to bind the patient’s MHC complexes (i.e., binding with HLA proteins, Figure 1, lower center), and generating peptides based upon the neoantigens (Figure 1, lower left).
Richters further teaches that after neoantigen prioritization, personalized vaccines are designed from predicted immunogenic candidate sequences, and the vaccine is administered to the patient (page 14, left column, second paragraph).
Richters further teaches performing next generation sequencing can be used to detect neoantigens (page 2, left column, first paragraph), which is pertinent to claim 2.
Richters further teaches that matched tumor and normal DNA sequencing data are processed and analyzed to determine somatic mutations (page 2, left column, first paragraph), which is pertinent to claim 4.
Richters further teaches that the patient specific mutations may be single nucleotide variants (i.e., point mutations), insertions, or deletions (Figure 1, upper right).
Richters further teaches that mutant versus wild-type peptide binding affinity for MHC/HLA is critical in neoantigen prediction (page 12, right column).
Richters further teaches performing HLA haplotyping (i.e., identifying MHC I and II genotypes) of the subject (page 5, left column, second paragraph).
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.
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 8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Richters as applied to claim 1 above, and further in view of Dogan (Eur J Immunol. 2004 Feb;34(2):598-607) and Zimmerman (Drug Discov Today. 2016 Nov;21(11):1828-1834).
The teachings of Richters has been discussed supra. However, Richters does not teach a library of peptide constructs, wherein each peptide construct of the library comprises a peptide portion and an identifying nucleic acid portion that identifies the peptide portion, and the peptide portion of at least one of the peptide constructs is capable of specific binding to the HLA proteins or fragments thereof.
Dogan teaches a method of assessing peptide binding to MHC, comprising generating a genetically encoded library of polypeptides with phage display (page 604: "4.1 Phage constructions and library design"), contacting HLA proteins with said library and separating peptides that bind to HLA from peptides that do not bind HLA (page 605: "4.3 ELISA").
Zimmerman teaches the use of DNA barcodes connected to a compound of interest, and libraries of barcode DNA-compound conjugates can be rapidly screened against proteins of interest, with suitable hits identified by sequencing of the DNA barcode (abstract).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Richters, Dogan, and Zimmerman to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since all of Richters, Dogan, and Zimmerman are concerned with methods for screening compounds. Methods of assessing neoantigens for HLA binding in order to create a neoantigen vaccine were known in the art, according to the teachings of Richters. Dogan teaches that phage display is one method to construct a library of peptides in order to screen for binding to HLA proteins. Additionally, the DNA barcoding method of Zimmerman allows for high throughput detecting of bound species without the need for an antibody. One of ordinary skill could use the phage display method of Dogan and the DNA barcoding method of Zimmerman to construct a library of neoepitope antigens suitable for use in the method of Richters. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Richters as applied to claim 1 above, and further in view of Wucherpfennig (US20040197862A1).’
The teachings of Richters has been discussed supra. However, Richters does not teach the claimed method of determining specific binding between neoantigens and HLA proteins.
Wucherpfennig teaches a method of producing an MHC class II compound, comprising (1) culturing a cell transformed with at least one nucleic acid molecule comprising (a) an MHC class II component, wherein the MHC class II component comprises at least a portion of an MHC class II α chain and at least a portion of an MHC class II β chain, such that the MHC class II α chain and MHC class II β chain form a peptide binding groove; and (b) a spaceholder molecule which binds to the MHC class II compound by a processable linker, whereby the spaceholder molecule binds within the peptide binding groove and prevents the binding of any other peptide within the peptide binding groove of the MHC class II compound; (2) recovering the MHC class II compound; (3) processing the processable linker thereby releasing the spaceholder molecule from the peptide binding groove; (4) incubating the MHC class II compound in the presence of an antigenic peptide molecule whereby the incubation facilitates the binding of the antigen peptide molecule to the peptide binding groove of the MHC class II compound; and (5) recovering the MHC class II compound that has bound the antigenic peptide (para. 0015).
Wucherpfennig also teaches that the spaceholder molecule has a sequence of AAXAAAAAAAXAA (para. 0009).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Richters and Wucherpfennig to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Richters and Wucherpfennig are concerned with assessing antigen binding to MHC. Methods of assessing neoantigens for HLA/MHC binding in order to create a neoantigen vaccine were known in the art, according to the teachings of Richters. Wucherpfennig teaches a method of making suitable MHC molecules that are useful in assessing antigen binding to the MHC. One of ordinary skill could use the method of Wucherpfennig to make an MHC suitable for use in the method of Richters. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
All the claimed elements were known in the prior art and one of ordinary skill in the art could have arrived at the claimed invention by using known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results. Therefore, the invention, as a whole, was prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 6:00 to 2:00.
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/PETER JOHANSEN/Primary Examiner, Art Unit 1642
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