DETAILED ACTION
Reassignment of the Application
1. Please note that this application has been reassigned to Examiner Kaijiang Zhang, in Art Unit 1684. In order to expedite accurate processing of the application papers, all future correspondence with the Office should reflect this change.
Notice of Pre-AIA or AIA Status
2. 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
3. Applicant’s election without traverse of (1) peptides as the synthesized products species, and (2) claim 2 as the species for the set of selected proteins, in the reply filed on 4/23/2026 is acknowledged.
4. Claims 1-20 are pending in the application. Claims 3-4 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-2 and 5-20 are currently under examination.
Drawings
5. The drawings are objected to because Figures 1-18 contain texts that are illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
6. Claims 1-2 and 19 are objected to because of the following informalities:
Claim 1, line 8: “RNA sequences from the tumor biopsy” should be changed to “RNA sequences from the tumor biopsy;” for more clarity.
Claim 1, lines 13-15: “the fraction of RNA transcribed from that gene locus and expressing the protein containing mutated amino acids” should be changed to “the fraction of RNA transcribed from the genes and expressing the proteins containing mutated amino acids” for more clarity.
Claim 2, step a: “the RNA transcribed from that gene locus” should be changed to “the RNA transcribed from the genes” for more clarity.
Claim 19, line 3: “a predicted binding” should be changed to “a predicted binding affinity” for more clarity.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
7. 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.
8. Claims 1-2 and 5-20 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.
(1). Claim 1 recites a “group of one or more selected peptides” that is selected in the step of “selecting a group of one or more selected peptides from the array of alternative peptides which have a desired predicted binding affinity for one or more of the subject’s MHC alleles”, and also recites “those peptides” that are selected in the step of “selecting from the array of alternative peptides those peptides in which those amino acids not located within the T cell exposed motif provide desired characteristics for formulation and delivery”. Since the recited “group of one or more selected peptides” and the recited “those peptides” are selected independently and the selection of each is based on different criteria, it is not clear how the recited “group of one or more selected peptides” and the recited “those peptides” are related to each other. Furthermore, it is unclear whether the “selected peptides” to be synthesized in the step of “synthesizing” refer to the “group of one or more selected peptides” that is selected in the step of “selecting a group of one or more selected peptides from the array of alternative peptides which have a desired predicted binding affinity for one or more of the subject’s MHC alleles” or “those peptides” that are selected in the step of “selecting from the array of alternative peptides those peptides in which those amino acids not located within the T cell exposed motif provide desired characteristics for formulation and delivery”. In addition, if the “group of one or more selected peptides” recited in the step of “synthesizing” refers to the “group of one or more selected peptides” that is selected in the step of “selecting a group of one or more selected peptides from the array of alternative peptides which have a desired predicted binding affinity for one or more of the subject’s MHC alleles”, then the step of “selecting from the array of alternative peptides those peptides in which those amino acids not located within the T cell exposed motif provide desired characteristics for formulation and delivery” seems to be unrelated (or irrelevant) to the claimed method (i.e., what is the purpose of such a “selecting” step when “those peptides” selected in the step are not used in the final “synthesizing” step?).
Claims 2 and 5-20, each of which depends from claim 1, are also rejected for the same reasons as discussed above.
(2). Claim 9 recites the limitation “the T cell response” in line 1. There is insufficient antecedent basis for this limitation in the claim.
(3). Claim 10 recites the limitation “the T cell response” in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
9. 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 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.
10. 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.
11. Claims 1-2 and 5-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bremel et al. (WO 2019/217655 A1).
Regarding claim 1
Bremel et al. teach, throughout the whole document, a method for producing a personalized composition to treat a subject with cancer comprising designing a group of one or more tumor-specific T-cell stimulating peptides, or nucleic acids encoding T cell stimulating peptides, which have a desired predicted binding affinity for the MHC alleles of the subject, comprising the following steps: obtaining a biopsy of the subject’s tumor and a normal tissue sample (see paragraph bridging pages 3-4; Example 9); obtaining DNA sequences from the tumor biopsy and normal tissue and RNA sequences from the tumor biopsy (see page 6, lines 17-18; page 14, lines 1-7; page 15, lines 23-30); obtaining sequences for proteins in the biopsy (see Example 9); identifying proteins from the biopsy containing mutated amino acids and the peptide comprising each of the mutated amino acids (see Example 9); determining the fraction of the DNA in the tumor biopsy comprising genes that encode each of the proteins containing mutated amino acids, and the fraction of RNA transcribed from that gene locus and expressing the protein containing mutated amino acids (see page 6, lines 17-31); determining T cell exposed motifs (TCEM) which comprise mutated amino acids in each of the expressed proteins (see Example 9); determining the predicted binding affinity to the subject’s MHC alleles of peptides which comprises each of the T cell exposed motifs, or a subset thereof (see page 12, lines 10-21); generating an array of alternative peptides not present in the tumor, wherein each peptide in the array comprises the amino acids of one of the T cell exposed motifs, and in which the amino acids not within the T cell exposed motif are substituted to change the predicted MHC binding affinity (see paragraph bridging pages 3-4; page 71, lines 10-30); selecting a group of one or more selected peptides from the array of alternative peptides which have a desired predicted binding affinity for one or more of the subject’s MHC alleles (see page 12, lines 10-21; page 71, lines 10-30); selecting from the array of alternative peptides those peptides in which those amino acids not located within the T cell exposed motif provide desired characteristics for formulation and delivery (see paragraph bridging pages 3-4; page 12, lines 10-21; page 71, lines 10-30); and synthesizing the group of one or more selected peptides, or nucleic acids encoding the selected peptides (see page 12, lines 10-21; page 23, lines 7-11; page 67, lines 5-9).
Regarding claim 2
The method according to Bremel et al., further comprising: a. selecting from the proteins containing mutated amino acids in the biopsy those which are present in at least 10% of the DNA in the biopsy and expressed in at least 10% of the RNA transcribed from that gene locus in the biopsy (see page 6, lines 17-31); and b. generating the array of alternative peptides from these selected proteins (see paragraph bridging pages 3-4; page 71, lines 10-30).
Regarding claims 5-6
The method according to Bremel et al., wherein the MHC alleles are MHC I alleles (see page 5, lines 18-26; page 25, lines 24-31), wherein the selected peptides are 8 to 10 amino acids in length (see page 36, lines 33-34).
Regarding claims 7-8
The method according to Bremel et al., wherein the MHC alleles are MHC II alleles (see page 5, lines 18-26; page 25, lines 24-31), wherein the selected peptides are from 11 to 22 amino acids in length (see page 26, lines 5-7).
Regarding claim 9
The method according to Bremel et al., wherein the T cell response is a cytotoxic T cell response (see page 24, lines 14-17; page 71, lines 20-21).
Regarding claim 10
The method according to Bremel et al., wherein the T cell response is a T helper response (see page 24, lines 14-17).
Regarding claim 11
The method according to Bremel et al., wherein the group of selected peptides, or nucleic acids encoding the selected peptides, comprise peptides which bind an MHC I allele and peptides which bind an MHC II allele (see page 5, lines 18-26; page 25, lines 24-31).
Regarding claim 12
The method according to Bremel et al., wherein the desired binding affinity to an MHC allele is less than 500 nM (see page 29, lines 17-20).
Regarding claim 13
The method according to Bremel et al., wherein the desired binding affinity to an MHC allele is less than 200 nM (see page 29, lines 17-20).
Regarding claim 14
The method according to Bremel et al., wherein the desired binding affinity to an MHC allele is less than 100 nM (see page 29, lines 17-20).
Regarding claim 15
The method according to Bremel et al., wherein the desired binding affinity to an MHC allele is less than 50 nM (see page 29, lines 17-20).
Regarding claim 16
The method according to Bremel et al., wherein each of the peptides identified in the biopsy as comprising a mutated amino acid in the step of identifying proteins from the biopsy containing mutated amino acids and the peptide comprising each of the mutated amino acids is bound to one or more of the subject's MHC alleles (see page 5, lines 18-26; page 25, lines 24-31) with an affinity that is higher than 500 nanomolar (see page 29, lines 17-20).
Regarding claim 17
The method according to Bremel et al., wherein the T cell exposed motif comprising the mutated amino acid is absent from the normal human proteome (see page 12, lines 16-21; page 22, lines 7-11; Example 9).
Regarding claim 18
The method according to Bremel et al., wherein the T cell exposed motif comprising the mutated amino acid occurs in less than 10 other protein sequence contexts in the human proteome (see page 12, lines 16-21; page 22, lines 7-11; Example 9).
Regarding claim 19
The method according to Bremel et al., wherein the T cell exposed motif comprising the mutated amino acid occurs in less than 10 other protein sequence contexts in the human proteome (see page 12, lines 16-21; page 22, lines 7-11; Example 9) that have a predicted binding affinity to the subject's MHC of <200 nM (see page 29, lines 17-20).
Regarding claim 20
The method according to Bremel et al., wherein the mutated amino acids comprise a substituted amino acid that is a product of a missense mutation (see paragraph bridging pages 71-72).
Conclusion
12. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAIJIANG ZHANG whose telephone number is (571)272-5207. The examiner can normally be reached Monday - Friday, 8:30 am - 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached on 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KAIJIANG ZHANG/Primary Examiner, Art Unit 1684
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