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 .
DETAILED ACTION
Priority
This application is a continuation of U.S. Application Serial No. 18/192,274, filed March 29, 2023; which is a continuation of U.S. Application Serial No. 17/863,603, filed July 13, 2022, now U.S. Patent No. 11,673,936; which is a continuation of U.S. Application Serial No. 17/389,875, filed July 30, 2021, now U.S. Patent No. 11,421,015; which is a continuation of U.S. Application Serial No. 17/114,237, filed December 7, 2020, now U.S. Patent No. 11,161,892, that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 08/02/2024 is acknowledged. Claims 1-30 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/15/2024, 01/29/2025, 03/27/2025, 04/02/2025, 06/12/2025, 11/04/2025, 01/29/2026 and 08/24/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the Examiner.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application
specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and
(b)), and MPEP § 609.04(a), subsection I. states, "the list must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Drawings
The drawing filed on 08/02/2024 are acknowledged and accepted by the Examiner.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine
grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or
improper timewise extension of the "right to exclude" granted by a patent and to prevent
possible harassment by multiple assignees. A nonstatutory double patenting rejection is
appropriate where the conflicting claims are not identical, but at least one examined
application claim is not patentably distinct from the reference claim(s) because the examined
application claim is either anticipated by, or would have been obvious over, the reference
claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman,
11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Langi, 759 F.2d 887, 225 USPQ 645 (Fed.
Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d
438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be
used to overcome an actual or provisional rejection based on nonstatutory double patenting
provided the reference application or patent either is shown to be commonly owned with the
examined application, or claims an invention made as a result of activities undertaken within
the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159.
See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to
file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR
1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory
double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be
accompanied by a reply requesting reconsideration of the prior Office action. Even where the
NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For
a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37
CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be
filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used.
Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in
which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or
PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely
on line using web-screens. An eTerminal Disclaimer that meets all requirements is autoprocessed
and approved immediately upon submission. For more information about eTerminal
Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-8, 12-19, 23-27 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-8 and 12-15 of U.S. Patent No. 12091443. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are coextensive in scope and species with one another.
The patented claims are directed to:
1. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
creating a first peptide set by selecting one or more peptide sequences, wherein each peptide sequence of the one or more peptide sequences is derived from a first target, and wherein the first target is a protein sequence associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
creating a second peptide set by selecting two or more peptide sequences, wherein each peptide sequence of the two or more peptide sequences is derived from the first target, and wherein the second peptide set is larger than the first peptide set by one peptide sequence;
computing, with respect to the first peptide set, a first predicted vaccine performance value;
computing, with respect to the second peptide set, a second predicted vaccine performance value;
computing a first marginal predicted vaccine performance value by obtaining a difference between the first predicted vaccine performance value and the second predicted vaccine performance value;
computing a first weighted marginal predicted vaccine performance value based on the first marginal predicted vaccine performance value and a weight associated with the first target;
creating a third peptide set by selecting one or more peptide sequences, wherein each peptide sequence of the one or more peptide sequences is derived from a second target, and wherein the second target is a protein sequence associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
creating a fourth peptide set by selecting two or more peptide sequences, wherein each peptide sequence of the two or more peptide sequences is derived from the second target, and wherein the fourth peptide set is larger than the third peptide set by one peptide sequence;
computing, with respect to the third peptide set, a third predicted vaccine performance value;
computing, with respect to the fourth peptide set, a fourth predicted vaccine performance value;
computing a second marginal predicted vaccine performance value by obtaining a difference between the third predicted vaccine performance value and the fourth predicted vaccine performance value;
computing a second weighted marginal predicted vaccine performance value based on the second marginal predicted vaccine performance value and a weight associated with the second target;
creating a fifth peptide set comprising:
the first peptide set or the second peptide set; and
the third peptide set or the fourth peptide set,
wherein creating the fifth peptide set is based on the first weighted predicted marginal vaccine performance value and the second weighted predicted marginal performance value;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for one or more peptide sequences of the fifth peptide set; and
forming an immunogenic peptide composition comprising the one or more peptide sequences of the fifth peptide set for which the experimental assay was performed (instant claims 1-6 and 12-18).
2. The method of claim 1, wherein the first peptide set comprises two or more peptide sequences and the second peptide set comprises three or more peptide sequences (instant claim 1).
3. The method of claim 2, wherein the third peptide set comprises two or more peptide sequences and the fourth peptide set comprises three or more peptide sequences (instant claim 23).
4. The method of claim 1, wherein computing the first marginal predicted vaccine performance value and the second marginal predicted vaccine performance value comprises computing a population coverage.
5. The method of claim 4, wherein the population coverage is computed based on a frequency of an HLA allele in a human population (instant claim 1).
6. The method of claim 5, wherein the population coverage is computed based on a frequency of at least three HLA alleles in the human population (instant claims 1 and 23).
7. The method of claim 1, wherein computing the first marginal predicted vaccine performance value and the second marginal predicted vaccine performance value comprises computing an expected number of peptide-HLA hits (instant claims 1 and 6).
8. The method of claim 1, wherein the weight associated with the first target is a probability of a presentation of the first target in a subject diagnosed with a disease (instant claims 2 and 7).
9. The method of claim 1, wherein the weight associated with the second target is a probability of a presentation of the second target in a subject diagnosed with a disease (instant claims 2 and 4).
12. The method of claim 1, wherein computing the first marginal predicted vaccine performance value and the second marginal predicted vaccine performance value is based on an HLA type of a subject (instant claim 20).
13. The method of claim 12, wherein computing the first marginal predicted vaccine performance value and the second marginal predicted vaccine performance value comprises computing an expected number peptide-HLA hits in the subject (instant claim 20).
14. The method of claim 12, wherein computing the first marginal predicted vaccine performance value and second marginal predicted vaccine performance value comprises computing an expected fraction of HLA alleles in a subject that has a minimum number of peptide-HLA hits, wherein the minimum number of peptide-HLA hits is based on a threshold (instant claims 1, 23-26).
15. The method of claim 1, wherein each peptide sequence of the first peptide set, the second peptide set, the third peptide set, and the fourth peptide set is configured to bind to an HLA class I molecule or an HLA class II molecule expressed in a subject in vivo (instant claims 1, 8, 19, 27).
There is no patentable difference between the claimed composition and the patented composition in that the U.S. Patent No. 12091443 (‘443) discloses a method of forming an immunogenic peptide composition, the method comprising: performing an experimental assay to determine at least two HLA alleles present in a subject; using a processor to perform the steps of: determining a plurality of peptide-HLA binding scores; determining whether a peptide-HLA binding scores with respect to HLA alleles and a first peptide sequence; wherein the first peptide sequence is associated with a tumor neoantigen, a pathogen proteome, or a self-protein; determining whether a peptide-HLA binding score passes a threshold; creating a first, second and/or third peptide set comprising modified peptide sequences; determining a plurality of peptide-HLA binding scores; creating peptides sets; and forming an immunogenic peptide composition comprising at least one peptide. Further, the compositions of the methods capable of binding with the HLA alleles would be prima facia obvious over ‘443 since the ‘443 application teaches the method of the present invention; and the limitation of a third, fourth and fifth peptide set is not inventive and considered obvious to one of ordinary skill in the art to generate an optimal number of peptide sets. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success for the advantage of inducing a broader immune response in a subject. Moreover, The MPEP states “where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).
Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-13 and 15-30 of U.S. Patent No. 11673936. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are coextensive in scope and species with one another.
The patented claims are directed to:
1. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
determining a plurality of peptide-HLA binding scores for a first peptide sequence, wherein the first peptide sequence is associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
determining whether the first peptide sequence has a peptide-HLA binding score that passes a threshold with respect to at least one HLA allele;
creating a first peptide set comprising at least two modified peptide sequences that each comprise a substitution of at least one amino acid residue of the first peptide sequence;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the first peptide set; and
creating a second peptide set by selecting a subset of the first peptide set, wherein the selecting comprises excluding a peptide-HLA binding score with respect to a first HLA allele for a modified peptide sequence of the at least two modified peptide sequences if a peptide-HLA binding score for the first peptide sequence does not pass the threshold with respect to the first HLA allele;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence of the second peptide set; and
forming an immunogenic peptide composition comprising the at least one peptide sequence of the second peptide set for which the experimental assay was performed (instant claim 1).
2. The method of claim 1, wherein selecting the subset of the first peptide set further comprises computing a population coverage (instant claim 2).
4. The method of claim 2, wherein the population coverage is computed with respect to at least three HLA alleles (instant claim 3).
5. The method of claim 2, wherein the population coverage is computed based on a frequency of an HLA allele in a human population (instant claims 4 and 5).
6. The method of claim 1, wherein selecting the subset of the first peptide set further comprises computing a predicted vaccine performance (instant claim 6).
7. The method of claim 6, wherein computing the predicted vaccine performance is based on an HLA type of a subject (instant claim 7).
8. The method of claim 1, wherein each peptide sequence of the first peptide set binds to an HLA class I molecule or an HLA class II molecule (instant claim 8).
9. The method of claim 1, further comprising excluding from the second peptide set a peptide sequence with a predicted binding core that contains a target amino acid residue in an anchor position (instant claim 9).
10. The method of claim 1, wherein the threshold is a binding affinity of less than about 1000 nM (instant claim 10).
11. The method of claim 1, wherein the immunogenic peptide composition comprises nucleic acid sequences encoding an amino acid sequence of the at least one peptide sequence of the second peptide set (instant claim 11).
12. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
determining a plurality of peptide-HLA immunogenicity metrics for a first peptide sequence, wherein the first peptide sequence is associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
determining whether the first peptide sequence has a peptide-HLA immunogenicity metric that passes a threshold with respect to at least one HLA allele;
creating a first peptide set comprising at least two modified peptide sequences that each comprise a substitution of at least one amino acid residue of the first peptide sequence;
determining a plurality of peptide-HLA immunogenicity metrics for each peptide sequence in the first peptide set; and
creating a second peptide set by selecting a subset of the first peptide set, wherein the selecting comprises excluding a peptide-HLA immunogenic metric with respect to a first HLA allele for a modified peptide sequence of the at least two modified peptide sequences if a peptide-HLA immunogenicity metric for the first peptide sequence does not pass the threshold with respect to the first HLA allele;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence of the second peptide set; and
forming an immunogenic peptide composition comprising the at least one peptide sequence of the second peptide set for which the experimental assay was performed (instant claim 12).
13. The method of claim 12, wherein selecting the subset of the first peptide set further comprises computing a population coverage (instant claim 13).
15. The method of claim 13, wherein the population coverage is computed with respect to at least three HLA alleles (instant claim 14).
16. The method of claim 13, wherein the population coverage is computed based on a frequency of an HLA allele in a human population (instant claims 15 and 16).
17. The method of claim 12, wherein selecting the subset of the first peptide set further comprises computing a predicted vaccine performance (instant claim 17).
18. The method of claim 17, wherein computing the predicted vaccine performance is based on an HLA type of a subject (instant claim 18).
19. The method of claim 12, wherein each peptide sequence of the first peptide set binds to an HLA class I molecule or an HLA class II molecule (instant claim 19).
20. The method of claim 12, further comprising excluding from the second peptide set a peptide sequence with a predicted binding core that contains a target amino acid residue in an anchor position (instant claim 20).
21. The method of claim 12, wherein the threshold is a binding affinity of less than about 1000 nM (instant claim 21).
22. The method of claim 12, wherein the immunogenic peptide composition comprises nucleic acid sequences encoding an amino acid sequence of the at least one peptide sequence of the second peptide set (instant claim 22).
23. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
determining a plurality of peptide-HLA binding scores for a first peptide sequence, wherein the first peptide sequence is associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
creating a first peptide set comprising at least three modified peptide sequences that each comprise a substitution of at least one amino acid residue of the first peptide sequence;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the first peptide set;
determining whether each of the at least three modified peptide sequences has a peptide-HLA binding score that passes a threshold with respect to at least one HLA allele; and
creating a second peptide set by selecting a subset of the first peptide set, wherein the selecting comprises excluding a peptide-HLA binding score with respect to a first HLA allele for a modified peptide sequence of the at least three modified peptide sequences if a peptide-HLA binding score for the modified peptide sequence does not pass the threshold with respect to the first HLA allele;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least two peptide sequences of the second peptide set; and
forming an immunogenic peptide composition comprising the at least two peptide sequences of the second peptide set for which the experimental assay was performed (instant claim 23).
24. The method of claim 23, wherein selecting the subset of the first peptide set further comprises computing a population coverage, wherein the population coverage is computed with respect to at least three HLA alleles, and wherein the population coverage is computed based on a frequency of an HLA haplotype in a human population (instant claim 24).
25. The method of claim 23, wherein selecting the subset of the first peptide set further comprises computing a predicted vaccine performance (instant claim 25).
26. The method of claim 25, wherein computing the predicted vaccine performance is based on an HLA type of a subject (instant claim 26).
27. The method of claim 23, wherein each peptide sequence of the first peptide set binds to an HLA class I molecule or an HLA class II molecule (instant claim 27).
28. The method of claim 23, further comprising excluding from the second peptide set a peptide sequence with a predicted binding core that contains a target amino acid residue in an anchor position (instant claim 28).
29. The method of claim 23, wherein the threshold is a binding affinity of less than about 50 nM (instant claim 29).
30. The method of claim 23, wherein the immunogenic peptide composition comprises nucleic acid sequences encoding an amino acid sequence of the at least one peptide sequence of the second peptide set (instant claim 30).
There is no patentable difference between the claimed composition and the patented composition in that the U.S. Patent No. 11673936 (‘936) discloses a method of forming an immunogenic peptide composition, the method comprising: performing an experimental assay to determine at least two HLA alleles present in a subject; using a processor to perform the steps of: determining a plurality of peptide-HLA binding scores; determining whether a peptide-HLA binding scores with respect to HLA alleles and a first peptide sequence; wherein the first peptide sequence is associated with a tumor neoantigen, a pathogen proteome, or a self-protein; determining whether a peptide-HLA binding score passes a threshold; creating a first, second and/or third peptide set comprising modified peptide sequences; determining a plurality of peptide-HLA binding scores; creating peptides sets; and forming an immunogenic peptide composition comprising at least one peptide. Further, the compositions of the methods capable of binding with the HLA alleles would be prima facia obvious over ‘936 since the ‘936 application teaches the method of the present invention. Moreover, The MPEP states “where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).
Claims 1-27 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1, 3-10, 13-15 and 17-30 of U.S. Patent No. 11421015. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are coextensive in scope and species with one another.
The patented claims are directed to:
1. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein at least one peptide sequence of the plurality of unmodified peptide sequences is associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the first peptide set;
determining whether each peptide sequence in the first peptide set has a peptide-HLA binding score that passes a first threshold with respect to at least three HLA alleles;
creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the second peptide set; and
creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises computing a population coverage, wherein the computing of the population coverage comprises excluding a peptide-HLA binding score with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA binding score for an unmodified peptide sequence associated with the modified peptide sequence does not pass the first threshold with respect to the first HLA allele, and wherein the selected subset has a population coverage above a second threshold;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence of the third peptide set; and
forming an immunogenic peptide composition comprising the at least one peptide sequence of the third peptide set for which the experimental assay was performed (instant claims 1-7).
3. The method of claim 1, wherein each peptide sequence of the first peptide set binds to an HLA class I molecule or an HLA class II molecule (instant claim 8).
4. The method of claim 1, further comprising filtering the first peptide set to exclude a peptide sequence with a predicted binding core that contains a target amino acid residue in an anchor position (instant claims 1 and 9).
5. The method of claim 1, further comprising substituting at least one amino acid residue of each peptide sequence of the first peptide set, wherein for at least one peptide sequence of the first peptide set the at least one amino acid residue is in an anchor position (instant claim 1).
6. The method of claim 1, wherein the first threshold is a binding affinity of less than about 1000 nM (instant claim 10).
7. The method of claim 1, wherein the population coverage is computed with respect to the at least three HLA alleles (instant claim 1).
8. The method of claim 1, wherein the population coverage is computed based on a frequency of an HLA haplotype in a human population (instant claim 1).
9. The method of claim 1, wherein the population coverage is computed based on a frequency of the at least three HLA alleles in a human population (instant claim 1).
10. The method of claim 1, wherein the plurality of unmodified peptide sequences is derived from the tumor neoantigen, the pathogen proteome, or the self-protein that is present in a subject (instant claim 1).
13. The method of claim 1, wherein the pathogen proteome is associated with a pathogen infection in a human subject (instant claim 1).
14. The method of claim 1, wherein the immunogenic peptide composition comprises nucleic acid sequences encoding an amino acid sequence of the at least one peptide sequence of the third peptide set (instant claim 11).
15. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein the plurality of unmodified peptide sequences is associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
determining a plurality of peptide-HLA immunogenicity metrics for each peptide sequence in the first peptide set;
determining whether each peptide sequence in the first peptide set has a peptide-HLA immunogenicity metric that passes a threshold with respect to at least three HLA alleles;
creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
determining a plurality of peptide-HLA immunogenicity metrics for each peptide sequence in the second peptide set; and
creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises a predicted vaccine performance, wherein the computing of the predicted vaccine performance comprises excluding a peptide-HLA immunogenicity metric with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA immunogenicity metric for an unmodified peptide sequence associated with the modified peptide sequence does not pass the threshold with respect to the first HLA allele, and wherein the predicted vaccine performance is a function of a peptide-HLA immunogenicity metric of each peptide sequence in the third peptide set;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence of the third peptide set; and
forming an immunogenic peptide composition comprising the at least one peptide sequence of the third peptide set for which the experimental assay was performed (instant claims 1, 12-18).
17. The method of claim 15, wherein each peptide sequence of the first peptide set binds to an HLA class I molecule or an HLA class II molecule (instant claim 19).
18. The method of claim 15, further comprising filtering the first peptide set to exclude a peptide sequence with a predicted binding core that contains a target amino acid residue in an anchor position (instant claim 20).
19. The method of claim 15, further comprising substituting at least one amino acid residue of each peptide sequence of the first peptide set (instant claim 1).
20. The method of claim 15, wherein the threshold is a binding affinity of less than about 1000 nM (instant claim 21).
21. The method of claim 15, wherein the at least three HLA alleles are present in an HLA type of a subject.
22. The method of claim 21, wherein the plurality of peptide sequences is derived from the tumor neoantigen, the pathogen proteome, or the self-protein that is present in the subject (instant claim 15).
23. The method of claim 15, wherein the immunogenic peptide composition comprises nucleic acid sequences encoding an amino acid sequence of the at least one peptide sequence of the third peptide set (instant claim 22).
24. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein each peptide sequence of the plurality of unmodified peptide sequences is associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the first peptide set;
determining whether each peptide sequence in the first peptide set has a peptide-HLA binding score that passes a threshold with respect to at least three HLA alleles;
creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the second peptide set; and
creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises computing a predicted vaccine performance, wherein the computing of the predicted vaccine performance comprises excluding a peptide-HLA binding score with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA binding score for an unmodified peptide sequence associated with the modified peptide sequence does not pass the threshold with respect to the first HLA allele, and wherein the predicted vaccine performance is a function of a peptide-HLA binding score of each peptide sequence in the third peptide set;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence of the third peptide set; and
forming an immunogenic peptide composition comprising the at least one peptide sequence of the third peptide set for which the experimental assay was performed (instant claim 23).
25. The method of claim 24, wherein the threshold is determined from data obtained from one or more experimental assays (instant claim 24).
26. The method of claim 24, wherein the predicted vaccine performance is further a function of a peptide-HLA immunogenicity metric of at least one modified peptide sequence of the second peptide set with respect to a second HLA allele if a first peptide sequence of the first peptide set is predicted to be bound to the second HLA allele with a first binding core, wherein the first binding core is a binding core of the first peptide sequence, wherein the first binding core is identical to a second binding core, wherein the first binding core and the second binding score each comprise an amino acid position within a peptide sequence, and wherein the second binding core is a binding core of the at least one modified peptide sequence (instant claims 25 and 26).
27. The method of claim 24, wherein the plurality of peptide sequences is derived from the tumor neoantigen, the pathogen proteome, or the self-protein that is present in a subject (instant claim 23).
28. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein at least one peptide sequence of the plurality of unmodified peptide sequences is associated with a tumor neoantigen, a pathogen proteome, or a self-protein;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the first peptide set;
determining whether each peptide sequence in the first peptide set has a peptide-HLA binding score that passes a threshold with respect to at least three HLA alleles;
creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the second peptide set; and
creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises computing a predicted vaccine performance based on an HLA type of a subject, and wherein the computing of the predicted vaccine performance comprises excluding a peptide-HLA binding score with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA binding score for an unmodified peptide sequence associated with the modified peptide sequence does not pass the threshold with respect to the first HLA allele;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence of the third peptide set; and
forming an immunogenic peptide composition comprising the at least one peptide sequence of the third peptide set for which the experimental assay was performed (instant claims 23 and 28).
29. The method of claim 28, wherein each peptide sequence in the first peptide set binds to an HLA class I molecule or an HLA class II molecule (instant claim 27).
30. The method of claim 28, wherein the plurality of peptide sequences is derived from the tumor neoantigen, the pathogen proteome, or the self-protein that is present in the subject (instant claim 23).
There is no patentable difference between the claimed composition and the patented composition in that the U.S. Patent No. 11421015 (‘015) discloses a method of forming an immunogenic peptide composition, the method comprising: performing an experimental assay to determine at least two HLA alleles present in a subject; using a processor to perform the steps of: determining a plurality of peptide-HLA binding scores; determining whether a peptide-HLA binding scores with respect to HLA alleles and a first peptide sequence; wherein the first peptide sequence is associated with a tumor neoantigen, a pathogen proteome, or a self-protein; determining whether a peptide-HLA binding score passes a threshold; creating a first, second and/or third peptide set comprising modified peptide sequences; determining a plurality of peptide-HLA binding scores; creating peptides sets; and forming an immunogenic peptide composition comprising at least one peptide. Further, the compositions of the methods capable of binding with the HLA alleles would be prima facia obvious over ‘015 since the ‘015 application teaches the method of the present invention; and the limitation of a third peptide set is not inventive and considered obvious to one of ordinary skill in the art to generate an optimal number of peptide sets. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success for the advantage of inducing a broader immune response in a subject. Moreover, The MPEP states “where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).
Claims 1-30 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1, 3-7, 9-11, 14 and 16-30 of U.S. Patent No. 11161892. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are coextensive in scope and species with one another.
The patented claims are directed to:
1. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein at least one peptide sequence of the plurality of unmodified peptide sequences is associated with a tumor neoantigen or a self-protein;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the first peptide set;
determining whether each peptide sequence in the first peptide set has a peptide-HLA binding score that passes a first threshold with respect to at least three HLA alleles;
creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
determining whether each modified peptide sequence in the second peptide set has a peptide-HLA binding score that passes a second threshold with respect to the at least three HLA alleles, wherein the second threshold is more constrained than the first threshold; and
creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises computing a population coverage, wherein the computing of the population coverage comprises excluding a peptide-HLA binding score with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA binding score for an unmodified peptide sequence associated with the modified peptide sequence does not pass the first threshold with respect to the first HLA allele, and wherein the selected subset has a population coverage above a third threshold;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence in the third peptide set; and
forming an immunogenic peptide composition comprising the at least one peptide sequence in the third peptide set for which the experimental assay was performed (instant claims 1-16).
3. The method of claim 1, wherein each peptide sequence in the first peptide set binds to an HLA class I molecule or an HLA class II molecule (instant claim 19).
4. The method of claim 1, further comprising filtering the first peptide set to exclude a peptide sequence with a predicted binding core that contains a target residue in an anchor position (instant claim 20).
5. The method of claim 1, further comprising substituting at least one amino acid residue of each peptide sequence in the first peptide set, wherein for at least one peptide sequence in the first peptide set the at least one amino acid residue is in an anchor position (instant claim 20).
6. The method of claim 1, wherein the first threshold is a binding affinity of less than about 1000 nM (instant claim 21).
7. The method of claim 1, when the population coverage is computed with respect to the at least three HLA alleles.
9. The method of claim 1, wherein the population coverage is computed based on a frequency of an HLA haplotype in a human population (instant claim 1).
10. The method of claim 1, wherein the population coverage is computed based on a frequency of the at least three HLA alleles in a human population (instant claim 1).
11. The method of claim 1, wherein the plurality of unmodified peptide sequences is derived from the tumor neoantigen or the self-protein that is present in a subject (instant claim 1).
14. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein the plurality of unmodified peptide sequences is associated with a tumor neoantigen or a self-protein;
determining a plurality of peptide-HLA immunogenicity metrics for each peptide sequence in the first peptide set;
determining whether each peptide sequence in the first peptide set has a peptide-HLA immunogenicity metric that passes a first threshold with respect to at least three HLA alleles;
creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
determining whether each modified peptide sequence in the second peptide set has a peptide-HLA immunogenicity metric that passes a second threshold with respect to the at least three HLA alleles, wherein the second threshold is more constrained than the first threshold; and
creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises computing a predicted vaccine performance, wherein the computing of the predicted vaccine performance comprises excluding a peptide-HLA immunogenicity metric with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA immunogenicity metric for an unmodified peptide sequence associated with the modified peptide sequence does not pass the first threshold with respect to the first HLA allele, and wherein the predicted vaccine performance is a function of a non-excluded peptide-HLA immunogenicity metric of each peptide sequence in the third peptide set;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence in the third peptide set; and
forming an immunogenic peptide composition comprising the at least one peptide sequence in the third peptide set for which the experimental assay was performed (instant claims 1, 17 and 18).
16. The method of claim 14, wherein each peptide sequence in the first peptide set binds to an HLA class I molecule or an HLA class II molecule (instant claims 19 and 21).
17. The method of claim 14, further comprising filtering the first peptide set to exclude a peptide sequence with a predicted binding core that contains a target residue in an anchor position (instant claims 1, 12 and 23).
18. The method of claim 14, further comprising substituting at least one amino acid residue of each peptide sequence in the first peptide set (instant claims 1, 12 and 23).
19. The method of claim 14, wherein the first threshold is a binding affinity of less than about 1000 nM (instant claims 10 and 21).
20. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein each peptide sequence of the plurality of unmodified peptide sequences is associated with a tumor neoantigen or a self-protein;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the first peptide set;
determining whether each peptide sequence in the first peptide set has a peptide-HLA binding score that passes a first threshold with respect to at least three HLA alleles;
creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
determining whether each modified peptide sequence in the second peptide set has a peptide-HLA binding score that passes a second threshold with respect to the at least three HLA alleles, wherein the second threshold is more constrained than the first threshold; and
creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises computing a predicted vaccine performance, wherein the computing of the predicted vaccine performance comprises excluding a peptide-HLA binding score with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA binding score for an unmodified peptide sequence associated with the modified peptide sequence does not pass the first threshold with respect to the first HLA allele, and wherein the predicted vaccine performance is a function of a non-excluded peptide-HLA binding score of each peptide sequence in the third peptide set;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence in the third peptide set; and
forming an immunogenic peptide composition comprising the at least one peptide sequence in the third peptide set for which the experimental assay was performed (instant claims 1, 23-26).
21. The method of claim 20, wherein the second threshold is based on data obtained from one or more experimental assays (instant claim 24).
22. The method of claim 20, wherein the predicted vaccine performance is further a function of a peptide-HLA immunogenicity metric of at least one modified peptide sequence of the plurality of modified peptide sequences bound to a second HLA allele of the at least three HLA alleles if a first peptide sequence in the first peptide set is predicted to be bound to the second HLA allele of the at least three HLA alleles with a first binding core, wherein the first binding core is a binding core of the first peptide sequence, wherein the first binding core is identical to a second binding core, wherein the first binding core and the second binding core comprise an amino acid position within a peptide sequence, and wherein the second binding core is a binding core of the at least one modified peptide sequence of the plurality of modified peptide sequences bound to the second HLA allele (instant claim 18).
23. A method of forming an immunogenic peptide composition, the method comprising:
using a processor to perform the steps of:
creating a first peptide set by selecting a plurality of unmodified peptide sequences, wherein at least one peptide sequence of the plurality of unmodified peptide sequences is associated with a tumor neoantigen or a self-protein;
determining a plurality of peptide-HLA binding scores for each peptide sequence in the first peptide set;
determining whether each peptide sequence in the first peptide set has a peptide-HLA binding score that passes a first threshold with respect to at least three HLA alleles;
creating a second peptide set comprising the first peptide set and a plurality of modified peptide sequences, wherein each modified peptide sequence of the plurality of modified peptide sequences comprises a substitution of at least one amino acid residue of a peptide sequence in the first peptide set;
determining whether each modified peptide sequence in the second peptide set has a peptide-HLA binding score that passes a second threshold with respect to the at least three HLA alleles, wherein the second threshold is more constrained than the first threshold;
creating a third peptide set by selecting a subset of the second peptide set, wherein the selecting comprises computing a predicted vaccine performance based on an HLA type of a subject, and wherein the computing of the predicted vaccine performance comprises excluding a peptide-HLA binding score with respect to a first HLA allele for a modified peptide sequence if a peptide-HLA binding score for an unmodified peptide sequence associated with the modified peptide sequence does not pass the first threshold with respect to the first HLA allele;
performing an experimental assay to obtain a peptide-HLA immunogenicity metric for at least one peptide sequence in the third peptide set; and
forming an immunogenic peptide composition comprising the at least one peptide sequence in the third peptide set for which the experimental assay was performed (instant claims 1, 17-18 and 23).
24. The method of claim 23, wherein each peptide sequence in the first peptide set binds to an HLA class I molecule or an HLA class II molecule (instant claim 27).
25. The method of claim 14, wherein the plurality of unmodified peptide sequences is derived from the tumor neoantigen or the self-protein that is present in a subject (instant claim 1).
26. The method of claim 14, wherein the at least three HLA alleles are present in the HLA type of a subject (instant claim 1).
27. The method of claim 20, wherein the plurality of unmodified peptide sequences is derived from the tumor neoantigen or the self-protein that is present in a subject (instant claim 18).
28. The method of claim 23, wherein the plurality of unmodified peptide sequences is derived from the tumor neoantigen or the self-protein that is present in the subject (instant claim 23).
29. The method of claim 1, wherein the immunogenic peptide composition comprises nucleic acid sequences encoding an amino acid sequence of the at least one peptide sequence in the third peptide set (instant claim 22).
30. The method of claim 14, wherein the immunogenic peptide composition comprises nucleic acid sequences encoding an amino acid sequence of the at least one peptide sequence in the third peptide set (instant claim 30).
There is no patentable difference between the claimed composition and the patented composition in that the U.S. Patent No. 11161892 (‘892) discloses a method of forming an immunogenic peptide composition, the method comprising: performing an experimental assay to determine at least two HLA alleles present in a subject; using a processor to perform the steps of: determining a plurality of peptide-HLA binding scores; determining whether a peptide-HLA binding scores with respect to HLA alleles and a first peptide sequence; wherein the first peptide sequence is associated with a tumor neoantigen, a pathogen proteome, or a self-protein; determining whether a peptide-HLA binding score passes a threshold; creating a first, second and/or third peptide set comprising modified peptide sequences; determining a plurality of peptide-HLA binding scores; creating peptides sets; and forming an immunogenic peptide composition comprising at least one peptide. Further, the compositions of the methods capable of binding with the HLA alleles would be prima facia obvious over ‘892 since the ‘892 application teaches the method of the present invention; and the limitation of a third peptide set is not inventive and considered obvious to one of ordinary skill in the art to generate an optimal number of peptide sets. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success for the advantage of inducing a broader immune response in a subject. Moreover, The MPEP states “where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is (571)270-3546. The examiner can normally be reached on M-Th 8:00 to 4:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BARRY A CHESTNUT/Primary Examiner, Art Unit 1672
