IP Library › Granted Patent US 12,364,741
Granted Patent B2
US 12,364,741 · App. 17/815,086 · Granted Jul 22, 2025

Immunogenic compositions comprising nucleic acids for RAS peptides and their use for treating cancer

Inventors: David Kenneth Gifford (Newton, MA); Brandon Carter (Cambridge, MA)
Assignee: Think Therapeutics, Inc.
A61K39/0005A61K39/0011A61P35/00C12Y306/05002A61K2039/585
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Quick Facts
Patent No.
US 12,364,741
App. No.
17/815,086
Granted
Jul 22, 2025
Kind
B2
Abstract

The present disclosure provides for methods, systems, and compositions of nucleic acid and peptide sequences. The present disclosure provides for a nucleic acid sequence encoding two or more amino acid sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, and SEQ ID NO: 41. The present disclosure also provides for an immunogenic peptide composition comprising two or more peptides selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, and SEQ ID NO: 41. The present disclosure further provides for a nucleic acid sequence encoding one or more amino acid sequences selected from the group consisting of SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 65. The present disclosure additionally provides for an immunogenic peptide composition comprising one or more peptides selected from the group consisting of SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 65.

Claims (20)

1. An immunogenic composition comprising one or more polynucleotides encoding at least one amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, and SEQ ID NO: 41.

2. The immunogenic composition of claim 1 , wherein the one or more polynucleotides are contained in a construct for in vivo expression of at least one peptide encoded by the one or more polynucleotides.

3. The immunogenic composition of claim 2 , wherein an administration of the one or more polynucleotides causes the at least one peptide encoded by the one or more polynucleotides to be displayed by an HLA class I molecule in a subject.

4. The immunogenic composition of claim 1 , wherein the immunogenic composition comprises one or more polynucleotides encoding at least two amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, and SEQ ID NO: 41.

5. The composition of claim 4 , wherein the one or more polynucleotides are contained in a construct for in vivo expression in a subject of at least two peptides encoded by the one or more polynucleotides.

6. The composition of claim 5 , wherein an administration of the one or more polynucleotides causes the at least two peptides encoded by the one or more polynucleotides to be displayed by a HLA class I molecule in the subject.

7. The composition of claim 6 , wherein the administration of the one or more polynucleotides causes:

a first peptide of the at least two peptides to be displayed by a first plurality of HLA class I alleles; and

a second peptide of the at least two peptides to be displayed by a second plurality of HLA class I alleles,

wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele.

8. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the immunogenic composition of claim 1 , wherein the at least one amino acid sequence is selected based on a mutated KRAS protein that is expressed in the subject and is associated with the cancer.

9. An immunogenic composition comprising at least one peptide selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, and SEQ ID NO: 41.

10. The immunogenic composition of claim 9 , wherein the at least one peptide is capable of being displayed by an HLA class I molecule present in a subject.

11. The immunogenic composition of claim 9 , wherein the immunogenic composition comprises at least two peptides selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, and SEQ ID NO: 41.

12. The immunogenic composition of claim 11 , wherein the at least two peptides are capable of being displayed by an HLA class I molecule present in a subject.

13. The immunogenic composition of claim 12 , wherein:

a first peptide of the at least two peptides is capable of being displayed by a first plurality of HLA class I alleles; and

a second peptide of the at least two peptides is capable of being displayed by a second plurality of HLA class I alleles,

wherein the first plurality of HLA class I alleles and the second plurality of HLA class I alleles differ by at least one HLA class I allele.

14. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of the immunogenic composition of claim 9 , wherein the at least one peptide is selected based on a mutated KRAS protein that is expressed in the subject and is associated with the cancer.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 1, 2022
From: GIFFORD, DAVID; CARTER, BRANDON
To: THINK THERAPEUTICS, INC.
Reel/Frame 061937/0867 →
Continuity (4)
Division 17551679 · Dec 15, 2021
Continuation 17336960 · Jun 2, 2021
Continuation 17100630 · Nov 20, 2020
Related Publication 20230051404A1 · Feb 16, 2023
References Cited (219)
US 5443956A · Carney · 1995 [cited by applicant]
US 5961978A · Gaudernack et al. · 1999 [cited by applicant]
US 6602510B1 · Fikes et al. · 2003 [cited by applicant]
US 7488718B2 · Scheinberg et al. · 2009 [cited by applicant]
US 7756644B2 · Fridman et al. · 2010 [cited by applicant]
US 7973128B2 · Kosmatopoulos et al. · 2011 [cited by applicant]
US 8007810B2 · Fikes et al. · 2011 [cited by applicant]
US 8465747B2 · Kosmatopoulos et al. · 2013 [cited by applicant]
US 8653237B2 · Liu et al. · 2014 [cited by applicant]
US 8741576B2 · Tangri et al. · 2014 [cited by applicant]
US 8765687B2 · Scheinberg et al. · 2014 [cited by applicant]
US 8900600B2 · Kosmatopoulos et al. · 2014 [cited by applicant]
US 9340577B2 · Grey et al. · 2016 [cited by applicant]
US 9913884B2 · Fikes et al. · 2018 [cited by applicant]
US 10024868B2 · Kosmatopoulos et al. · 2018 [cited by applicant]
US 10238741B2 · Creusot · 2019 [cited by applicant]
US 10335473B2 · Eriksen · 2019 [cited by applicant]
US 10456457B2 · Eriksen · 2019 [cited by applicant]
US 10556943B2 · Knutson et al. · 2020 [cited by applicant]
US 10596239B2 · Eriksen · 2020 [cited by applicant]
US 10738355B2 · Sahin et al. · 2020 [cited by applicant]
US 10835585B2 · Fritsch et al. · 2020 [cited by applicant]
US 11058751B1 · Gifford et al. · 2021 [cited by applicant]
US 11161892B1 · Gifford et al. · 2021 [cited by applicant]
US 11222711B2 · Sahin et al. · 2022 [cited by applicant]
US 11235039B1 · Gifford et al. · 2022 [cited by applicant]
US 11464842B1 · Gifford et al. · 2022 [cited by applicant]
US 11466053B2 · Tang et al. · 2022 [cited by applicant]
US 11672850B2 · Gifford et al. · 2023 [cited by applicant]
US 20020155093A1 · Houghton et al. · 2002 [cited by applicant]
US 20020164346A1 · Nicolette · 2002 [cited by applicant]
US 20030220239A1 · Simard et al. · 2003 [cited by applicant]
US 20030224036A1 · Fikes et al. · 2003 [cited by applicant]
US 20040037843A1 · Fikes et al. · 2004 [cited by applicant]
US 20040072240A1 · Kosmatopoulos et al. · 2004 [cited by applicant]
US 20060018915A1 · Ishioka et al. · 2006 [cited by applicant]
US 20060093617A1 · Buyse et al. · 2006 [cited by applicant]
US 20070054262A1 · Baker et al. · 2007 [cited by applicant]
US 20070098776A1 · Fikes et al. · 2007 [cited by applicant]
US 20070224201A1 · Wu et al. · 2007 [cited by applicant]
US 20110002963A1 · Weinschenk et al. · 2011 [cited by applicant]
US 20110182926A1 · La Monica et al. · 2011 [cited by applicant]
US 20110257890A1 · Weinschenk et al. · 2011 [cited by applicant]
US 20140178421A1 · Kosmatopoulos · 2014 [cited by applicant]
US 20160101170A1 · Hacohen et al. · 2016 [cited by applicant]
US 20160125129A1 · Sahin et al. · 2016 [cited by applicant]
US 20180066017A1 · Hunt et al. · 2018 [cited by applicant]
US 20180102585A1 · Forster · 2018 [cited by applicant]
US 20180117133A1 · Chaplin et al. · 2018 [cited by applicant]
US 20180134804A1 · Scheinberg et al. · 2018 [cited by applicant]
US 20180141998A1 · Nguyen et al. · 2018 [cited by applicant]
US 20190175727A1 · Huang et al. · 2019 [cited by applicant]
US 20190307868A1 · Rooney · 2019 [cited by applicant]
US 20190322714A1 · Petit et al. · 2019 [cited by applicant]
US 20200061166A1 · Sahin et al. · 2020 [cited by applicant]
US 20200069782A1 · Biskup et al. · 2020 [cited by applicant]
US 20200078454A1 · Kosmatopoulos et al. · 2020 [cited by applicant]
US 20200105378A1 · Abelin et al. · 2020 [cited by applicant]
US 20200237885A1 · Levey et al. · 2020 [cited by applicant]
US 20210154280A1 · Martin et al. · 2021 [cited by applicant]
US 20210177954A1 · Juneja · 2021 [cited by applicant]
US 20210177955A1 · Petit et al. · 2021 [cited by applicant]
US 20210196806A1 · Yelensky et al. · 2021 [cited by applicant]
US 20210196809A1 · Maianti et al. · 2021 [cited by applicant]
US 20210268086A1 · Zhong et al. · 2021 [cited by applicant]
US 20210268091A1 · Juneja · 2021 [cited by applicant]
US 20210275657A1 · Juneja et al. · 2021 [cited by applicant]
US 20210290746A1 · Sahin et al. · 2021 [cited by applicant]
US 20210389280A1 · Wang · 2021 [cited by applicant]
US 20220160848A1 · Gifford et al. · 2022 [cited by applicant]
US 20220194999A1 · Krishna et al. · 2022 [cited by applicant]
WO WO9733602A1 · 1997 [cited by applicant]
WO WO9963945A2 · 1999 [cited by applicant]
WO WO2005042698A2 · 2005 [cited by applicant]
WO WO2009002418A2 · 2008 [cited by applicant]
WO WO2013177214A2 · 2013 [cited by applicant]
WO WO2016172722A1 · 2016 [cited by applicant]
WO WO2016187508 · 2016 [cited by applicant]
WO WO2017075531A1 · 2017 [cited by applicant]
WO WO2018081459A1 · 2018 [cited by applicant]
WO WO2018081480A1 · 2018 [cited by applicant]
WO WO2018102585A1 · 2018 [cited by applicant]
WO WO2018187356A2 · 2018 [cited by applicant]
WO WO2019246286 · 2019 [cited by applicant]
WO WO2020037239A1 · 2020 [cited by applicant]
WO WO2020123300A2 · 2020 [cited by applicant]
WO WO2020154617A1 · 2020 [cited by applicant]
WO WO2020252039A1 · 2020 [cited by applicant]
WO WO2020253643A1 · 2020 [cited by applicant]
WO WO2021055594 · 2021 [cited by applicant]
WO WO2021087840A1 · 2021 [cited by applicant]
WO WO2021207152A1 · 2021 [cited by applicant]
WO WO2022036142A2 · 2022 [cited by applicant]
WO WO2022132596A2 · 2022 [cited by applicant]
WO WO2022171032A1 · 2022 [cited by applicant]
WO WO2022180219A1 · 2022 [cited by applicant]
WO WO2023170535A2 · 2023 [cited by applicant]
WO WO2023230014A1 · 2023 [cited by applicant]
Betts et al., “Amino Acid Properties and Consequences of Substitutions,” Chapter 14 in Bioinformatics for Geneticists, Wiley & Sons, Ltd., Apr. 18, 2003, pp. 289-316. [cited by applicant]
Carter et al., “A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-COV-2 Beta,” bioRxiv preprint, posted Sep. 26, 2022. 38 pages. (https://www.biorxiv.org/content… [cited by applicant]
Carter et al., “A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-COV-2 Beta,” Frontiers in Immunology, Mar. 9, 2023, vol. 14:1135815, pp. 1-9. [cited by applicant]
Chu et al., “A transformer-based model to predict peptide-HLA class I binding and optimize mutated peptides for vaccine design,” Nature Machine Intelligence, vol. 4(3), Mar. 23, 2022, pp. 300-311 and figures. 15 pages. [cited by applicant]
Chu et al., “TransMut: a program to predict HLA-I peptide binding and optimize mutated peptides for vaccine design by the Transformer-derived self-attention model,” Research Square, Sep. 30, 2021. 47 pages. (https://doi… [cited by applicant]
Getentry Accession No. CU234118, DNA Data Bank of Japan. (Year 2015). 1,543 pages. [cited by applicant]
NCBI Database, GenBank Accession No. AB051004. (Year 2016). 1 page. [cited by applicant]
NCBI Database, GenBank Accession No. FRAP01000011. (Year 2016). 73 pages. [cited by applicant]
NCBI Database, GenBank Accession No. PYDT01000009. (Year 2019). 983 pages. [cited by applicant]
Racle et al., “Robust prediction of HLA class II epitopes by deep motif deconvolution of immunopeptidomes,” Nature Biotechnology, Nov. 2019, vol. 37(11), pp. 1283-1286, Methods and Reporting Summary. 12 pages. [cited by applicant]
UniProt Accession No. A0A1M6V319-A0A1M6V319_PSETH. (Year 2017). 5 pages. [cited by applicant]
UniProt Accession No. A0A4S8INI8-A0A4S8INI8_MUSBA. (Year 2019). 6 pages. [cited by applicant]
UniProt Accession No. A4YTR3-A4YTR3_BRASO. (Year 2007). 5 pages. [cited by applicant]
Aurisicchio et al., “A novel minigene scaffold for therapeutic cancer vaccines,” Oncolmmunology, published online Jan. 16, 2014, vol. 3, e27529, pp. 1-13. 14 pages. [cited by applicant]
Fridman et al., “An efficient T-cell epitope discovery strategy using in silico prediction and the iTopia assay platform,” Oncolmmunology, published online Nov. 30, 2012, vol. 1:8, pp. 1258-1270 and Supplemental Materia… [cited by applicant]
Zhang et al., “Epitope-based minigene vaccine targeting fibroblast activation protein α induces specific immune responses and anti-tumor effects in 4 T1 murine breast cancer model,” International Immunopharmacology, ava… [cited by applicant]
Antunes et al., “General Prediction of Peptide-MHC Binding Modes Using Incremental Docking: A Proof of Concept,” Scientific Reports, published online Mar. 12, 2018, vol. 8(1):4327-4339. 13 pages. [cited by applicant]
Badrinath et al., “A vaccine targeting resistant tumours by dual T cell plus NK cell attack,” Nature, Jun. 30, 2022, vol. 606, pp. 992-998 and Methods. 31 pages. [cited by applicant]
Bear et al., “Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting,” Nature Communications, published online Jul. 16, 2021, vol. 12(1):4365-4380. 16 … [cited by applicant]
Brito et al., “A cationic nanoemulsion for the delivery of next-generation RNA vaccines,” Molecular Therapy, Dec. 2014, vol. 22(12), pp. 2118-2129. [cited by applicant]
Bulik-Sullivan et al., “Deep learning using tumor HLA peptide mass spectrometry datasets improves neoantigen identification,” Nature Biotechnology (2019), published online Dec. 17, 2018, vol. 37, pp. 55-63 and Online Me… [cited by applicant]
Dai et al., “Constrained Submodular Optimization for Vaccine Design,” arXiv preprint, arXiv:2206.08336v2. https://arxiv.org/abs/2206.08336, version 2, Jan. 27, 2023. 24 pages. [cited by applicant]
Geall et al., “Nonviral delivery of self-amplifying RNA vaccines,” Proc. Natl. Acad. Sci., Sep. 4, 2012, vol. 109(36), pp. 14604-14609. [cited by applicant]
Hie et al., “Learning the language of viral evolution and escape,” Science, Jan. 15, 2021, vol. 371(6526):284-288. 5 pages. [cited by applicant]
Li et al., “Circular RNA cancer vaccines drive immunity in hard-to-treat malignancies,” Theranostics, Aug. 29, 2022, vol. 12(14), pp. 6422-6436. [cited by applicant]
London et al., “Rosetta FlexPepDock web server—high resolution modeling of peptide-protein interactions,” Nucleic Acids Research, published online May 27, 2011, vol. 39, Web Server issue: W249-253. [cited by applicant]
Parkhurst et al., “Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues,” The Journal of Immunology, Sep. 15, 1996, vol. 157(6), pp. 2539-2548. [cited by applicant]
Postigo-Fernandez et al., “A multi-epitope DNA vaccine enables a broad engagement of diabetogenic T cells for tolerance in Type 1 diabetes,” Journal of Autoimmunity (2019), available online Nov. 17, 2018, vol. 98, pp. 1… [cited by applicant]
Slingluff et al., “Immunologic and clinical outcomes of a randomized phase II trial of two multipeptide vaccines for melanoma in the adjuvant setting,” Clin. Cancer Res., Nov. 2007, vol. 13(21), pp. 6386-6395. [cited by applicant]
Wang et al., “A benchmark study of sequence alignment methods for protein clustering,” BMC Bioinformatics, Dec. 31, 2018, vol. 19(Suppl 19):529, pp. 95-104. [cited by applicant]
Wang et al., “Direct Detection and Quantification of Neoantigens,” Cancer Immunology Research, published online Sep. 16, 2019, vol. 7(11), pp. 1748-1754. [cited by applicant]
Bakker et al., “Analogues of CTL epitopes with improved MHC class-I binding capacity elicit anti-melanoma CTL recognizing the wild-type epitope,” Int. J. Cancer, Jan. 27, 1997, vol. 70(3), pp. 302-309. [cited by applicant]
Gross et al., “High vaccination efficiency of low-affinity epitopes in antitumor immunotherapy,” The Journal of Clinical Investigation, Feb. 2004, vol. 113(3), pp. 425-433. [cited by applicant]
International Search Report and Written Opinion mailed Apr. 2, 2024, in the International Application No. PCT/US23/74984. 11 pages. [cited by applicant]
Menez-Jamet et al., “Optimized tumor cryptic peptides: the basis for universal neo-antigen-like tumor vaccines,” Ann. Transl. Med., Jul. 2016, 4(14):266, Review Article pp. 1-11. [cited by applicant]
Scardino et al., “HER-2/neu and hTERT cryptic epitopes as novel targets for broad spectrum tumor immunotherapy,” The Journal of Immunology, Jun. 2002, 168(11):5900-6. 8 pages. [cited by applicant]
Tourdot et al., “A general strategy to enhance immunogenicity of low-affinity HLA-A2.1-associated peptides: implication in the identification of cryptic tumor epitopes,” Eur. J. Immunol., Dec. 2000, vol. 30(12), pp. 341… [cited by applicant]
Valmori et al., “Enhanced generation of specific tumor-reactive CTL in vitro by selected Melan-A/MART-1 immunodominant peptide analogues,” The Journal of Immunology, Feb. 15, 1998, 160(4):1750-8. 10 pages. [cited by applicant]
U.S. Appl. No. 17/243,096, Gifford et al. [cited by applicant]
U.S. Appl. No. 17/551,679, Gifford et al. [cited by applicant]
Abelin et al., “Defining HLA-II Ligand Processing and Binding Rules with Mass Spectrometry Enhances Cancer Epitope Prediction,” Immunity, Oct. 15, 2019, vol. 51(4), pp. 766-779; e1-e17, and Update (Feb. 9, 2021, 54(2):3… [cited by applicant]
Alhadj-Ali et al., “Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes,” Science Translation Medicine, Aug. 9, 2017, vol. 9;9(402):eaaf7779. 9 pages. [cited by applicant]
Alvarez, B. et al., “NNAlign_MA; MHC Peptidome Deconvolution for Accurate MHC Binding Motif Characterization and Improved T-cell Epitope Predictions”, Molecular & Cellular Proteomics, Dec. 2019, vol. 18(12), pages: cove… [cited by applicant]
Asahara et al., “Phase I/II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer,” Journal of Translational Medicine, Nov. 16, 2013, vol. 11:291. 13 pa… [cited by applicant]
Bae et al., “Myeloma-Specific Multiple Peptides Able to Generate Cytotoxic T Lymphocytes: A Potential Therapeutic Application in Muliple Myeloma and other Plasma Cell Disorders,” Clinical Cancer Research, published onli… [cited by applicant]
Berzofsky et al., “Progress on new vaccine strategies for the immunotherapy and prevention of cancer,” The Journal of Clinical Investigation, Jun. 2004, vol. 113(11), pp. 1515-1525. [cited by applicant]
Berzofsky et al., “Strategies for designing and optimizing new generation vaccines,” Nature Reviews: Immunology, vol. 1(3), Dec. 2001, pp. 209-219. [cited by applicant]
Berzofsky, “Epitope selection and design of synthetic vaccines. Molecular approaches to enhancing immunogenicity and cross-reactivity of engineered vaccines,” Annals of the New York Academy of Sciences, Aug. 12, 1993, v… [cited by applicant]
Bhasin, M. and Raghava, G.P.S., “Prediction of Promiscuous and High-Affinity Mutated MHC Binders”, Hybridoma and Hybridomics, Nov. 4, 2003, vol. 22, 229-234, (8 pages). [cited by applicant]
Candia et al., “On Peptides and Altered Peptide Ligands: From Origin, Mode of Action and Design to Clinical Application (Immunotherapy),” International Archives of Allergy and Immunology, published online Sep. 20, 2016;… [cited by applicant]
Chicz et al., “Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size,” Nature, Aug. 27, 1992, vol. 358(6389), pp. 764-768. [cited by applicant]
Cleveland et al., “Routine large-scale production of monoclonal antibodies in a protein-free culture medium,” Journal of Immunological Methods, Jan. 28, 1983, vol. 56, Issue 2, pp. 221-234. [cited by applicant]
Croft et al., “Most viral peptides displayed by class I MHC on infected cells are immunogenic,” Proceedings of the National Academy of Sciences, Feb. 19, 2019, vol. 116(8), pp. 3112-3117. [cited by applicant]
Dai et al., “Machine learning optimization of peptides for presentation by class II MHCs,” bioRxiv, posted Aug. 18, 2020 (https://doi.org/10.1101/2020.08.18.256081). 35 pages. [cited by applicant]
Dastagir et al., “Efficient Presentation of Multiple Endogenous Epitopes to Both CD4+ and CD8+ Diabetogenic T Cells for Tolerance,” Molecular Therapy: Methods & Clinical Development, Mar. 2017, vol. 4, pp. 27-38. [cited by applicant]
Dey et al., “A Bioinformatics approach to designing a Zika virus vaccine,” Computational Biology and Chemistry, available online Mar. 10, 2017, vol. 68, pp. 143-152. [cited by applicant]
Dyall et al., “Heteroclitic Immunization Induces Tumor Immunity,” J. Exp. Med., Nov. 2, 1998, vol. 188(9), pp. 1553-1561. [cited by applicant]
Fong et al., “Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy,” PNAS, Jul. 17, 2001, vol. 98(15), pp. 8809-8814. [cited by applicant]
Gibson et al., “Proinsulin multi-peptide immunotherapy induces antigen-specific regulatory T cells and limits autoimmunity in a humanized model,” Clinical Experimental Immunology, Dec. 2015, vol. 182(3), pp. 251-260. [cited by applicant]
Guevara-Patino et al., “Optimization of a self antigen for presentation of multiple epitopes in cancer immunity,” The Journal of Clinical Investigation, May 2006, vol. 116(5), pages: cover, 1382-1390. [cited by applicant]
Hollingsworth et al., “Turning the corner on therapeutic cancer vaccines,” npj Vaccines, published online Feb. 8, 2019, vol. 4(7), pp. 1-10. [cited by applicant]
Hong et al., “Epitope-optimized alpha-fetoprotein genetic vaccines prevent carcinogen-induced murine autochthonous hepatocellular carcinoma,” Hepatology, Apr. 2014, vol. 59(4), pp. 1448-1458. [cited by applicant]
Hoppes et al., “Altered Peptide Ligands Revisited: Vaccine Design through Chemically Modified HLA-A2-Restricted T Cell Epitopes,” Journal of Immunology, published online Oct. 13, 2014, vol. 193, pp. 4803-4813. (12 pages… [cited by applicant]
Houghton et al., “Immunological validation of the EpitOptimizer program for streamlined design of heteroclitic epitopes,” Vaccine, available online Jun. 4, 2007, vol. 25(29), pp. 5330-5342. [cited by applicant]
International Search Report and Written Opinion mailed Mar. 28, 2022, in the International Application No. PCT/US2021/060013. 14 pages. [cited by applicant]
International Search Report and Written Opinion mailed Oct. 14, 2022, in the International Application No. PCT/US22/26354. 21 pages. [cited by applicant]
Jain et al., “Synthetic Tumor-Specific Breakpoint Peptide Vaccine in Patients With Chronic Myeloid Leukemia and Minimal Residual Disease,” Cancer, Sep. 1, 2009, vol. 115, pp. 3924-3934. [cited by applicant]
Jaravine et al., “Assessment of cancer and virus antigens for cross-reactivity in human tissues,” Bioinformatics, Jan. 1, 2017, vol. 33, No. 1, pp. 104-111. [cited by applicant]
Jaravine et al., “Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues,” BMC Cancer, Dec. 28, 2017, vol. 17:892. 9 pages. [cited by applicant]
Jurtz, V et al., “NetMHCpan-4.0: Improved Peptide-MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data”, The Journal of Immunology, prepublished online Oct. 4, 2017, vol. 199, … [cited by applicant]
Keogh et al., “Identification of new epitopes from four different tumor-associated antigens: Recognition of naturally processed epitopes correlates with HLA-A*0201-binding affinity,” The Journal of Immunology, Jul. 15, … [cited by applicant]
Klinger et al., “Multiplex identification of antigen-specific T cell receptors using a combination of immune assays and immune receptor sequencing,” PLOS One, Oct. 28, 2015, vol. 10(10), e0141561. 21 pages. [cited by applicant]
Kranz et al., “Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy,” Nature, Jun. 16, 2016, vol. 534(7607), pp. 396-401, and Methods. 16 pages. [cited by applicant]
Kreiter, et al., “Increased antigen presentation efficiency by coupling antigens to MHC class I trafficking signals,” The Journal of Immunology, Jan. 2008, vol. 180(1), pp. 309-318, and Corrections. 12 pages. [cited by applicant]
Krienke, C. et al., “A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis”, Science, Jan. 8, 2021, vol. 371, pp. 145-153 (10 pages). [cited by applicant]
Liu et al. “Computationally Optimized SARS-CoV-2 MHC Class I and II Vaccine Formulations Predicted to Target Human Haplotype Distributions,” Cell Systems, Aug. 26, 2020, vol. 11(2), pp. 131-144, e1-e6, Supplementary Tab… [cited by applicant]
Liu et al., “Maximum n-times Coverage for COVID-19 Vaccine Design,” arXiv (arXiv:2101.10902v1), submitted Jan. 24, 2021. 13 pages. [cited by applicant]
Liu et al., “Predicted Cellular Immunity Population Coverage Gaps for SARS-CoV-2 Subunit Vaccines and their Augmentation by Compact Peptide Sets,” bioRxiv, posted Oct. 21, 2020, 29 pages. (https://www.biorxiv.org/conten… [cited by applicant]
Liu et al., “Predicted Cellular Immunity Population Coverage Gaps for SARS-CoV-2 Subunit Vaccines and their Augmentation by Compact Peptide Sets,” Cell Systems, Journal Pre-proof, Nov. 26, 2020. (https://doi.org/10.1016… [cited by applicant]
Longmate et al., “Population coverage by HLA class-I restricted cytotoxic T-lymphocyte epitopes,” Immunogenetics (2001), published online Dec. 19, 2000, vol. 52, pp. 165-173. [cited by applicant]
Maa et al., “Biopharmaceutical Powders: Particle Formation and Formulation Considerations,” Current Pharmaceutical Biotechnology, Nov. 2000, vol. 1, No. 3, pp. 283-302. [cited by applicant]
Mahanty et al., “Immunogenicity of infectious pathogens and vaccine antigens,” BMC Immunology, published online May 29, 2015, vol. 16(1), pp. 1-6. [cited by applicant]
Mashiba et al., “Identification of CTL epitopes in hepatitis C virus by a genome-wide computational scanning and a rational design of peptide vaccine,” Immunogenetics, published online Jan. 16, 2007, vol. 59, pp. 197-20… [cited by applicant]
Merriam-Webster, “Prevent”, available online at https://www.merriam-webster.com/dictionary/prevent. 10 pages. Accessed on Sep. 24, 2021. [cited by applicant]
Mösch et al., “Machine Learning for Cancer Immunotherapies Based on Epitope Recognition by T Cell Receptors,” Frontiers in Genetics, Nov. 19, 2019, vol. 10, Article 1141. 17 pages. [cited by applicant]
Nair et al., “A simple practice guide for dose conversion between animals and human,” Journal of Basic and Clinical Pharmacy, Article Review, Mar.-May 2016, vol. 7, Issue 2, pp. 27-31. [cited by applicant]
Ng et al., “In silico-guided sequence modifications of K-ras epitopes improve immunological outcome against G12V and G13D mutant KRAS antigens,” PeerJ, published Jul. 20, 2018, 6:e5056. doi: 10.7717/peerj.5056. 21 pages. [cited by applicant]
Nielsen et al., “NNAlign: a platform to construct and evaluate artificial neural network models of receptor-ligand interactions,” Nucleic Acids Research, published online Apr. 12, 2017, vol. 45, pp. W344-W349. [cited by applicant]
Nielsen et al., “The role of the proteasome in generating cytotoxic T-cell epitopes: insights obtained from improved predictions of proteasomal cleavage,” Immunogenetics, published online Mar. 3, 2005, vol. 57, pp. 33-4… [cited by applicant]
Nielsen, M. and Lund, O., “NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction”, BMC Bioinformatics, Sep. 18, 2009, vol. 10:296, pp. 1-10 (10 pages). [cited by applicant]
Nielsen, M. et al., “Quantitative Predictions of Peptide Binding to Any HLA-DR Molecule of Known Sequence: NetMHCIIpan”, PLoS Computational Biology, Jul. 4, 2008, vol. 4(7):e1000107, pp. 1-10 (10 pages). [cited by applicant]
O'Donnell, T.J. et al., “MHCflurry 2.0: Improved Pan-Allele Prediction of MHC Class I-Presented Peptides by Incorporating Antigen Processing”, Cell Systems, Jul. 22, 2020, vol. 11, pages: cover, 42-48 (15 pages). [cited by applicant]
O'Donnell, T.J. et al., “MHCflurry: Open-Source Class I MHC Binding Affinity Prediction”, Cell Systems, Jul. 25, 2018, vol. 7, pages: cover, 129-132 (9 pages). [cited by applicant]
Ogishi et al., “Quantitative Prediction of the Landscape of T Cell Epitope Immunogenicity in Sequence Space,” Frontiers in Immunology, Apr. 16, 2019, vol. 10, Article 827. 20 pages. [cited by applicant]
Park et al., “Accurate structure prediction of peptide-MHC complexes for identifying highly immunogenic antigens, ” Mol. Immunol., Nov. 2013, vol. 56(0):81-90. NIH Author Manuscript. 25 pages. [cited by applicant]
Reynisson et al., “NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data,” Nucleic Acids Research, published o… [cited by applicant]
Rist et al., “HLA peptide length preferences control CD8+ T cell responses,” The Journal of Immunology, published online Jun. 7, 2013, vol. 191(2), pp. 561-571. 12 pages. [cited by applicant]
Rosenberg et al., “Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma,” Nature Medicine, Mar. 1998, vol. 4(3), pp. 321-327. [cited by applicant]
Sahin et al., “Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer,” Nature, Jul. 13, 2017, vol. 547(7662), pp. 222-226, and Methods. 19 pages. [cited by applicant]
Schipper et al., “Minimal Phenotype Panels, A Method for Achieving Maximum Population Coverage with a Minimum of HLA Antigens,” Human Immunology, vol. 51, Dec. 1996, pp. 95-98. [cited by applicant]
Sette et al., “Peptides and Methods for Creating Synthetic Peptides With Modulated Binding Affinity for HLA Molecules,” U.S. Appl. No. 09/226,775, filed Jan. 6, 1999—not published, abandoned. 133 pages. [cited by applicant]
Sette et al., “The Relationship Between Class I Binding Affinity and Immunogenicity of Potential Cytotoxic T Cell Epitopes,” The Journal of Immunology, Dec. 15, 1994, vol. 153, pp. 5586-5592. [cited by applicant]
Shimokawa, C. et al., “CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes”, Nature Communications, Apr. 22, 2020, vol. 11:1922, pp. 1-9 (9 pages). [cited by applicant]
Sim et al., “Correction—High-affinity oligoclonal TCRs define effective adoptive T cell therapy targeting mutant KRAS-G12D,” Proc. Natl. Acad. Sci. USA, Nov. 3, 2020, vol. 117(44), pp. 27743-27744. [cited by applicant]
Sim et al., “High-affinity oligoclonal TCRs define effective adoptive T cell therapy targeting mutant KRAS-G12D,” Proc. Natl. Acad. Sci. USA, first published May 27, 2020, vol. 117(23), pp. 12826-12835. [cited by applicant]
Slansky et al., “Enhanced antigen-specific antitumor immunity with altered peptide ligands that stabilize the MHC-peptide-TCR complex,” Immunity, Oct. 2000, vol. 13(4), pp. 529-538. [cited by applicant]
Slota et al., “ELISpot for measuring human immune responses to vaccines,” Expert Review of Vaccines, Mar. 2011, vol. 10(3), pp. 299-306. NIH Author Manuscript. 14 pages. [cited by applicant]
Soria-Guerra et al., “An overview of bioinformatics tools for epitope prediction: implications on vaccine development,” Journal of Biomedical Informatics (2015), available online Nov. 10, 2014, vol. 53, pp. 405-414. [cited by applicant]
Takahashi et al., “Induction of Broadly Cross-Reactive Cytotoxic T Cells Recognizing an HIV-1 Envelope Determinant,” Science, Jan. 17, 1992, vol. 255(5042), pp. 333-336. [cited by applicant]
Tangri et al., “Structural Features of Peptide Analogs of Human Histocompatibility Leukocyte Antigen Class I Epitopes That Are More Potent and Immunogenic than Wild-Type Peptide,” Journal of Experimental Medicine, Sep. … [cited by applicant]
Tapia-Calle et al., “A PBMC-Based System to Assess Human T Cell Responses to Influenza Vaccine Candidates In Vitro,” Vaccines, Nov. 13, 2019, vol. 7(4):181. 26 pages. [cited by applicant]
Toussaint, N.C. et al., “A Mathematical Framework for the Selection of an Optimal Set of Peptides for Epitope-Based Vaccines”, PLoS Computational Biology, Dec. 26, 2008, vol. 4(12):e1000246, pp. 1-10 (10 pages). [cited by applicant]
Trolle et al., “The length distribution of class I-restricted T cell epitopes is determined by both peptide supply and MHC allele-specific binding preference,” The Journal of Immunology, Feb. 15, 2016, vol. 196(4), 1480… [cited by applicant]
Vita et al., “The Immune Epitope Database (IEDB): 2018 update,” Nucleic Acids Research (2019), published online Oct. 24, 2018, vol. 47, database issue D339-D343. 5 pages. [cited by applicant]
Woodham et al., “Nanobody-Antigen Conjugates Elicit HPV-Specific Antitumor Immune Responses,” Cancer Immunology Research, Jul. 2018, vol. 6(7); pp. 870-880. [cited by applicant]
Zaremba et al., “Identification of an enhancer agonist cytotoxic T lymphocyte peptide from human carcinoembryonic antigen,” Cancer Research, Oct. 15, 1997, vol. 57(20), pp. 4570-4577. [cited by applicant]
Zhang et al., “Cancer vaccines: Targeting KRAS-driven cancers,” Expert Review of Vaccines, published online Mar. 14, 2020, vol. 19(2), pp. 163-173. 12 pages. [cited by applicant]
Zirlik et al., “Cytotoxic T cells generated against heteroclitic peptides kill primary tumor cells independent of the binding affinity of the native tumor antigen peptide,” Blood, Dec. 1, 2006, Vo. 108, No. 12, pp. 3865… [cited by applicant]
Fikes et al., “Design of multi-epitope, analogue-based cancer vaccines,” Expert Opinion on Biological Therapy, published online Mar. 3, 2005, vol. 3:6, pp. 985-993. 10 pages. [cited by applicant]
Bell et al., “Dynamics-Based Peptide—MHC Binding Optimization by a Convolutional Variational Autoencoder: A Use-Case Model for CASTELO,” Journal of Chemical Theory and Computation, Nov. 18, 2021, vol. 17, pp. 7962-7971. [cited by applicant]
Xiao et al., “In silico design of MHC class I high binding affinity peptides through motifs activation map,” BMC Bioinformatics, published Dec. 31, 2018, vol. 19(Suppl 19):516. 12 pages. [cited by applicant]