IP Library Granted Patent US 12,616,746
Granted Patent B2
US 12,616,746 · App. 17/937,751 · Granted May 5, 2026

Infectious disease antigens and vaccines

Inventors: Andrew Ferguson (Hingham, MA); Raphael Rousseau (Los Altos, CA); Roman Yelensky (Newton, MA); James Xin Sun (Newton, MA); Matthew Joseph Davis (Scituate, MA); Karin Jooss (San Diego, CA); Amy Rachel Rappaport (Daly City, CA); Ciaran Daniel Scallan (San Francisco, CA); Leonid Gitlin (Foster City, CA); Christine Denise Palmer (Cambridge, MA)
Assignee: Seattle Project Corp.
A61K39/145A61P31/16C12N15/86A61K2039/5256A61K2039/545A61K2039/55555B82Y5/00
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Quick Facts
Patent No.
US 12,616,746
App. No.
17/937,751
Granted
May 5, 2026
Kind
B2
Abstract

Disclosed herein are compositions that include antigen-encoding nucleic acid sequences and/or antigen peptides. Also disclosed are nucleotides, cells, and methods associated with the compositions including their use as vaccines, including vectors and methods for a heterologous prime/boost vaccination strategy.

Claims (156)

1 . A composition for delivery of a self-replicating alphavirus-based expression system,

wherein the composition for delivery of the self-replicating alphavirus-based expression system comprises:

(A) the self-replicating alphavirus-based expression system, wherein the self-replicating alphavirus-based expression system comprises one or more vectors, wherein the one or more vectors comprises:

(a) an RNA alphavirus backbone, wherein the RNA alphavirus backbone comprises:

(i) at least one promoter nucleotide sequence, and

(ii) at least one polyadenylation (poly(A)) sequence; and

(b) a cassette, wherein the cassette comprises:

(i) at least one antigen-encoding nucleic acid sequence comprising:

a. a nucleic acid sequence encoding an infectious disease organism peptide selected from the group consisting of: a pathogen-derived peptide, a virus-derived peptide, a bacteria-derived peptide, a fungus-derived peptide, and a parasite-derived peptide,

b. optionally a 5′ linker sequence, and

c. optionally a 3′ linker sequence;

(ii) optionally, a second promoter nucleotide sequence operably linked to the at least one antigen-encoding nucleic acid sequence; and

(iii) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the alphavirus,

wherein an ordered sequence of each element of the cassette in the composition for delivery of the self-replicating alphavirus-based expression system is described in the formula, from 5′ to 3′, comprising:

P a -(L5 b -N c -L3 d ) X -(G5 e -U f ) Y -G3 g

wherein P comprises the second promoter nucleotide sequence, where a=0 or 1,

N comprises one of the epitope-encoding nucleic acid sequences, wherein the epitope-encoding nucleic acid sequence comprises an MHC class I epitope-encoding nucleic acid sequence, where c=1,

L5 comprises the 5′ linker sequence, where b=0 or 1,

L3 comprises the 3′ linker sequence, where d=0 or 1,

G5 comprises one of the at least one nucleic acid sequences encoding a GPGPG amino acid linker, where e=0 or 1,

G3 comprises one of the at least one nucleic acid sequences encoding a GPGPG amino acid linker, where g=0 or 1,

U comprises one of the at least one MHC class II epitope-encoding nucleic acid sequence, where f=1,

X=1 to 400, where for each X the corresponding N c is an MHC class I epitope-encoding nucleic acid sequence, and

Y=0, 1, or 2, where for each Y the corresponding U f is an MHC class II epitope-encoding nucleic acid sequence

optionally wherein:

(a) for each X the corresponding N c is a distinct MHC class I epitope encoding nucleic acid sequence; and/or

(b) for each Y the corresponding U f is a distinct MHC class II antigen-encoding nucleic acid sequence; and/or

(c) wherein:

a=0, b=1, d=1, e=1, g=1, h=1, X=20, Y=2,

the at least one promoter nucleotide sequence is a single 26S promoter nucleotide sequence provided by the backbone,

the at least one polyadenylation poly(A) sequence is a poly(A) sequence of at least 100 consecutive A nucleotides provided by the backbone,

each N encodes a MHC class I epitope 7-15 amino acids in length,

L5 is a native 5′ linker sequence that encodes a native N-terminal amino acid sequence of the MHC I epitope, and wherein the 5′ linker sequence encodes a peptide that is at least 2 amino acids in length,

L3 is a native 3′ linker sequence that encodes a native C-terminal acid sequence of the MHC I epitope, and wherein the 3′ linker sequence encodes a peptide that is at least 2 amino acids in length,

U is each of a PADRE class II sequence and a Tetanus toxoid MHC class II sequence,

wherein the alphavirus vector is a Venezuelan equine encephalitis virus vector,

each of the MHC class I antigen-encoding nucleic acid sequences encodes a polypeptide that is between 13 and 25 amino acids in length, and

optionally wherein at least two of the antigen-encoding nucleic acid sequences encode polypeptide sequences or portions thereof that are presented by MHC class I on the tumor cell surface, and

(B) a lipid-nanoparticle (LNP), wherein the LNP encapsulates the self-replicating alphavirus-based expression system.

2 . The composition of claim 1 , wherein the nucleic acid sequence encoding the peptide comprises encoding a peptide selected from: an epitope, a full-length protein, a protein subunit, a protein domain, and combinations thereof of the protein expressed in the infectious disease organism.

3 . The composition of claim 1 , wherein the nucleic acid sequence encoding the peptide comprises two or more distinct epitope-encoding nucleic acid sequences, between 1-10, between 1-20, between 1-30, between 1-40, between 1-50, between 1-100, between 1-200, between 1-300, between 1-400, between 1-500, between 2-10, between 2-20, between 2-30, between 2-40, between 2-50, between 2-100, between 2-200, between 2-300, between 2-400, or between 2-500 distinct epitope-encoding nucleic acid sequences distinct epitope-encoding nucleic acid sequences.

4 . The composition of claim 1 , wherein the encoded peptide or peptides is capable of stimulating an immune response, a T cell response, a B cell response, and/or a T cell response and a B cell response.

5 . The composition of claim 1 , wherein the infectious disease organism is selected from the group consisting of: Severe acute respiratory syndrome-related coronavirus (SARS), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Ebola, HIV, Hepatitis B virus (HBV), influenza, Hepatitis C virus (HCV), Human papillomavirus (HPV), Cytomegalovirus (CMV), Chikungunya virus, Respiratory syncytial virus (RSV), Dengue virus, a orthymyxoviridae family virus, and tuberculosis.

6 . The composition of claim 1 , wherein the LNP comprises a lipid selected from the group consisting of:

an ionizable amino lipid, a phosphatidylcholine, cholesterol, a PEG-based coat lipid, or a combination thereof; or

the LNP comprises an ionizable amino lipid, a phosphatidylcholine, cholesterol, and a PEG-based coat lipid; and

optionally wherein the ionizable amino lipids comprise MC3-like (dilinoleylmethyl-4-dimethylaminobutyrate) molecules; and/or

the LNP-encapsulated expression system has a diameter of about 100 nm.

7 . The composition of claim 1 , wherein the RNA alphavirus backbone comprises at least one nucleotide sequence of an Aura virus, a Fort Morgan virus, a Venezuelan equine encephalitis virus, a Ross River virus, a Semliki Forest virus, a Sindbis virus, or a Mayaro virus, optionally wherein

a. the RNA alphavirus backbone comprises at least sequences for nonstructural protein-mediated amplification, a 26S promoter sequence, a poly(A) sequence, a nonstructural protein 1 (nsP1) gene, a nsP2 gene, a nsP3 gene, and a nsP4 gene encoded by the nucleotide sequence of the Aura virus, the Fort Morgan virus, the Venezuelan equine encephalitis virus, the Ross River virus, the Semliki Forest virus, the Sindbis virus, or the Mayaro virus, or

b. the RNA alphavirus backbone comprises at least sequences for nonstructural protein-mediated amplification, a 26S promoter sequence, and a poly(A) sequence encoded by the nucleotide sequence of the Aura virus, the Fort Morgan virus, the Venezuelan equine encephalitis virus, the Ross River virus, the Semliki Forest virus, the Sindbis virus, or the Mayaro virus; optionally wherein sequences for nonstructural protein-mediated amplification are selected from the group consisting of: an alphavirus 5′ UTR, a 51-nt CSE, a 24-nt CSE, a 26S subgenomic promoter sequence, a 19-nt CSE, an alphavirus 3′ UTR, or combinations thereof; and/or

the RNA alphavirus backbone comprises does not encode structural virion proteins capsid, E2 and E1, optionally wherein the antigen cassette is inserted in place of structural virion proteins within the nucleotide sequence of the Aura virus, the Fort Morgan virus, the Venezuelan equine encephalitis virus, the Ross River virus, the Semliki Forest virus, the Sindbis virus, or the Mayaro virus; and/or

the insertion of the antigen cassette provides for transcription of a polycistronic RNA comprising the nsP1-4 genes and the at least one antigen-encoding nucleic acid sequence, wherein the nsP1-4 genes and the at least one antigen-encoding nucleic acid sequence are in separate open reading frames; and

optionally wherein the Venezuelan equine encephalitis virus comprises:

the sequence of SEQ ID NO:3 or SEQ ID NO:5, optionally further comprising a deletion between base pair 7544 and 11175, or the sequence set forth in SEQ ID NO:6 or SEQ ID NO:7, optionally

wherein the antigen cassette is inserted at position 7544 to replace the deletion between base pairs 7544 and 11175 as set forth in the sequence of SEQ ID NO:3 or SEQ ID NO:5.

8 . The composition of claim 1 , wherein the at least one promoter nucleotide sequence is:

the native 26S promoter nucleotide sequence encoded by the RNA alphavirus backbone or wherein the at least one promoter nucleotide sequence is an exogenous RNA promoter; and/or

wherein the second promoter nucleotide sequence is a 26S promoter nucleotide sequence, or comprises multiple 26S promoter nucleotide sequences, wherein each 26S promoter nucleotide sequence provides for transcription of one or more of the separate open reading frames; and/or

the at least one promoter nucleotide sequence or the second promoter nucleotide sequence is inducible or non-inducible; and/or

the at least one poly(A) sequence comprises a poly(A) sequence native to the backbone or exogenous to the backbone; and/or

the at least one poly(A) sequence is operably linked to at least one of the at least one antigen-encoding nucleic acid sequences; and/or

the at least one poly(A) sequence is at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, or at least 90 consecutive A nucleotides or at least 100 consecutive A nucleotides.

9 . The composition of claim 1 , wherein the epitope-encoding nucleic acid sequence comprises a MHC class I epitope-encoding nucleic acid sequence, and wherein the MHC class I epitope-encoding nucleic acid sequence is selected by performing the steps of:

(a) obtaining at least one of exome, transcriptome, or whole genome nucleotide sequencing data from the infectious disease organism, wherein the infectious disease organism nucleotide sequencing data is used to obtain data representing peptide sequences of each of a set of epitopes;

(b) inputting the peptide sequence of each epitope into a presentation model to generate a set of numerical likelihoods that each of the epitopes is presented by one or more of the MHC alleles on the infected cell surface, the set of numerical likelihoods having been identified at least based on received mass spectrometry data; and

(c) selecting a subset of the set of epitopes based on the set of numerical likelihoods to generate a set of selected epitopes which are used to generate the MHC class I epitope-encoding nucleic acid sequence

optionally wherein

each of the MHC class I epitope-encoding nucleic acid sequences is selected by performing the above steps (a)-(c); and/or

a number of the set of selected epitopes is 2-20; and/or

the presentation model represents dependence between:

(a) presence of a pair of a particular one of the MHC alleles and a particular amino acid at a particular position of a peptide sequence, and

(b) likelihood of presentation on the tumor cell surface, by the particular one of the MHC alleles of the pair, of such a peptide sequence comprising the particular amino acid at the particular position; and/or

selecting the set of selected epitopes comprises selecting epitopes that have an increased likelihood of being presented on the tumor cell surface relative to unselected epitopes based on the presentation model; and/or

selecting the set of selected epitopes comprises selecting epitopes that have an increased likelihood of being capable of inducing a tumor-specific immune response in the subject relative to unselected epitopes based on the presentation model; and/or

selecting the set of selected epitopes comprises selecting epitopes that have an increased likelihood of being capable of being presented to naïve T cells by professional antigen presenting cells (APCs) relative to unselected epitopes based on the presentation model, optionally wherein the APC is a dendritic cell (DC); and/or

selecting the set of selected epitopes comprises selecting epitopes that have a decreased likelihood of being subject to inhibition via central or peripheral tolerance relative to unselected epitopes based on the presentation model; and/or

the set of selected epitopes comprises selecting epitopes that have a decreased likelihood of being capable of inducing an autoimmune response to normal tissue in the subject relative to unselected epitopes based on the presentation model; and/or

exome or transcriptome nucleotide sequencing data is obtained by performing sequencing on the tumor tissue, optionally wherein the sequencing is next generation sequencing (NGS) or any massively parallel sequencing approach.

10 . The composition of claim 1 , wherein:

the cassette comprises junctional epitope sequences formed by adjacent sequences in the cassette, optionally wherein

at least one or each junctional epitope sequence has an affinity of greater than 500 nM for MHC and/or wherein each junctional epitope sequence is non-self; and/or

the cassette does not encode a non-therapeutic MHC class I or class II epitope nucleic acid sequence comprising a translated, wild-type nucleic acid sequence, wherein the non-therapeutic epitope is predicted to be displayed on an MHC allele of the subject, optionally wherein the non-therapeutic predicted MHC class I or class II epitope sequence is a junctional epitope sequence formed by adjacent sequences in the cassette; and/or

the prediction is based on presentation likelihoods generated by inputting sequences of the non-therapeutic epitopes into a presentation model; and/or

an order of the antigen-encoding nucleic acid sequences in the cassette is determined by a series of steps comprising:

(a) generating a set of candidate cassette sequences corresponding to different orders of the antigen-encoding nucleic acid sequences;

(b) determining, for each candidate cassette sequence, a presentation score based on presentation of non-therapeutic epitopes in the candidate cassette sequence; and

(c) selecting a candidate cassette sequence associated with a presentation score below a predetermined threshold as the cassette sequence for a vaccine.

11 . The composition of claim 1 , wherein the epitope-encoding nucleic acid sequences comprises at least one MHC class I epitope-encoding nucleic acid sequence, and wherein each antigen-encoding nucleic acid sequence encodes a polypeptide sequence between 8 and 35 amino acids in length, optionally 9-17, 9-25, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34 or 35 amino acids in length.

12 . The composition of claim 1 , wherein:

one or more of the epitope-encoding nucleic acid sequences are derived from an infection in or an infected cell of a subject; or

each of the epitope-encoding nucleic acid sequences are derived from an infection in or an infected cell of a subject; or

one or more of the epitope-encoding nucleic acid sequences are not derived from an infection in or an infected cell of a subject; or

each of the epitope-encoding nucleic acid sequences are not derived from an infection in or an infected cell of a subject.

13 . A method for stimulating an immune response in a subject, the method comprising administering to the subject the composition for delivery of the self-replicating alphavirus-based expression system of claim 1 , and optionally administering to the subject a composition for delivery of a chimpanzee adenovirus (ChAdV)-based expression system, and,

optionally wherein the composition for delivery of the ChAdV-based expression system is administered as a priming dose and either the composition for delivery of the ChAdV-based expression system or the composition for delivery of the self-replicating alphavirus-based expression system is administered as one or more boosting doses, or

the composition for delivery of the self-replicating alphavirus-based expression system is administered as a priming dose either the composition for delivery of the ChAdV-based expression system or the composition for delivery of the self-replicating alphavirus-based expression system is administered as one or more boosting doses; and/or

optionally

wherein two or more, or 1, 2, 3, 4, 5, 6, 7, or 8 boosting doses are administered; and/or

optionally wherein the cassette of the composition for delivery of the ChAdV-based expression system is identical to the cassette of the composition for delivery of the self-replicating alphavirus-based expression system.

14 . The method of claim 13 , wherein the composition for delivery of the self-replicating alphavirus-based expression system of claim 1 is administered as the priming dose and administered as one or more boosting doses.

15 . A composition for delivery of a self-replicating alphavirus-based expression system,

wherein the composition for delivery of the self-replicating alphavirus-based expression system comprises:

(A) the self-replicating alphavirus-based expression system, wherein the self-replicating alphavirus-based expression system comprises one or more vectors, wherein the one or more vectors comprises:

(a) an RNA alphavirus backbone, wherein the RNA alphavirus backbone comprises:

(i) at least one promoter nucleotide sequence, and

(ii) at least one polyadenylation (poly(A)) sequence; and

(b) a cassette, wherein the cassette comprises:

(i) at least one antigen-encoding nucleic acid sequence comprising:

a. a nucleic acid sequence encoding an infectious disease organism peptide selected from the group consisting of: a pathogen-derived peptide, a virus-derived peptide, a bacteria-derived peptide, a fungus-derived peptide, and a parasite-derived peptide,

b. optionally a 5′ linker sequence, and

c. optionally a 3′ linker sequence;

(ii) optionally, a second promoter nucleotide sequence operably linked to the at least one antigen-encoding nucleic acid sequence; and

(iii) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the alphavirus,

wherein the at least one promoter nucleotide sequence is:

the native 26S promoter nucleotide sequence encoded by the RNA alphavirus backbone or wherein the at least one promoter nucleotide sequence is an exogenous RNA promoter; and/or

wherein the second promoter nucleotide sequence is a 26S promoter nucleotide sequence, or comprises multiple 26S promoter nucleotide sequences, wherein each 26S promoter nucleotide sequence provides for transcription of one or more of the separate open reading frames; and/or

the at least one promoter nucleotide sequence or the second promoter nucleotide sequence is inducible or non-inducible; and/or

the at least one poly(A) sequence comprises a poly(A) sequence native to the backbone or exogenous to the backbone; and/or

the at least one poly(A) sequence is operably linked to at least one of the at least one antigen-encoding nucleic acid sequences; and/or

the at least one poly(A) sequence is at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, or at least 90 consecutive A nucleotides or at least 100 consecutive A nucleotides, and

(B) a lipid-nanoparticle (LNP), wherein the LNP encapsulates the self-replicating alphavirus-based expression system.

16 . A method for stimulating an immune response in a subject, the method comprising administering to the subject the composition for delivery of the self-replicating alphavirus-based expression system of claim 15 , and optionally administering to the subject a composition for delivery of a chimpanzee adenovirus (ChAdV)-based expression system, and,

optionally wherein the composition for delivery of the ChAdV-based expression system is administered as a priming dose and either the composition for delivery of the ChAdV-based expression system or the composition for delivery of the self-replicating alphavirus-based expression system is administered as one or more boosting doses, or

the composition for delivery of the self-replicating alphavirus-based expression system is administered as a priming dose either the composition for delivery of the ChAdV-based expression system or the composition for delivery of the self-replicating alphavirus-based expression system is administered as one or more boosting doses; and/or

optionally

wherein two or more, or 1, 2, 3, 4, 5, 6, 7, or 8 boosting doses are administered; and/or

optionally wherein the cassette of the composition for delivery of the ChAdV-based expression system is identical to the cassette of the composition for delivery of the self-replicating alphavirus-based expression system.

17 . A composition for delivery of a self-replicating alphavirus-based expression system,

wherein the composition for delivery of the self-replicating alphavirus-based expression system comprises:

(A) the self-replicating alphavirus-based expression system, wherein the self-replicating alphavirus-based expression system comprises one or more vectors, wherein the one or more vectors comprises:

(a) an RNA alphavirus backbone, wherein the RNA alphavirus backbone comprises:

(i) at least one promoter nucleotide sequence, and

(ii) at least one polyadenylation (poly(A)) sequence; and

(b) a cassette, wherein the cassette comprises:

(i) at least one antigen-encoding nucleic acid sequence comprising:

a. a nucleic acid sequence encoding an infectious disease organism peptide selected from the group consisting of: a pathogen-derived peptide, a virus-derived peptide, a bacteria-derived peptide, a fungus-derived peptide, and a parasite-derived peptide,

b. optionally a 5′ linker sequence, and

c. optionally a 3′ linker sequence;

(ii) optionally, a second promoter nucleotide sequence operably linked to the at least one antigen-encoding nucleic acid sequence; and

(iii) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the alphavirus,

wherein the cassette comprises junctional epitope sequences formed by adjacent sequences in the cassette, optionally wherein:

at least one or each junctional epitope sequence has an affinity of greater than 500 nM for MHC and/or wherein each junctional epitope sequence is non-self; and/or

the cassette does not encode a non-therapeutic MHC class I or class II epitope nucleic acid sequence comprising a translated, wild-type nucleic acid sequence, wherein the non-therapeutic epitope is predicted to be displayed on an MHC allele of the subject, optionally wherein the non-therapeutic predicted MHC class I or class II epitope sequence is a junctional epitope sequence formed by adjacent sequences in the cassette; and/or

the prediction is based on presentation likelihoods generated by inputting sequences of the non-therapeutic epitopes into a presentation model; and/or

an order of the antigen-encoding nucleic acid sequences in the cassette is determined by a series of steps comprising:

(a) generating a set of candidate cassette sequences corresponding to different orders of the antigen-encoding nucleic acid sequences;

(b) determining, for each candidate cassette sequence, a presentation score based on presentation of non-therapeutic epitopes in the candidate cassette sequence; and

(c) selecting a candidate cassette sequence associated with a presentation score below a predetermined threshold as the cassette sequence for a vaccine, and

(B) a lipid-nanoparticle (LNP), wherein the LNP encapsulates the self-replicating alphavirus-based expression system.

18 . A method for stimulating an immune response in a subject, the method comprising administering to the subject the composition for delivery of the self-replicating alphavirus-based expression system of claim 17 , and optionally administering to the subject a composition for delivery of a chimpanzee adenovirus (ChAdV)-based expression system, and,

optionally wherein the composition for delivery of the ChAdV-based expression system is administered as a priming dose and either the composition for delivery of the ChAdV-based expression system or the composition for delivery of the self-replicating alphavirus-based expression system is administered as one or more boosting doses, or

the composition for delivery of the self-replicating alphavirus-based expression system is administered as a priming dose either the composition for delivery of the ChAdV-based expression system or the composition for delivery of the self-replicating alphavirus-based expression system is administered as one or more boosting doses; and/or

optionally

wherein two or more, or 1, 2, 3, 4, 5, 6, 7, or 8 boosting doses are administered; and/or

optionally wherein the cassette of the composition for delivery of the ChAdV-based expression system is identical to the cassette of the composition for delivery of the self-replicating alphavirus-based expression system.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE ERRONEOUS REFERENCE TO APPLICATION NUMBERS 10847252, 10847253 AND 11183286 TO INSTEAD REFLECT THE PATENT NUMBERS LISTED IN THE RECORDED ASSIGNMENT DOCUMENT PREVIOUSLY RECORDED ON REEL 70760 FRAME 165. ASSIGNOR(S) HEREBY CONFIRMS THE THE ASSIGNMENT. Recorded Apr 25, 2025
From: GRITSTONE BIO, INC.
To: SEATTLE PROJECT CORP.
Reel/Frame 071079/0653 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 7, 2025
From: GRITSTONE BIO, INC.
To: SEATTLE PROJECT CORP.
Reel/Frame 070760/0165 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 6, 2022
From: FERGUSON, ANDREW; ROUSSEAU, RAPHAEL; YELENSKY, ROMAN; SUN, JAMES XIN; DAVIS, MATTHEW JOSEPH; JOOSS, KARIN; RAPPAPORT, AMY RACHEL; SCALLAN, CIARAN DANIEL; GITLIN, LEONID; PALMER, CHRISTINE DENISE
To: GRITSTONE BIO, INC.
Reel/Frame 061334/0686 →
Continuity (3)
Continuation PCTUS2021025828 · Apr 5, 2021
Provisional Application 63005160 · Apr 3, 2020
Related Publication 20240050550A1 · Feb 15, 2024
References Cited (211)
US 4235871A · Papahadjopoulos et al. · 1980 [cited by applicant]
US 4501728A · Geho et al. · 1985 [cited by applicant]
US 4722848A · Paoletti et al. · 1988 [cited by applicant]
US 4837028A · Allen · 1989 [cited by applicant]
US 5019369A · Presant et al. · 1991 [cited by applicant]
US 5204253A · Sanford et al. · 1993 [cited by applicant]
US 5240846A · Collins et al. · 1993 [cited by applicant]
US 5279833A · Rose · 1994 [cited by applicant]
US 5580859A · Felgner et al. · 1996 [cited by applicant]
US 5589466A · Felgner et al. · 1996 [cited by applicant]
US 5849589A · Tedder et al. · 1998 [cited by applicant]
US 5891994A · Goldstein · 1999 [cited by applicant]
US 5972596A · Pavlakis et al. · 1999 [cited by applicant]
US 6083716A · Wilson et al. · 2000 [cited by applicant]
US 6193981B1 · Goldstein · 2001 [cited by applicant]
US 6376236B1 · Dubensky, Jr. et al. · 2002 [cited by applicant]
US 6770283B1 · Garoff et al. · 2004 [cited by applicant]
US 8093021B2 · Hurtado et al. · 2012 [cited by applicant]
US 8216834B2 · Colloca et al. · 2012 [cited by applicant]
US 9340830B2 · Lipson et al. · 2016 [cited by applicant]
US 9416370B2 · Smith et al. · 2016 [cited by applicant]
US 10055540B2 · Yelensky et al. · 2018 [cited by applicant]
US 11504421B2 · Blair et al. · 2022 [cited by applicant]
US 11510973B2 · Blair et al. · 2022 [cited by applicant]
US 12109257B2 · Blair et al. · 2024 [cited by applicant]
US 20030114369A1 · Takiguchi et al. · 2003 [cited by applicant]
US 20050271676A1 · Sette et al. · 2005 [cited by applicant]
US 20060093623A1 · Andrieu et al. · 2006 [cited by applicant]
US 20110293637A1 · Hacohen et al. · 2011 [cited by applicant]
US 20110300205A1 · Geall et al. · 2011 [cited by applicant]
US 20170199961A1 · Yelensky et al. · 2017 [cited by applicant]
US 20180008690A1 · Ng et al. · 2018 [cited by applicant]
US 20200010849A1 · Blair et al. · 2020 [cited by applicant]
US 20210113673A1 · Boucher et al. · 2021 [cited by applicant]
US 20220226453A1 · Blair et al. · 2022 [cited by applicant]
US 20240067985A1 · Blair et al. · 2024 [cited by applicant]
US 20250249084A1 · Blair et al. · 2025 [cited by applicant]
US 20250270589A1 · Blair et al. · 2025 [cited by applicant]
EP 1371730A2 · 2003 [cited by applicant]
JP 2007518414A · 2007 [cited by applicant]
JP 2019511255A · 2019 [cited by applicant]
WO 1991006309A1 · 1991 [cited by applicant]
WO 1993024640A2 · 1993 [cited by applicant]
WO 199513392A1 · 1995 [cited by applicant]
WO 1996013597A2 · 1996 [cited by applicant]
WO 1996018372 · 1996 [cited by applicant]
WO 1999016884A1 · 1999 [cited by applicant]
WO 2000018433A2 · 2000 [cited by applicant]
WO 200127291A1 · 2001 [cited by applicant]
WO 200147955A2 · 2001 [cited by applicant]
WO 2001054719A2 · 2001 [cited by applicant]
WO 2001055177A2 · 2001 [cited by applicant]
WO 2005071093A2 · 2005 [cited by applicant]
WO 2010037402A1 · 2010 [cited by applicant]
WO 2011005799A2 · 2011 [cited by applicant]
WO 2016081859A2 · 2016 [cited by applicant]
WO 2016122414A1 · 2016 [cited by applicant]
WO 2016187508A3 · 2017 [cited by applicant]
WO 2017070626A2 · 2017 [cited by applicant]
WO 2017106638A1 · 2017 [cited by applicant]
WO 2017123652A1 · 2017 [cited by applicant]
WO 2018195357A1 · 2018 [cited by applicant]
WO 2018208856A1 · 2018 [cited by applicant]
WO 2018232330A1 · 2018 [cited by applicant]
WO 2020035609A2 · 2020 [cited by applicant]
WO 2020181240A1 · 2020 [cited by applicant]
WO 2021003348A1 · 2021 [cited by applicant]
WO 2021203104A1 · 2021 [cited by applicant]
WO 2021236854A1 · 2021 [cited by applicant]
WO 2022118226A1 · 2022 [cited by applicant]
WO 2024238412A1 · 2024 [cited by applicant]
WO 2025121052A1 · 2025 [cited by applicant]
Brito et al., “Chapter Seven—Self-amplifying mRNA vaccines”, Advances in Genetics, 2015, 89, book pp. 179-233: pdf pp. 1-10. [cited by examiner]
Aarnoudse et al., “TCR reconstitution in Jurkat reporter cells facilitates the identification of novel tumor antigens by cDNA expression clonin,” International Journal of Vancer, May 1, 2002;99(1):7-13. [cited by applicant]
Abelin et al., “Complementary IMAC enrichment methods for HLA-associated phosphopeptide identification by mass spectrometry,” Nature Protocols 10(9) (2015): 1308-1318. [cited by applicant]
Alexander et al., “Development of High Potency Universal DR-Restricted Helper Epitopes by Modification of High Affinity DR-Blocking Peptides.” Immunity vol. 1, Issue 9 (1994): 751-761. [cited by applicant]
Altschul et al., “Basic Local Alignment Search Tool.” Journal of Molecular Biology vol. 215, Issue 3 (1990): 403-410. [cited by applicant]
Amara et al., “Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine.” Science. Apr. 6, 2001;292(5514):69-74. doi: 10.1126/science.1058915. [cited by applicant]
Anders et al., “HTSeq-a Python framework to work with high-throughput sequencing data.” Bioinformatics vol. 31, No. 2 (Jan. 15, 2015): 166-169. [cited by applicant]
Andreatta et al., “Accurate pan-specific prediction of peptide-MHC class II binding affinity with improved binding core identification.” Immunogenetics 67, No. 11-12 (Nov. 2015): 641-650. [cited by applicant]
Andreatta et al., “Gapped sequence alignment using artificial neural networks: application to the MHC class I system,” Bioinformatics, Feb. 15, 2016;32(4):511-7. [cited by applicant]
Banu et al., “Building and Optimizing a Virus-specific T Cell Receptor Library for Targeted Immunotherapy in Viral Infections.” Scientific Reports, Feb. 25, 2014;4:1-10. [cited by applicant]
Barnstable et al., “Production of Monoclonal Antibodies to Group A Erythrocytes, HLA and Other Human Cell Surface Antigens—New Tools for Genetic Analysis,” Cell vol. 14, 9-20, 1978. [cited by applicant]
Barouch et al., “Elicitation of high-frequency cytotoxic T-lymphocyte responses against both dominant and subdominant simian-human immunodeficiency virus epitopes by DNA vaccination of rhesus monkeys.” Journal of Virolo… [cited by applicant]
Bassani-Sternberg et al., “Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation,” Molecular & Cellular Proteomics Vo. 14, Issue… [cited by applicant]
Bodini et al., “The hidden genomic landscape of acute myeloid leukemia: subclonal structure revealed by undetected mutations,” Blood, The Journal of the American Society of Hematology vol. 125, No. 4 (Jan. 22, 2015): 60… [cited by applicant]
Boegel et al., “HLA typing from RNA-Seq sequence reads,” Genome Medicine, Dec. 22, 2012;4(12):1-12. [cited by applicant]
Boisvert et al., “A Quantitative Spatial Proteomics Analysis of Proteome Turnover in Human Cells,” Molecular & Cellular Proteomics, Mar. 2012; 11(3):1-15. [cited by applicant]
Boshart et al., “A Very Strong Enhancer is Located Upstream of an Immediate Early Gene of Human Cytomegalovirus,” Cell vol. 41, No. 2, 521-530, 1985. [cited by applicant]
Brumme Z.L, et al. “HLA-associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins,” PLoS One. Aug. 19, 2009;4(8)1-12. [cited by applicant]
Brumme, Z.L. “Pol protein, partial [Human immunodeficiency virus 1],” Online, www.ncbi.nlm.nih.gov/accession, Jul. 24, 2016 (2 pages). [cited by applicant]
Brumme, Z.L., “HIV-1 isolate D3521TOB8U from USA pol protein (pol) gene, partial cds,” Online, www.ncbi.nlm.nih.gov/nuccore, Jul. 24, 2016, (2 pages). [cited by applicant]
Calis et al., “Properties of MHC Class I Presented Peptides That enhance immunogenicity.” PLoS Comput Biol. vol. 9, Issue 10 (Oct. 24, 2013): e1003266, 13 pages. [cited by applicant]
Callendret et al., “Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS.” Virology. Jul. 5… [cited by applicant]
Cancer Genome Atlas Research Network, “Comprehensive molecular profiling of lung adenocarcinoma,” Nature, vol. 511, pp. 543-550, 2014. [cited by applicant]
Carithers et al., “A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project,” Biopreservation and Biobanking, vol. 13, No. 5, 311-319, Oct. 1, 2015. [cited by applicant]
Carreno et al., “A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells.” Science, May 15, 2015;348(6236):803-8. [cited by applicant]
Carter et al., “Absolute quantification of somatic DNA alterations in human cancer,” Nature Biotechnology vol. 30, No. 5, 413-421, 2012. [cited by applicant]
Cibulskis et al., “Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples,” Nature Biotechnology vol. 31, No. 3, pp. 213-219, 2013. [cited by applicant]
Cieslik et al., “The use of exome capture RNA-seq for highly degraded RNA with application to clinical cancer sequencing,” Genome Research vol. 25, No. 9, 1372-1381, Sep. 1, 2015. [cited by applicant]
Cooper et al., “Rescue of splicing-mediated intron loss maximizes expression in lentiviral vectors containing the human ubiquitin C promoter,” Nucleic Acids Research vol. 43, No. 1, pp. 682-690, Dec. 17, 2014. [cited by applicant]
Cornet et al., “Optimal organization of a polypeptide-based candidate cancer vaccine composed of cryptic tumor peptides with enhanced immunogenicity,” Vaccine vol. 24, No. 12, pp. 2102-2109, 2006. [cited by applicant]
Davis et al., “Alphavirus replicon particles as candidate HIV vaccines,” IUBMB Life. Apr.-May 2002;53(4-5):209-211. [cited by applicant]
Depla et al., “Rational Design of a Multiepitope Vaccine Encoding T-Lymphocyte Epitopes for Treatment of Chronic Hepatitis B Virus Infections,” Journal of Virology vol. 82, No. 1, pp. 435-450, 2008. [cited by applicant]
Desrichard et al., “Cancer neoantigens and applications for immunotherapy,” Clinical Cancer Research vol. 22, No. 4, pp. 807-812, Feb. 15, 2016. [cited by applicant]
Duan et al., “Genomic and bioinformatic profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity,” Journal of Experimental Medicine, Oct. 20, 2014;211(11):2231-48. [cited by applicant]
Fang et al., “Stable antibody expression at therapeutic levels using the 2A peptide.” Nature biotechnology 23, No. 5 (2005): 584-590. [cited by applicant]
Felgner et al., “Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure.” Proceedings of the National Academy of Sciences 84, No. 21 (1987): 7413-7417. [cited by applicant]
Frampton et al., “Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing,” Nature Biotechnology Nov. 2013;31(11):1023-31. [cited by applicant]
Frolov et al., “Cis-acting RNA elements at the 5′ end of Sindbis virus genome RNA regulate minus- and plus-strand RNA synthesis,” RNA vol. 7, No. 11, pp. 1638-1651, 2001. [cited by applicant]
Furney et al., “SF3B1 Mutations Are Associated with Alternative Splicing in Uveal Melanoma,” Cancer Discovery vol. 3, Issue 10, pp. 1122-1129, 2013. [cited by applicant]
Gen Bank: AF394196.1—Simian adenovirus 25, complete genome, 15 pages, 2001. [cited by applicant]
Goldman et al, “HLA-DA monoclonal antibodies inhibit the proliferation of normal and chronic granulocytic leukaemia myeloid progenitor cell,” British Journal of Haematology 52, No. 3 (1982): 411-420. [cited by applicant]
Gros et al., “Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients,” Nature Medicine vol. 22, Issue 4, pp. 433-438, Feb. 22, 2016. [cited by applicant]
Gubin et al., “Tumor neoantigens: Building a framework for personalized cancer immunotherapy,” The Journal of Clinical Investigation, vol. 125, No. 9, pp. 3413-3421, Sep. 2015. [cited by applicant]
Hu et al., “Immunization Delivered by Lentiviral Vectors for Cancer and Infectious Diseases,” Immunological Reviews, vol. 239, Issue 1, pp. 45-61, 2011. [cited by applicant]
Huang et al., “The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product,” Proceedings of the National Academy of Sciences … [cited by applicant]
Hung CF, et al. (2007), “DNA vaccines encoding li-PADRE generates potent PADRE-specific CD4+ T-cell immune responses and enhances vaccine potency,” Mol. Ther., 15(6):1211-9. [cited by applicant]
Hunt et al., “Characterization of Peptides Bound to the Class I MHC Molecule HLA-A2. 1 by Mass Spectrometry,” Science vol. 255, pp. 1261-1263, 1992. [cited by applicant]
Ishioka et al., “Utilization of MHC Class I Transgenic Mice for Development of Minigene DNA Vaccines Encoding Multiple HLA-Restricted CTL Epitopes,” The Journal of Immunology vol. 162, No. 7, pp. 3915-3925, 1999. [cited by applicant]
Janetzki et al., “Guidelines for the automated evaluation of Elispot assays,” Nature Protocols vol. 10, No. 7, pp. 1098-1115, Jul. 2015. [cited by applicant]
Jensen et al., “Improved methods for predicting peptide binding affinity to MHC class II molecules,” Immunology vol. 154, Issue 3, pp. 394-406, 2018. [cited by applicant]
Johnson et al., “Molecular Determinants of Alphavirus Neurovirulence: Nucleotide and Deduced Protein Sequence Changes during Attenuation of Venezuelan Equine Encephalitis Virus,” Journal of General Virology vol. 67, Iss… [cited by applicant]
Skelly et al., “A powerful and flexible statistical framework for testing hypotheses of allele-specific gene expression from RNA-seq data,” Genome Research vol. 21, No. 10, pp. 1728-1737, 2011. [cited by applicant]
Slansky et al., “Enhanced Antigen-Specific Antitumor Immunity with Altered Peptide Ligands that Stabilize the MHC-Peptide-TCR Complex,” Immunity vol. 13, No. 4, pp. 529-538, 2000. [cited by applicant]
Snyder et al., “Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma,” New England Journal of Medicine, vol. 371, No. 23, pp. 2189-2199, 2014. [cited by applicant]
Song et al., “Class: constrained transcript assembly of RNA-seq reads,” BMC Bioinformatics, BioMed Central, 2013;14 Suppl 5(Suppl 5):1-8. [cited by applicant]
Stover et al., “New use of BCG for recombinant vaccines,” Nature vol. 351, No. 6326, pp. 456-460, 1991. [cited by applicant]
Strauss et al., “The Alphaviruses: Gene Expression, Replication, and Evolution,” Microbiological Reviews, vol. 58, No. 3, pp. 491-562, 1994. [cited by applicant]
Szoka et al., “Comparative properties and methods of preparation of lipid vesicles (liposomes).” Annual review of biophysics and bioengineering 9, No. 1 (1980): 467-508. [cited by applicant]
Tatsis et al., “Adenoviruses as vaccine vectors,” Molecular Therapy vol. 10, No. 4, pp. 616-629, 2004. [cited by applicant]
Tran et al., “Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer,” Science vol. 344, No. 6184, pp. 641-645, 2014. [cited by applicant]
Van Allen et al., “Genomic correlates of response to CTLA-4 blockade in metastatic melanoma,” Science vol. 350, No. 6257, pp. 207-211, Nov. 11, 2015. [cited by applicant]
Van Loo et al., “Allele-specific copy number analysis of tumors,” Proceedings of the National Academy of Sciences, vol. 107, No. 39, pp. 16910-16915, 2010. [cited by applicant]
Verhoef et al., “Des-enkephalin-gamma-endorphin (DE gamma E): biotransformation in rat, dog and human plasma.” Eur J Drug Metab Pharmacokinet. Oct.-Dec. 1986;11(4):291-302. doi: 10.1007/BF03189114. [cited by applicant]
Vitiello et al., “Analysis of the HLA-restricted Influenza-specific Cytotoxic T Lymphocyte Response in Transgenic Mice Carrying a Chimeric Human-Mouse Class I Major Histocompatibility Complex,” The Journal of Experiment… [cited by applicant]
Vitting-Seerup et al., “spliceR: an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data,” BMC Bioinformatics, vol. 15, Issue 1, pp. 1-7, 2014. [cited by applicant]
Walter et al., “Clonal Architecture of Secondary Acute Myeloid Leukemia,” New England Journal of Medicine, vol. 366, Issue 12, pp. 1090-1098, 2012. [cited by applicant]
Wilkerson et al., “Integrated RNA and DNA sequencing improves mutation detection in low purity tumors,” Nucleic Acids Research, Jul. 2014;42(13):1-12. [cited by applicant]
Wolff et al., “Direct gene transfer into mouse muscle in vivo.” Science 247, No. 4949 (1990): 1465-1468. [cited by applicant]
Wu et al., “Targeting genes: delivery and persistent expression of a foreign gene driven by mammalian regulatory elements in vivo.” Journal of Biological Chemistry 264, No. 29 (1989): 16985-16987. [cited by applicant]
Xu et al., “RNA CoMPASS: A Dual Approach for Pathogen and Host Transcriptome Analysis of RNA-Seq Datasets,” PloS One, vol. 9, Issue 2, p. e89445, 2014. [cited by applicant]
Yachi et al., “Altered Peptide Ligands Induce Delayed CD8-T Cell Receptor Interaction—a Role for CD8 in Distinguishing Antigen Quality,” Immunity vol. 25, No. 2, pp. 203-211, 2006. [cited by applicant]
Yadav et al., “Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing,” Nature, vol. 515, No. 7528, pp. 572-576, 2014. [cited by applicant]
Ye et al., “Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads,” Bioinformatics vol. 25, No. 21, pp. 2865-2871, 2009. [cited by applicant]
Yoshida et al., “Splicing factor mutations and cancer,” Wiley Interdisciplinary Reviews: RNA 5, No. 4 (2014): 445-459. [cited by applicant]
Zarling et al., “Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy,” Proceedings of the National Academy of Sciences, vol. 103, No. 40, pp. 14889-14894, 2006. [cited by applicant]
Zhang et al., “Intra-tumor Heterogeneity in Localized Lung Adenocarcinomas Delineated by Multi-region Sequencing,” Science vol. 346, No. 6206, pp. 256-259, 2014. [cited by applicant]
Zhang, et al., “Peaks DB: De Novo Sequencing Assisted Database Search for Sensitive and Accurate Peptide Identification,” Molecular & Cellular Proteomics, Apr. 2012;11(4):1-8. [cited by applicant]
Zhou et al., “A Chemical Genetics Approach for the Functional Assessment of Novel Cancer Genes,” Cancer Research vol. 75, No. 10, pp. 1949-1958, May 15, 2015. [cited by applicant]
Zufferey et al., “Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery,” Journal of Virology vol. 72, No. 12, pp. 9873-9880, 1998. [cited by applicant]
McKay, et al. “Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice,” Biorxiv, Apr. 25, 2020, pp. 1-14. [cited by applicant]
Grifoni, A., et al., “A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2,” Cell Host Microbe. Apr. 8, 2020;27(4):671-680. [cited by applicant]
E. Fast, et al., “Potential T-cell and B-cell epitopes of 2019-nCOV.” BioRxiv, (2020): Feb. 2020, Abstract. [cited by applicant]
Agnihothram, S., et al. “Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform,” J Virol. May 14, 2018;92(11):e00027-18. [cited by applicant]
Tarke, A., et al., Comprehensive analysis of TÂ cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases. Cell Rep Med. Feb. 16, 2021;2(2):1-20. [cited by applicant]
Grifoni Alba et al: “Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals”, Cell, Elsevier, Amsterdam NL, vol. 181, No. 7, May 14, 2020, p. 1489. [cited by applicant]
Dupuis et al., “Dendritic cells internalize vaccine adjuvant after intramuscular injection.” Cell Immunol. May 25, 1998;186(1):18-27. doi: 10.1006/cimm.1998.1283. [cited by applicant]
UniProtKB Accession FOSJ75 (FOSJ75_RUBBR) Rubinisphaera brasiliensis (strain ATCC 49424 / DSM 5305 / JCM 21570 / NBRC 103401 / IFAM 1448) (Planctomyces brasiliensis) Uncharacterized protein, Jun. 3, 2011 [online]. [Retr… [cited by applicant]
UniProtKB Accession A0A1V4QDP4 (A0A1V4QDP4_9BACT) candidate division WOR-3 bacterium 4484_100 Uncharacterized protein, Jun. 7, 2017 [online]. [Retrieved on Sep. 24, 2021]. Retrieved from the internet: <URL: https://www.… [cited by applicant]
Fisher et al., “The transmembrane domain of diphtheria toxin improves molecular conjugate gene transfer.” Biochemical Journal 321, No. 1 (1997): 49-58. [cited by applicant]
Jørgensen et al., “NETMHCSTAB-predicting stability of peptide—MHC-I complexes; impacts for cytotoxic T lymphocyte epitope discovery,” Immunology vol. 141, No. 1, pp. 18-26, 2014. [cited by applicant]
Jose et al., “A structural and functional perspective of alphavirus replication and assembly,” Future Microbiology, vol. 4, No. 7, pp. 837-856, 2009. [cited by applicant]
Käll et al., “Assigning Significance to Peptides Identified by Tandem Mass Spectrometry Using Decoy Databases,” Journal of Proteome Research vol. 7, No. 01, pp. 29-34, 2008. [cited by applicant]
Käll et al., “Non-parametric estimation of posterior error probabilities associated with peptides identified by tandem mass spectrometry,” Bioinformatics vol. 24, No. 16, pp. i42-i48, 2008. [cited by applicant]
Käll et al., “Semi-supervised learning for peptide identification from shotgun proteomics datasets,” Nature Methods vol. 4, No. 11, pp. 923-925, 2007. [cited by applicant]
Kinney et al., “Nucleotide sequence of the 26 S mRNA of the virulent Trinidad donkey strain of Venezuelan equine encephalitis virus and deduced sequence of the encoded structural proteins,” Virology 152, No. 2 (1986): 4… [cited by applicant]
Kost et al., “The nucleotide sequence of the chick cytoplasmic b-actin gene,” Nucleic Acids Research vol. 11, No. 23, pp. 8287-8301, 1983. [cited by applicant]
Kreiter et al., “Mutant MHC class II epitopes drive therapeutic immune responses to cancer,” Nature, vol. 520, No. 7549, pp. 692-696, Apr. 2015. [cited by applicant]
Lam et al., “Nucleotide-resolution analysis of structural variants using BreakSeq and a breakpoint library,” Nature Biotechnology vol. 28, No. 1, pp. 47-55 2010. [cited by applicant]
Larsen et al., “An integrative approach to CTL epitope prediction: a combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions,” European Journal of Immunology, v… [cited by applicant]
Lazzaro et al., “CD8 T-cell priming upon mRNA vaccination is restricted to bone-marrow-derived antigen-presenting cells and may involve antigen transfer from myocytes,” Immunology, Oct. 2015;146(2):312-26. [cited by applicant]
Li et al., “RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome.” BMC bioinformatics 12, No. 1 (2011): 323, 16 pages. [cited by applicant]
Liepe et al., “A large fraction of HLA class I ligands are proteasome-generated spliced peptides,” Science vol. 354, No. 6310, Oct. 21, 2016. [cited by applicant]
Liu et al., “ATHLATES: accurate typing of human leukocyte antigen through exome sequencing,” Nucleic Acids Research Aug. 2013;41(14):1-8. [cited by applicant]
Lu et al., “Efficient identification of mutated cancer antigens recognized by T cells associated with durable tumor regressions,” Clinical Cancer Research vol. 20, No. 13, pp. 3401-3410, 2014. [cited by applicant]
Lundegaard et al., “State of the art and challenges in sequence based T-cell epitope prediction,” Immunome Research vol. 6, No. 2, pp. 1-14, 2010. [cited by applicant]
Lundstrom, “Self-Replicating RNA Viruses for RNA Therapeutics.” Molecules. Dec. 13, 2018;23(12):3310. doi: 10.3390/molecules23123310. [cited by applicant]
Lyons et al., “Influence of Human CD8 on Antigen Recognition by T-Cell Receptor-Transduced Cells,” Cancer Research vol. 66, No. 23, pp. 11455-11461, 2006. [cited by applicant]
Magini et al, “Self-Amplifying mRNA Vaccines Expressing Multiple Conserved Influenza Antigens Confer Protection against Homologous and Heterosubtypic Viral Challenge,” PLoS One. Aug. 15, 2016;11(8)1-25. [cited by applicant]
Maguire et al., “SF3B1 mutations constitute a novel therapeutic target in breast cancer,” The Journal of Pathology vol. 235, No. 4 pp. 571-580, Mar. 2015. [cited by applicant]
Mannino et al., “Liposome mediated gene transfer.” Biotechniques 6, No. 7 (1988): 682-690. [cited by applicant]
Maretty et al. “Bayesian transcriptome assembly,” Genome Biology, 2014;15(10):1-11. [cited by applicant]
Mayor et al., “HLA typing for the next generation,” PLoS One, May 27, 2015;10(5):1-12. [cited by applicant]
Mcgranahan et al., “Allele-specific HLA loss and immune escape in lung cancer evolution,” Cell vol. 171, No. 6, pp. 1259-1271, 2017. [cited by applicant]
Mohammed et al., “Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for the presentation of transformed self.” Nature immunology 9, No. 11 (2008): 1236-1243. [cited by applicant]
Mommen et al., “Sampling from the Proteome to the Human Leukocyte Antigen-DR (HLA-DR) Ligandome ProceedsVia High Specificity,” Molecular & Cellular Proteomics, vol. 15, No. 4, pp. 1412-1423, Apr. 1, 2016. [cited by applicant]
Mose et al., “ABRA: improved coding indel detection via assembly-based realignment,” Bioinformatics, vol. 30, No. 19, pp. 2813-2815, 2014. [cited by applicant]
Nagai et al., “Aurora kinase A-specific T-cell receptor gene transfer redirects T lymphocytes to display effective antileukemia reactivity,” Blood, The Journal of the American Society of Hematology, vol. 119, No. 2, pp.… [cited by applicant]
Nielsen et al., “NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction,” BMC Bioinformatics, Sep. 18, 2009;10:1-10. [cited by applicant]
Nielsen et al., “Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method,” BMC Bioinformatics, Jul. 4, 2007;8:1-12. [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 vol. 57, No. 1-2, pp. 33-41, 2005. [cited by applicant]
Panina-Bordignon et al., “Universally immunogenic T cell epitopes: promiscuous binding to human MHC class II and promiscuous recognition by T cells,” European Journal of Immunology 19, No. 12 (1989): 2237-2242. [cited by applicant]
PCT/US2020/040630—International Preliminary Report on Patentability, Jan. 13, 2022, 15 pages. [cited by applicant]
PCT/US2020/040630—International Searech Report and Wirtten Opinion, Nov. 20, 2020, 23 pages. [cited by applicant]
PCT/US2021/025828—International Prelimiary Report on Patentability, Oct. 13, 2022, 10 pages. [cited by applicant]
PCT/US2021/025828—International Search Report and Written Opinion, Jul. 28, 2021, 13 pages. [cited by applicant]
Pearson et al., “MHC class I-associated peptides derive from selective regions of the human genome,” The Journal of Clinical Investigation, vol. 126, No. 12, pp. 4690-4701, Dec. 1, 2016. [cited by applicant]
Pertea et al., “StringTie enables improved reconstruction of a transcriptome from RNA-seq reads,” Nature Biotechnology vol. 33, No. 3, pp. 290-295, Mar. 2015. [cited by applicant]
Pushko et al., “Replicon-Helper Systems from Attenuated Venezuelan Equine Encephalitis Virus: Expression of Heterologous Genes in Vitro and Immunization against Heterologous Pathogens in Vivo,” Virology vol. 239, No. 2,… [cited by applicant]
Rajasagi et al., “Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia,” Blood, vol. 124, No. 3, pp. 453-462, 2014. [cited by applicant]
Rhême et al., “Alphaviral cytotoxicity and its implication in vector development,” Experimental Physiology vol. 90, No. 1, pp. 45-52, 2005. [cited by applicant]
Riley et al., “Recent advances in nanomaterials for gene delivery—a review,” Nanomaterials, Apr. 28, 2017;7(5):1-19. [cited by applicant]
Rivas et al., “Effect of predicted protein-truncating genetic variants on the human transcriptome,” Science vol. 348, No. 6235, pp. 666-669, May 8, 2015. [cited by applicant]
Rizvi et al., “Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer,” Science, Apr. 3, 2015;348(6230):1-12. [cited by applicant]
Roberts et al., “Identification of novel transcripts in annotated genomes using RNA-Seq,” Bioinformatics vol. 27, No. 17, pp. 2325-2329, 2011. [cited by applicant]
Roy et al., “Assessing long-distance RNA sequence connectivity via RNA-templated DNA-DNA ligation,” Elife. Apr. 13, 2015;4:1-21. [cited by applicant]
Sakuma et al., “Lentiviral vectors: basic to translational,” Biochemical Journal 443, No. 3 (2012): 603-618. [cited by applicant]
Saunders et al., Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs, Bioinformatics vol. 28, No. 14, pp. 1811-1817, 2012. [cited by applicant]
Schumacher et al., “Neoantigens in cancer immunotherapy,” Science vol. 348, Issue 6230, pp. 69-74, Apr. 3, 2015. [cited by applicant]
Shukla et al., “Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes,” Nature Biotechnology vol. 33, No. 11. pp. 1152-1158, Nov. 2015. [cited by applicant]