Granted Patent
B2
US 12,303,561 · App. 16/500,707 · Granted May 20, 2025
Protein antigens and uses thereof
Assignee:
BioNTech US Inc.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The field of the present invention relates to immunotherapeutic peptides, peptide binding agents, and their use, for example, in the immunotherapy of cancer.
Claims (30)
1. A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject a polypeptide or a polynucleotide encoding the polypeptide, wherein the polypeptide comprises an amino acid sequence comprising at least 8 contiguous amino acids of a viral protein epitope sequence encoded by (I) an E6 gene of Human papillomavirus type 16 (HPV-16) or (II) an E7 gene of HPV-16, wherein:
(a) the subject expresses an MHC encoded by an HLA B07:02 allele and wherein the amino acid sequence is encoded by the E6 gene of HPV-16 and comprises a sequence of RGRWTGRCM (SEQ ID NO: 70);
(b) the subject expresses an MHC encoded by an HLA B08:01 allele and wherein the amino acid sequence is encoded by the E6 gene of HPV-16; or
(c) the subject expresses an MHC encoded by an HLA A24:02 allele and
(i) the amino acid sequence is encoded by the E7 gene of HPV-16 and comprises the sequence of RAHYNIVTF (SEQ ID NO: 83), or
(ii) the amino acid sequence is encoded by the E6 gene of HPV-16 and comprises a sequence of MHQKRTAMF (SEQ ID NO: 66);
wherein the cancer is a cancer expressing an antigen encoded by the E6 gene of HPV-16 or the E7 gene of HPV-16; and wherein the subject is a human.
2. The method of claim 1 , wherein the amino acid sequence comprises a first amino acid sequence comprising at least 8 contiguous amino acids of the viral protein epitope sequence encoded by the E6 gene of HPV-16, and a second amino acid sequence comprising at least 8 contiguous amino acids of the viral protein epitope sequence encoded by the E7 gene of HPV-16.
3. The method of claim 2 , wherein the polypeptide comprises a first polypeptide comprising the first amino acid sequence and a second polypeptide comprising the second amino acid sequence.
4. The method of claim 1 , wherein the method comprises administering to the subject the polynucleotide encoding the polypeptide, and wherein the polynucleotide is a messenger-RNA (mRNA).
5. The method of claim 4 , wherein the mRNA is a part of a lipid nanoparticle.
6. The method of claim 1 , wherein the viral protein epitope sequence binds an MHC class I with a binding affinity of 500 nM or less.
7. The method of claim 3 , wherein the first polypeptide or the second polypeptide is less than or equal to 600 amino acids in length.
8. The method of claim 1 , wherein the polypeptide further comprises a modification which increases in vivo half-life, cellular targeting, antigen uptake, antigen processing, MHC affinity, MHC stability, or antigen presentation.
9. The method of claim 1 , wherein the polypeptide further comprises a poly-glycine or poly-serine linker.
10. The method of claim 1 , wherein the polypeptide further comprises a peptide sequence of QYIKANSKFIGITE (SEQ ID NO: 1).
11. The method of claim 1 , wherein the cancer is selected from the group consisting of cervical cancer, head and neck cancer, anal cancer, urogenital cancer, and gynecological cancer.
12. The method of claim 1 , further comprising administering an additional therapeutic agent to the subject for a combination therapy, wherein the additional therapeutic agent comprises a chemotherapeutic agent, an immunotherapeutic agent, or an immune checkpoint inhibitor.
13. The method of claim 1 , wherein the subject expresses the MHC encoded by the HLA B07:02 allele.
14. The method of claim 13 , wherein the amino acid sequence is encoded by the E6 gene of HPV-16 and comprises a sequence of RGRWTGRCM (SEQ ID NO: 70).
15. The method of claim 1 , wherein the subject expresses the MHC encoded by the HLA B08:01 allele and the amino acid sequence is encoded by the E6 gene of HPV-16.
16. The method of claim 15 , wherein the amino acid sequence comprises a sequence selected from the group consisting of CVYCKQQLL (SEQ ID NO: 51), DKKQRFHNI (SEQ ID NO: 54), EYRHYCYSL (SEQ ID NO: 55), MHQKRTAMF (SEQ ID NO: 66), SEYRHYCYSL (SEQ ID NO: 73), and SSRTRRETQL (SEQ ID NO: 74).
17. The method of claim 1 , wherein the subject expresses the MHC encoded by the HLA A24:02 allele, and wherein the amino acid sequence is encoded by the E7 gene of HPV-16 and comprises the sequence of RAHYNIVTF (SEQ ID NO: 83).
18. The method of claim 1 , wherein the subject expresses the MHC encoded by the HLA A24:02 allele, and wherein the amino acid sequence is encoded by the E6 gene of HPV-16 and comprises the sequence of MHQKRTAMF (SEQ ID NO: 66).
19. The method of claim 15 , wherein the amino acid sequence comprises a sequence of CVYCKQQLL (SEQ ID NO: 51).
20. The method of claim 15 , wherein the amino acid sequence comprises a sequence of DKKQRFHNI (SEQ ID NO: 54).
21. The method of claim 15 , wherein the amino acid sequence comprises a sequence of EYRHYCYSL (SEQ ID NO: 55).
22. The method of claim 15 , wherein the amino acid sequence comprises a sequence of MHQKRTAMF (SEQ ID NO: 66).
23. The method of claim 15 , wherein the amino acid sequence comprises a sequence of SEYRHYCYSL (SEQ ID NO: 73).
24. The method of claim 15 , wherein the amino acid sequence comprises a sequence of SSRTRRETQL (SEQ ID NO: 74).
Assignments (2)
MERGER AND CHANGE OF NAME
Recorded Jun 4, 2020
From: NEON THERAPEUTICS, INC.; BIONTECH US INC.
To: BIONTECH US INC.
Reel/Frame 052842/0786 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 13, 2019
From: ROONEY, MICHAEL
To: NEON THERAPEUTICS, INC.
Reel/Frame 051289/0227 →
Continuity (4)
Provisional Application
62480593
· Apr 3, 2017
Provisional Application
62480596
· Apr 3, 2017
Provisional Application
62480597
· Apr 3, 2017
References Cited (400)
US 4235871A
· Papahadjopoulos et al.
· 1980
[cited by applicant]
US 4501728A
· Geho et al.
· 1985
[cited by applicant]
US 4683195A
· Mullis et al.
· 1987
[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 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 5973007A
· Demarchez et al.
· 1999
[cited by applicant]
US 6406705B1
· Davis et al.
· 2002
[cited by applicant]
US 7026443B1
· Sette
· 2006
[cited by examiner]
US 8252893B2
· Kim et al.
· 2012
[cited by applicant]
US 8501167B2
· Apelian et al.
· 2013
[cited by applicant]
US 8999937B2
· Srinivasan
· 2015
[cited by applicant]
US 9862927B2
· Banchereau et al.
· 2018
[cited by applicant]
US 20040029114A1
· Mack et al.
· 2004
[cited by applicant]
US 20040076955A1
· Mack et al.
· 2004
[cited by applicant]
US 20040087478A1
· Gillen et al.
· 2004
[cited by applicant]
US 20050222062A1
· Arai et al.
· 2005
[cited by applicant]
US 20090270482A1
· Schuebeler et al.
· 2009
[cited by applicant]
US 20100105051A1
· Lillie et al.
· 2010
[cited by applicant]
US 20110092388A1
· Lillie et al.
· 2011
[cited by applicant]
US 20120288509A1
· Schuebeler et al.
· 2012
[cited by applicant]
US 20130210014A1
· Sharman
· 2013
[cited by applicant]
US 20130323279A1
· Nixon et al.
· 2013
[cited by applicant]
US 20140056986A1
· Desai et al.
· 2014
[cited by applicant]
US 20160252511A1
· Czemiecki et al.
· 2016
[cited by applicant]
US 20160317654A1
· Noelle et al.
· 2016
[cited by applicant]
US 20160331822A1
· Hacohen et al.
· 2016
[cited by applicant]
US 20160331834A1
· Mondoulet et al.
· 2016
[cited by applicant]
US 20170204140A1
· Suphioglu
· 2017
[cited by applicant]
US 20170261508A1
· Czerniecki et al.
· 2017
[cited by applicant]
US 20190099475A1
· Benz et al.
· 2019
[cited by applicant]
CA 2343602A1
· 2001
[cited by applicant]
CN 1299769C
· 2007
[cited by applicant]
CN 101885778B
· 2013
[cited by applicant]
CN 105693828A
· 2016
[cited by applicant]
DE 102008010954A1
· 2009
[cited by applicant]
EP 1338606A1
· 2003
[cited by applicant]
EP 1498145A1
· 2005
[cited by applicant]
EP 2105511A1
· 2009
[cited by applicant]
EP 2390363A1
· 2011
[cited by applicant]
EP 1827385B1
· 2013
[cited by applicant]
JP 2019513373A
· 2019
[cited by applicant]
WO WO9106309A1
· 1991
[cited by applicant]
WO WO9324640A2
· 1993
[cited by applicant]
WO WO9403205A1
· 1994
[cited by applicant]
WO WO9420127A1
· 1994
[cited by applicant]
WO WO9507707A1
· 1995
[cited by applicant]
WO WO9618372A2
· 1996
[cited by applicant]
WO WO20000587A3
· 2000
[cited by applicant]
WO WO0066153A1
· 2000
[cited by applicant]
WO W02001000225
· 2001
[cited by applicant]
WO WO0119408A1
· 2001
[cited by applicant]
WO WO2001055177
· 2001
[cited by applicant]
WO WO2004011650A2
· 2004
[cited by applicant]
WO WO2004037175A2
· 2004
[cited by applicant]
WO WO2006121168A1
· 2006
[cited by applicant]
WO WO2007049737A1
· 2007
[cited by applicant]
WO WO2008096831A1
· 2008
[cited by applicant]
WO WO2010033949A1
· 2010
[cited by applicant]
WO WO2011146862A1
· 2011
[cited by applicant]
WO WO2012079000A1
· 2012
[cited by applicant]
WO WO2012095639A2
· 2012
[cited by applicant]
WO WO2012101112A1
· 2012
[cited by applicant]
WO WO2012159643A1
· 2012
[cited by applicant]
WO WO2012159754A2
· 2012
[cited by applicant]
WO WO2013026027A1
· 2013
[cited by applicant]
WO WO2013039889A1
· 2013
[cited by applicant]
WO WO2013086464A1
· 2013
[cited by applicant]
WO WO2013123031A2
· 2013
[cited by applicant]
WO WO2013151672A2
· 2013
[cited by applicant]
WO WO2013166321A1
· 2013
[cited by applicant]
WO WO2013173223A1
· 2013
[cited by applicant]
WO WO2013176915A1
· 2013
[cited by applicant]
WO WO2014011987A1
· 2014
[cited by applicant]
WO WO2014012051A1
· 2014
[cited by applicant]
WO WO2014018863A1
· 2014
[cited by applicant]
WO WO2014056986A1
· 2014
[cited by applicant]
WO WO2014134165A1
· 2014
[cited by applicant]
WO WO2014150924A2
· 2014
[cited by applicant]
WO WO2014172606A1
· 2014
[cited by applicant]
WO WO2014184744A1
· 2014
[cited by applicant]
WO WO2014191128A1
· 2014
[cited by applicant]
WO WO2014197369A1
· 2014
[cited by applicant]
WO WO2015085233A1
· 2015
[cited by applicant]
WO WO2015107081A1
· 2015
[cited by applicant]
WO WO2016011487A1
· 2016
[cited by applicant]
WO WO2016020710A1
· 2016
[cited by applicant]
WO WO2016100975A1
· 2016
[cited by applicant]
WO WO2016141324A2
· 2016
[cited by applicant]
WO WO2016144976A1
· 2016
[cited by applicant]
WO WO2016156478A1
· 2016
[cited by applicant]
WO WO2016187508A2
· 2016
[cited by applicant]
WO WO2016203577A1
· 2016
[cited by applicant]
WO WO2017004153A1
· 2017
[cited by applicant]
WO WO2017011710A2
· 2017
[cited by applicant]
WO WO2017069958A2
· 2017
[cited by applicant]
WO WO2017074788A1
· 2017
[cited by applicant]
WO WO2017088012A1
· 2017
[cited by applicant]
WO WO2017139694A1
· 2017
[cited by applicant]
WO WO2017148888A1
· 2017
[cited by applicant]
WO WO2017173321A1
· 2017
[cited by applicant]
WO WO2017180989A2
· 2017
[cited by applicant]
WO WO2017184590A1
· 2017
[cited by applicant]
WO WO2018037416A1
· 2018
[cited by applicant]
WO WO2018078053A1
· 2018
[cited by examiner]
WO WO2018140391A1
· 2018
[cited by applicant]
Ponti et al., Critical Reviews in Clinical Laboratory Sciences 2023, vol. 60, No. 8, 640-650 (Year: 2023).
[cited by examiner]
Pierce et al., Viruses 2024, 16, 803. https:/ /doi.org/10.3390/v16050803 (Year: 2024).
[cited by examiner]
Allison, “The Mode of Action of Immunological Adjuvants,” Dev Biol Stand, 92: 3-11 (1998).
[cited by applicant]
Coleman et al.: Human papillomavirus type 16 viral load is decreased following a therapeutic vaccination. Cancer Immunology Immunotherapy. 65(5):563-573 (2016).
[cited by applicant]
European Application No. 18720480.5 Search Report dated Nov. 8, 2023.
[cited by applicant]
Greenfield et al.: A phase I dose-escalation clinical trial of a peptidebased human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cer…
[cited by applicant]
Yang et al.: Perspectives for therapeutic HPV vaccine development. Journal of Biomedical Science. 23(1):1-19 (2016).
[cited by applicant]
Brito, Luis et al., Self-amplifying mRNA Vaccines,Adv. Genet. 2015; 89:179-233.
[cited by applicant]
Busch et al., Degenerate binding of immunogenic peptides to HLA-DR proteins on B cell surfaces, Int. Immunol. 2:443 (1990).
[cited by applicant]
Cai, A et al., Mutated BCR-ABL Generates Immunogenic T-Cell Epitopes in CML Patients, Clinical Cancer Research vol. 18, No. 20, Aug. 21, 2012.
[cited by applicant]
Ceppellini et al., Binding of labelled influenza matrix peptide to Hla Dr in living B lymphoid cells, Nature 339:392 (1989).
[cited by applicant]
Cerundolo et al., The binding affinity and dissociated rates of peptides for class I major histocompatibility complex molecules, Eur. Immunol., 21:2069-75 (1991).
[cited by applicant]
Christnick et al., Peptide binding to class 1MHC on living cells and quantitation of complexes required for CTL lysis, Nature 352:67 (1991).
[cited by applicant]
Del Guercio, M.F., et al., Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype, J. Immunol. 154:685-693 (1995).
[cited by applicant]
Deres, K., et al., In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic peptide vaccine, Nature 342:561, 1989.
[cited by applicant]
Dupont, J., et al., Artificial Antigen-Presenting Cells Transduces with Telomerase Efficiently Expand Epitope-Specific, Human Leukocyte Antigen-Restricted Cytotoxic T Cells, 2005 Cancer Res 65:5417-5427.
[cited by applicant]
Dupuis, M., et al., Dendritic Cells Internalize Vaccine Adjuvant after Intramuscular Injection, Cell Immunol. 1998; 186(1):18-27.
[cited by applicant]
Felgner et al., Lipofection: A highly efficient, lipid-mediated DNA-transfection procedure, Proc. Natl. Acad. Sci. USA 84: 7413-7414 (1987).
[cited by applicant]
Fritsch, Edward F et al., HLA-binding properties of tumor neoepitopes in humans, Cancer Immunology Research, Jun. 2014, vol. 2, No. 6, Jun. 2014, pp. 522-529.
[cited by applicant]
Gabrilovich, et al., “IL-12 and Mutant P53 Peptide-Pulsed Dendritic Cells for the Specific Immunotherapy of Cancer,” J Immunother Emphasis Tumor Immunol, 19(6): 414-418 (1997).
[cited by applicant]
Gamvrellis, A et al., Vaccines that facilitate antigen entry into dendritic cells, Immunol & Cell Biol. 2004; 82: 506-516.
[cited by applicant]
Geall, A.J., et al. Nonviral delivery of self-amplifying RNA vaccines. Proc Natl Acad Sci U S A. Sep. 4, 2012;109(36):14604-9.
[cited by applicant]
Hammer, J. et al., Precise prediction of major histocompatibility complex class Il-peptide interaction based on peptide side chain scanning, J. Exp. Med. 180:2353 (1994).
[cited by applicant]
Hill et al., Conformational and structural characteristics of peptides binding to HLA-DR molecules, J. Immunol. 147:189 (1991).
[cited by applicant]
Hill et al., Exploration of requirements for peptide binding to HLA DRB10101 and DRBI*0401, J. Immunol. 152, 2890 (1994).
[cited by applicant]
International Search Report and Written Opinion for PCT/US16/033452 (WO2016/187508).
[cited by applicant]
International Search Report and Written Opinion for PCT/US17/25462 (WO2017/173321).
[cited by applicant]
International Search Report and Written Opinion for PCT/US18/025933 (WO2018/187356).
[cited by applicant]
Khilko, Sergi N. et al., Direct Detection of Major Histocompatibility Complex Class I Binding to Antigenic Peptides Using Surface Plasmon Resonance, J. Biol. Chem. 268:15425 (1993).
[cited by applicant]
Koide, Shohei et al., Target-Binding Proteins Based on the 10th Human Fibronectin Type III Domain (10Fn3), Methods Enzymol. 2012;503:135-56.
[cited by applicant]
Krieg, Arthur M., Therapeutic potential of Toll-like receptor 9 activation, Nature Reviews, Drug Discovery, 5, Jun. 2006, 471-484).
[cited by applicant]
Ljunggren et al., Empty MHC class I molecules come out in the cold, Nature 346:476 (1990).
[cited by applicant]
Mannino & Gould-Fogerite, Lipsome mediated gene transfer, BioTechniques 6(7): 682-691 (1988).
[cited by applicant]
Matteucci, et al. Synthesis of deoxyoligonucleotides on a polymer support. J. Am. Chem. Soc. 103(11):3185-3191, 1981.
[cited by applicant]
Morgan, R. A., et al., (2006), Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes, Science 314:126-129.
[cited by applicant]
Mosca, Paul J. et al., Dendritic cell vaccines, Frontiers in Bioscience, (2007) 12:4050-4060).
[cited by applicant]
Panelli, M. C., et al. (2000), A Tumor-Infiltrating from a Melanoma Metastasis with Decreased Expression of Melanoma Differentiation Antigens Recognizes MAGE-12, J Immunol 164:4382-4392.
[cited by applicant]
Panelli, M. C., et al., (2000), Expansion of Tumor-T Cell Pairs from Fine Needle Aspirates of Melanoma Metastases, J Immunol 164:495-504.
[cited by applicant]
Papanicolaou, G. A., et al., (2003) , Rapid expansion of cytomegalovirus-specific cytotoxic T lymphocytes by artificial antigen-presenting cells expressing a single HLA allele, Blood 102:2498-2505).
[cited by applicant]
Parker et al., The beta 2-microglobulin dissociation rate is an accurate measure of the stability of MHC Class I heterotrimers and depends on which peptide is bound, J. Immunol. 149:1896 (1992).
[cited by applicant]
Reay, Phillip A. et al., (1992), pH dependence and exchange of high and low responder peptides binding to a class II MHC molecule, EMBO J. 11:2829-39.
[cited by applicant]
Rooney, M. et al., Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. Jan. 15, 2015; 160(1-2): 48-61.doi: 10.1016/j.cell.2014.12.033.
[cited by applicant]
Sadelain et al. Targeting tumours with genetically enhanced T lymphocytes. Nat Rev Cancer 3(1):35-45 (2003).
[cited by applicant]
Salter, Russell D. et al., Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids, Immunogenetics 21:235-46 (1985).
[cited by applicant]
Salter, Russell, et al., Impaired assembly and transport of HLA-A and -B antigens in a mutant TxB cell hybrid, EMBO J. 5:943-49 (1986).
[cited by applicant]
Schumacher, Ton N.M., et al., (1990), Direct binding of peptide to empty MHC Class I molecules on intact cells and in vitro, Cell 62:563 (1990).
[cited by applicant]
Sette, et al., (1994) Peptide binding to the most frequent HLA-A class I alleles measured by quantitative molecular bindings assays, Mol. Immunol. 31:813.
[cited by applicant]
Sioud, Mouldy et al., A novel peptide carrier for efficient targeting of antigens and nucleic acids to dendritic cells, FASEB J 27: 3272-3283 (2013).
[cited by applicant]
Southwood, Scott et al., Several Common HLA-DR Types Share Largely Overlapping Peptide Binding Repertoires, J. Immunol. 160:3363-3373, 1998).
[cited by applicant]
Stover, C.K. et al., New use of BCG for recombinant vaccines, Nature 351:456-460 (1991).
[cited by applicant]
Szoka, Comparative properties and methods of preparation of lipid vesicles (liposomes);Ann Rev Biophys Eng 9:467 (1980).
[cited by applicant]
Townsend, A., et al., Assembly of MHC Class I molecules analyzed in vitro, Cell 62:285, Jul. 27, 1990.
[cited by applicant]
Verhoef, et al., Des-enkephalin-Y-Error! Hyperlink reference not valid.endorphin (DEyE): Biotransformation in rat, dog, and human plasma, Eur. J. Drug Metab. Pharmacokinetics 11:291 (1986).
[cited by applicant]
Wolff et al. Direct gene transfer into mouse muscle in vivo. Science 247:1465-1468 (1990).
[cited by applicant]
Jaravine, V. et al., “Assessment of cancer and virus antigens for cross-reactivity in human tissues,” Bioinformatics, 2016, vol. 33, No. 1, pp. 104-111.
[cited by applicant]
Karran, L. et al., “Expression of a family of complementary-strand transcripts in Epstein-Barr virus-infected cells,” Proc. Nati. Acad. Sci. USA, 1992, vol. 89, No. 17, pp. 8058-8062.
[cited by applicant]
Riemer, A.B. et al., “A conserved E7-derived cytotoxic T lymphocyte epitope expressed on human papillomavirus 16-transformed HLA-A2+ epithelial cancers,” J Biol Chem., 2010, vol. 285, No. 38, pp. 29608-29622.
[cited by applicant]
Yao et al.: HPV-16 E6 and E7 protein T cell epitopes prediction analysis based on distributions of HLA-A loci across populations: An in silico approach. Elsevier, Vaccine 31(18): 2289-2294 (2013).
[cited by applicant]
Acevedo et al., Analysis of the mechanisms mediating tumor-specific changes in gene expression in human liver tumors, Cancer Res, 68(8):2641-2651 (2008).
[cited by applicant]
Acknowledgment of Receipt dated Jun. 28, 2017 for Response to Notices of Opposition of EP2569633.
[cited by applicant]
Adams, Toll-like receptor agonists in cancer therapy, Immunotherapy, 1(6):949-964 (2009).
[cited by applicant]
Adomas, et al. “Breast tumor specific mutation in GATA3 affects physiological mechanisms regulating transcription factor turnover,” BMC Cancer 2014, 14:278.
[cited by applicant]
Akiyama et al., GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer, Mol Cell Biol, 23:8429-8439 (2003).
[cited by applicant]
Alarcon et al., DNA vaccines: technology and application as anti-parasite and anti-microbial agents, Advances in Parasitology, 42:343-410 (1999).
[cited by applicant]
Albert et al., “Direct Selection of Human Genomic Loci by Microarray Hybridization,” Nat Methods, 4(11): 903-905 (2007).
[cited by applicant]
Ali et al., In situ regulation of DC subsets and T cells mediates tumor regression in mice, Cancer Immunotherapy, 1(8):1-10 (2009).
[cited by applicant]
Ali et al., “Infection-mimicking materials to program dendritic cells in situ,” Nat Mater, 8:151-8 (2009).
[cited by applicant]
Almeida et al., “CTdatabase: a knowledge-base of high- throughput and curated data on cancer-testis antigens,” Nucleic acids research, 37:D816-819 (2008).
[cited by applicant]
Altman et al., Phenotypic analysis of antigen-specific T lymphocytes, Science, 274(5284):94-6 (1996).
[cited by applicant]
Alvarez, Present and future evolution of advanced breast cancer therapy, Breast Cancer Research, 12(Suppl 2):S1 (2010).
[cited by applicant]
Alyea et al., “Toxicity and Efficacy of Defined Doses of CD4+ Donor Lymphocytes for Treatment of Relapse After Allogeneic Bone Marrow Transplant,” Blood, 91(10):3671-3680 (1998).
[cited by applicant]
Amara et al., “Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine,” Science, 292(5514):69-74 (2001).
[cited by applicant]
Amato et al., “Vaccination of metastatic renal cancer patients with MVA-5T4: a randomized, double-blind, placebo-controlled phase III study,” Clin Can Res, 16(22):5539-47 (2010).
[cited by applicant]
Amato et al., “Vaccination of renal cell cancer patients with modified vaccinia ankara delivering tumor antigen 5T4 (TroVax) administered with interleukin 2: a phase II trial,” Clin Cancer Res, 14(22):7504-10 (2008).
[cited by applicant]
Anders et al., HTSeq-A Python framework to work with high-throughput sequencing data, Bioinformatics, 31(2):166-169 (2015).
[cited by applicant]
Andersen et al., Parallel detection of antigen-specific T cell responses by combinatorial encoding of MHC multimers, Nature protocols, 7(5):891-902 (2012).
[cited by applicant]
Anderson et al., “Next Generation DNA Sequencing and the Future of Genomic Medicine,” Genes, 1:38-69 (2010).
[cited by applicant]
Andreatta et al., Gapped sequence alignment using artificial neural networks: application to the MHC class I system, Bioinformatics 32(4):511-517 (2016).
[cited by applicant]
Annunziata et al., “Frequent Engagement of the Classical and Alternative NF-KB Pathways by Diverse Genetic Abnormalities in Multiple Myeloma,” Cancer Cell, 12(2):115-130 (2007).
[cited by applicant]
Antoine et al., “The complete genomic sequence of the modified vaccinia Ankara strain: comparison with other orthopoxviruses,” Virology, 244(2):365-96 (1998).
[cited by applicant]
Antonis et al., “Vaccination with recombinant modified vaccinia virus Ankara expressing bovine respiratory syncytial virus (bRSV) proteins protects calves against RSV challenge,” Vaccine, 25(25):4818-4827 (2007).
[cited by applicant]
Attia et al., “Autoimmunity Correlates With Tumor Regression in Patients With Metastatic Melanoma Treated with Anti-Cytotoxic T-Lymphocyte Antigen-4,” J Clin Oncol, 23.(25):6043-6053 (2005).
[cited by applicant]
Aucouturier et al., “Adjuvants designed for veterinary and human vaccines,” Vaccine, 19(17-19):2666-2672 (2001).
[cited by applicant]
Austen et al., “Mutations in the ATM Gene Lead to Impaired Overall and Treatment-Free Survival that is Independent of IGVH Mutation Status in Patients with B-CLL,” Blood, 106(9):3175-3182 (2005).
[cited by applicant]
Ausubel, A botanical macroscope, Proceedings of the National Academy of Sciences, 106(31):12569-12570 (2009).
[cited by applicant]
Avogadri et al. “Modulation of CTLA-4 and GITR for Cancer Immunotherapy,” Curr Top Microbiol Immunol, 344:211 (2011).
[cited by applicant]
Azvolinsky et al., “PD-1 Inhibitor MK-3475 Again Shows Promise in Advanced Melanoma,” Cancer Network, 2013. [Retrieved online] http://www.cancernetwork.com/melanoma/pd-1-inhibitor-mk-3475-again-shows-promise-advanced-me…
[cited by applicant]
Bachem et al., “Superior antigen cross-presentation and XCR1 expression define human CD11c+ CD141+ cells as homologues of mouse CD8+ dendritic cells,” Journal of Experimental Medicine, 207(6):1273-1281 (2010).
[cited by applicant]
Bachireddy et al., “Reversal of in situ T cell exhaustion during effective human anti-leukemia responses to donor lymphocyte infusion,” Blood, 123(9):1412-1421 (2013).
[cited by applicant]
Backert et al., Immunoinformatics and epitope prediction in the age of genomic medicine, Genome Medicine, 7:119 (2015).
[cited by applicant]
Baden et al., “First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 FfIV-1 Env vaccine (IPCAVD 001),” J Infect Dis, 207(2):240-247 (2012).
[cited by applicant]
Balaggan et al., “Stable and efficient intraocular gene transfer using pseudotyped EIAV lentiviral vectors,” J Gene Med, 8:275-285 (2005).
[cited by applicant]
Balakrishnan et al., “Novel Somatic and Germline Mutations in Cancer Candidate Genes in Glioblastoma, Melanoma, and Pancreatic Carcinoma,” Cancer Res, 67: 3545-3550 (2007).
[cited by applicant]
Balazsi et al., Cellular decision making and biological noise: from microbes to mammals, Cell, 144(6):910-925 (2011).
[cited by applicant]
Balch et al., Final version of 2009 AJCC melanoma staging and classification, Journal of clinical oncology, 27(36):6199-6206 (2009).
[cited by applicant]
Barbie et al., Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1, Nature, 462:108-112 (2009).
[cited by applicant]
Barretina et al., The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity, Nature, 483:603-607 (2012).
[cited by applicant]
Baskar et al., “Autologous Lymphoma Vaccines Induce Human T Cell Responses Against Multiple, Unique Epitopes,” J Clin Invest, 113:1498-1510 (2004).
[cited by applicant]
Bassani-Sternberg et al., Mass Spectrometry of Human Leukocyte Antigen Class | Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation, Mol Cell Proteomics, 14:658-673 (2015).
[cited by applicant]
Baurain et al., “High Frequency of Autologous Anti-Melanoma CTL Directed Against an Antigen Generated by a Point Mutation in a New Helicase Gene,” J Immunol, 164: 6057-6066 (2000).
[cited by applicant]
Baylin, A decade of exploring the cancer epigenome-biological and translational implications, Nat Rev Cancer, 11:726-734 (2005).
[cited by applicant]
Baylin, DNA methylation and gene silencing in cancer, Nat Clin Pract Oncol 2, Suppl 1, S4-11 (2005).
[cited by applicant]
Beck et al., “Enterocolitis in Patients With Cancer After Antibody Blockade of Cytotoxicity TLymphocyte-Associated Antigen 4,” J Clin Oncol, 24(15): 2283-2289 (2006).
[cited by applicant]
Behrends et al., Network organization of the human autophagy system, Nature, 466(7302):68-76 (2010).
[cited by applicant]
Bellucci et al., “Complete Response to Donor Lymphocyte Infusion in Multiple Myeloma is Associated with Antibody Responses to Highly Expressed Antigens,” Blood, 103: 656-663 (2004).
[cited by applicant]
Benson, Tandem repeats finder: a program to analyze DNA sequences, Nucleic acids research, 27(2):573-580 (1999).
[cited by applicant]
Bentley et al., “Accurate Whole Human Genome Sequencing using Reversible Terminator Chemistry,” Nature, 456(7218): 53-59 (2008).
[cited by applicant]
Benton et al., Screening lambdagt recombinant clones by hybridization to single plaques in situ, Science, 196(4286):180-182 (1977).
[cited by applicant]
Berg et al., Detection of artifacts and peptide modifications in liquid chromatography/mass spectrometry data using two-dimensional signal intensity map data visualization, Rapid Commun Mass Spectrom, 20(10):1558-1562 (…
[cited by applicant]
Berger et al., Melanoma genome sequencing reveals frequent PREX2 mutations, Nature, 485(7399):502 (2012).
[cited by applicant]
Berger et al., The genomic complexity of primary human prostate cancer, Nature, 470:214-220 (2011).
[cited by applicant]
Berman et al., Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains, Nat Genet, 44:40-46 (2012).
[cited by applicant]
Bettelli et al., “TH-17 cells in the circle of immunity and autoimmunity,” Nat Immunol, 8:345-350 (2007).
[cited by applicant]
Bhardwaj et al., “TLR Agonists: Are They Good Adjuvants?,” Cancer J, 16:382-391 (2010).
[cited by applicant]
Bindea et al., Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer, Immunity, 39:782-795 (2013).
[cited by applicant]
Bird, DNA methylation patterns and epigenetic memory, Genes Dev, 16:6-21 (2002).
[cited by applicant]
Birrell et al., A genome-wide screen in Saccharomyces cerevisiae for genes affecting UV radiation sensitivity, Proceedings of the National Academy of Sciences 98(22):12608-12613 (2001).
[cited by applicant]
Bishop et al., APOBEC-mediated editing of viral RNA, Science, 305:645 (2004).
[cited by applicant]
Bisht et al., “Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice,” Proc Natl Acad Sci, 101:6641-46 (2004).
[cited by applicant]
Blanchard et al., “Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine,” Journal of General Virology, 79(5):11…
[cited by applicant]
Bock et al., BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing, Bioinformatics, 21:4067-4068 (2005).
[cited by applicant]
Bock et al., “Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines,” Cell, 144:439-452 (2011).
[cited by applicant]
Boen et al., Identification of T Cell Ligands in a Library of Peptides Covalently Attached to Hla- DR4, J Immunol, 165:2040-2047 (2000).
[cited by applicant]
Bogunovic et al., TLR4 engagement during TLR3-induced proinflammatory signaling in dendritic cells promotes IL-10-mediated suppression of antitumor immunity, Cancer Res, 71(16):5467-5476 (2011).
[cited by applicant]
Bohm et al., DNA vector constructs that prime hepatitis B surface antigen-specific cytotoxic T lymphocyte and antibody responses in mice after intramuscular injection. Journal of immunological methods 193(1): 29-40 (199…
[cited by applicant]
Boisgerault et al., Definition of the HLA-A29 peptide ligand motif allows prediction of potential T-cell epitopes from the retinal soluble antigen, a candidate autoantigen in birdshot retinopathy, PNAS, 93:3466-3470 (19…
[cited by applicant]
Boisguerin et al., “Translation of genomis-guided RNA-based personalised cancer vaccaines: towards the bedside,” British J Cancer, 111:1469-1475 (2014).
[cited by applicant]
Boller et al. Characterization of the antibody response specific for the human endogenous retrovirus HTDV/HERV-K, Journal of virology, 7I(6):4581-4588 (1997).
[cited by applicant]
Boni et al. “Adoptive transfer of allogeneic tumor-specific T cells mediates effective regression of large tumors across major histocompatibility barriers,” Blood, 112(12):4746-4754 (2008).
[cited by applicant]
Boon et al., “Human T Cell Responses Against Melanoma,” Annu Rev Immunol, 24: 175-208 (2006).
[cited by applicant]
Boon, “Toward a Genetic Analysis of Tumor Rejection Antigens,” Adv Cancer Res, 58:177-210 (1992).
[cited by applicant]
Boquest et al., Isolation and transcription profiling of purified uncultured human stromal stem cells: alteration of gene expression after in vitro cell culture, Molecular biology of the cell, 16(3):1131-1141 (2005).
[cited by applicant]
Boscardin et al., “Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses,” Journal of Experimental Medicine, 203(3):599-606 (2006).
[cited by applicant]
Bourdetsky et al., The nature and extent of contributions by defective ribosome products to the HLA peptidome, PNAS, III, E1591-E1599 (2014).
[cited by applicant]
Bowerman et al., “Engineering the binding properties of the T cell receptor:peptide:MHC ternary complex that governs T cell activity,” Mol Immunol, 46(15):3000-3008 (2009).
[cited by applicant]
Boyle et al., “Gel-free multiplexed reduced representation bisulfite sequencing for large-scale DNA methylation profiling,” Genome Biol, 13:R92 (2012).
[cited by applicant]
Boyle et al., “Tapasin-related protein TAPBPR is an additional component of the MHC class I presentation pathway,” Proceedings of the National Academy of Sciences, 110: 3465-3470 (2013).
[cited by applicant]
Bozic et al., Dynamics of targeted cancer therapy, Trends Mol Med, 18:311-316 (2012).
[cited by applicant]
Bozic et al., Evolutionary dynamics of cancer in response to targeted combination therapy, Elife, 2:e00747 (2013).
[cited by applicant]
Brahmer et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455-2465 (2012).
[cited by applicant]
Brandle et al., “A Mutated HLA-A2 Molecule Recognized by Autologous Cytotoxic T Lymphocytes on a Human Renal Cell Carcinoma,” J Exp Med, 183: 2501-2508 (1996).
[cited by applicant]
Bremel et al., An integrated approach to epitope analysis I: Dimensional reduction, visualization and prediction of MHC binding using amino acid principal components and regression approaches, Immunome Res, 6:7 (2010).
[cited by applicant]
Brinckerhoff et al., “Melanoma Vaccines,” Curr Opin Oncol, 12:163-173 (2000).
[cited by applicant]
Broad Institute Article, Jan. 29, 2009, “Turning Cancer's Strength Into Weakness,” (2009).
[cited by applicant]
Brochier et al., “Large-scale eradication of rabies using recombinant vaccinia-rabies vaccine,” Nature, 354:520-552 (1991).
[cited by applicant]
Brown et al., Integrative genomic analysis implicates gain of PIK3CA at 3g26 and MYC at 8q24 in chronic lymphocytic leukemia, Clin Cancer Res, 8:3791-802 (2012).
[cited by applicant]
Brown et al., “Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival,” Genome Res, 24(5):743-750 (2014).
[cited by applicant]
Brunsvig et al., “Telomerase Peptide Vaccination: A Phase I/II Study in Patients with Non-Small Cell Lung Cancer,” Cancer Immunol Immunother, 55(12): 1553-1564 (2006).
[cited by applicant]
Buchschacher et al., “Human immunodeficiency virus vectors for inducible expression of foreign genes.” Journal of virology, 66(5):2731-2739 (1992).
[cited by applicant]
Buckwalter et al., “It is the antigen(s), stupid' and other lessons from over a decade of vaccitherapy of human cancer,” Seminar in Immunology, 20(5):296-300 (2008).
[cited by applicant]
Buller et al., “Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype,” Nature, 317:813-815 (1985).
[cited by applicant]
Buller et al., “Deletion of the vaccinia virus growth factor gene reduces virus virulence,” Journal of virology, 62(3):866-874 (1988).
[cited by applicant]
Burger et al., “Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study,” Lancet Oncology, 15(10):1090-1099 (2014).
[cited by applicant]
Burger et al., B cell receptor signaling in chronic lymphocytic leukemia, Trends Immunol, 34:592-601 (2013).
[cited by applicant]
Burkhardt et al., Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells, The Journal of clinical investigation, 123(9):3756-3765 (2013).
[cited by applicant]
Buser et al., Unique composite hematolymphoid tumor consisting of a pro-T lymphoblastic lymphoma and an indeterminate dendritic cell tumor: evidence for divergent common progenitor cell differentiation, Pathobiology, 81…
[cited by applicant]
Byrd et al., Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia, The New England journal of medicine, 369:32-42 (2013).
[cited by applicant]
Bystryn et al., Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine, Clin Cancer Res, 7(7):1882-1887 (2001).
[cited by applicant]
Cahill et al., 450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments, Leukemia, 27:150-158 (2013…
[cited by applicant]
Cai et al., “Peptides Derived From Mutated BCR-ABL Elicit T Cell Immunity In CML Patients,” BLOOD, 116(21): 388-388 (2010).
[cited by applicant]
Cancer Genome Atlas Network, Comprehensive molecular portraits of human breast tumours, Nature, 490:61-70 (2012).
[cited by applicant]
Cancer Genome Atlas Research Network, Comprehensive genomic characterization defines human glioblastoma genes and core pathways, Nature, 455(7216):1061-1068 (2008).
[cited by applicant]
Cancer Genome Atlas Research Network, “Comprehensive genomic characterization of squamous cell lung cancers,” Nature, 489, 519-525 (2012).
[cited by applicant]
Cancer Genome Atlas Research Network, Comprehensive molecular characterization of clear cell renal cell carcinoma, Nature, 499:43-49 (2013).
[cited by applicant]
Cancer Genome Atlas Research Network, Comprehensive molecular characterization of gastric adenocarcinoma, Nature, 513:202-209 (2014).
[cited by applicant]
Cancer Genome Atlas Research Network, Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia, New England Journal of Medicine, 368(22):2059-2074 (2013).
[cited by applicant]
Cancer Genome Atlas Research Network, Integrated genomic analyses of ovarian carcinoma, Nature, 474: 609-615 (2011).
[cited by applicant]
Carithers, L.J.., et al. (2015). A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project. Biopreservation Biobanking 13, 311-319.
[cited by applicant]
Caron et al., Analysis of MHC immunopeptidomes using mass spectrometry, Mol Cell Proteomics (2015), doi: 10.1074/mcp.0115.052431.
[cited by applicant]
Carpten et al., “A transforming mutation in the pleckstrin homology domain of AKT1 in cancer,” Nature, 448(26):439-444 (2004).
[cited by applicant]
Carreno et al., A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells, Science, 348(6239):803-808 (2015).
[cited by applicant]
Carreno et al., “IL-12p70-producing patient DC vaccine elicits Tcl-polarized immunity,” Journal of Clinical Investigation, 123(8):3383-94 (2013).
[cited by applicant]
Carter et al., Absolute quantification of somatic DNA alterations in human cancer, Nat Biotechnol, 30:413-21 (2012).
[cited by applicant]
Carter et al., Accurate estimation of homologue-specific DNA concentration-ratios in cancer samples allows long-range haplotyping, Nature Precedings, 59-87 (2011).
[cited by applicant]
Carter et al., “Identification and validation of cell surface antigens for antibody targeting in oncology,” Endocrine-Related Cancer, 11:659-687 (2004).
[cited by applicant]
Caskey et al., “Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans,” The Journal of experimental medicine, 208(12):2357-2366 (2011).
[cited by applicant]
Castle et al., Exploiting the mutanome for tumor vaccination, Cancer research, 72(5):1081-1091 (2012).
[cited by applicant]
CBOL Plant Working Group, A DNA barcode for land plants, PNAS, 106(31):12794-12797 (2009).
[cited by applicant]
Chang et al., Immune selection of hot-spot beta 2-microglobulin gene mutations, HLA-A2 allospecificity loss, and antigen-processing machinery component down-regulation in melanoma cells derived from recurrent metastases…
[cited by applicant]
Chang et al., “Peptide length-based prediction of peptide-MHC class II binding,” Bioinformatics, 22(22): 2761-2767 (2006).
[cited by applicant]
Chapman et al., Initial genome sequencing and analysis of multiple myeloma, Nature, 471:467-472 (2011).
[cited by applicant]
Chatila, “The Regulatory T Cell Transcriptosome: E Pluribus Unum,” Immunity, 27(5):693-695 (2007).
[cited by applicant]
Cheever, Twelve immunotherapy drugs that could cure cancers, Immunological reviews, 222:357-368 (2008).
[cited by applicant]
Chen, et al. “Hotspot mutations delineating diverse mutational signatures and biological utilities across cancer types,” BMC Cenomics (2016)17(Suppl 2):394.
[cited by applicant]
Chen et al., Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes, Genome Res, 20:447-457 (2010).
[cited by applicant]
Chen et al., “Langerhans Cell Sarcoma Arising from Chronic Lymphocytic Lymphoma/Small Lymphocytic Leukemia: Lineage Analysis and BRAF V600E Mutation Study,” N Am J Sci, 5:386-91 (2013).
[cited by applicant]
Chen et al., Molecular mechanisms of T cell co-stimulation and co-inhibition, Nature reviews Immunology, 13:227-242 (2013).
[cited by applicant]
Chen et al., Molecular Pharmaceutics, 3:109-111 (2010).
[cited by applicant]
Chen et al., “Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor bin…
[cited by applicant]
Chianese-Bullock et al., “Multi-peptide vaccines vialed as peptide mixtures can be stable reagents for use in peptide-based immune therapies,” Vaccine, 27(11):1764-1770 (2009).
[cited by applicant]
Chiari et al., “Two Antigens Recognized by Autologous Cytolytic T Lymphocytes on a Melanoma Result from a Single Point Mutation in an Essential Housekeeping Gene,” Cancer Res, 59:5785-5792 (1999).
[cited by applicant]
Child et al., “Insertional inactivation of the large subunit of ribonucleotide reductase encoded by vaccinia virus is associated with reduced virulence in vivo,” Virology, 174(2):625-629 (1990).
[cited by applicant]
Chim et al., Epigenetic dysregulation of the Wnt signalling pathway in chronic lymphocytic leukaemia, J Clin Pathol, 61:1214-1219 (2008).
[cited by applicant]
Chiron et al., Cell-cycle reprogramming for P13K inhibition overrides a relapse-specific C4815 Btk mutation revealed by longitudinal functional genomics in mantle cell lymphoma, Cancer Discov, 4:1022-35 (2014).
[cited by applicant]
Chowell et al., TCR contact residue hydrophobicity is a hallmark of immunogenic CD8(+) T cell epitopes, PNAS, 112:E1754-E1762 (2015).
[cited by applicant]
Christian et al., Targeting DNA double-strand breaks with TAL effector nucleases, Genetics, 186(2):757-761 (2010).
[cited by applicant]
Christianson et al., Defining human ERAD networks through an integrative mapping strategy, Nat Cell Biol, 14:93-105 (2012).
[cited by applicant]
Chroboczek et al., “The Sequence of the Genome of Adenovirus Type 5 and Its Comparison with the Genome of Adenovirus Type 2,” Virology, 186:280-285 (1992).
[cited by applicant]
Church, Genomes for all, Sci Am, 294(1):46-54 (2006).
[cited by applicant]
Cibulskis et al., ContEst: estimating cross-contamination of human samples in next-generation sequencing data, Bioinformatics, 27:2601-2602 (2011).
[cited by applicant]
Cibulskis et al. Sensitive detection of somatic point mutations in impure and heterogenous cencer samples. Nat Biotechnol 31:213-219 (2013).
[cited by applicant]
Ciofani et al., “A Validated Regulatory Network for Th17 Cell Specification,” Cell, 151(2):289-303 (2012).
[cited by applicant]
Cleveland, Lowess: A program for smoothing scatterplots by robust locally weighted regression, The American Statistician, 35:54 (1981).
[cited by applicant]
Clinical trial NCT 01970358, Patrick Ott, A Phase I Study With a Personalized NeoAntigen Cancer Vaccine in Melanoma, p. 1-6, Retrieved from https://clinicaltrials.gov/ct2/show/NCT01970358 downloaded Jun. 20, 2017.
[cited by applicant]
Coffman et al., “Vaccine Adjuvants: Putting Innate Immunity to Work,” Immunity 33:492-503 (2010).
[cited by applicant]
Cohen, et al. “Shift in GATA3 functions, and GATA3 mutations, control progression and clinical presentation in breast cancer,” Breast Cancer Research DOI 10.1186/s13058-014-0464-0.
[cited by applicant]
Conlon et al., “Mouse, but not Human STING, Binds and Signals in Response to the Vascular Disrupting Agent 5 ,6-Dimethylxanthenone-4- Acetic Acid,” Journal of Immunology, 190:5216-25 (2013).
[cited by applicant]
Consolidated Table of Documents filed in Opposition to date in Response to Notices of Opposition of EP2569633 dated Jun. 28, 2017.
[cited by applicant]
Corbett et al., “Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic,” Proc Natl Acad Sci, 105(6):2046-51 (2008).
[cited by applicant]
Coulie et al., A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma, Proc Natl Acad Sci USA, 92(17):7976-7980 (1995).
[cited by applicant]
Cox et al., “Induction of cytotoxic T lymphocytes by recombinant canarypox (ALVAC) and attenuated vaccinia (NYVAC) viruses expressing the HIV-1 envelope glycoprotein,” Virology, 195(2):845-850 (1993).
[cited by applicant]
Crozat et al., “The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8a+ dendritic cells,” Journal of Experimental Medicine, 207(6):1283-1292 (2010).
[cited by applicant]
CT-011 and p53 Genetic Vaccine for Advance Solid Tumor, National Library of Medicine, updated: Jun. 30, 2011, XP002738554.
[cited by applicant]
Daheshia et al., “Suppression of ongoing ocular inflammatory disease by topical administration of plasmid DNA encoding IL-10,” The Journal of Immunology 159(4):1945-1952 (1997).
[cited by applicant]
De et al., Aberration in DNA methylation in B-cell lymphomas has a complex origin and increases with disease severity, PLoS Genet. 9:e1003137 (2013).
[cited by applicant]
De Magalhaes et al., Next-generation sequencing in aging research: emerging applications, problems, pitfalls and possible solutions, Ageing Research Reviews, 9(3):315-323 (2010).
[cited by applicant]
De Plaen et al., “Immunogenic (tum-) Variants of Mouse Tumor P815: Cloning of the Gene of Tum- Antigen P91A and Identification of the Tum- Mutation,” PNAS, 85: 2274-2278 (1988).
[cited by applicant]
Declaration by Professor John Haanen, M.D., Ph.D.
[cited by applicant]
Declaration by Stephen Johnston filed during the prosecution of granted U.S. Pat. No. 8,796,414 Nov. 20, 2013.
[cited by applicant]
Declaration of Dr. John C. Castle executed on Nov. 9, 2016.
[cited by applicant]
Declaration of Dr Nir Hacohen on Feb. 16, 2014.
[cited by applicant]
DeLuca et al., RNA-SeQC: RNA-seq metrics for quality control and process optimization, Bioinformatics, 28:1530-2 (2012).
[cited by applicant]
Dengjel et al., “Glycan side chains on naturally presented MHC class II ligands,” J. Mass Spectrom, 40:100-104 (2005).
[cited by applicant]
Depristo et al. A framework for variation discovery and genotyping using next generation DNA sequencing data. Nat Genetics 43:491-498 (2011).
[cited by applicant]
Dermer et al., “Another Anniversary for the War on Cancer,” Biotech, 12:320 (1994).
[cited by applicant]
Di Stasi et al., “Inducible apoptosis as a safety switch for adoptive cell therapy,” New England Journal of Medicine, 365(18):1673-1683 (2011).
[cited by applicant]
Didierlaurent et al., “Attenuated poxviruses expressing a synthetic HIV protein stimulate HLA-A2-restricted cytotoxic T-cell responses,” Vaccine, 22(25-26):3395-3403 (2004).
[cited by applicant]
Ding et al., “Genome remodelling in a basal-like breast cancer metastasis and xenograft,” Nature, 464:999-1005 (2010).
[cited by applicant]
Ding et al., Somatic mutations affect key pathways in lung adenocarcinoma, Nature, 455:1069-1075 (2008).
[cited by applicant]
Dohner et al., Genomic aberrations and survival in chronic lymphocytic leukemia, The New England journal of medicine, 343:1910-1916 (2000).
[cited by applicant]
Doody et al., “PRDMI/BLIMP-1 Modulates IFN- -Dependent Control of the MHC Class I Antigen-Processing and Peptide-Loading Pathway,” The Journal of Immunology, 179:7614-7623 (2007).
[cited by applicant]
Dossinger et al., MHC multimer-guided and cell culture-independent isolation of functional T cell receptors from single cells facilitates TCR identification for immunotherapy, PloS one, 8(4):e61384 (2013).
[cited by applicant]
Dreicer et al., “MVA-MUC1-IL2 vaccine immunotherapy (TG4010) improves PSA doubling time in patients with prostate cancer with biochemical failure,” Investigational new drugs, 27(4):379-386 (2009).
[cited by applicant]
Dubey et al., The immunodominant antigen of an ultraviolet-induced regressor tumor is generated by a somatic point mutation in the DEAD (SEQ ID No. 62) box helicase p68, The Journal of experimental medicine, 185(4):695-…
[cited by applicant]
DuPage et al., “Expression of tumour-specific antigens underlies cancer immunoediting,” Nature, 482(7385):405-409 (2012).
[cited by applicant]
Earl et al., “Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox,” Nature, 428:182 (2004).
[cited by applicant]
Eckhardt et al., DNA methylation profiling of human chromosomes 6, 20 and 22, Nat Genet, 38:1378-1385 (2006).
[cited by applicant]
Eden et al., Discovering motifs in ranked lists of DNA sequences, PLoS computational biology, 3, e39 (2007).
[cited by applicant]
Eden et al., GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists, BMCBioinformatics, 10:48 (2009).
[cited by applicant]
Eggermont et al., Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991, EurJ Cancer, 48(2):218-225 (2012).
[cited by applicant]
Ehrlich, DNA hypomethylation in cancer cells, Epigenomics, 1:239-259 (2009).
[cited by applicant]
Eichmann et al., Identification and characterisation of peptide binding motifs of six autoimmune disease-associated human leukocyte antigen-class I molecules including HLA-B*39:06, Tissue Antigens 84(4):378-388 (2014).
[cited by applicant]
Elias et al., Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry, Nat Meth, 4:207-214 (2007).
[cited by applicant]
Engelhard, “Structure of peptides associated with MHC class I molecules,” Curr Opin Immunol, 6(1):13-23 (1994).
[cited by applicant]
Engler et al., A one pot, one step, precision cloning method with high throughput capability, PloS one 3(11):e3647 (2008).
[cited by applicant]
Engler et al., Golden gate shuffling: a one-pot DNA shuffling method based on type IIs restriction enzymes, PloS one, 4(5):e5553 (2009).
[cited by applicant]
Erlich et al., “Next-generation sequencing for HLA typing of class I loci,” BMC Genomics, 12:42 (2011).
[cited by applicant]
Escobar et al., Bayesian density estimation and inference using mixtures, Journal of the American Statistical Association, 90:577-588 (1995).
[cited by applicant]
Esteban, “Attenuated poxvirus vectors MVA and NYVAC as promising vaccine cadidates against HIV/AIDS,” Human vaccines, 5(12):867-871 (2009).
[cited by applicant]
Estep et al., “Mutation Analysis of Braf, MEK1 and MEK2 in 15 Ovarian Cancer Cell Lines: Implications for Therapy,” PLOS One, 12:e1279 (2007).
[cited by applicant]
European Search Report dated Oct. 24, 2019, for EP Appl. No. 177768116.
[cited by applicant]
Extended European Search Report dated Apr. 11, 2016, which issued during prosecution of EP Application No. 15198284.0.
[cited by applicant]
Extended European Search Report received for EP patent application No. EP11781409, mailed Apr. 10, 2014.
[cited by applicant]
Extended Search Report in Corresponding European Application No. 11781409.5, dated Apr. 14, 2014.
[cited by applicant]
Eyers et al., CONSeQuence: prediction of reference peptides for absolute quantitative proteomics using consensus machine learning approaches, Mol Cell Proteomics (2011); 10(11):M110.003384. doi: 10.1074/mcp.MI 10.003384…
[cited by applicant]
Ezzell, “Cancer ‘Vaccines’: An idea whose time has come?,” J NIH Res, 7:46 (1995).
[cited by applicant]
Fais et al., Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors, The Journal of clinical investigation, 102:1515-25 (1998).
[cited by applicant]
Fan et al., The multi substrate adapter Gabl regulates hepatocyte growth factor (scatter factor)-c-Met signaling for cell survival and DNA repair, Molecular and Cellular Biology, 21:4968-4984 (2001).
[cited by applicant]
Fantom Consortium et al., A promoter-level mammalian expression atlas, Nature, 507:462-470 (2014).
[cited by applicant]
Farsaci et al., Consequence of dose scheduling of sunitinib on host immune response elements and vaccine combination therapy, Int J Cancer, 130:1948-1959 (2012).
[cited by applicant]
Feigner et al., Lipofection: A Highly Efficient, Lipid-Mediated DNA-Transfection Procedure, PNAS, 84(21): 7413-7417 (1987).
[cited by applicant]
Feng, Du et al., The Significance and Therapeutic Potential of GATA3 Expression and Mutation in Breast Cancer: A Systematic Review, Medicinal Research Reviews, vol. 35, No. 6, Nov. 1, 1015, pp. 1300-1315, XP002791786.
[cited by applicant]
Ferrier-Rembert et al., Short-and long-term immunogenicity and protection induced by non-replicating smallpox vaccine candidates in mice and comparison with the traditional 1st generation vaccine, Vaccine, 26(14):1794-1…
[cited by applicant]
Final Rejection for U.S. Appl. No. 15/187,174, Compositions and Methods of Identifying Tumor Specific Neoantigens, dated Oct. 12, 2018.
[cited by applicant]
Finke et al., Sunitinib Reverses Type-1 Immune Suppression and Decreases T-Regulatory Cells in Renal Cell Carcinoma Patients, Clin Cancer Res, 14(20):6674-6682 (2008).
[cited by applicant]
Fisher et al., A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries, Genome Biol, 12:R1 (2011).
[cited by applicant]
Flaherty et al., From genes to drugs: targeted strategies for melanoma, Nat Rev Cancer, 12(5):349-361 (2012).
[cited by applicant]
Flexner et al., “Prevention of vaccinia virus infection in imiminodeficient mice by vector-directed IL-2 expression,” Nature, 330(6145):259-262 (1987).
[cited by applicant]
Flynn et al., Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates, Proc Natl Acad Sci, 108(17):7131-7136 (2011).
[cited by applicant]
Forconi et al., Genome-wide DNA analysis identifies recurrent imbalances predicting outcome in chronic lymphocytic leukaemia with 17p deletion, British journal of haematology, 143:532-6 (2008).
[cited by applicant]
Fransen et al., Controlled local delivery of CTLA-4 blocking antibody induces CD8+ T-cell-dependent tumor eradication and decreases risk of toxic side effects, Clin Cancer Res, 19(19):5381-5389 (2013).
[cited by applicant]
Frederick et al., “BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma,” Clin Cancer Res, 19:1225-1231 (2013).
[cited by applicant]