IP Library › Granted Patent US 12,275,956
Granted Patent B2
US 12,275,956 · App. 17/893,579 · Granted Apr 15, 2025

Regulatory T cell epitopes

Inventors: William Martin (Providence, RI); Amy S. Rosenberg (Silver Spring, MD)
Assignees: EpiVax Inc.; Food and Drug Administration
C12N5/0637C07K14/52A61K38/00C07K2317/34
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,275,956
App. No.
17/893,579
Granted
Apr 15, 2025
Kind
B2
Abstract

The present is directed to compositions comprising regulatory T cell epitopes, wherein said epitopes comprise a polypeptide comprising at least a portion of SEQ NOS: 1-14, fragments and/or variants thereof, as well as methods of producing and using the same.

Claims (16)

1. A T-cell epitope composition comprising an isolated T-cell epitope polypeptide consisting of the amino acid sequence of SEQ ID NO:1, wherein the isolated T-cell epitope polypeptide is joined directly to, linked directly to, or inserted directly into a heterologous peptide.

2. The composition of claim 1 , further comprising at least one isolated T-cell epitope polypeptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 2-14.

3. The composition of claim 1 , wherein said T-cell epitope polypeptide is located at an N-terminus or a C-terminus of said heterologous peptide.

4. The composition of claim 1 , wherein said heterologous peptide is an antibody.

5. The composition of claim 4 , wherein said antibody is an Fab, F(ab′) 2 , Fv, disulphide linked Fv, scFv, single domain antibody, closed conformation multispecific antibody, disulphide-linked scfv, or diabody.

6. A method of inducing regulatory T-cells to suppress an immune response in a subject comprising administrating to a subject a therapeutically effective amount of a T-cell epitope composition, wherein the T-cell epitope composition comprises the composition of claim 1 .

7. The method of claim 6 , wherein the T-cell epitope composition further comprises at least one isolated T-cell epitope polypeptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOS: 2-14.

8. The method of claim 6 , wherein the T-cell epitope composition further comprises an effective amount of one or more antigens and/or allergens.

9. The method of claim 6 , wherein the immune suppressive effect is mediated by natural regulatory T cells.

10. The method of claim 6 , wherein the immune suppressive effect is mediated by adaptive regulatory T-cells.

11. The method of claim 6 , wherein the T-cell epitope composition suppresses an effector T-cell response.

12. The method of claim 6 , wherein the T-cell epitope composition suppresses a helper T-cell response.

13. The method of claim 6 , wherein the T-cell epitope composition suppresses a B-cell response.

14. The method of claim 6 , wherein the T-cell epitope composition suppresses a cytokine secretion of effector T-cells.

15. The method of claim 6 , wherein said at least one of the T-cell epitope polypeptide is located at an N-terminus or a C-terminus of said heterologous polypeptide.

16. The method of claim 6 , wherein said heterologous peptide is an antibody or a fragment of an antibody.

Assignments (4)
SECURITY INTEREST Recorded Jun 30, 2026
From: EPIVAX, INC.; EPV INTERMEDIATE HOLDINGS, LLC
To: FIFTH THIRD BANK, N.A.
Reel/Frame 075141/0047 →
SECURITY INTEREST Recorded Mar 31, 2026
From: EPIVAX, INC.
To: ESCALATE CAPITAL V, LP
Reel/Frame 074239/0943 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2024
From: MARTIN, WILLIAM D.
To: EPIVAX, INC.
Reel/Frame 068134/0108 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2024
From: ROSENBERG, AMY S.
To: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Reel/Frame 068134/0378 →
Continuity (5)
Continuation 16753522
Provisional Application 62729792 · Sep 11, 2018
Provisional Application 62568625 · Oct 5, 2017
Provisional Application 62568630 · Oct 5, 2017
Related Publication 20230212512A1 · Jul 6, 2023
References Cited (72)
US 4458066A · Caruthers et al. · 1984 [cited by applicant]
US 4522811A · Eppstein et al. · 1985 [cited by applicant]
US 5328470A · Nabel et al. · 1994 [cited by applicant]
US 7884184B2 · De Groot et al. · 2011 [cited by applicant]
US 8586006B2 · Hood · 2013 [cited by applicant]
US 20030008307A1 · Griffin · 2003 [cited by applicant]
US 20040096456A1 · Conti-Fine · 2004 [cited by applicant]
US 20090018067A1 · De Groot et al. · 2009 [cited by applicant]
US 20160030555A1 · Kishimoto et al. · 2016 [cited by applicant]
EP 1598367A1 · 2005 [cited by applicant]
WO WO2003087161A1 · 2003 [cited by applicant]
WO 2007101106A2 · 2007 [cited by applicant]
WO WO2014145524A2 · 2014 [cited by applicant]
WO 2016005564A2 · 2016 [cited by applicant]
WO 2019210187A1 · 2019 [cited by applicant]
Marquette, 1995, J. Biol. Chem. Vol. 270: 10297-10303 Berry, 2003, Hybridoma and Hybridomics, vol. 22: 23-31. [cited by examiner]
MHC-II Binding Prediction Results, 2024, pp. 1-2. [cited by examiner]
UniProt P12259.1, Sep. 2018, pp. 1-27. [cited by examiner]
Cheong, 2010, Blood. vol. 116: 3828-3838. [cited by examiner]
Adams, et al.. “Hindered Dialkylamino Nucleoside Phosphite Reagents in the Synthesis of Tow DNA 51-Mers”, J. Am. Chem. Soc. (1983), pp. 661-663. [cited by applicant]
Akdis, et al., “Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells”, J. Exp. Med., (Jun. 7, 2004), pp. 1567-1575. [cited by applicant]
Ausubel, et al., “Current Protocols in Molecular Biology”, John Wiley & Sons, (1992). [cited by applicant]
Beaucage, et al., “Deoxynucleoside Phosphoramidites—A New Class of Key Intermediates for Deoxypolynucleotide Synthesis”, Tetrahedron Letters, (1981), pp. 1859-1862. [cited by applicant]
Belousov, et al., “Sequence-specific targeting and covalent modification of human genomic DNA”, Nucleic Acids Research, (1997), pp. 3440-3444. [cited by applicant]
Bettini, et al., “Cutting Edge: Accelerated Autoimmune Diabetes in the Absence of LAG-3”, J. Immunol., (2011), pp. 3493-3498. [cited by applicant]
Blommers, et al., “Effects of the Introduction of L-Nucleotides into DNA. Solution Structure of the Heterochiral Duplex d(G-C-G-(L)T-G-C-G)-d(C-G-C-A-C-G-C) Studied by NMR Spectroscopy”, Biochemistry, (1994), pp. 7886-7… [cited by applicant]
Boisvert, et al., “Alpha2beta1 integrin is the major collagen-binding integrin expressed on human Th17 Cells”, Eur. J. Immunol., (2010), pp. 2710-2719. [cited by applicant]
Brannigan, et al., “Protein engineering 20 years on”, Nature Reviews Molecular Cell Biology 3, (Dec. 2002), pp. 964-970. [cited by applicant]
Brown, et al., “Chemical Synthesis and Cloning of a Tyrosine tRNA Gene”, Methods in Enzymology, (1979), pp. 109-151. [cited by applicant]
Bruniquel, et al., “Regulation of Expresssion of the human lymphocyte activation gene-3 (LAG-3) molecule, a igand for MHC class II”, Immunogenetics, (1998), pp. 116-124. [cited by applicant]
Butterfield, “Dendritic cells in cancer immunotherapy clinical trials: are we making progress?”, Frontiers in Immunology, (Dec. 2013), pp. 1-7. [cited by applicant]
Camisaschi, et al., “LAG-3 Expression Defines a Subset of CD4+CD25highFoxp3+ Regulatory T Cells That are expanded at Tumor Sites”, J. Immunol., (2010), pp. 6545-6551. [cited by applicant]
Charbonnier, et al., “Immature Dendritic Cells Suppress Collagen-Induced Arthritis by In Vivo Expansion of CD49b+ Regulatory T Cells”, J. Immunol., (2006), pp. 3806-3813. [cited by applicant]
Chaudhry, et al., “Interleukin-10 Signaling in Regulatory T Cells is Required for Suppression of Th17 Cell-Mediated Inflammation”, Immunity 34., (Apr. 22, 2011), pp. 566-578. [cited by applicant]
Chen, et al., “Gene Therapy for brain tumors: Regression of experimental gliomas by adenovirus-mediated gene transfer in vivo”, Proc. Natl. Acad. Sci. USA, (Apr. 1994), pp. 3054-3057. [cited by applicant]
De Groot, et al., “From genome to vaccine: in silico predictions, ex vivo verification”, Vaccine, 19, (2001), pp. 4385-4395. [cited by applicant]
De Groot, et al., “Mapping cross-clade HIV-1 vaccine epitopes using a bioinformatics approach”, Vaccine 21, (2003) pp. 4486-4505. [cited by applicant]
De Groot, et al., “Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics”, Clinical Immunology, (2009), pp. 189-201. [cited by applicant]
De Groot, et al., “An Interactive Web Site Providing Major Histocompatibility Ligand Predictions: Application to HIV Research”, Aids Research and Human Retroviruses, (1997), pp. 529-531. [cited by applicant]
Dimitrov, “Therapeutic Proteins”, Methods Mol Biol., (2012), pp. 1-26. [cited by applicant]
Dissanayake, et al., “Peptide-Pulsed Dendritic Cells Have Superior Ability to Induce Immune-Mediated Tissue Destruction Compared to Peptide with Adjuvant”, Plos One, (Mar. 2014), pp. 1-10. [cited by applicant]
Feng, et al., “HBcAg-specific CD4+CD25+ regulatory T cells modulate immune tolerance and acute exacerbation on the natural history of chronic hepatitis B virus infection”, Journal of Biomedical Science, (2007), pp. 43-5… [cited by applicant]
Frenkel, et al., “7, 12-Dimethylbenz[A]Anthracene Induces Oxidative DNA Modification in Vivo”, Free Radical Biology & Medicine, (1995), pp. 373-380. [cited by applicant]
Groux, et al., “A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis”, Nature, (Oct. 16, 1997), pp. 737-742. [cited by applicant]
Haringer, et al., “Identification and characterization of IL-10/IFN-y-producing effector-like T cells with regulatory function in human blood”, J. Exp. Med., (2009), pp. 1009-1017. [cited by applicant]
Joshi, et al., “Molecular analysis of expression and function of hFcyRllb1 and b2 isoforms in myeloid cells”, Molecular Immunology 43, (2006), pp. 839-850. [cited by applicant]
Kassiotis, et al., “Functional Specialization of Memory Th Cells Revealed by Expression of Integrin CD49b”, J. Immunol., (2006), pp. 968-975. [cited by applicant]
Lee, et al., “Induction and molecular signature of pathogenic Th17 cells”, Nat Immunol, (2012), pp. 991-999. [cited by applicant]
Mack, et al., “Common and Well-Documented HLA Alleles: 2012 Update to the CWD Catalogue”, Tissue Antigens, (2013), pp. 194-203. [cited by applicant]
Magnani, et al., “Killing of myeloid ACSs via HLA class I, CD2 and CD226 defines a novel mechanism of suppression by human Tr1 cells”, Eur. J. Immunol., (2011), pp. 1652-1662. [cited by applicant]
Maynard, et al., “Regulatory T cells expressing interleuken 10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin 10”, Nature Immunology, (Sep. 2007), pp. 931-941. [cited by applicant]
Mudd, et al., “Regulatory T Cells and Systemic Lupus Erythematosus”, Scandinavian Journal of Immunology, (2006) pp. 211-218. [cited by applicant]
Narang, et al., “Improved Phosphotriester Method for the Synthesis of Gene Fragments”, Methods in Enzymology, (1979), pp. 90-98. [cited by applicant]
Noble, et al., “Separation of Blood Leukocytes by Ficoll Gradient”, Can. Vet. J., (May 1967), pp. 110-111. [cited by applicant]
Okamura, et al., “CD4+CD25-LAG3+ regulatory T cells controlled by the transcription factor Egr-2”, PNAS, (Aug. 18, 2009), pp. 13974-13979. [cited by applicant]
Pearse, et al., “SHIP Recruitment Attenuates FcyRIIB-Induced B Cell Apoptosis”, Immunity, (Jun. 1999), pp. 753-760. [cited by applicant]
Pipe, et al., “Differential Interaction of Coagulation Factor VIII and Factor V with Protein Chaperones Calnexin and Calreticulin”, The Journal of Biological Chemistry, (Apr. 3, 1998), pp. 8537-8544. [cited by applicant]
Pot, et al., “Type 1 regulatory T cells (Tr1) in autoimmunity”, Seminars in Immunology 23, (2011), pp. 202-208. [cited by applicant]
Ravetch, et al., “Structrual Heterogeneity and Functional Domains of Murine Immunoglobulin G Fc Receptors”, Science, (Nov. 7, 1986), pp. 718-725. [cited by applicant]
Roncarlo, et al., “Clinical tolerance in allogeneic hematopoietic stem cell transplantation”, Immunological Reviews, (2011), pp. 145-163. [cited by applicant]
Roncarlo, et al., “Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans”, Nature Reviews Immunology, (Aug. 2007), pp. 585-598. [cited by applicant]
Schafer, et al., “Prediction of well-conserved HIV-1 ligands using a matrix-based algorithm, EpiMatrix”, Vaccine, vol. 16, (1998), pp. 1880-1884. [cited by applicant]
Shevach, “CD4+CD25+ Supressor T Cells: More Questions than Answers”, Nature Reviews Immunology, vol. 2, (Jun. 2002), pp. 389-400. [cited by applicant]
Steere, et al., “Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide”, www.jem.org/cgi/doi/10.1084/jem.20052471, Jem, (Apr. 17, 2006), pp. 961-971. [cited by applicant]
Sturniolo, et al., “Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices”, Nature Biotechnology, (Jun. 1999), pp. 555-561. [cited by applicant]
Turanli-Yildiz, et al., “Protein Engineering Methods and Applications”, www.intechopen.com, (Feb. 2012), pp. 33-58. [cited by applicant]
De Groot et al., “Identification of a Tolerogenic Factor V Peptide and its Potential Role in Factor VIII Tolerance Induction”, 2018 epivax.com/pub_title/identification-of-a-tolerogenic-factor-v-peptide-and-its-potential… [cited by applicant]
Extended European Search Report pertaining to corresponding European Patent Application No. 18864161.7, dated May 10, 2021. [cited by applicant]
Cousens, L. et al., Tregitope update: Mechanism of action parallels IVIg, 12: 436-443, 2013. [cited by applicant]
Piaggio, E., et al., Multimerized T cell epitopes protect from experimental autoimmune diabetes by inducing dominant tolerance, Proceedings of the National Academy of Sciences, 104(22): 9393-9398, 2007. [cited by applicant]
Genbank Accession No. 11SRJ2, Jul. 11, 2012. [cited by applicant]
Genbank Accession No. B7Z2W0, Mar. 3, 2009. [cited by applicant]