Cd40l-specific tn3-derived scaffolds for the treatment and prevention of sjögren's syndrome
AssigneeViela Bio, Inc.
InventorsIlias ALEVIZOS ALEVIZOS, William A. REES, Claire L. EMSON, Michael SMITH, Tuyet-Hang T. PHAM
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Abstract
Provided are compositions and methods comprising a CD40L-specific Tn3 scaffold. Also provided are methods of utilizing the same for the prevention and treatment of Sjögren's Syndrome.
Claims63
A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising administering a Tn3 scaffold comprising a CD40L-specific monomer subunit that binds CD40L to the subject, wherein the monomer subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein the AB loop comprises SEQ ID NO:
- 11, the BC loop comprises SEQ ID NO:
- 12, the CD loop comprises SEQ ID NO:
- 13, the DE loop comprises SEQ ID NO:
- 14, the EF loop comprises SEQ ID NO:
- 15, and the FG loop SEQ ID NO:
- 16, and wherein the subject in need has increased B cells of subsets selected from the group consisting of:
- Ki67+CD27+ memory cells, CD27 high CD38 high plasmablasts, and CD11c high atypical memory cells, as compared to a baseline level of the subject or a level in an untreated subject.
A method of treating Sjögren's syndrome (SS) in a subject in need thereof comprising:
- administering a Tn3 scaffold at a dose of about 1500 mg, about 2500 mg, or about 3000 mg to the subject, wherein the Tn3 scaffold comprises SEQ ID NO:
- 1, and wherein the subject in need has increased B cells of subsets selected from the group consisting of:
- Ki67+CD27+ memory cells, CD27 high CD38 high plasmablasts, and CD11c high atypical memory cells, as compared to an otherwise healthy subject.
A method for treating autoimmune disease in a subject in need thereof comprising administering a Tn3 scaffold comprising a CD40L-specific monomer subunit that binds CD40L to the subject when a level of a biomarker is increased in a sample of the subject as compared to a healthy baseline level, wherein the monomer subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein the AB loop comprises SEQ ID NO:
- 11, the BC loop comprises SEQ ID NO:
- 12, the CD loop comprises SEQ ID NO:
- 13, the DE loop comprises SEQ ID NO:
- 14, the EF loop comprises SEQ ID NO:
- 15, and the FG loop SEQ ID NO:
- 16.
A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising administering a Tn3 scaffold comprising a CD40L-specific monomer subunit that binds CD40L to the subject, wherein the monomer subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein the AB loop comprises SEQ ID NO:
- 11, the BC loop comprises SEQ ID NO:
- 12, the CD loop comprises SEQ ID NO:
- 13, the DE loop comprises SEQ ID NO:
- 14, the EF loop comprises SEQ ID NO:
- 15, and the FG loop SEQ ID NO:
- 16, and wherein the treatment of the subject with the Tn3 scaffold decreases the level of B cells selected from the group consisting of:
- Ki67+CD27+ memory cells, CD27 high CD38 high plasmablasts, and CD11c high atypical memory cells, as compared to a baseline level of the subject or a level in an untreated subject.
A method for treating Sjögren's syndrome (SS) in a subject in need thereof comprising administering a Tn3 scaffold comprising a CD40L-specific monomer subunit that binds CD40L to the subject, wherein the monomer subunit comprises seven beta strands designated A, B, C, D, E, F, and G, and six loop regions designated AB, BC, CD, DE, EF, and FG, wherein the AB loop comprises SEQ ID NO:
- 11, the BC loop comprises SEQ ID NO:
- 12, the CD loop comprises SEQ ID NO:
- 13, the DE loop comprises SEQ ID NO:
- 14, the EF loop comprises SEQ ID NO:
- 15, and the FG loop SEQ ID NO:
- 16, and wherein the Tn3 scaffold is administered to a subject having increased levels of T cells selected from a subset of the group consisting of:
- Ki67+/CD3+, Ki67+/CD4+ cells, Ki67+/CD3+/CD4+ cells, Ki67+/CD3+/CD4+/CD45RA−/CCRT7+ cells, Ki67+/CD3+/CD4+/CD45RA−/CCR7− cells, Ki67+/CD3+/CD4+/CXCR5+/ICOS+ cells, Ki67+/CD3+/CD8+ cells, Ki67+/CD3+/CD8+/CD45RA−/CCR7+ cells, Ki67+/CD3+/CD8+/CD45RA/CCR7− cells, and Ki67+/CD3+/CD8+/CXCR5+ cells, and CXCR5+/ICOS+/CD3+/CD4+ cells, as compared to a baseline level of the subject or a level in an untreated subject.
Dependencies are inferred from the claim text.