Immunomodulatory fusion proteins
AssigneeEpicentRx, Inc.
InventorsChristopher LARSON, Tony R. REID, Bryan T. ORONSKY
Life of this patent
Estimating the term…
Abstract
Provided is a fusion protein, e.g., a cytokine receptor fusion protein, e.g., a TGFβ trap, with a novel linker sequence to permit the fusion protein to functionally optimally, e.g., to permit a cytokine receptor portion of a cytokine receptor fusion protein to bind optimally to its target cytokine. The fusion proteins, or expression vectors encoding for the fusion proteins, e.g., oncolytic adenoviral expression vectors, can be used to treat cell proliferative diseases and disorders, including certain forms of cancer and inflammatory disorders.
Claims23
1-93. (canceled)
A method of inhibiting tumor growth in a subject in need thereof, the method comprising administering to the subject an effective amount of an expression vector to inhibit growth of the tumor,
- wherein the expression vector comprises a nucleic acid comprising a nucleotide sequence encoding a fusion protein comprising, in an N- to C-terminal orientation:
- (i) a soluble portion of an extracellular domain of a human TGFβ type II receptor wherein the soluble portion of the extracellular domain of the human TGFβ type II receptor has at least 90% identity to amino acid residues 23-159 of SEQ ID NO:
- 12 and binds to TGFβ;
- (ii) an amino acid linker;
- (iii) an immunoglobulin (Ig) hinge region;
- and
- (iv) an immunoglobulin (Ig) Fc domain,
- wherein the linker consists of 10 to 40 amino acid residues obtained from a C-terminal portion of a human immunoglobulin (Ig) CH1 domain and the linker comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:
- 1, SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 5, SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, SEQ ID NO:
- 60, or SEQ ID NO:
- 61.
A method of treating cancer in a subject in need thereof, the method comprising administering an effective amount of an expression vector to the subject to treat the cancer,
- wherein the expression vector comprises a nucleic acid comprising a nucleotide sequence encoding a fusion protein comprising, in an N- to C-terminal orientation:
- (i) a soluble portion of an extracellular domain of a human TGFβ type II receptor wherein the soluble portion of the extracellular domain of the human TGFβ type II receptor has at least 90% identity to amino acid residues 23-159 of SEQ ID NO:
- 12 and binds to TGFβ;
- (ii) an amino acid linker;
- (iii) an immunoglobulin (Ig) hinge region;
- and
- (iv) an immunoglobulin (Ig) Fc domain,
- wherein the linker consists of 10 to 40 amino acid residues obtained from a C-terminal portion of a human immunoglobulin (Ig) CH1 domain and the linker comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:
- 1, SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 5, SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, SEQ ID NO:
- 60, or SEQ ID NO:
- 61.
A method of reducing TGFβ activity in a cell of a subject, the method comprising exposing the cell to an effective amount of an expression vector to reduce TGFβ activity,
- wherein the expression vector comprises a nucleic acid comprising a nucleotide sequence encoding a fusion protein comprising, in an N- to C-terminal orientation:
- (i) a soluble portion of an extracellular domain of a human TGFβ type II receptor wherein the soluble portion of the extracellular domain of the human TGFβ type II receptor has at least 90% identity to amino acid residues 23-159 of SEQ ID NO:
- 12 and binds to TGFβ;
- (ii) an amino acid linker;
- (iii) an immunoglobulin (Ig) hinge region;
- and
- (iv) an immunoglobulin (Ig) Fc domain,
- wherein the linker consists of 10 to 40 amino acid residues obtained from a C-terminal portion of a human immunoglobulin (Ig) CH1 domain and the linker comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO:
- 1, SEQ ID NO:
- 2, SEQ ID NO:
- 3, SEQ ID NO:
- 5, SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, SEQ ID NO:
- 60, or SEQ ID NO:
- 61.
97-98. (canceled)
103-107. (canceled)
Dependencies are inferred from the claim text.