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US 2025/0051404 A1Published application
Fusion proteins for inhibiting angiogenesis
AssigneeAllgenesis Biotherapeutics Inc.
InventorsPei-tzu WU, Jia-Hau SHIU, Madhu CHERUKURY, Tan NGUYEN, Kevin ZEN
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Abstract
The present invention relates to a biologic that inhibits angiogenesis. In particular, the present invention relates to fusion proteins that inhibit the integrin activated pathway and one other angiogenic factor-activated pathway, the compositions of these fusion proteins, as well as methods for producing and using the same.
Claims19
A fusion protein comprising, from N-terminus to C-terminus in the following order:
- an extracellular domain of a Vascular Endothelial Growth Factor (VEGF) receptor comprising an Ig-like domain D2 of a VEGFR1 having the amino acid sequence of SEQ ID NO:
- 8 and an Ig-like domain D3 of VEGFR2 having the amino acid sequence of SEQ ID NO:
- 9;
- a Fc domain;
- an integrin binding peptide comprising disintegrin having a binding selectivity for integrin αvβx and α5β1, wherein the integrin binding peptide has a mutated amino acid sequence of SEQ ID NO:
- 1 comprising a first mutation, wherein the amino acid sequence at positions 46 to 53 of SEQ ID NO:
- 1 is substituted with the amino acid sequence of SEQ ID NO:
- 24, and at least one mutation selected from the group consisting of
- (a) a second mutation, wherein the amino acid sequence at positions 39 to 45 of SEQ ID NO:
- 1 is substituted with the amino acid sequence of SEQ ID NOs:
- 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39;
- and
- (b) a third mutation, wherein the amino acid sequence at positions 65 to 68 of SEQ ID NO:
- 1 is substituted with the amino acid sequence of SEQ ID NO:
- 43;
- wherein x is 3, 5, or 6.
13 more elements
A fusion protein comprising, from N-terminus to C-terminus in the following order:
- an extracellular domain of a Vascular Endothelial Growth Factor (VEGF) receptor comprising an Ig-like domain D2 of a VEGFR1 having the amino acid sequence of SEQ ID NO:
- 8 and an Ig-like domain D3 of VEGFR2 having the amino acid sequence of SEQ ID NO:
- 9;
- a Fc domain;
- an integrin binding peptide comprising disintegrin having a binding selectivity for integrin αvβx and α5β1, wherein the integrin binding peptide has a mutated amino acid sequence of SEQ ID NO:
- 1 comprising a first mutation, wherein the amino acid sequence at positions 46 to 53 of SEQ ID NO:
- 1 is substituted with the amino acid sequence selected from the group consisting of SEQ ID NO:
- 24, 25 and 28, and at least one mutation selected from the group consisting of
- (a) a second mutation, wherein the amino acid sequence at positions 39 to 45 of SEQ ID NO:
- 1 is substituted with the amino acid sequence of SEQ ID NOs:
- 29;
- and
- (b) a third mutation, wherein the amino acid sequence at positions 65 to 68 of SEQ ID NO:
- 1 is substituted with the amino acid sequence of SEQ ID NO:
- 43;
- wherein x is 3, 5, or 6.
13 more elements
A fusion protein comprising, from N-terminus to C-terminus in the following order:
- an extracellular domain of a Vascular Endothelial Growth Factor (VEGF) receptor comprising an Ig-like domain D2 of a VEGFR1 having the amino acid sequence of SEQ ID NO:
- 8 and an Ig-like domain D3 of VEGFR2 having the amino acid sequence of SEQ ID NO:
- 9;
- a Fc domain;
- an integrin binding peptide comprising disintegrin having a binding selectivity for integrin αvβx and α5β1, wherein the integrin binding peptide has a mutated amino acid sequence of SEQ ID NO:
- 1 comprising:
- (a) a first mutation, wherein the amino acid sequence at positions 46 to 53 of SEQ ID NO:
- 1 is substituted with the amino acid sequence of SEQ ID NO:
- 26;
- (b) a second mutation, wherein the amino acid sequence at positions 39 to 45 of SEQ ID NO:
- 1 is substituted with the amino acid sequence of SEQ ID NO:
- 36;
- and
- (c) a third mutation, wherein the amino acid sequence at positions 65 to 68 of SEQ ID NO:
- 1 is substituted with the amino acid sequence selected from the group consisting of SEQ ID NO:
- 44, 45, 46, 47, 48, 49;
- wherein x is 3, 5, or 6.
14 more elements
Dependencies are inferred from the claim text.