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US 10,851,157 B2Granted
Antagonists targeting the TGF-β pathway
AssigneeGensun Biopharma Inc.
InventorsMargaret Karow, Jackie Sheng, Wei Zhang
Life of this patent
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Abstract
Antitumor antagonists that bind specifically to immune checkpoint regulators, angiogenesis pathway regulators and/or TGF pathway regulators are disclosed. Also disclosed are methods for treating proliferative disorders, infections, and immunological disorders with the antitumor antagonists described herein.
Claims34
An antitumor antagonist comprising:
- a first targeting domain comprising a mutated TGF-β1 RII extracellular domain (mutated ECD);
- and
- an immunoglobulin scaffold having an amino terminus and a carboxy terminus,
- wherein the mutated ECD comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:
- 114-123 and 251-270, and
- wherein the antitumor antagonist comprises an immunoglobulin heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:
- 124-133, 145, 147, 148, 150 and 271-303.
4 more elements
An antitumor antagonist comprising:
- a first targeting domain comprising a mutated TGF-β1 RII extracellular domain (mutated ECD);
- and
- an immunoglobulin scaffold having an amino terminus and a carboxy terminus, wherein the mutated ECD comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:
- 114-123 and 251-270,
- wherein the antitumor antagonist comprises an immunoglobulin heavy chain paired to an immunoglobulin light chain, and
- wherein the antitumor antagonist comprises:
- (1) a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 126 or SEQ ID NO:
- 283 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 93;
- (2) a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 145 or SEQ ID NO:
- 303 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 95;
- or
- (3) a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 148 or SEQ ID NO:
- 295 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 103.
16 more elements
Dependencies are inferred from the claim text.