Single-chain CD137-receptor agonist proteins
AssigneeApogenix AG
InventorsChristian Gieffers, Oliver Hill, Meinolf Thiemann, Tim Schnyder
Life of this patent
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Abstract
Provided herein are specific CD137 receptor agonist proteins, nucleic acids encoding the same, and methods of treating a subject having a CD137L-associated disease or disorder. The CD137 receptor agonist proteins provided herein comprise three soluble CD137L domains and an Fe fragment. The CD137 receptor agonist proteins are substantially non-aggregating and suitable for therapeuctic, diagnostic and/or research applications.
Claims15
A CD137 receptor agonist protein comprising a single-chain fusion polypeptide comprising:
- (i) a first soluble CD137L domain,
- (ii) a first peptide linker having 3 to 8 amino acids,
- (iii) a second soluble CD137L domain,
- (iv) a second peptide linker having 3 to 8 amino acids, and
- (v) a third soluble CD137L domain, and
- (vi) a hinge-linker selected from the group comprising SEQ ID NOs:
- 16 and 19-24, and
- (vii) an antibody Fc fragment, wherein the antibody Fc fragment (vii) consists of the amino acid sequence as shown in SEQ ID NO:
- 13 or amino acids 1-217 of SEQ ID NO:
- 13, and the soluble CD137L domains (i), (iii), and (v) independently comprise amino acids 90-240, of SEQ ID NO:
- 1.
A dimer comprising two polypeptides each having the amino acid sequence as set forth in SEQ ID NOs:
- 27, 29, 30, 32, 33, 34 or 35, fused via three disulfide bridges.
A CD137 receptor agonist protein comprising a single-chain fusion polypeptide comprising:
- (i) a first soluble CD137L domain,
- (ii) a first peptide linker having 3 to 8 amino acids,
- (iii) a second soluble CD137L domain,
- (iv) a second peptide linker having 3 to 8 amino acids, and
- (v) a third soluble CD137L domain, and
- (vi) a hinge-linker selected from the group comprising SEQ ID NOs:
- 16 and 19-24, and
- (vii) an antibody Fc fragment consisting of the amino acid sequence of SEQ ID NO:
- 13 or amino acids 1-217 of SEQ ID NO:
- 13,
- wherein the soluble CD137L domain (i) comprises amino acids 89-240 of SEQ ID NO:
- 1, with the Glu89 being post-translationally modified to pyroglutamate, and the soluble CD137L domains (iii) and (v) independently comprise amino acids 90-240 of SEQ ID NO:
- 1.
Dependencies are inferred from the claim text.