Use of transthyretin peptide/protein fusions to increase the serum half-life of pharmacologically active peptides/proteins
OwnerKenneth Walker, Fei Xionginventors
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Abstract
The present invention provides a means for increasing the serum half-life of a selected biologically active agent by utilizing transthyretin (TTR) as a fusion partner with a biologically active agent. Specifically, the present invention provides substantially homogenous preparations of TTR (or a TTR variant)-biologically active agent fusions and PEG-TTR (PEG-TTR variant)-biologically active agent fusions. As compared to the biologically active agent alone, the TTR-biologically active agent fusion and/or PEG-TTR-biologically active agent fusion has substantially increased serum half-life.
Claims37
A method for increasing the serum half-life of a biologically active agent comprising fusing the biologically active agent to transthyretin (TTR) or a TTR variant.
A substantially homogenous preparation of a TTR-biologically active agent fusion, optionally in a pharmaceutically acceptable diluent, carrier or adjuvant.
A substantially homogenous preparation of a PEG-TTR-biologically active agent fusion, optionally in a pharmaceutically acceptable diluent, carrier or adjuvant.
A substantially homogenous preparation of a TTR variant-biologically active agent fusion, optionally in a pharmaceutically acceptable diluent, carrier or adjuvant.
A substantially homogenous preparation of a PEG-TTR variant-biologically active agent fusion, optionally in a pharmaceutically acceptable diluent, carrier or adjuvant.
A process for preparing a substantially homogenous preparation of a TTR-biologically active agent fusion comprising:
- (a) fusing said TTR to a biologically active agent to provide a TTR-biologically active agent fusion;
- and (b) isolating said TTR-biologically active agent fusion.
A process for preparing a substantially homogenous preparation of a TTR variant-biologically active agent fusion comprising:
- (a) engineering a cysteine residue into a specific amino acid position within the amino acid sequence of said TTR to provide a variant of said TTR;
- (b) fusing said TTR variant to a biologically active agent to provide a TTR variant-biologically active agent fusion;
- and (c) isolating said TTR variant-biologically active agent fusion.
A process for preparing a substantially homogenous preparation of a PEG-TTR-biologically active agent fusion comprising:
- (a) conjugating a polyethylene glycol to said TTR to provide a PEG-TTR;
- (b) fusing said PEG-TTR to a biologically active agent to provide a PEG-TTR-biologically active agent fusion;
- and (c) isolating said PEG-TTR-biologically active agent fusion.
A process for preparing a substantially homogenous preparation of a PEG-TTR variant-biologically active agent fusion comprising:
- (a) engineering a cysteine residue into a specific amino acid position within the amino acid sequence of said TTR to provide a variant of said TTR;
- (b) conjugating a polyethylene glycol to said TTR variant at said cysteine residue to provide a PEG-TTR variant;
- (c) fusing said PEG-TTR variant to a biologically active agent to provide a PEG-TTR-biologically active agent fusion;
- and (d) isolating said PEG-TTR-biologically active agent fusion.
A fusion protein comprising a TTR protein fused to a heterologous sequence.
Dependencies are inferred from the claim text.