Compositions and methods for alpha-1-antitrypsin disorders
AssigneeSpin Therapeutics, LLC
InventorsAaron Sato, Mark DeSouza
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Abstract
Disclosed herein are compositions and methods useful for treating an alpha-1-antitrypsin deficiency.
Claims50
A recombinant protein comprising:
- (a) an alpha-1-antitrypsin serpin domain;
- and
- (b) a human serum albumin binding domain.
The recombinant protein of any one of the preceding claims, wherein the C-terminus of the alpha-1-antitrypsin serpin domain is fused to the N-terminus of the human serum albumin binding domain.
The recombinant protein of any one of the preceding claims, wherein the human serum albumin binding domain is at least a portion of a human serum albumin having either SEQ ID NO:
- 3 or SEQ ID NO:
- 5.
The recombinant protein of any one of the preceding claims, wherein half-life of the alpha-1-antitrypsin serpin domain compared to wild type alpha-1-antitrypsin is increased.
The recombinant protein of any one of the preceding claims, wherein a number of N-glycans or polysialyation of the recombinant protein in the alpha-1-antitrypsin serpin domain is greater than a wild type alpha-1-antitrypsin serpin domain.
The recombinant protein according to any one of the preceding claims, wherein the alpha-1-antitrypsin serpin domain has one or more mutations as compared to a wild type alpha-1-antitrypsin serpin domain.
The recombinant protein of any one of the preceding claims, wherein the alpha-1-antitrypsin retains activity against human neutrophil elastase and/or PR3 compared to wild type alpha-1-antitrypsin.
The recombinant protein according to any one of the preceding claims, wherein the human serum albumin binding domain comprises a polypeptide having a sequence set forth in any one of SEQ ID NOs:
- 22-36.
An isolated nucleic acid encoding the recombinant protein of any of the preceding claims.
The method of 19, wherein the mammalian host is a CHO cell.
A recombinant protein comprising:
- (a) an alpha-1-antitrypsin serpin domain;
- and
- (b) a human serum albumin domain.
The method of 45, wherein the mammalian host is a CHO cell.
A recombinant protein comprising:
- (a) an alpha-1-antitrypsin serpin domain and
- (b) a human serum albumin domain;
- wherein the alpha-1-antrypsin serpin domain and the human serum albumin are not wild-type alpha-1-antrypsin and human serum albumin.
Dependencies are inferred from the claim text.