Compositions and methods for treatment of homocystinuria
AssigneeThe Regents of the University of Colorado, a body corporate
InventorsJan P. Kraus, Tomas Majtan, Erez Bublil
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Abstract
Provided herein are improved compositions and methods for enzyme replacement therapy using modified human cystathionine beta synthase (CBS) in the treatment of homocystinuria and related diseases and disorders.
Claims21
An isolated polypeptide dimer comprising two monomeric human truncated cystathionine β-synthase (htCBS) mutant polypeptide subunits, wherein each monomeric htCBS mutant polypeptide subunit independently comprises:
- an amino acid sequence sharing an amino acid sequence identity of at least 80%, at least 90%, at least 95%, or at least 99% compared with SEQ ID NO:2, wherein the amino acid sequence of the htCBS mutant polypeptide further comprises
- a carboyxyl-terminal truncation, wherein the truncation comprises residues 383-551, 397-551, 414-551, 442-551, 489-551, 497-551, 524-551, 534-551, or 544-551 of SEQ ID NO:
- 2;
- and
- a mutation of a cysteine to a serine at amino acid position 15 (C15S) compared to a cystathionine β-synthase (CBS) protein comprising the amino acid sequence of SEQ ID NO:
- 2;
- wherein each htCBS mutant polypeptide subunit is independently covalently linked to at least one polyethylene glycol (PEG) molecule, wherein the at least one PEG molecule is an NHS ester-activated PEG molecule or has a molecular weight greater than or equal to 20 kDa.
An isolated polypeptide dimer comprising two monomeric human truncated cystathionine β-synthase (htCBS) mutant polypeptide subunits, wherein each monomeric htCBS mutant polypeptide subunit independently comprises an amino acid sequence sharing an amino acid sequence identity of at least 99% compared with SEQ ID NO:
- 13, wherein each htCBS mutant polypeptide subunit is independently covalently linked to at least one 20 kDa NHS ester-actived PEG molecule.
Dependencies are inferred from the claim text.