Motif-grafted hybrid polypeptides and uses thereof
First Claim
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1. A hybrid immunoglobulin or a Fab fragment of the hybrid immunoglobulin that specifically binds to the infectious form of a prion protein, comprising antibody b12 or a fragment thereof, wherein:
- residues 119-131 of antibody b12 whose sequence is set forth in SEQ ID NO;
4 or corresponding residues in a fragment thereof are replaced with residues 121-158 of the Syrian hamster prion polypeptide having a sequence set forth in SEQ ID NO;
5 or the corresponding residues of a prion polypeptide from another species or a portion of residues 121-158 or the corresponding residues that binds to the infectious form of a prion protein.
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Abstract
Provided herein are hybrid polypeptides that specifically bind to a disease-associated isoform of a polypeptide involved in diseases of protein aggregation. The hybrid polypeptides can be used for diagnosis and treatment of such diseases. In a particular embodiment, a hybrid protein that specifically binds to the infectious form of a prion (PrPSc) is provided.
38 Citations
37 Claims
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1. A hybrid immunoglobulin or a Fab fragment of the hybrid immunoglobulin that specifically binds to the infectious form of a prion protein, comprising antibody b12 or a fragment thereof, wherein:
residues 119-131 of antibody b12 whose sequence is set forth in SEQ ID NO;
4 or corresponding residues in a fragment thereof are replaced with residues 121-158 of the Syrian hamster prion polypeptide having a sequence set forth in SEQ ID NO;
5 or the corresponding residues of a prion polypeptide from another species or a portion of residues 121-158 or the corresponding residues that binds to the infectious form of a prion protein.- View Dependent Claims (2, 16, 34)
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3. A hybrid immunoglobulin or a Fab fragment of the hybrid immunoglobulin that specifically binds to the infectious form of a prion protein, comprising antibody b12 or a fragment thereof, wherein:
residues 119-131 of antibody b12 whose sequence is set forth in SEQ ID NO;
4 or corresponding residues in a fragment thereof are replaced with residues 87-112 of the Syrian hamster prion polypeptide having a sequence set forth in SEQ ID NO;
5 or the corresponding residues from prion polypeptides of another species or a portion of residues 87-112 or the corresponding residues that binds to the infectious form of a prion protein.
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4. A hybrid immunoglobulin polypeptide or a fragment of the hybrid immunoglobulin, wherein:
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a polypeptide motif is inserted within a complementarity-determining region (CDR) of the immunoglobulin molecule or fragment thereof, said polypeptide motif consisting of a sufficient number of contiguous amino acid residues from residues 136-158, 89 105, 89-112 or 95-112 of the Syrian hamster prion polypeptide having a sequence set forth in SEQ ID NO;
5 or the corresponding residues of a prion polypeptide from another species so that the resulting fragment or hybrid immunoglobulin preferentially binds to the infectious PrPSc form of the prion compared to the PrPc form; andthe fragment is a Fab, an F(ab)2 or single chain Fv. - View Dependent Claims (5)
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6. A hybrid immunoglobulin or a Fab fragment of the hybrid immunoglobulin, wherein:
a polypeptide motif is inserted within the third complementarity-determining region (CDR) of an immunoglobulin molecule or a Fab fragment of the immunoglobulin molecule, said polypeptide motif consisting of a sufficient number of contiguous amino acid residues from residues 87-169 of the Syrian hamster prion polypeptide having a sequence set forth in SEQ ID NO;
5 or the corresponding residues of a prion polypeptide from another species so that the resulting Fab fragment or hybrid immunoglobulin preferentially binds to the infectious PrPSc form of the prion compared to the PrPc form.- View Dependent Claims (7, 8, 9, 10, 11, 12, 13, 14, 15, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 35, 36, 37)
Specification