MULTIVALENT FIBRONECTIN BASED SCAFFOLD DOMAIN PROTEINS
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Abstract
The present invention relates to multivalent polypeptides comprising at least two fibronectin scaffold domains connected via a polypeptide linker. The invention also relates to multivalent polypeptides for use in diagnostic, research and therapeutic applications. The invention further relates to cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative proteins.
41 Citations
25 Claims
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1-24. -24. (canceled)
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25. A polypeptide comprising:
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(a) an N-terminal domain comprising a first fibronectin type III tenth domain (10Fn3), wherein the 10Fn3 domain (i) comprises a loop, AB;
a loop, BC;
a loop, CD;
a loop, DE;
a loop EF; and
a loop FG;
(ii) has at least one loop selected from loop BC, DE, and FG with an altered amino acid sequence relative to the sequence of the corresponding loop of the human 10Fn3 domain, (iii) comprises an amino acid sequence that is at least 60% identical to SEQ ID NO;
1, and (iv) binds to a first target molecule with a KD of less than 500 nM;(b) a C-terminal domain comprising a second fibronectin type III tenth domain (10Fn3), wherein the 10Fn3 domain (i) comprises a loop, AB;
a loop, BC;
a loop, CD;
a loop, DE;
a loop EF; and
a loop FG;
(ii) has at least one loop selected from loop BC, DE, and FG with an altered amino acid sequence relative to the sequence of the corresponding loop of the human 10Fn3 domain, (iii) comprises an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO;
1, and (iv) binds to a second target molecule with a KD of less than 500 nM;wherein the first and second 10Fn3 domains are linked via a polypeptide selected from a glycine-serine based linker, a glycine-proline based linker, a proline-alanine based linker, or the amino acid sequence of SEQ ID NO;
20.
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Specification