ανβ3 integrin-binding polypeptide monobodies and their use
First Claim
Patent Images
1. A fibronectin type III (Fn3) polypeptide monobody derived from the amino acid sequence of SEQ ID NO:
- 2 or SEQ ID NO;
3, the polypeptide monobody comprising;
at least two adjacent Fn3 β
-strand domain sequences selected from the group of A-G with a loop region sequence linked between adjacent β
-strand domain sequences, the loop region sequence being selected from the group of loops AB, BC, CD, DE, EF, and FG; and
optionally, an N-terminal tail of at least about 2 to about 25 amino acids, a C-terminal tail of at least about 2 to about 25 amino acids, or both;
wherein;
at least one loop region sequence, selected from the group of AB, BC, CD, DE, and FG loop region sequences, comprises a modified amino acid sequence which varies from a corresponding loop region sequence present in SEQ ID NO;
2 or 3 by deletion of up to all but one amino acid residue, insertion of two to about 25 amino acid residues, or replacement of two to substantially all amino acid residues,one modified amino acid sequence comprises RGDWXE (residues 2-7 of SEQ ID No;
26), andwherein the polypeptide monobody binds selectively to α
vβ
3 integrin.
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Abstract
The present invention relates to a polypeptide monobody which includes a modified acid sequence and renders the polypeptide monobody able to bind selectively to ανβ3 integrin. Fusion proteins and conjugates which include the polypeptide monobody, as well as compositions containing the polypeptide monobody, fusion proteins, or conjugates are also disclosed. Uses thereof include: treating or preventing an ανβ3 integrin-mediated disease or disorder, inhibiting ανβ3 integrin activity, treating a cancerous or precancerous condition, imaging tissues using positron emission tomography or magnetic resonance imaging, assessing the metastatic characteristics of a tumor, and delivering DNA to a cell.
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Citations
31 Claims
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1. A fibronectin type III (Fn3) polypeptide monobody derived from the amino acid sequence of SEQ ID NO:
- 2 or SEQ ID NO;
3, the polypeptide monobody comprising;at least two adjacent Fn3 β
-strand domain sequences selected from the group of A-G with a loop region sequence linked between adjacent β
-strand domain sequences, the loop region sequence being selected from the group of loops AB, BC, CD, DE, EF, and FG; andoptionally, an N-terminal tail of at least about 2 to about 25 amino acids, a C-terminal tail of at least about 2 to about 25 amino acids, or both; wherein; at least one loop region sequence, selected from the group of AB, BC, CD, DE, and FG loop region sequences, comprises a modified amino acid sequence which varies from a corresponding loop region sequence present in SEQ ID NO;
2 or 3 by deletion of up to all but one amino acid residue, insertion of two to about 25 amino acid residues, or replacement of two to substantially all amino acid residues,one modified amino acid sequence comprises RGDWXE (residues 2-7 of SEQ ID No;
26), andwherein the polypeptide monobody binds selectively to α
vβ
3 integrin. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)
- 2 or SEQ ID NO;
Specification
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Current AssigneeUniversity of Rochester
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Original AssigneeUniversity of Rochester
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InventorsMiller, Michelle, Richards, Julie, Koide, Shohei, Koide, Akiko, Dewhurst, Stephen
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Primary Examiner(s)Rao; Manjunath N
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Assistant Examiner(s)Shafer; Shulamith H
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Application NumberUS10/473,770Publication NumberTime in Patent Office2,651 DaysField of SearchNoneUS Class Current435/7.1CPC Class CodesA61K 2039/505 comprising antibodiesA61K 51/088 conjugates with carriers be...C07K 14/78 Connective tissue peptides,...C07K 16/00 Immunoglobulins [IGs], e.g....C07K 16/2848 against integrin beta3-subu...C07K 2317/34 Identification of a linear ...
