Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including IGF-IR
First Claim
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1. A polypeptide comprising an altered tenth fibronectin type III (10Fn3) domain, wherein the altered 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 having the amino acid sequence of SEQ ID NO;
1, and (iii) binds human insulin-like growth factor-I receptor (IGF-IR) with a disassociation constant of about 1 μ
M or less;
wherein the altered 10Fn3 domain comprises an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs;
184-203.
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Abstract
The present invention provides innovative proteins that bind to insulin-like growth factor-I receptor (IGF-IR), as well as other important proteins. The invention also provides innovative proteins in pharmaceutical preparations and derivatives of such proteins and the uses of same in diagnostic, research and therapeutic applications. The invention further provides cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and vectors comprising the polynucleotides encoding the innovative proteins.
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Citations
13 Claims
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1. A polypeptide comprising an altered tenth fibronectin type III (10Fn3) domain, wherein the altered 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 having the amino acid sequence of SEQ ID NO;
1, and (iii) binds human insulin-like growth factor-I receptor (IGF-IR) with a disassociation constant of about 1 μ
M or less;wherein the altered 10Fn3 domain comprises an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs;
184-203. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
- a loop, BC;
Specification