SERUM ALBUMIN BINDING MOLECULES
First Claim
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1. A polypeptide comprising a fibronectin type III tenth (10Fn3) domain, wherein the 10Fn3 domain binds to domain 1 or 2 of human serum albumin with a KD of 1 uM or less, and wherein the serum half-life of the polypeptide in the presence of albumin is at least 5-fold greater than the serum half-life of the polypeptide in the absence of serum albumin.
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Abstract
The present invention relates to an antibody-like protein based on the tenth fibronectin type III domain (10Fn3) that binds to serum albumin. The invention further relates to fusion molecules comprising a serum albumin-binding 10Fn3 joined to a heterologous protein for use in diagnostic and therapeutic applications.
22 Citations
65 Claims
- 1. A polypeptide comprising a fibronectin type III tenth (10Fn3) domain, wherein the 10Fn3 domain binds to domain 1 or 2 of human serum albumin with a KD of 1 uM or less, and wherein the serum half-life of the polypeptide in the presence of albumin is at least 5-fold greater than the serum half-life of the polypeptide in the absence of serum albumin.
- 5. A polypeptide comprising a fibronectin type III tenth (10Fn3) domain, wherein the 10Fn3 domain binds to human serum albumin and comprises an amino acid sequence at least 70% identical to SEQ ID NO:
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17. A polypeptide comprising a fibronectin type III tenth (10Fn3) domain, wherein the 10Fn3 domain binds to human serum albumin and comprises a BC loop comprising the amino acid sequence set forth in SEQ ID NO:
- 5, a DE loop comprising the amino acid sequence set forth in SEQ ID NO;
6, and an FG loop comprising the amino acid sequence set forth in SEQ ID NO;
7. - View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26)
- 5, a DE loop comprising the amino acid sequence set forth in SEQ ID NO;
- 27. A fusion polypeptide comprising a fibronectin type III tenth (10Fn3) domain and a heterologous protein, wherein the 10Fn3 domain binds to human serum albumin with a KD of 1 uM or less.
- 46. A polypeptide comprising a fibronectin type III tenth (10Fn3) domain, wherein the 10Fn3 domain (i) comprises a modified amino acid sequence in one or more of the AB, BC, CD, DE, EF and FG loops relative to the wild-type 10Fn3 domain, (ii) binds to a target molecule not bound by the wild-type 10Fn3 domain, and (iii) comprises a C-terminal tail having a sequence (ED)n, wherein n is an integer from 3 to 7.
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54. A polypeptide comprising a fibronectin type III tenth (10Fn3) domain, wherein the 10Fn3 domain binds to human serum albumin and comprises an amino acid sequence at least 70% identical to SEQ ID NO:
- 8, 12, 16, 20, and 24-44.
Specification