SERUM ALBUMIN-BINDING FIBRONECTIN TYPE III DOMAINS
First Claim
1. A polypeptide comprising a fibronectin type III tenth domain (10Fn3) wherein the 10Fn3 domain comprises a) AB, BC, CD, DE, EF, and FG loops, b) a CD loop with an altered amino acid sequence relative to the sequence of the corresponding CD loop of the human 10Fn3 domain, c) wherein the polypeptide binds to human serum albumin with a KD of less than 500 nM, and d) wherein the 10Fn3 domain further binds to one or more of rhesus serum albumin, cynomolgus serum albumin, mouse serum albumin, and rat serum albumin with a KD of less than 500 nM, for example, less than 100 nM, or less than 10 nM.
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Abstract
The present invention relates to polypeptides which include tenth fibronectin type III domains (10Fn3) that binds to serum albumin, with south pole loop substitutions. 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.
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Citations
20 Claims
- 1. A polypeptide comprising a fibronectin type III tenth domain (10Fn3) wherein the 10Fn3 domain comprises a) AB, BC, CD, DE, EF, and FG loops, b) a CD loop with an altered amino acid sequence relative to the sequence of the corresponding CD loop of the human 10Fn3 domain, c) wherein the polypeptide binds to human serum albumin with a KD of less than 500 nM, and d) wherein the 10Fn3 domain further binds to one or more of rhesus serum albumin, cynomolgus serum albumin, mouse serum albumin, and rat serum albumin with a KD of less than 500 nM, for example, less than 100 nM, or less than 10 nM.
- 9. A fusion polypeptide comprising a fibronectin type III tenth (10Fn3) domain and a heterologous protein, wherein the 10Fn3 domain comprises a) AB, BC, CD, DE, EF, and FG loops, b) a CD loop with an altered amino acid sequence relative to the sequence of the corresponding loop of the human 10Fn3 domain, c) wherein the polypeptide binds to human serum albumin with a KD of less than 500 nM, and wherein the 10Fn3 domain further binds to one or more of rhesus serum albumin, cynomolgus serum albumin, mouse serum albumin, and rat serum albumin with a KD of less than 500 nM, for example, less than 100 nM, or less than 10 nM.
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14. A polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 81, 88, 23-80, 82-87, 89-100, 168-169, 184-209 and 235-261.
Specification