ANTIBODIES THAT SPECIFICALLY BIND TO SERUM ALBUMIN WITHOUT INTERFERING WITH ALBUMIN'S CAPABILITY TO INTERACT WITH THE FCRN
Antibodies that specifically bind to an epitope on the serum albumin, including human and/or mouse serum albumin are provided. Nucleic acids encoding such antibodies and cells capable of expressing such antibodies are also provided.
1 . A heavy chain domain antibody that specifically binds to an epitope on serum albumin, comprising a heavy chain complementarity determining region (CDR) 1 having the amino acid sequence of SEQ ID NO:146 or SEQ ID NO:147, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO:149 or SEQ ID NO:150, and a heavy chain CDR3 having an amino acid sequence having at least 95% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:26, SEQ ID NO:44, SEQ ID NO:62, SEQ ID NO:80, SEQ ID NO:98, SEQ ID NO:116, and SEQ ID NO:134, wherein a heavy chain domain antibody comprising a heavy chain CDR3 having an amino acid sequence having less than 100% sequence identity with the amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:26, SEQ ID NO:44, SEQ ID NO:62, SEQ ID NO:80, SEQ ID NO:98, SEQ ID NO:116, and SEQ ID NO:134 has serum albumin binding activity.
2 . The heavy chain domain antibody of claim 1 , wherein the antibody comprises a heavy chain framework (FWR) 1 having the amino acid sequence of SEQ ID NO: 145, a heavy chain FWR2 having the amino acid sequence of SEQ ID NO: 148 or SEQ ID NO:174, a heavy chain FWR3 having the amino acid sequence of SEQ ID NO: 151, and a heavy chain FWR4 having the amino acid sequence of SEQ ID NO: 152.
3 . The heavy chain domain antibody of claim 1 , wherein the serum albumin is human serum albumin or mouse serum albumin.
4 . The heavy chain domain antibody of claim 1 , wherein the serum albumin is human serum albumin.
5 . The heavy chain domain antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:17.
6 . The heavy chain domain antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:35.
7 . The heavy chain domain antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:53.
8 . The heavy chain domain antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:71.
9 . The heavy chain domain antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:89.
10 . The heavy chain domain antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:107.
11 . The heavy chain domain antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:125.
12 . The heavy chain domain antibody of claim 1 , wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:143.
13 . The heavy chain domain antibody of claim 1 , wherein the heavy chain domain antibody is conjugated to a detectable label, a chemotherapeutic agent, or biotin.
14 . The heavy chain domain antibody of claim 1 , wherein the affinity of the antibody for serum albumin is less than about 1×10 −6 M.
15 . The heavy chain domain antibody of claim 1 , wherein the affinity of the antibody for serum albumin is less than about 1×10 −8 M.
16 . The heavy chain domain antibody of claim 1 , wherein the affinity of the antibody for serum albumin is less than about 1×10 −10 M.
17 . A composition, comprising the heavy chain domain antibody of claim 1 and a pharmaceutically acceptable carrier.
18 . An isolated polynucleotide encoding the heavy chain domain antibody of claim 1 .
19 . A vector, wherein the vector comprises the polynucleotide of claims 18 .
20 . A transformed cell, wherein the transformed cell comprises the vector of claim 19 .
21 . The transformed cell of claim 20 , wherein the cell is a mammalian cell, a yeast cell, or a bacteria cell.
22 . A method for enhancing the circulating half-life of the heavy chain domain antibody of claim 1 , comprising contacting the heavy chain domain antibody with serum albumin in the blood of a subject.