US 2016/0250341 A1 · DESIGNED REPEAT PROTEINS BINDING TO SERUM ALBUMIN

Abstract

New designed repeat proteins with binding specificity for serum albumin are described, as well as nucleic acids encoding such serum albumin binding proteins, pharmaceutical compositions comprising such proteins, the use of such proteins to modify the pharmacokinetics of therapeutic relevant polypeptides and the use of such proteins in the treatment of diseases. The repeat proteins of the invention have a substantially increased half-life in plasma compared to proteins not binding serum albumin.

Claims22

Dependent claims

1-16. (canceled)

The method of claim 1, wherein said ankyrin repeat domain comprises an ankyrin repeat module having an amino acid sequence selected from the group consisting of:

(1) SEQ ID NO:49;
(2) SEQ ID NO:50;
(3) SEQ ID NO:51;
(4) SEQ ID NO:52;
(5) an amino acid sequence with up to 6 amino acids in SEQ ID NO:
49 exchanged by any amino acid and having the ankyrin repeat sequence motif
(SEQ ID NO:
53)
X1DX2X3X4X5TPLHLAAX6X7GHLX8IVEVLLKX9GADVNA
wherein
X1 represents an amino acid residue selected from the group consisting of A, D, M, F, S, I, T, N, Y, and K;
X2 represents an amino acid residue selected from the group consisting of E, K, D, F, M, N, I and Y;
X3 represents an amino acid residue selected from the group consisting of W, R, N, T, H, K, A and F;
X4 represents an amino acid residue selected from the group consisting of G and S;
X5 represents an amino acid residue selected from the group consisting of N, T and H;
X6 represents an amino acid residue selected from the group consisting of N, V and R;
X7 represents an amino acid residue selected from the group consisting of E, Y, N, D, H,
S, A, Q, T and G;
X8 represent an amino acid residue selected from the group consisting of E and K;
X9 represent an amino acid residue selected from the group consisting of S, A, Y, H and N;
and
wherein optionally up to 5 amino acids in other than in positions denoted with X in SEQ ID NO:53 are exchanged by any amino acid;
(6) an amino acid sequence with up to 6 amino acids in SEQ ID NO:
51 exchanged by any amino acid and having the ankyrin repeat sequence motif
(SEQ ID NO:
10)
X1DX2X3GX4TPLHLAAX5X6GHLEIVEVLLKX7GADVNA
wherein
X1 represents an amino acid residue selected from the group consisting of A, D, M, F, S, I, T, N, Y and K;
X2 represents an amino acid residue selected from the group consisting of E, K, D, F, M, N, I and Y;
X3 represents an amino acid residue selected from the group consisting of W, R, N, T, H, K, A and F;
X4 represents an amino acid residue selected from the group consisting of N, T and H;
X5 represents an amino acid residue selected from the group consisting of N, V and R;
X6 represents an amino acid residue selected from the group consisting of E, Y, N, D, H, S, A, Q, T and G;
X7 represent an amino acid residue selected from the group consisting of S, A, Y, H and N;
and
wherein optionally up to 5 amino acids in other than in positions denoted with X in SEQ ID NO:10 are exchanged by any amino acid;
(7) an amino acid sequence with up to 6 amino acids in SEQ ID NO:
49 exchanged by any amino acid and having the ankyrin repeat sequence motif
(SEQ ID NO:
11)
X1DYFX2HTPLHLAARX3X4HLX5IVEVLLKX6GADVNA
wherein
X1 represents an amino acid residue selected from the group consisting of D, K and A;
X2 represents an amino acid residue selected from the group consisting of D, G and S;
X3 represents an amino acid residue selected from the group consisting of E, N, D, H, S, A, Q, T and G;
X4 represents an amino acid residue selected from the group consisting of G and D;
X5 represents an amino acid residue selected from the group consisting of E, K and G;
X6 represents an amino acid residue selected from the group consisting of H, Y, A and N;
and
wherein optionally up to 5 amino acids in other than in positions denoted with X in SEQ ID NO:11 are exchanged by any amino acid;
(8) an amino acid sequence with up to 6 amino acids in SEQ ID NO:
50 exchanged by any amino acid and having the ankyrin repeat sequence motif
(SEQ ID NO:
54)
X1DFX2GX3TPLHLAAX4X5GHLEIVEVLLKX6GADVNA
wherein
X1 represents an amino acid residue selected from the group consisting of F, S, L and K;
X2 represents an amino acid residue selected from the group consisting of V and A;
X3 represents an amino acid residue selected from the group consisting of R and K;
X4 represents an amino acid residue selected from the group consisting of S and N;
X5 represents an amino acid residue selected from the group consisting N, D, Q, S, A, T and E;
X6 represents an amino acid residue selected from the group consisting of A, H, Y, S and N;
and
wherein optionally up to 5 amino acids in other than in positions denoted with X in SEQ ID NO:54 are exchanged by any amino acid;
(9) an amino acid sequence with up to 6 amino acids in SEQ ID NO:
50 exchanged by any amino acid and has the ankyrin repeat sequence motif
(SEQ ID NO:
12)
X1DFX2GX3TPLHLAAX4DGHLEIVEVLLKX5GADVNA
wherein
X1 represents an amino acid residue selected from the group consisting of F, S, L and K;
X2 represents an amino acid residue selected from the group consisting of V and A;
X3 represents an amino acid residue selected from the group consisting of R and K;
X4 represents an amino acid residue selected from the group consisting of S and N;
X5 represents an amino acid residue selected from the group consisting of A, H, Y, S and N;
and
wherein optionally up to 5 amino acids in other than in positions denoted with X in SEQ ID NO:12 are exchanged by any amino acid;
(10) an amino acid sequence with up to 6 amino acids in SEQ ID NO:
51 exchanged by any amino acid and has the ankyrin repeat sequence motif
(SEQ ID NO:
13)
X1DX2X3GTTPLHLAAVYGHLEX4VEVLLKX5GADVNA
wherein
X1 represents an amino acid residue selected from the group consisting of K, A, D, M, F, S, I, T, N, and Y;
X2 represents an amino acid residue selected from the group consisting of E, K, D, F, M, N and Y;
X3 represents an amino acid residue selected from the group consisting of R, N, T, H, K, A and F;
X4 represents an amino acid residue selected from the group consisting of I and M;
X5 represents an amino acid residue selected from the group consisting of H, Y, K, A and N;
and
wherein optionally up to 5 amino acids in other than in positions denoted with X in SEQ ID NO:13 are exchanged by any amino acid;
and
(11) an amino acid sequence with up to 6 amino acids in SEQ ID NO:
52 exchanged by any amino acid and has the ankyrin repeat sequence motif
(SEQ ID NO:
14)
X1NETGYTPLHLADSSGHX2EIVEVLLKX3X4X5DX6NA
wherein
X1 represents an amino acid residue selected from the group consisting of Q and K;
X2 represents an amino acid residue selected from the group consisting of L and P;
X3 represents an amino acid residue selected from the group consisting of H, N, Y and A;
X4 represents an amino acid residue selected from the group consisting of G and S;
X5 represents an amino acid residue selected from the group consisting of A, V, T and S;
X6 represents an amino acid residue selected from the group consisting of V and F;
and
wherein optionally up to 5 amino acids in other than in positions denoted with X in SEQ ID NO:14 are exchanged by any amino acid.

103 more elements

Dependencies are inferred from the claim text.

Designed repeat proteins binding to serum albumin

Life of this patent

Designed repeat proteins binding to serum albumin

Life of this patent

Abstract

Claims22