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US 9,284,361 B2Granted
Designed repeat proteins binding to serum albumin
AssigneeMolecular Partners AG
InventorsDaniel Steiner, Hans Kaspar Binz, Maya Gulotti-Georgieva, Frieder W. Merz, Douglas Phillips, Ivo Sonderegger
Life of this patent
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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.
Claims31
A binding protein comprising at least one ankyrin repeat domain, wherein said ankyrin repeat domain has binding specificity for a mammalian serum albumin and 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)
- X1DFX2G X3TPLHLAAX4X5GHLEIVEVLLKX6GADVNA
- 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)
- X1DFX2G X3TPLHLAAX4DGHLEIVEVLLKX5GADVNA
- 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.
102 more elements
A binding protein comprising at least one ankyrin repeat domain, wherein said repeat domain has binding specificity for a mammalian serum albumin and wherein said ankyrin repeat domain comprises an amino acid sequence that has at least 85% amino acid sequence identity with one ankyrin repeat domain selected from the group consisting of SEQ ID NOs:
- 17 to 31 and 43 to 48, wherein G at position 1 and/or S at position 2 of said ankyrin repeat domain are optionally missing.
A binding protein comprising at least one ankyrin repeat domain, wherein said ankyrin repeat domain has binding specificity for a mammalian serum albumin and 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 5 amino acids in SEQ ID NO:
- 49 exchanged by any amino acid;
- (6) an amino acid sequence with up to 4 amino acids in SEQ ID NO:
- 50 exchanged by any amino acid;
- (7) an amino acid sequence with up to 3 amino acids in SEQ ID NO:
- 51 exchanged by any amino acid;
- and
- (8) an amino acid sequence with up to 6 amino acids in SEQ ID NO:
- 52 exchanged by any amino acid.
10 more elements
Dependencies are inferred from the claim text.