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US 6,387,638 B1Granted
Heregulin variants
AssigneeGenentech, Inc.
InventorsMarcus D. Ballinger, Jennifer T. Jones, Wayne J. Fairbrother, Mark X. Sliwkowski, James A. Wells
Life of this patent
Estimating the term…
Abstract
The present invention provides heregulin variants that are capable of binding an ErbB receptor. Included in the invention are variants of human heregulins, and, in particular, variants of human heregulin-β1 having enhanced affinity for the ErbB-3 and ErbB-4 receptors. These variants include at least one amino acid substitution and can include further modifications. The invention also provides nucleic acid molecules encoding heregulin variants and related vectors, host cells, pharmaceutical compositions, and methods.
Claims24
A method for binding an ErbB receptor comprising contacting a variant of a heregulin with a cell that expresses said ErbB receptor, said variant having the ability to bind an ErbB receptor, wherein said variant comprises a different amino acid than in said heregulin, wherein:
- at residue number 177 said different amino acid is A, F, W, or Y;
- at residue number 178 said different amino acid is A, D, E, G, L, N, P, Q, R, T V, or W;
- at residue number 179 said different amino acid is A, G, L, M, P, S or V;
- at residue number 180 said different amino acid is A, D, E, G, H, I, K, M, N, P, Q, or R;
- at residue number 181 said different amino acid is A, G, I, L, P, or V;
- at residue number 183 said different amino acid is A, G, I, L, M, S, or T;
- at residue number 184 said different amino acid is A, F, G, H, I, K, L, M, N, P, Q, R, S, V, or W;
- at residue number 185 said different amino acid is A, G, H, I, K, L, M, N, P, Q, S, T, or V;
- at residue number 186 said different amino acid is A, K, R, or S;
- at residue number 187 said different amino acid is A, E, G, I, L, M, N, P, Q, S, or T;
- at residue number 188 said different amino acid is A, H, K, N, or R;
- at residue number 195 said different amino acid is A, H, N, Q, R, or S;
- at residue number 197 said different amino acid is A, F, L, V, or W;
- at residue number 198 said different amino acid is A, H, K, R, or S;
- at residue number 200 said different amino acid is A, H, R, or S;
- at residue number 201 said different amino acid is G, H, I, L, M, P, R, S, T, or V;
- at residue number 205 said different amino acid is A, F, H, I, K, R, T, V, W, or Y;
- at residue number 206 said different amino acid is A, F, G, H, I, K, L, M, P, R, S, V, W, or Y;
- at residue number 207 said different amino acid is F, H, I, L, P, R, V, W, or Y;
- at residue number 208 said different amino acid is A, H, K, R, or S;
- at residue number 209 said different amino acid is G, M, P, S, T, or V;
- at residue number 211 said different amino acid is A, H, R, or S;
- at residue number 213 said different amino acid is A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, W, or Y;
- at residue number 214 said different amino acid is A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, W, or Y;
- at residue number 215 said different amino acid is A, C, D, F, H, I, K, L, M, N, P, Q, R, S, T, V, W, or Y;
- at residue number 216 said different amino acid is A, G, L, M, P, or V;
- at residue number 223 said different amino acid is A, F, H, R, S, or W;
- or
- at residue number 226 said different amino acid is A, G, L, or P;
- wherein said residue numbers correspond to residue numbers of human heregulin-β1 (SEQ ID NO:
- 93) numbered from the N-terminus.
28 more elements
A method of determining whether a sample contains an ErbB receptor that binds a heregulin comprising:
- (a) contacting a variant of a heregulin with said sample;
- and
- (b) determining whether said heregulin variant specifically binds a component of said sample as an indication of the presence of an ErbB receptor;
- said variant having the ability to bind an ErbB receptor, wherein said variant comprising a different amino acid than in said heregulin, wherein:
- at residue number 177 said different amino acid is A, F, W, or Y;
- at residue number 178 said different amino acid is A, D, E, G, L, N, P, Q, R, T V or W;
- at residue number 179 said different amino acid is A, G, L, M, P, S or V;
- at residue number 180 said different amino acid is A, D, E, G, H, I, K, M, N, P, Q, or R;
- at residue number 181 said different amino acid is A, G, I, L, P, or V;
- at residue number 183 said different amino acid is A, G, I, L, M, S, or T;
- at residue number 184 said different amino acid is A, F, G, H, I, K, L, M, N, P, Q, R, S, V, or W;
- at residue number 185 said different amino acid is A, G, H, I, K, L, M, N, P, Q, S, T, or V;
- at residue number 186 said different amino acid is A, K, R, or S;
- at residue number 187 said different amino acid is A, E, G, I, L, M, N, P, Q, S, or T;
- at residue number 188 said different amino acid is A, H, K, N, or R;
- at residue number 195 said different amino acid is A, H, N, Q, R, or S;
- at residue number 197 said different amino acid is A, F, L, V, or W;
- at residue number 198 said different amino acid is A, H, K, R, or S;
- at residue number 200 said different amino acid is A, H, R, or S;
- at residue number 201 said different amino acid is G, H, I, L, M, P, R, S, T, or V;
- at residue number 205 said different amino acid is A, F, H, I, K, R, T, V, W, or Y;
- at residue number 206 said different amino acid is A, F, G, H, I, K, L, M, P, R, S, V, W, or Y;
- at residue number 207 said different amino acid is F, H, I, L, P, R, V, W, or Y;
- at residue number 208 said different amino acid is A, H, K, R, or S;
- at residue number 209 said different amino acid is G, M, P, S, T, or V;
- at residue number 211 said different amino acid is A, H, R, or S;
- at residue number 213 said different amino acid is A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, W, or Y;
- at residue number 214 said different amino acid is A, C, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, W, or Y;
- at residue number 216 said different amino acid is A, G, L, M, P, or V;
- at residue number 223 said different amino acid is A, F, H, R, S, or W;
- or
- at residue number 226 said different amino acid is A, G, L, or P;
- wherein said residue numbers correspond to residue numbers of human heregulin-β1 (SEQ ID NO:
- 93) numbered from the N-terminus.
31 more elements
Dependencies are inferred from the claim text.