CTLA4-Ig immunoadhesins
The present application relates to CTLA4-Ig immunoadhesins that target CD80 and CD86, and their use, particularly for therapeutic purposes.
1. An immunoadhesin comprising a first domain comprising a variant CTLA4 as compared to SEQ ID NO:6 and a second domain comprising an IgG Fc region, wherein said CTLA4 variant comprises an amino acid modification selected from the group consisting of T51N, A29H, M53Y, L61E, and K93Q, wherein said variant provides enhanced binding to B7-1, B7-2, or both B7-1 and B7-2 as compared to SEQ ID NO:6, and wherein amino acid numbering is according to the EU index.
2. The immunoadhesin of claim 1 , wherein said immunoadhesin has an amino acid sequence selected from the group consisting of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:37, and SEQ ID NO:38.
3. The immunoadhesin of claim 1 , wherein said variant comprises a combination of substitutions selected from the group consisting of A29H/K93Q, A29H/M53Y, A29H/T51N, T51N/K93Q, T51N/M53Y, A29H/L61E/K93Q, A29H/M53Y/K93Q, A29H/M53Y/L61E, A29H/T51N/L61E, M53Y/L61E/K93Q, T51N/L61E/K93Q, T51N/M53Y/L61E, A29H/M53Y/L61E/K93Q, A29H/T51N/L61E/K93Q, A29H/T51N/M53Y/K93Q, A29H/T51N/M53Y/L61E, T51N/M53Y/L61E/K93Q, and A29H/T51N/M53Y/L61E/K93Q.
4. The immunoadhesin of claim 3 , wherein said variant comprises a combination of substitutions selected from the group consisting of T51N/L61E/K93Q, A29H/T51N/L61E/K93Q, A29H/T51N, T51N/M53Y, and T51N/M53Y/L61E.
5. The immunoadhesin of claim 3 , wherein said variant comprises substitutions A29H/T51N/L61E/K93Q.
6. The immunoadhesin of claim 3 , wherein said variant comprises substitutions T51N/L61E/K93Q.
7. The immunoadhesin of claim 3 , wherein said variant comprises substitutions A29H/T51N.
8. The immunoadhesin of claim 3 , wherein said variant comprises substitutions T51N/M53Y.
9. The immunoadhesin of claim 3 , wherein said variant comprises substitutions T51N/M53Y/L61E.