Immunoconjugates comprising signal regulatory protein alpha
AssigneeDingfu Biotarget Co., Ltd.
InventorsTing Xu, Kai Fu, Yan Luan, Xiaojuan Liu, Jianjian Peng
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Abstract
Provided is an immunoconjugate useful in inhibiting tumor growth, and a composition and/or protein mixture comprising the immunoconjugate. Also provided are methods for the production of the immunoconjugate, as well as pharmaceutical uses of the immunoconjugate in inhibiting tumor growth, including but not limited to treatment of cancers.
Claims18
An immunoconjugate, which is a proteinaceous heterodimer consisting of a first member and a second member, said first member, called the first Fc subunit, comprises a targeting moiety fused to the first subunit of the human IgG Fc domain, and said second member, called the second Fc subunit, comprises a single copy of a signal regulatory protein α, or SIRPα, fused to the second subunit of the human IgG Fc domain, wherein said first Fc subunit associates with said second Fc subunit to form said proteinaceous heterodimer and wherein said first Fc subunit comprises a first modification, and the second Fc subunit comprises a second modification, and the first modification and the second modification consist of substitution mutations selected from any one of the following groups;
- 1) the first modification:
- Y349C and T366W;
- and the second modification:
- D356C, T366S, L368A, Y407V and F405K;
- 2) the first modification:
- Y349C, T366W, and F405K;
- and the second modification:
- D356C, T366S, L368A and Y407V;
- 3) the first modification:
- Y349C, T366W and K409E;
- and the second modification:
- D356C, T366S, L368A, Y407V and F405K;
- 4) the first modification:
- Y349C, T366W and K409A;
- and the second modification:
- D356C, T366S, L368A, Y407V and F405K;
- 5) the first modification:
- Y349C, T366W, F405K, K360E and Q347E;
- and the second modification:
- D356C, T366S, L368A, Y407V and Q347R;
- 6) the first modification:
- Y349C, T366W, F405K and Q347R;
- and the second modification:
- D356C, T366S, L368A, Y407V, K360E and Q347E;
- 7) the first modification:
- Y349C, T366W, K409A, K360E and Q347E;
- and the second modification:
- D356C, T366S, L368A, Y407V, F405K and Q347R;
- 8) the first modification:
- Y349C, T366W, K409A and Q347R;
- and the second modification:
- D356C, T366S, L368A, Y407V, F405K, K360E and Q347E;
- 9) the first modification:
- T366W, K409A and K392D;
- and the second modification:
- T366S, L368A, Y407V, D399S and F405K;
- 10) the first modification:
- T366W and K409A;
- and the second modification:
- T366S, L368G, Y407A and F405K;
- 11) the first modification:
- T366W, K409A and Y349D;
- and the second modification:
- T366S, L368A, Y407V, F405K and E357A;
- 12) the first modification:
- T366W, K409A, Y349D and S354D;
- and the second modification:
- T366S, L368A, Y407V, F405K and E357A;
- 13) the first modification:
- T366W and F405K;
- and the second modification:
- T366S, L368A, Y407V and K409A;
- 14) the first modification:
- T366W, F405K and D399S;
- and the second modification:
- T366S, L368A, Y407V, K409A and K392D;
- 15) the first modification:
- T366W and F405K;
- and the second modification:
- T366S, L368G, Y407A and K409A;
- 16) the first modification:
- T366W, F405K and Y349D;
- and the second modification:
- T366S, L368A, Y407V, K409A and E357A;
- 17) the first modification:
- T366W, F405K, Y349D and S354D;
- and the second modification:
- T366S, L368A, Y407V, K409A and E357A;
- wherein the position of the amino acid is determined according to the EU index of the KABAT number;
- and wherein said Fc domain is a human IgG Fc domain;
- wherein said targeting moiety comprises an antigen-binding domain of an anti-PD-L1 antibody, and said SIRPα has an amino acid sequence as set forth in SEQ ID NO:
- 122 or 123.
Dependencies are inferred from the claim text.