Bifunctional molecules for treatment of immune disorders
AssigneeJN Biosciences LLC
InventorsNaoya Tsurushita, J. Yun Tso
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Abstract
The invention provides bifunctional molecules including an antibody specifically binding to CD122 and an extracellular domain of CTLA-4. The bifunctional molecules specifically bind to CD122 and CTLA-4 ligands, CD80 and CD86 and inhibit their function in immune activation. The bifunctional molecules can inhibit interaction of CD122 with its ligands IL-2 and IL-15 and inhibit interaction of CD80 and CD86 with their counter-receptor, CD28. These bifunctional molecules can suppress Signals 2 and 3 of immune responses as a single therapeutic agent for treatment of immune disorders.
Claims25
A bifunctional molecule comprising an antibody that binds to CD122 and inhibits its interaction with IL-2 and IL-15, comprising
- (a) a mature light chain linked to a CTLA-4 extracellular domain as a chain comprising SEQ ID NO:34 or 42 and a mature heavy chain comprising SEQ ID NO:8 or 33 provided the C-terminal lysine can be omitted, or
- (b) a mature heavy chain linked to a CTLA-4 extracellular domain as a chain comprising SEQ ID NO:39 provided the C-terminal lysine can be omitted, and a mature light chain comprising SEQ ID NO:9.
A bifunctional molecule comprising a mature heavy chain linked to a CTLA-4 extracellular domain as a chain comprising SEQ ID NO:13 or 16 and a mature light chain comprising SEQ ID NO:9.
A bifunctional molecule comprising a mature heavy chain linked to a CTLA-4 extracellular domain as a chain comprising SEQ ID NO:57 and a mature light chain comprising SEQ ID NO:54.
A bifunctional molecule comprising a mature heavy chain linked to a CLTA-4 extracellular domain as a chain comprising SEQ ID NO:56 provided the C-terminal lysine can be omitted, and the mature light chain comprises SEQ ID NO:54.
A bifunctional molecule comprising an antibody that binds to CD122 and inhibits its interaction with IL-2 and IL-15, wherein the antibody comprises a heavy chain comprising a mature heavy chain variable region linked to a heavy chain constant region, and a light chain comprising a mature light chain variable region linked to a light chain constant region, wherein the antibody is linked to a CTLA-4 extracellular domain having at least 90% sequence identity with SEQ ID NO:10 and the mature heavy chain variable region comprises three heavy chain CDRs comprising SEQ ID NOS:59-61 respectively and the mature light chain variable region comprises three light chain CDRs comprising SEQ ID NOS:63-65 respectively.
A bifunctional molecule comprising a mature heavy chain linked to a CTLA-4 extracellular domain as a chain comprising SEQ ID NO:71 and a mature light chain comprising SEQ ID NO:67.
Dependencies are inferred from the claim text.