CTLA4 binders
AssigneeMerck Sharp & Dohme Corp.
InventorsJuha Punnonen, Maribel Beaumont, Marie-Ange Buyse, Carlo Boutton, Bruno Dombrecht, Bjorn Victor, Robert A. Kastelein
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Abstract
The present invention provides molecules, such as ISVDs and Nanobodies, that bind to CTLA4 or human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.
Claims15
A CTLA4 binder comprising one or more immunoglobulin single variable domains (ISVDs) that bind to human CTLA4
- wherein the one or more ISVDs independently comprises the amino acid sequence:
- XVQLVESGGGVVQPGGSLRLSCAASGGTFSFYGMG WFRQAPGKEREFVADIRTSAGRTYYADSVKGRFTISRDNSKNTVYLQMNSLRPEDTALYYCAAEPSGISGWDYWGQG TLVTVSS (SEQ ID NO:
- 60);
- and
- optionally comprising a half-life extender and/or a C-terminal extender.
A CTLA4 binder comprising one or more immunoglobulin single variable domains (ISVDs) that bind to human CTLA4
- wherein the one or more ISVDs independently comprises the amino acid sequence selected from SEQ ID NOs:
- 93-109;
- and
- optionally lacking the signal sequence amino acids AAADYKDHDGDYKDHDIDYKDDDDKGAAHHHHHH (amino acids 120-153 of each of SEQ ID Nos:
- 93-109) thereof.
A CTLA4 binder comprising one or more immunoglobulin single variable domains (ISVDs) that bind to human CTLA4 which comprises the amino acid sequence:
- (SEQ ID NO:
- 62)
- DVQLVESGGGVVQPGGSLRLSCAASGGTFSFYGMG
- WFRQAPGKEREFVADIRTSAGRTYYADSVKGRFTISRDNSKNTVYLQMN
- SLRPEDTALYYCAAEPSGISGWDYWGQGTLVTVSSGGGGSGGGGSGGGG
- SGGGGSGGGGSGGGGSGGGGSEVQLVESGGGVVQPGGSLRLSCAASGGT
- FSFYGMGWFRQAPGKEREFVADIRTSAGRTYYADSVKGRFTISRDNSKN
- TVYLQMNSLRPEDTALYYCAAEPSGISGWDYWGQGTLVTVSSGGGGSGG
- GGSGGGGSGGGGSGGGGSGGGGSGGGGSEVQLVESGGGVVQPGNSLRLS
- CAASGFTFSSFGMSWVRQAPGKGLEWVSSISGSGSDTLYADSVKGRFTI
- SRDNAKTTLYLQMNSLRPEDTALYYCTIGGSLSRSSQGTLVTVSSA.
A CTLA4 binder consisting of SEQ ID NO:
- 62.
A CTLA4 binder comprising one or more immunoglobulin single variable domains (ISVDs) that bind to human which comprises
- the amino acid sequence:
- (SEQ ID NO:
- 64)
- DVQLVESGGGVVQPGGSLRLSCAASGGTFSFYGMG
- WERQAPGKEREEVADIRTSAGRTYYADSVKGRFTISRDNSKNTVYLQMN
- SLRPEDTALYYCAAEPSGISGWDYWGQGTLVTVSSGGGGSGGGGSGGGG
- SGGGGSGGGGSGGGGSGGGGSEVQLVESGGGVVQPGNSLRLSCAASGET
- FSSFGMSWVRQAPGKGLEWVSSISGSGSDTLYADSVKGRFTISRDNAKT
- TLYLQMNSLRPEDTALYYCTIGGSLSRSSQGTLVTVSSA.
Dependencies are inferred from the claim text.