Merus N.v.

Ono Pharmaceutical Co., Ltd.

Pieter Fokko Van Loo

Alexander Berthold Hendrik Bakker

Shiro Shibayama

Mark Throsby

Rinse Klooster

Tomoya Tezuka

Cornelis Adriaan De Kruif

Ton Logtenberg

Takuya Shimbo

Robertus Cornelis Roovers

Cornelis Jacob Johannes George Bol

Leonardo Andres Sirulnik

Ernesto Isaac Wasserman

Alexander Berthold Bakker

The invention relates to heavy chain variable regions, binding domains and antibodies specific for human CD3, and CD3 binding proteins. The invention further relates to the use of a CD3 binding protein, preferably an antibody, of the invention in the treatment of cancer or autoimmune disease.

CD3 binding molecules

An agent for preventing, suppressing the progression of symptoms of, suppressing the recurrence of or treating autoimmune diseases, comprising a bispecific antibody or an antibody fragment thereof, having a first arm specifically binding to PD-1 and a second arm specifically binding to CD19, as described herein.

Bispecific antibody

A bispecific antibody which is capable of specifically binding to PD-1 and CD3 is disclosed. The bispecific antibody is suitable for preventing, suppressing symptom progression or recurrence of, and/or treating autoimmune diseases. Also disclosed is a formulation which can reduce occurrence of adverse infusion reactions or adverse reaction called cytokine release syndrome. The bispecific antibody has the feature to allow interaction between PD-1 and PD-L1 as its ligand, contributes enhancement or duration of its effects.

Bispecific IgG antibodies which bind to CLEC12A and an antigen on an immune effector cell are provided.

Bispecific IgG antibodies as T cell engagers

The disclosure relates to means and methods of treating a subject for a CLEC12A positive cancer. In some embodiments the method comprises treating the subject in need thereof with two or more administrations of a bispecific antibody that binds CD3 and CLEC12A, wherein in a first administration an first amount of the bispecific antibody is administered and wherein in each of the subsequent administrations the amount of bispecific antibody is higher than the amount of bispecific antibody in the first administration. In some embodiments CLEC12A positive cancer treatment methods are provided at intervals and dosing regimens that spare hemopoietic stem cell compartment allowing for recovery of normal CLEC12A positive hemopoietic cells.

CLEC12AxCD3 bispecific antibodies and methods for the treatment of disease

The invention is among others concerned with human CD3 binding antibodies comprising a heavy chain and light chain wherein said heavy chain comprises a variable region that comprises the amino acid sequence: QVQLV QSGGG VVQPG RSLRL SCVAS GFTFS SYGMH WVRQA PGKGL EWVAA IWYXXRKQDY ADSVK GRFTI SRDNS KNTLY LQMNS LRAED TAVYY CTRGT GYNWF DPWGQ GTLVT VSS with 0-5 amino acid insertions, deletions, substitutions, additions or a combination thereof at one or more positions other than the position indicated by XX; wherein X=N and X=A; X=N and X=T; X=S and X=G; X=H and X=G; X=D and X=G; or X=H and X=A. The invention is also concerned with bispecific antibodies that have a heavy chain as defined herein above. The invention is also concerned with methods of production of the antibody, cells producing the antibody and with (medical) uses of the antibody.

Human CD3 binding antibody

The invention is among others concerned with human CD3 binding antibodies comprising a heavy chain and light chain wherein said heavy chain comprises a variable region that comprises the amino acid sequence: QVQLV QSGGG VVQPG RSLRL SCVAS CFTFS SYGMH WVRQA PGKGL EWVAA IWYXXRKQDY ADSVK GRFTI SRDNS KNTLY LQMNS LRAED TAVYY CTRGT GYNWF DPWGQ GTLVT VSS with 0-5 amino acid insertions, deletions, substitutions, additions or a combination thereof at one or more positions other than the position indicated by XX; wherein X=N and X=A; X=N and X=T; X=S and X=G; X=H and X=G; X=D and X=G; or X=H and X=A. The invention is also concerned with bispecific antibodies that have a heavy chain as defined herein above. The invention is also concerned with methods of production of the antibody, cells producing the antibody and with (medical) uses of the antibody.

The invention is among others concerned with human CD3 binding antibodies comprising a heavy chain and light chain wherein said heavy chain comprises a variable region that comprises the amino acid sequence (SEQ ID NO: 61): QVQLV QSGGG VVQPG RSLRL SCVAS GFTFS SYGMH WVRQA PGKGL EWVAA IWYXXRKQDY ADSVK GRFTI SRDNS KNTLY LQMNS LRAED TAVYY CTRGT GYNWF DPWGQ GTLVT VSS with 0-5 amino acid insertions, deletions, substitutions, additions or a combination thereof at one or more positions other than the position indicated by XX; wherein X=N and X=A; X=N and X=T; X=S and X=G; X=H and X=G; X=D and X=G; or X=H and X=A. The invention is also concerned with bispecific antibodies that have a heavy chain as defined herein above. The invention is also concerned with methods of production of the antibody, cells producing the antibody and with (medical) uses of the antibody.

Growing community of inventors

Utrecht, Netherlands

Pieter Fokko Van Loo