Kyowa Hakko Kirin Co., Limited

Kyowa Hakko Kogyo Co., Ltd.

Kyowa Kirin Co., Ltd.

Kenya Shitara

Shiro Akinaga

Toshihiko Ishii

Yuka Sasaki

Junji Kanazawa

So Ohta

Rinpei Niwa

Kazuyasu Nakamura

Nobuo Hanai

Akiko Furuya

Akito Natsume

Kenji Shibata

Motoo Yamasaki

Mikiko Sakurada

Emi Shoji

Mami Tsuchiya

Takuya Murakami

Tsuguo Kubota

Kazuhiro Masuda

Sayaka Hori

Tomoaki Nakagawa

Yuta Tezuka

Nobuaki Takahashi

Yuji Ohki

Sayaka Maeda

Yuka Sakai

Makoto Nakayama

An object of the present invention is to provide a bispecific antibody comprising an antigen-binding domain that binds to CD40 and an antigen-binding domain that binds to an epithelial cell adhesion molecule (EpCAM). The present invention relates to a bispecific antibody comprising an antigen-binding domain that binds to CD40 and an antigen-binding domain that binds to EpCAM.

Bispecific antibody which binds to CD40 and EpCAM

According to the present invention, a heterodimer protein composition that is composed of a first polypeptide comprising an immunoglobulin heavy chain constant region and a second polypeptide comprising CL-Fc prepared by fusion of an immunoglobulin light chain constant region (CL) and Fc region, and also has a deletion or substitution of Cys residues involved in disulfide bonds between CL and CH1, a purification method of the protein composition thereof, a preparation method of the protein composition thereof, a DNA and a vector encoding the protein composition thereof are provided.

Heterodimer protein composition

Among N-glycoside-linked sugar chains which are bound to the Fc region of an antibody, sugar chains which are bound to Asn at position 297 relates to the activity and stability of the antibody in blood, but there is a possibility that extra sugar chains bound to the amino acid residues at positions other than 297 have influences upon the antibody constant region-mediated activity and a possibility of causing a problem of uniformity as a therapeutic antibody preparation. Accordingly, among N-glycoside-linked sugar chains which bind to the Fc region of the antibody, a method for controlling extra sugar chains which are bound to Asn residues at positions other than position 297 according to the EU index is required. The present invention provides an antibody variant composition, comprising amino acid residues of an Asn-X-Ser/Thr (X represents an amino acid residue other than Pro) sequence at positions other than positions 297 to 299 according to the EU index in an Fc region of a human IgG antibody, in which at least one amino acid substitution selected from an amino acid substitution of Asn to other amino acid residue, an amino acid substitution of X to Pro and an amino acid substitution of Ser/Thr to other amino acid residue is carried out, and a fragment of the antibody variant composition.

Antibody variants composition

A medicament having a higher therapeutic effect than that provided by administration of a recombinant antibody against human CC chemokine receptor 4 or an antibody fragment thereof or an agent alone is provided.

Medicament comprising recombinant antibody against chemokine receptor CCR4

The present invention relates to a recombinant antibody composition having higher complement-dependent cytotoxic activity than a human IgG1 antibody and a human IgG3 antibody, wherein a polypeptide comprising a CH2 domain in the Fc region of a human IgG1 antibody is replaced by a polypeptide comprising an amino acid sequence which corresponds to the same position of a human IgG3 antibody indicated by the EU index as in Kabat, et al.; a DNA encoding the antibody molecule or a heavy chain constant region of the antibody molecule contained in the recombinant antibody composition; a transformant obtainable by introducing the recombinant vector into a host cell; a process for producing the recombinant antibody composition using the transformant; and a medicament comprising the recombinant antibody composition as an active ingredient.

Recombinant antibody composition

An anti-CD4 antibody which binds to CD4, has a high affinity and has a high effector activity, such as an antibody-dependent cellular cytotoxicity (ADCC activity) or complement-dependent cellular cytotoxicity (CDC activity), is required for a disease relating to a CD4-expressing cell. The present invention can provide a monoclonal antibody or an antibody fragment thereof, which binds to a CD4 extracellular region with high affinity and also exhibits a high ADCC activity or a high CDC activity; a hybridoma which produces the antibody; a DNA which encodes the antibody; a vector which contains the DNA; a transformant obtainable by introducing the vector; a process for producing an antibody or an antibody fragment thereof using the hybridoma or the transformant; and a therapeutic agent using the antibody or the antibody fragment thereof or a diagnostic agent using the antibody or the antibody fragment thereof.

Anti-CD4 antibody

A recombinant antibody or the antibody fragment thereof which specifically reacts with an extracellular domain of human CCR4; a DNA which encodes the recombinant antibody or the antibody fragment thereof; a method for producing the recombinant antibody or the antibody fragment thereof; a method for immunologically detecting CCR4, a method for immunologically detecting a cell which expressed CCR4 on the cell surface, a method for depleting a cell which expresses CCR4 on the cell surface, and a method for inhibiting production of Th2 cytokine, which comprise using the recombinant antibody according or antibody fragment thereof; a therapeutic or diagnostic agent for Th2-mediated immune diseases; and a therapeutic or diagnostic agent for a blood cancer.

Method for producing recombinant antibody and antibody fragment thereof

Disclosed are a recombinant antibody composition which is a human IgG1 antibody, comprises a CH2 domain in which amino acids at positions 276 and 339 indicated by the EU index as in Kabat, et al. are replaced by other amino acids and has more improved complement-dependent cytotoxic activity than an antibody comprising a CH2 domain before the amino acids are replaced; a DNA encoding the antibody molecule or a heavy chain constant region of the antibody molecule contained in the recombinant antibody composition; a transformant obtainable by introducing the DNA into a host cell; a process for producing the recombinant antibody composition using the transformant; and a medicament comprising the recombinant antibody composition as an active ingredient.

Effector function enhanced recombinant antibody composition

Method for treating the Th2-mediated disease

The present invention relates to a recombinant antibody composition which is a human IgG1 antibody, comprises a CH2 domain in which amino acids at positions 276 and 339 indicated by the EU index as in Kabat, et al. are replaced by other amino acids and has more improved complement-dependent cytotoxic activity than an antibody comprising a CH2 domain before the amino acids are replaced; a DNA encoding the antibody molecule or a heavy chain constant region of the antibody molecule contained in the recombinant antibody composition; a transformant obtainable by introducing the DNA into a host cell; a process for producing the recombinant antibody composition using the transformant; and a medicament comprising the recombinant antibody composition as an active ingredient.

Growing community of inventors

Machida, Japan

Rinpei Niwa