Juridical Foundation the Chemo-sero-therapeutic Research Institute

Km Biologics Co., Ltd.

Astellas Pharma Gmbh

Kowa Company Limited

Japan Science and Technology Agency

Kumamoto University

The Chemo-sero-therapeutic Research Institute

Judicial Foundation the Chemo-sero-therapeutic Res.

The Chemo-sero-therapeutic Reserach Institute

National University Corporation Kumamoto University

Toshihiro Nakashima

Masaharu Torikai

Kazuhisa Sugimura

Hirofumi Higuchi

Kenji Soejima

Nobuchika Yamamoto

Tsukasa Nishihara

Yu Su

Hirofumi Jono

Yukio Ando

Takumi Sasaki

Fumihiko Sakai

Akihiko Hosoi

Tomoyo Takeo

Masayo Ueno

Masao Ohkuchi

Tomoyuki Koshi

Toshiyuki Edano

Hirotada Fujita

Daisuke Ishikawa

Atsuko Sakata

Mineyuki Mizuguchi

Kenji Nakanishi

Hiroyuki Shimizu

Hiroaki Maeda

Kazuhiko Kimachi

Toshimitsu Uede

Shigeyuki Kon

Kazuyuki Yoshizaki

Miyuki Matsumoto

Sumiyo Takemoto

Katsunari Taguchi

Shigeki Kuwata

Yoshiyuki Tokieda

Masato Yuguchi

Sho Matsushita

Kenji Uehara

A human antibody which comprises a complementarity determining region of an H chain consisting of the amino acid sequence as shown in SEQ ID NOs: 1 to 3 and a complementarity determining region of an L chain consisting of the amino acid sequence as shown in SEQ ID NOs: 4 to 6. The human antibody of the present invention has the activity to specifically bind to transthyretin (TTR) with structural change and the activity to inhibit fibrillization of TTR and is a human antibody suitable for application to human body.

Anti-transthyretin human antibody

A humanized antibody which comprises a complementarity determining region of an H chain consisting of the amino acid sequence as shown in SEQ ID NOs: 1 to 3 and a complementarity determining region of an L chain consisting of the amino acid sequence as shown in SEQ ID NOs: 4 to 6. The humanized antibody of the present invention has the activity to specifically bind to transthyretin (TTR) with structural change and the activity to inhibit fibrillization of TTR and is a humanized antibody suitable for application to human body.

Anti-transthyretin humanized antibody

The present invention relates to a human anti-human IL-18 antibody which reacts with human interleukin-18 (human IL-18) and does not react with a K53A variant of human IL-18.

Human antibody against IL-18

The present invention provides for a method for improving properties of an antibody such as an expression level and stability. A method for obtaining an antibody with an improved expression level and/or stability by modifying human antibody or a humanized antibody, characterized by that at least any one of the amino acid residues at position 8, 12, 15 or 18 (according to Kabat numbering) in a light chain variable region (hereinafter referred to as 'VL chain') of a human antibody or a humanized antibody is substituted with a different amino acid other than proline or cysteine, and a human antibody or a humanized antibody or a human antibody fragment or a humanized antibody fragment with an improved expression level and/or stability which are obtained by said method.

Method for improving antibody

The present invention provides for a method for improving properties of an antibody such as an expression level and stability. A method for obtaining an antibody with an improved expression level and/or stability by modifying a human antibody or a humanized antibody, characterized by that at least any one of the amino acid residues at position 8, 12, 15 or 18 (according to Kabat numbering) in a light chain variable region (hereinafter referred to as 'VL chain') of a human antibody or a humanized antibody is substituted with a different amino acid other than proline or cysteine, and a human antibody or a humanized antibody or a human antibody fragment or a humanized antibody fragment with an improved expression level and/or stability which are obtained by said method.

The present invention provides a human anti-&#x3b1;9 integrin antibody or an antibody fragment which specifically recognize human &#x3b1;9 integrin and mouse &#x3b1;9 integrin, inhibit interaction with their ligands, particularly, the antibody or antibody fragment which recognize loop regions of human and mouse &#x3b1;9 integrins, a gene encoding the antibody or antibody fragment, a recombinant expression vector containing the gene, a transformant harboring the gene, production method of human anti-&#x3b1;9 integrin antibody or antibody fragment using the transformant, and an agent for the prophylaxis or treatment of rheumatoid arthritis which contains the antibody or antibody fragment.

Human anti-&#x3b1;9 integrin antibody

The present invention provides a humanized anti-human &#x3b1;9 integrin antibody having improved activity and/or property as compared to a donor mouse anti-human &#x3b1;9 integrin antibody, namely, a humanized anti-human &#x3b1;9 integrin antibody containing a heavy-chain variable region consisting of the amino acid sequence shown by SEQ ID NO:11 and a light-chain variable region consisting of the amino acid sequence shown by SEQ ID NO:17, a humanized anti-human &#x3b1;9 integrin antibody containing a heavy-chain variable region consisting of the amino acid sequence shown by SEQ ID NO:13 and a light-chain variable region consisting of the amino acid sequence shown by SEQ ID NO:17, a humanized anti-human &#x3b1;9 integrin antibody containing a heavy-chain variable region consisting of the amino acid sequence shown by SEQ ID NO:15 and a light-chain variable region consisting of the amino acid sequence shown by SEQ ID NO:9, and a means for the prophylaxis or treatment of various diseases involving human &#x3b1;9 integrin in the pathogenesis, which uses the antibody.

Humanized anti-human &#x3b1;9-integrin antibody

A novel prophylactic/remedy for immunopathy is provided which is not neutralized by a neutralizing antibody to Staphylococcal enterotoxin B (SEB), known as one of superantigens, and may effectively act as a superantigen. A modified SEB having a reduced reactivity with a neutralizing antibody to SEB (anti-SEB antibody) and a prophylactic/remedy for immunopathy comprising as an active ingredient said modified SEB. The modified SEB of the present invention may be prepared with the evolutionary molecular engineering technique by introducing amino acid substitution in the amino acid sequence of SEB, especially at an epitope recognition site of the anti-SEB antibody in the amino acid sequence of SEB.

Modified SEB and prophylactics/remedies for immunopathy containing the same

A human anti-amyloid &#x3b2; peptide (hereinafter referred to as 'A&#x3b2;') antibody that binds to A&#x3b2; to thereby inhibit aggregation of A&#x3b2; molecules, and a fragment of said antibody are provided. The antibody and a fragment thereof according to the present invention, comprising a variable region of a human-derived anti-A&#x3b2; antibody, strongly reacts with A&#x3b2; to thereby inhibit its aggregation and hence may be used as a medicament for the prophylaxis and treatment of Alzheimer dementia.

Human anti-amyloid beta peptide antibody and fragment of said antibody

A modified Staphylococcal enterotoxin B (SEB) having resistance to a protease and a reduced toxicity and a vaccine comprising said modified SEB are provided. A modified SEB which has an amino acid sequence as set forth in SEQ ID NO: 1 wherein each of the lysine at 97-position and the lysine at 98-position are substituted with any other amino acid, or a derivative thereof and a vaccine comprising said modified SEB or a derivative thereof.

Protease-resistant modified SEB and vaccine containing the same

The present invention provides a humanized anti-human osteopontin antibody having better activities (antigen binding activity, leukocyte migration inhibitory activity and the like) and/or stability (resistance to heat, low-pH conditions, denaturants and the like) than those of conventional anti-human osteopontin antibodies.

Humanized anti-human osteopontin antibody

Human anti-amyloid &#x3b2; peptide antibody and fragment of said antibody

A human-derived human anti-human IL-18 antibody of the present invention is an antibody against human IL-18, the antibody including: an H-chain complementarity determining region consisting of (a) a polypeptide consisting of amino-acid sequences represented by SEQ ID NOS: 4 to 6, or (b) a polypeptide which is a mutant of the polypeptide (a) and which serves as the H-chain complementarity determining region; and an L-chain complementarity determining region against human interleukin-18 consisting of (c) a polypeptide consisting of amino-acid sequences represented by SEQ ID NOS: 10 to 12, or (d) a polypeptide which is a mutant of the polypeptide (c) and which serves as the L-chain complementarity determining region. This makes it possible to provide a human anti-human IL-18 antibody and a method for using the antibody.

Human anti-human interleukin-18 antibody, fragment thereof and method for using same

A substance effective for treating immunopathy where interleukin 6 (IL-6) is involved is provided. A human anti-human IL-6 antibody and a human anti-human IL-6 antibody fragment having a high affinity to human IL-6 were obtained using phage antibody technique. The antibody and antibody fragment are expected to be useful as a medicament for treating inflammation and immunopathy caused by IL-6.

Human antihuman interleukin-6 antibody and fragment of antibody

Growing community of inventors

Kikuchi, Japan

Toshihiro Nakashima