Chugai Seiyaku Kabushiki Kaisha

Hitoshi Katada

Tomoyuki Igawa

Futa Mimoto

Taichi Kuramochi

Shojiro Kadono

Yuji Hori

Yoshinao Ruike

Hiroyasu Muramatsu

Atsunori Ueyama

Hirotake Shiraiwa

Atsuhiko Maeda

Tatsuhiko Tachibana

Yuki Iwayanagi

Kenta Haraya

Meiri Kawazoe

Takeaki Kawai

The present inventors produced a heterodimerized polypeptide having an Fc region formed from two polypeptides with different amino acid sequences (a first polypeptide and a second polypeptide), and succeeded in producing a heterodimerized polypeptide containing an Fc region with improved Fc region function compared to that of a homodimer in which the Fc region is composed of only the first polypeptide or only the second polypeptide by conventional technology.

Heterodimerized polypeptide

It is intended to provide a method for efficiently and stably producing a heteromultimer by incubating homo variants of plural types of heavy chain constant region-containing polypeptides differing in antigen-binding activity under a reducing condition that reorganize the inter-polypeptide disulfide bond between cysteine residues outside of core hinge regions. A feature of the production method of the present invention is that amino acid residues in the core hinge regions do not form any disulfide bond.

Method for producing polypeptide hetero-oligomer

The disclosure provides anti-myostatin antibodies and methods of making and using the same. Nucleic acids encoding the anti-myostatin antibodies and host cells comprising the nucleic acids are also provided. The anti-myostatin antibodies have uses that include treating a muscle wasting disease, reducing body fat accumulation, and increasing mass and strength of muscle tissue. The disclosure also provides polypeptides containing a variant Fc region and methods of making and using the same. Nucleic acids encoding the polypeptides and host cells comprising the nucleic acids are also provided. The polypeptides have uses that include suppressing the activation of immune cells; treating an immunological inflammatory disease, autoimmune disease, or viral infection; and increasing muscle mass and strength or reducing body fat accumulation.

Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use

The present invention relates to pharmaceutical compositions containing a combination of a first antigen-binding molecule and a second antigen-binding molecule, wherein the first antigen-binding molecule and the second antigen-binding molecule are not linked by a covalent bond, and they are more likely to form a heterodimer than homodimers when mixed in solution. Furthermore, the present invention relates to antigen-binding molecules, therapeutic methods, and screening methods that are associated with the combination.

Compositions comprising antigen-binding molecules

The present invention demonstrated that the modification of the Fc region of an antigen-binding molecule into an Fc region that does not form in a neutral pH range a heterotetramer complex containing two molecules of FcRn and an active Fc&#x3b3; receptor improved the pharmacokinetics of the antigen-binding molecule and reduced the immune response to the antigen-binding molecule. The present invention also revealed methods for producing antigen-binding molecules having the properties described above, and successfully demonstrated that pharmaceutical compositions containing as an active ingredient such an antigen-binding molecule or an antigen-binding molecule produced by a production method of the present invention have excellent features over conventional antigen-binding molecules in that when administered, they exhibit improved pharmacokinetics and reduced in vivo immune response.

Method for altering plasma retention and immunogenicity of antigen-binding molecule

Anti-myostatin antibodies, polypeptides containing variant Fc regions, and methods of use

A polypeptide containing an antibody Fc region variant which has an amino acid sequence in which an amino acid alteration at position 238 according to EU numbering is combined with other specific amino acid alteration(s), was found to have decreased binding activities to all activating Fc&#x3b3;Rs, in particular Fc&#x3b3;RIIa (R type), while maintaining its Fc&#x3b3;RIIb-binding activity, when compared to a polypeptide containing a native IgG Fc region.

Fc region variant

It is intended to provide a method for efficiently and stably producing a heteromultimer by incubating, under a reducing condition, homo variants of plural types of polypeptides in which the alteration of amino acids that form the interface between Fc regions and/or the alteration to destabilize the stability of a heavy chain CH3 region has been introduced in the heavy chain CH3 regions so at to achieve the promotion of the dissociation of the Fc regions and/or the control of the association thereof through the use of charge repulsion.

Method for producing polypeptide heteromultimer

An objective of the present invention is to provide an Fc region variant with enhanced Fc&#x3b3;RIIb-binding activity, and/or enhanced binding selectivity to Fc&#x3b3;RIIb compared to Fc&#x3b3;RIIa (type R), as compared to those of a polypeptide containing an Fe region to which an amino acid alteration(s) has not been introduced; a polypeptide which includes the Fc region variant; a pharmaceutical composition containing the polypeptide; preventing therapeutic or preventive agent for immunological inflammatory diseases that includes the pharmaceutical composition; a production method thereof; and a method of enhancing Fc&#x3b3;RIIb-binding activity and also enhancing binding selectivity to Fc&#x3b3;RIIb compared to Fc&#x3b3;RIIa (type R). It was found that a polypeptide containing an antibody Fc region variant that contains an amino acid sequence in which an amino-acid alteration at position 238 (EU numbering) is combined with other specific amino-acid alterations enhances Fc&#x3b3;RIIb-binding activity, and/or enhances binding selectivity to Fc&#x3b3;RIIb compared to Fc&#x3b3;RIIa (type R).

FcgammaRIIB-specific Fc region variant

The present inventors produced a heterodimerized polypeptide having an Fc region formed from two polypeptides with different amino acid sequences (a first polypeptide and a second polypeptide), and succeeded in producing a heterodimerized polypeptide containing an Fc region with improved function compared to that of a homodimer in which the Fc region is composed of only the first polypeptide or the second polypeptide by conventional technology.

Growing community of inventors

Shizuoka, Japan

Hitoshi Katada