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公开(公告)号：US20220064264A1
公开(公告)日：2022-03-03
申请号：US17530542
申请日：2021-11-19
摘要： By altering amino acid sequences, the present inventors successfully produced constant regions that can confer antibodies with particularly favorable properties for pharmaceutical agents. When used to produce antibodies, the altered constant regions produced according to the present invention significantly reduce heterogeneity. Specifically, the antibody homogeneity can be achieved by using antibody heavy chain and light chain constant regions introduced with alterations provided by the present invention. More specifically, the alterations can prevent the loss of homogeneity of antibody molecules due to disulfide bond differences in the heavy chain. Furthermore, in a preferred embodiment, the present invention can improve antibody pharmacokinetics as well as prevent the loss of homogeneity due to C-terminal deletion in antibody constant region.
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公开(公告)号：US20220010030A1
公开(公告)日：2022-01-13
申请号：US17483898
申请日：2021-09-24
发明人： Tomoyuki Igawa , Hitoshi Katada , Yuji Hori , Shojiro Kadono
摘要： 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.
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公开(公告)号：US11214623B2
公开(公告)日：2022-01-04
申请号：US15512094
申请日：2015-09-24
摘要： The present inventors attempted to produce antibodies that neutralize the activity of a substance having an activity of functionally substituting for FVIII to be used for the method of measuring the reactivity of FVIII in the presence of a substance having an activity of functionally substituting for FVIII. As a result, the inventors discovered that by using the produced antibodies, FVIII activity in the plasma of a hemophilia A patient can be evaluated accurately by one-stage clotting assay based on APTT, and also that FVIII inhibitor titer in the plasma of a hemophilia A patient carrying a FVIII inhibitor can be evaluated accurately by Bethesda assay based on APTT.
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公开(公告)号：US11180548B2
公开(公告)日：2021-11-23
申请号：US16697310
申请日：2019-11-27
发明人： Tomoyuki Igawa , Atsuhiko Maeda , Kenta Haraya , Tatsuhiko Tachibana , Yuki Iwayanagi , Yuji Hori , Genki Nakamura , Masaru Muraoka
IPC分类号： A61K39/00 , C07K16/24 , C07K16/36 , C07K16/18 , C07K16/28 , C07K16/40 , C07K16/42 , G01N33/68
摘要： One nonexclusive aspect provides molecules further improved from antibodies that can bind to antigens in an ion concentration-dependent manner. An alternative nonexclusive aspect provides safe and more advantageous Fc region variants that have decreased binding to pre-existing ADA. An alternative nonexclusive aspect provides novel IL-8 antibodies that are superior as pharmaceuticals.
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公开(公告)号：US20210324109A1
公开(公告)日：2021-10-21
申请号：US17359867
申请日：2021-06-28
IPC分类号： C07K16/40
摘要： The present inventors discovered that the half-life in blood of an IgG antibody which is a polypeptide comprising an FcRn-binding domain can be controlled by controlling the surface charge through modification of residues exposed on the surface among residues in the variable regions of the IgG antibody. Antibodies whose half-life in blood had been controlled by the methods of the present invention were confirmed to actually retain the original activity. The methods of the present invention are widely applicable to polypeptides comprising an FcRn-binding domain, such as IgG antibodies, which are recycled via the FcRn salvage pathway regardless of the type of target antigen.
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公开(公告)号：US11142563B2
公开(公告)日：2021-10-12
申请号：US14406232
申请日：2013-06-14
发明人： Tomoyuki Igawa , Naoka Hironiwa , Shojiro Kadono , Atsushi Matsuo , Taichi Kuramochi , Futa Mimoto
摘要： The present inventors have successfully prepared an antibody Fc region dimer that has binding activity against each of an antigen and FcγR, but does not bind to the antigen and the FcγR at the same time, and a polypeptide comprising the Fc region dimer. The present invention enables the preparation of a multispecific binding polypeptide capable of avoiding an adverse reaction that may be caused by its binding to an antigen and FcγR at the same time. Thus, the present invention provides a polypeptide suitable as a drug.
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公开(公告)号：US11059881B2
公开(公告)日：2021-07-13
申请号：US16742053
申请日：2020-01-14
IPC分类号： G01N33/68 , G01N11/00 , G01N23/201 , C07K16/00 , C07K16/18 , C07K16/28 , C07K16/30 , C07K16/36
摘要： The inventors discovered that viscosity of a protein solution can be estimated by measuring the apparent particle size or apparent molecular weight by a small angle X-ray scattering (SAXS) method or X-ray solution scattering method, which enables measurement of small amounts of samples, and then correlating those measurement results with viscosity of the protein solution.
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公开(公告)号：US11001643B2
公开(公告)日：2021-05-11
申请号：US15963221
申请日：2018-04-26
发明人： Junichi Nezu , Atsushi Narita , Takahiro Ishiguro , Mika Sakurai , Hirotake Shiraiwa , Naoka Hironiwa , Tomoyuki Igawa , Yumiko Kawai
摘要： Multi specific antigen-binding molecules maintaining excellent cellular cytotoxicity and high stability, which comprise a domain that contains an antibody variable region having glypican 3-binding activity and a domain that contains an antibody variable region having T-cell receptor complex-binding activity are provided. Since the provided molecules show a strong cytotoxicity against cells and tissues expressing glypican 3, it is possible to produce pharmaceutical compositions for treating or preventing various cancers.
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公开(公告)号：US10759870B2
公开(公告)日：2020-09-01
申请号：US16099341
申请日：2018-09-27
发明人： Yuri Teranishi , Kazuki Kato , Hikaru Koga , Tomoyuki Igawa , Kazuki Yamaguchi , Tetsuhiro Soeda
IPC分类号： A61K39/395 , C07K16/36
摘要： Bispecific antibodies whose FIX activation-inhibiting activity is not elevated and whose FVIII cofactor function-substituting activity is elevated have been successfully discovered.
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公开(公告)号：US20190218309A1
公开(公告)日：2019-07-18
申请号：US16108897
申请日：2018-08-22
发明人： Tomoyuki Igawa , Naoka Hironiwa
CPC分类号： C07K16/4291 , A61K2039/505 , C07K16/248 , C07K16/303 , C07K16/4283 , C07K2317/31 , C07K2317/52 , C07K2317/92 , C07K2317/94 , G01N33/686 , G01N2500/04
摘要： The present inventors discovered that by forming a large immune complex comprising antigens containing two or more antigenic binding units (epitopes) and two or more antigen-binding molecules (for example, antibodies), elimination from the plasma of the antigens containing two or more antigenic binding units can be accelerated. Moreover, they found that by using this characteristic and by further using antigen-binding molecules having an ion-dependent antigen-binding activity, elimination of the antigens can further be accelerated and the above problem can be solved.
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