Abstract: Antigen-binding domains that are capable of binding to CD3 and CD137 but do not bind to CD3 and CD137 at the same time and methods of using the same are provided. Methods to obtain antigen binding domains which bind to two or more different antigen more efficiently are also provided.

Abstract: In a technique for controlling a first vehicle, display information and position specifying information are received from a second vehicle different from the first vehicle via inter-vehicle communications. The display information is information for display and independently set for the second vehicle in the second vehicle. The position specifying information is information for specifying a position of the second vehicle. The position of the second vehicle relative to the first vehicle is specified based on the position specifying information. Display on a display device is controlled to superimpose information indicated by the display information on the position of the second vehicle in a landscape in front of the first vehicle based on the position of the second vehicle and the display information.

Abstract: A human machine interface is configured to select an information display destination from among a plurality of display areas. The HCU acquires a sight line direction of a driver based on an image of an in-vehicle camera. The HCU displays, upon detecting a hop-off action of the driver based on an output signal of an in-vehicle sensor in a situation in which an attention target event such as a puddle, a step, other vehicle or the like exists on a road surface near a door of a driver's seat, in the display area corresponding to the driver's sight line direction, text or an image practically indicating (a) a content of an attention target event or (b) how to deal with a situation.

Abstract: The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

Abstract: The present invention provides methods for treating or preventing cancer by administering an anticancer agent and an antigen-binding molecule comprising a domain that binds to a molecule expressed on the surface of a cell having an immune response-suppressing function and a T cell receptor complex-binding domain. The present invention also provides pharmaceutical compositions for treating or preventing cancer, each comprising a combination of the anticancer agent and the antigen-binding molecule.

Abstract: It was discovered that the use of an antigen-binding molecule having a cancer-specific antigen-binding domain, and a TNF superfamily-binding domain or a TNF receptor superfamily-binding domain enables agonist activity against a factor belonging to the TNF superfamily or the TNF receptor superfamily to be exhibited only in the presence of cancer-specific antigen-expressing cells, thus leading to activation of immune cells and thereby maintain anti-tumor activity while avoiding side effects such as hepatotoxicity. It was also discovered that concomitant use of the antigen-binding molecule with an antigen-binding molecule having a cancer-specific antigen-binding domain and a T cell receptor complex-binding domain can avoid side effects while increasing the anti-tumor activity.

Abstract: It was discovered that the use of an antigen-binding molecule having a cancer-specific antigen-binding domain, and a TNF superfamily-binding domain or a TNF receptor superfamily-binding domain enables agonist activity against a factor belonging to the TNF superfamily or the TNF receptor superfamily to be exhibited only in the presence of cancer-specific antigen-expressing cells, thus leading to activation of immune cells and thereby maintain anti-tumor activity while avoiding side effects such as hepatotoxicity. It was also discovered that concomitant use of the antigen-binding molecule with an antigen-binding molecule having a cancer-specific antigen-binding domain and a T cell receptor complex-binding domain can avoid side effects while increasing the anti-tumor activity.

Abstract: A message management unit receives and accumulates a message, wherein the message is distributed for every update, is the message data representing a latest situation of a competition, an explanation generation unit generates an explanatory text for conveying unconveyed information detected from the message, based on conveyed information, a speech synthesis unit outputs a speech converted from the explanatory text, wherein the explanation generation unit stores the unconveyed information for the explanatory text as the conveyed information, stands by until completion of completion of the speech, and initiates a procedure for generating a new explanatory text based on updated unconveyed information.

Abstract: The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

Abstract: The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

Abstract: An objective of the present disclosure is to provide anti-CD137 antigen-binding molecules which have immunocyte-activating effect, cytotoxic activity, or anti-tumor activity, and meanwhile have reduced effect on non-tumor tissues such as normal tissues and produce less side effects, and methods of using the same. Anti-CD137 antigen-binding molecules which have immunocyte-activating effect, cytotoxic activity, or anti-tumor activity, and meanwhile have reduced effect on non-tumor tissues such as normal tissues and produce less side effects, are provided by discovering and producing CD137 antigen-binding molecules whose binding activity to CD137 depends on various substances (for example, small molecule compounds) in target tissues. Methods of using the same, pharmaceutical formulations, and such are also provided. The present disclosure also provides an antigen-binding molecule whose binding activity to an antigen varies depending on a small molecule compound, a preparation method thereof, and uses thereof.

Abstract: The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

Abstract: Antigen-binding domains that are capable of binding to CD3 and CD137 but do not bind to CD3 and CD137 at the same time and methods of using the same are provided. Methods to obtain antigen binding domains which bind to two or more different antigen more efficiently are also provided.

Abstract: The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

Abstract: A message management unit receives and accumulates a message, wherein the message is distributed for every update, is the message data representing a latest situation of a competition, an explanation generation unit generates an explanatory text for conveying unconveyed information detected from the message, based on conveyed information, a speech synthesis unit outputs a speech converted from the explanatory text, wherein the explanation generation unit stores the unconveyed information for the explanatory text as the conveyed information, stands by until completion of completion of the speech, and initiates a procedure for generating a new explanatory text based on updated unconveyed information.

Abstract: The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

Abstract: The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

Abstract: It was discovered that antigen-binding molecules comprising (1) a domain that binds to a molecule expressed on the surface of cells having immune response-suppressing functions and (2) a T cell receptor complex-binding domain, crosslink T cells with the cells having immune response-suppressing functions and induce damage to the cells having immune response-suppressing functions to thereby exhibit more superior antitumor effects than conventional antigen-binding molecules. It was also discovered that combined use of the antigen-binding molecules and other anticancer agents further increases the antitumor effects.

Abstract: The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.

Abstract: The present invention is based on the finding that combined use of a multispecific antibody comprising: (1) a cancer-specific antigen-binding domain, (2) a CD3-binding domain, and (3) a domain comprising an Fc region having decreased Fc? receptor-binding activity with a tumor necrosis factor (TNF) receptor superfamily agonist antibody can reduce side effects such as liver injury observed when the agonist antibody is prescribed alone, and achieve effective therapeutic effects.