Abstract: The present invention relates to a fusion protein containing an erythropoietin polypeptide fused to the Fc region of mammal-derived IgG (hereinafter to be also abbreviated as EPO-Fc fusion protein). The fusion protein in which erythropoietin polypeptide has the amino acid sequence shown in SEQ ID NO: 9 or 10, and the Fc region has the amino acid sequence shown in SEQ ID NO: 3 or 4 is more superior in the property and activity and can be obtained at a high yield.

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: The present invention is directed to a variant of a parent polypeptide containing an Fc region of a dog or cat IgG, that shows a higher binding activity to a dog or cat neonatal Fc receptor (FcRn) than a binding activity of the parent polypeptide to a dog or cat FcRn, wherein the Fc region contains at least one amino acid modification. The variant shows an enhanced FcRn binding activity under acidic conditions. Using the variant, therefore, an antibody (IgG) and Fc fusion protein having longer retention in plasma can be 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: 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: 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: 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: 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: Provided herein is an animal having a persistent hypercoagulable state by implanting a cell, for example a tumor cell, in which the gene of human tissue factor is implanted to an experimental animal such as a mouse and then growing the cell, thereby persistently supplying human tissue factor to the experimental animal. This animal model is useful for research and development of therapeutic agents for diseases having a persistent hypercoagulable state. Also provided are preventive or therapeutic agents for diseases having a persistent hypercoagulable state, a hypercoagulable state resulting from infections, venous thrombosis, arterial thrombosis, and diseases resulting from the hypertrophy of vascular media, the agent comprising an antibody against human tissue factor (human TF) as an active ingredient.

Abstract: Provided herein is an animal having a persistent hypercoagulable state by implanting a cell, for example a tumor cell, in which the gene of human tissue factor is implanted to an experimental animal such as a mouse and then growing the cell, thereby persistently supplying human tissue factor to the experimental animal. This animal model is useful for research and development of therapeutic agents for diseases having a persistent hypercoagulable state. Also provided are preventive or therapeutic agents for diseases having a persistent hypercoagulable state, a hypercoagulable state resulting from infections, venous thrombosis, arterial thrombosis, and diseases resulting from the hypertrophy of vascular media, the agent comprising an antibody against human tissue factor (human TF) as an active ingredient.

Abstract: The present inventors succeeded in constructing bispecific antibodies, which bind to both the blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X, and functionally substitute for blood coagulation factor VIII/activated blood coagulation factor VIII which enhances the enzymatic reaction.

Abstract: In a storage apparatus comprising a communication interface that receives an I/O request sent from a host apparatus, a storage device controller that performs writing and reading of data with respect to a storage device, and a cache memory that stores data to be written in the storage device or data read from the storage device, a journal volume operated as a volume for which update writing is prohibited and write once is permitted is provided, on the basis of a storage area provided by the storage device, and a virtual volume is provided as a volume accessible from the host apparatus, the journal volume being the entity of the virtual volume, the virtual volume being a volume for which an attribute (Read/Add) that permits only reading and write once is settable.

Abstract: The present invention detects patterns that conform to the user conditions in cases where a disaster recovery constitution is constructed by connecting a plurality of sites. The design system is used in cases where the disaster recovery constitution is provided in a storage system. The site information acquisition section acquires information relating to the constitution in the sites and information relating to the connections between the sites, and stores the information in the site information table. The candidate pattern generation section generates candidate patterns for each of the parameters on the basis of the site information table and a basic pattern table. The candidate pattern evaluation section evaluates the respective candidate patterns by using the user condition table and presents patterns which conform to the user conditions to the user. The document output section generates a construction procedure and operating procedure on the basis of patterns selected by the user.

Abstract: In a storage apparatus comprising a communication interface that receives an I/O request sent from a host apparatus, a storage device controller that performs writing and reading of data with respect to a storage device, and a cache memory that stores data to be written in the storage device or data read from the storage device, a journal volume operated as a volume for which update writing is prohibited and write once is permitted is provided, on the basis of a storage area provided by the storage device, and a virtual volume is provided as a volume accessible from the host apparatus, the journal volume being the entity of the virtual volume, the virtual volume being a volume for which an attribute (Read/Add) that permits only reading and write once is settable.

Abstract: In the case when there are two objective biological activities, and the aim is to isolate a compound having at least one biological activity, the present inventors developed an assay method wherein a common detection marker is utilized for separately detecting the presence or absence of each of the biological activities. The present inventors discovered that a compound having at least one of two or more distinct biological activities can be efficiently and conveniently detected by simultaneously assaying at least one test sample or more by the above-mentioned method. Furthermore, for a test sample that proved to be positive by the detection method, they found that it is possible to efficiently and conveniently screen for a test sample having an objective specific biological activity by combining with a method wherein an individual activity of a test sample can be detected to specify the biological activity.