This invention provides a tetrahedral antibody comprising a first, second, third, and fourth domain, wherein each of the first and second domains are selected from the group consisting of a Fab domain and an Fc domain, wherein each of the first and second domains comprise a first polypeptide chain comprising a first N-terminus and a first C-terminus of the domain, and a second polypeptide chain comprising a second N-terminus and a second C-terminus of the domain, and wherein the first domain and the second domain are joined to each other by a non-peptidyl linkage between the first N-terminus of the first domain and the first N-terminus of the second domain, between first C-terminus of the first domain and the first C-terminus of the second domain, between the first N-terminus of the first domain and the first C-terminus of the second domain, or between the first C-terminus of the first domain and the first N-terminus of the second domain.

This invention provides a tetrahedral antibody comprising a first, second, third, and fourth domain, wherein each of the first and second domains are selected from the group consisting of a Fab domain and an Fc domain, wherein each of the first and second domains comprise a first polypeptide chain comprising a first N-terminus and a first C-terminus of the domain, and a second polypeptide chain comprising a second N-terminus and a second C-terminus of the domain, and wherein the first domain and the second domain are joined to each other by a non-peptidyl linkage between the first N-terminus of the first domain and the first N-terminus of the second domain, between first C-terminus of the first domain and the first C-terminus of the second domain, between the first N-terminus of the first domain and the first C-terminus of the second domain, or between the first C-terminus of the first domain and the first N-terminus of the second domain.

The present invention relates to Tri-Specific Binding Molecules, which are multi-chain polypeptide molecules that possess three Binding Domains and are thus capable of mediating coordinated binding to three epitopes. The Tri-Specific Binding Molecule is preferably characterized in possessing binding domains that permit it to immunospecifically bind to: (1) an epitope of a first Cancer Antigen, (2) an epitope of a second Cancer Antigen, and (3) an epitope of a molecule that is expressed on the surface of an immune system effector cell, and are thus capable of localizing an immune system effector cell to a cell that expresses a Cancer Antigen, so as to thereby facilitate the killing of such cancer cell.

The present invention relates to antigen-binding molecules, preferably antibodies or antigen-binding fragments thereof, that specifically bind to a GP73, or to an antigenic portion thereof, wherein the antigen-binding molecule binds to an epitope within the extracellular part of GP73 that is internalized into a cell usually subsequent to proteolytic cleavage. The invention further relates to immunoconjugates comprising the antigen-binding molecules, in particular the anti-GP73 antibodies, or antigen-binding fragments thereof. The antigen-binding molecules and immunoconjugates of the invention may be administered alone, as a therapeutic conjugate or in combination with other naked antibodies, or with therapeutic agents, or with other immunoconjugates or as a diagnostic conjugate. The present invention also relates to nucleotide sequences encoding anti GP73 antibodies, and immunoconjugates, vectors and host cells containing the nucleotide sequences, and methods of making anti-GP73-antibodies. The antigen-binding molecules, antibodies and compositions of the invention are useful in diagnostic and therapeutic applications for diseases in which expression of GP73 is altered, in particular in which GP73 is overexpressed, such as cancer.

Non-human animal cells and non-human animals comprising a humanized Asgr1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms.

The present disclosure provides antibody sequences found in antibodies that bind to human CD25, in particular an anti CD25-a-674 antibody which do not block the binding of CD25 to IL-2 or IL-2 signalling. The claimed antibody binds to the epitopes: QCVQGYRA and RWTQPQLICTG on CD25 Antibodies and antigen-binding portions thereof including such sequences can be used in pharmaceutical compositions and methods of treatment, in particular for treating cancer.

Various bispecific antibodies that specifically bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.

The present invention relates to bispecific antibody against human vascular endothelial growth factor (VEGF/VEGF-A) and against human angiopoietin-2 (ANG-2) of human IgG1 or IgG4 subclass with mutations I253A, H310A, and H435A, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

The present invention is directed to particular monoclonal antibodies and fragments thereof that find use in the detection, prevention and treatment of Streptococcus pneumoniae infections. In particular, these antibodies may kill Streptococcus pneumoniae or limit the replication of Streptococcus pneumoniae. Also disclosed are improved methods for producing such monoclonal antibodies.

Described herein is a bispecific molecule containing an Fc polypeptide chain and immunoglobulin variable regions. Also provided are pharmaceutical formulations comprising such molecules, nucleic acids encoding such molecules, host cells containing such nucleic acids, methods of making such molecules, and methods of using such molecules.