Abstract: The invention provides bifunctional molecules including an antibody specifically binding to CD122 and an extracellular domain of CTLA-4. The bifunctional molecules specifically bind to CD122 and CTLA-4 ligands, CD80 and CD86 and inhibit their function in immune activation. The bifunctional molecules can inhibit interaction of CD122 with its ligands IL-2 and IL-15 and inhibit interaction of CD80 and CD86 with their counter-receptor, CD28. These bifunctional molecules can suppress Signals 2 and 3 of immune responses as a single therapeutic agent for treatment of immune disorders.

Abstract: The invention provides bifunctional molecules including an antibody specifically binding to CD122 and an extracellular domain of CTLA-4. The bifunctional molecules specifically bind to CD122 and CTLA-4 ligands, CD80 and CD86 and inhibit their function in immune activation. The bifunctional molecules can inhibit interaction of CD122 with its ligands IL-2 and IL-15 and inhibit interaction of CD80 and CD86 with their counter-receptor, CD28. These bifunctional molecules can suppress Signals 2 and 3 of immune responses as a single therapeutic agent for treatment of immune disorders.

Abstract: The invention provides monoclonal antibodies that specifically bind to TIGIT. The monoclonal antibodies have the capacity for substantial activation of T cells and natural killer cells by inhibiting binding of TIGIT to CD155. The monoclonal antibodies can be used for treatment of cancer and infectious disease, among other applications.

Abstract: The invention provides bispecific antibodies having one arm binding to a cancer associated antigen on a cancer cell, such as CD33, EGFR or PD-L1, and a second arm binding to a costimulatory molecule, such as OX40, CD40, GITR, ICOS or 4-1BB. Bridging by the bispecific antibody between cancer cells expressing the cancer associated antigen and immune cells expressing the costimulatory molecule results in clustering of the costimulatory molecules and selective activation of the immune cells at a location proximate to the cancer cells. Thus, the immune cells can exert an immunotherapeutic effect against the cancer cells with reduced toxicity to healthy tissue.

Abstract: The invention provides monoclonal antibodies that specifically bind to TIGIT. The monoclonal antibodies have the capacity for substantial activation of T cells and natural killer cells by inhibiting binding of TIGIT to CD155. The monoclonal antibodies can be used for treatment of cancer and infectious disease, among other applications.

Abstract: The invention provides hybrid constant regions and antibodies or fusion proteins incorporating the same. The hybrid constant regions include at least CH2 and CH3 regions of an IgG or IgA constant region and C?3 and C?4 regions of a C? constant region. The hybrids retain properties of both component constant regions. The hybrids retain the ability of a C? constant region to form multivalent complexes, e.g., pentameric or hexameric structures. IgG hybrids also retain IgG properties including pH-dependent FcRn binding, which is associated with a relatively long in vivo half-life, and specific binding to protein G, which facilitates purification. Depending on the isotype and subtype, the nature of the antigen and presence of additional IgG CH1 and hinge domains, IgG hybrids may also retain properties of specific binding to protein A, and effector functions ADCC, CDC and opsonization. IgA hybrids retain the property of IgA of binding to an Fc-alpha receptor CD89.

Abstract: The invention provides constant regions incorporating a cysteine mutation and linked to a ? tailpiece and antibodies or fusion proteins incorporating the same. The constant regions include at least CH2 and CH3 regions of an IgG heavy chain constant region including a cysteine mutation and ? tailpiece. Antibodies or fusion proteins incorporating the constant regions gains the ability to form multivalent complexes, e.g., pentameric or hexameric structures. Antibodies or fusion proteins incorporating the constant regions also retain IgG properties including specific binding to protein G, which facilitates purification and may exhibit pH-dependent FcRn binding, which is associated with a relatively long in vivo half-life. Depending on the isotype and subtype, the nature of the antigen and presence of an additional IgG hinge domain, such antibodies or fusion proteins may also have properties of specific binding to protein A, and effector functions such as ADCC, CDC and opsonization.

Abstract: The invention provides hybrid constant regions and antibodies or fusion proteins incorporating the same. The hybrid constant regions include at least CH2 and CH3 regions of an IgG or IgA constant region and C?3 and C?4 regions of a C? constant region. The hybrids retain properties of both component constant regions. The hybrids retain the ability of a C? constant region to form multivalent complexes, e.g., pentameric or hexameric structures. IgG hybrids also retain IgG properties including pH-dependent FcRn binding, which is associated with a relatively long in vivo half-life, and specific binding to protein G, which facilitates purification. Depending on the isotype and subtype, the nature of the antigen and presence of additional IgG CH1 and hinge domains, IgG hybrids may also retain properties of specific binding to protein A, and effector functions ADCC, CDC and opsonization. IgA hybrids retain the property of IgA of binding to an Fc-alpha receptor CD89.

Abstract: The invention provides monoclonal antibodies that specifically bind to CD122, which is one component of receptors for IL-2 and IL-15. The monoclonal antibodies have the capacity for substantial inhibition of both IL-2 and IL-15 mediated functions by inhibiting binding of these cytokines to their receptors. The monoclonal antibodies can be used for inhibiting undesired immune responses or treatment of cancer, among other applications.

Abstract: The invention provides hybrid constant regions and antibodies or fusion proteins incorporating the same. The hybrid constant regions include at least CH2 and CH3 regions of an IgG or IgA constant region and C?3 and C?4 regions of a C? constant region. The hybrids retain properties of both component constant regions. The hybrids retain the ability of a C? constant region to form multivalent complexes, e.g., pentameric or hexameric structures. IgG hybrids also retain IgG properties including pH-dependent FcRn binding, which is associated with a relatively long in vivo half-life, and specific binding to protein G, which facilitates purification. Depending on the isotype and subtype, the nature of the antigen and presence of additional IgG CH1 and hinge domains, IgG hybrids may also retain properties of specific binding to protein A, and effector functions ADCC, CDC and opsonization. IgA hybrids retain the property of IgA of binding to an Fc-alpha receptor CD89.

Abstract: This present invention provides an expression vector system that uses alternative RNA processing to express in a single cell a polypeptide in both membrane-bound and soluble forms. By incorporating a mimetic structure of the 3? terminal region of human mu gene and introducing other exogenous genetic elements, an artificial gene can be constructed that is capable of simultaneously expressing membrane-bound and secreted forms of polypeptides in myeloma cells and other cells of the B lymphocyte lineage, as well as in non-B cells. If an immunoglobulin heavy chain is co-expressed with a light chain using this vector, whole antibodies can be produced that are both displayed on the surface of a single cell and secreted into the cell culture supernatant. Membrane-bound antibodies facilitate isolation and expansion of those cells displaying antibodies with desired antigen binding characteristics, while secreted antibodies facilitate identification of antibodies having desired biological function(s).

Abstract: The invention provides hybrid constant regions and antibodies or fusion proteins incorporating the same. The hybrid constant regions include at least CH2 and CH3 regions of an IgG or IgA constant region and C?3 and C?4 regions of a C? constant region. The hybrids retain properties of both component constant regions. The hybrids retain the ability of a C? constant region to form multivalent complexes, e.g., pentameric or hexameric structures. IgG hybrids also retain IgG properties including pH-dependent FcRn binding, which is associated with a relatively long in vivo half-life, and specific binding to protein G, which facilitates purification. Depending on the isotype and subtype, the nature of the antigen and presence of additional IgG CH1 and hinge domains, IgG hybrids may also retain properties of specific binding to protein A, and effector functions ADCC, CDC and opsonization. IgA hybrids retain the property of IgA of binding to an Fc-alpha receptor CD89.

Abstract: The invention provides antibodies or fusion proteins with modified heavy chain IgG constant regions that promote assembly of multimeric complexes. Within an antibody or fusion protein unit there are two heavy chains each including at least CH2 and CH3 regions. The two heavy chains bear complementary modifications (e.g., knob and hole) to promote coupling of the heavy chains within a unit. One and only one of the heavy chains in a unit is fused at its C-terminus to a homomultimerizing peptide. The presence of the homomultimerizing peptide promotes association between units. For example, if the homomultimerizing peptide is a homotrimerizing peptide it promotes association of three units to form a trimeric complex.

Abstract: The invention provides hybrid constant regions and antibodies or fusion proteins incorporating the same. The hybrid constant regions include at least CH2 and CH3 regions of an IgG or IgA constant region and C?3 and C?4 regions of a C? constant region. The hybrids retain properties of both component constant regions. The hybrids retain the ability of a C? constant region to form multivalent complexes, e.g., pentameric or hexameric structures. IgG hybrids also retain IgG properties including pH-dependent FcRn binding, which is associated with a relatively long in vivo half-life, and specific binding to protein G, which facilitates purification. Depending on the isotype and subtype, the nature of the antigen and presence of additional IgG CH1 and hinge domains, IgG hybrids may also retain properties of specific binding to protein A, and effector functions ADCC, CDC and opsonization. IgA hybrids retain the property of IgA of binding to an Fc-alpha receptor CD89.

Abstract: The invention provides constant regions incorporating a cysteine mutation and linked to a ? tailpiece and antibodies or fusion proteins incorporating the same. The constant regions include at least CH2 and CH3 regions of an IgG heavy chain constant region including a cysteine mutation and ? tailpiece. Antibodies or fusion proteins incorporating the constant regions gains the ability to form multivalent complexes, e.g., pentameric or hexameric structures. Antibodies or fusion proteins incorporating the constant regions also retain IgG properties including specific binding to protein G, which facilitates purification and may exhibit pH-dependent FcRn binding, which is associated with a relatively long in vivo half-life. Depending on the isotype and subtype, the nature of the antigen and presence of an additional IgG hinge domain, such antibodies or fusion proteins may also have properties of specific binding to protein A, and effector functions such as ADCC, CDC and opsonization.

Abstract: The invention provides hybrid constant regions and antibodies or fusion proteins incorporating the same. The hybrid constant regions include at least CH2 and CH3 regions of an IgG or IgA constant region and C?3 and C?4 regions of a C? constant region. The hybrids retain properties of both component constant regions. The hybrids retain the ability of a C? constant region to form multivalent complexes, e.g., pentameric or hexameric structures. IgG hybrids also retain IgG properties including pH-dependent FcRn binding, which is associated with a relatively long in vivo half-life, and specific binding to protein G, which facilitates purification. Depending on the isotype and subtype, the nature of the antigen and presence of additional IgG CH1 and hinge domains, IgG hybrids may also retain properties of specific binding to protein A, and effector functions ADCC, CDC and opsonization. IgA hybrids retain the property of IgA of binding to an Fc-alpha receptor CD89.

Abstract: The invention provides monoclonal antibodies that specifically bind to CD122, which is one component of receptors for IL-2 and IL-15. The monoclonal antibodies have the capacity for substantial inhibition of both IL-2 and IL-15 mediated functions by inhibiting binding of these cytokines to their receptors. The monoclonal antibodies can be used for inhibiting undesired immune responses or treatment of cancer, among other applications.

Abstract: This present invention provides an expression vector system that uses alternative RNA processing to express in a single cell a polypeptide in both membrane-bound and soluble forms. By incorporating a mimetic structure of the 3? terminal region of human mu gene and introducing other exogenous genetic elements, an artificial gene can be constructed that is capable of simultaneously expressing membrane-bound and secreted forms of polypeptides in myeloma cells and other cells of the B lymphocyte lineage, as well as in non-B cells. If an immunoglobulin heavy chain is co-expressed with a light chain using this vector, whole antibodies can be produced that are both displayed on the surface of a single cell and secreted into the cell culture supernatant. Membrane-bound antibodies facilitate isolation and expansion of those cells displaying antibodies with desired antigen binding characteristics, while secreted antibodies facilitate identification of antibodies having desired biological function(s).