Abstract: The present invention relates to targetable constructs which may be bound by a bi-specific antibody or antibody fragment having at least one arm that specifically binds a targeted tissue and at least one other arm that specifically binds the targetable construct. The targetable construct comprises a carrier portion which comprises or bears at least one epitope recognizable by at least one arm of said bi-specific antibody or antibody fragment. The targetable construct further comprises one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the targetable constructs and bi-specific antibodies or antibody fragments, as well as methods for using them.

Abstract: The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that specifically binds a targeted tissue and at least one other arm that specifically binds a targetable conjugate. The targetable conjugate comprises a carrier portion which comprises or bears at least one epitope recognizable by at least one arm of said bi-specific antibody or antibody fragment. The targetable conjugate further comprises one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bi-specific antibodies or antibody fragments, as well as methods for using them.

Abstract: The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that is reactive against a targeted tissue and at least one other arm that is reactive against a linker moiety. The linker moiety encompasses a hapten to which antibodies have been prepared. The antigenic linker is conjugated to one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bispecific antibodies or antibody fragments, as well as methods for using them.

Abstract: The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that specifically binds a targeted tissue and at least one other arm that specifically binds a targetable construct. The targetable construct comprises a carrier portion which comprises or bears at least one epitope recognizable by at least one arm of said bi-specific antibody or antibody fragment. The targetable construct further comprises one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bi-specific antibodies or antibody fragments, as well as methods for using them.

Abstract: The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that is reactive against a targeted tissue and at least one other arm that is reactive against a linker moiety. The linker moiety encompasses a hapten to which antibodies have been prepared. The antigenic linker is conjugated to one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bispecific antibodies or antibody fragments, as well as methods for using them.

Abstract: A method of making a glycosylated antibody or antibody fragment having a reactive ketone group on the glycosylated site is provided. The method comprises expressing a cell transfected with a vector encoding an antibody having one or more glycosylation sites in a culture medium comprising a ketone derivative of a saccharide or saccharide precursor and, in the case of an antibody fragment, fragmenting the resulting antibody into an antigen-binding antibody fragment. Methods of making immunoconjugates comprising the glycosylated antibodies or antibody fragments also are provided, wherein the antibody or antibody fragment is reacted with an agent comprising a ketone-reactive group. Glycosylated antibodies and antibody fragments having a reactive ketone group on the glycosylated site, immunoconjugates comprising such antibodies and antibody fragments and in vivo targeting methods using such antibodies, antibody fragments and immunoconjugates also are provided.

Abstract: A chimeric LL2 monoclonal antibody is described in which the complementarity determining regions (CDRs) of the light and heavy chains of the murine LL2 anti-B-lymphoma, anti-leukemia cell monoclona lantibody has been recombinantly joined to the human kappa and IgG1 constant region domains, respectively, which retains the immunospecificity and B-cell lymphoma and leukemia cell internalization capacity of the parental murine LL2 monoclonal antibody, and which has the potential of exhibiting reduced human anti-mouse antibody production activity.

Abstract: A humanized form of an anti-idiotype antibody to CEA, e.g., hWI2, has conserved immunoreactivity. The clinical benefits of anti-CEA antibodies are maximized by using the humanized anti-idiotype as a clearing agent for anti-CEA antibodies or antibody fragments. The humanized anti-idiotype also can be used as an immunogenic vaccine.

Abstract: A humanized specific monoclonal antibody or antibody fragment, especially a B-cell specific antibody or antibody fragment, is engineered to contain a glycosylation site in the non-Fc constant region. The glycosylated antibody is useful for diagnosis and/or therapy whenever a targeting antibody or fragment is used, especially for B-cell malignancies. The carbohydrate moiety allows conjugation of labeling or therapeutic agents of increased size, without affecting the binding affinity or specificity of the antibody.

Abstract: The present invention provides humanized, chimeric and human anti-CD74 antibodies, CD74 antibody fusion proteins, immunoconjugates, vaccines and bispecific that bind to CD74, the major histocompatibility complex (MHC) class-II invariant chain, Ii, which is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies, other malignancies in which the cells are reactive with CD74, and autoimmune diseases, and methods of treatment and diagnosis.

Abstract: A humanized form of an anti-idotype antibody to CEA, e.g., hW12, has conserved immunoreactivity. The clinical benefits of anti-CEA antibodies are maximized by using the humanized anti-idotype as a clearing agent for anti-CEA antibodies or antibody fragments. The humanized anti-idotype also can be used as an immunogenic vaccine.

Abstract: A chimeric LL2 monoclonal antibody is described in which the complementarity determining regions (CDRs) of the light and heavy chains of the murine LL2 anti-B-lymphoma, anti-leukemia cell monoclonal antibody has been recombinantly joined to the human kappa and IgG1 constant region domains, respectively, which retains the immunospecificity and B-cell lymphoma and leukemia cell internalization capacity of the parental murine LL2 monoclonal antibody, and which has the potential of exhibiting reduced human anti-mouse antibody production activity.

Abstract: The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that specifically binds a targeted tissue and at least one other arm that specifically binds a targetable construct. The targetable construct comprises a carrier portion which comprises or bears at least one epitope recognizable by at least one arm of said bi-specific antibody or antibody fragment. The targetable construct further comprises one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bi-specific antibodies or antibody fragments, as well as methods for using them.

Abstract: A chimeric LL2 monoclonal antibody is described in which the complementarity determining regions (CDRs) of the light and heavy chains of the murine LL2 anti-B-lymphoma, anti-leukemia cell monoclonal antibody has been recombinantly joined to the human kappa and IgG1 constant region domains, respectively, which retains the immunospecificity and B-cell lymphoma and leukemia cell internalization capacity of the parental murine LL2 monoclonal antibody, and which has the potential of exhibiting reduced human anti-mouse antibody production activity.

Abstract: Recombinantly-produced Onconase molecules and fusion proteins containing the same are disclosed. The recombinantly-produced Onconase molecule has the sequence of native Onconase, retains the proper folding of native Onconase and has cytotoxic activity similar to that of Onconase purified from oocytes of Rana pipiens. cDNA coding for Onconase is extended by one triplet which codes for N-formyl-methionine. When expressed recombinantly, the mutant Onconase has N-formyl-methionine as the N-terminal amino acid, and glutaminyl as the penultimate N-terminal residue. Following expression, the N-formyl methionine residue is cleaved and the penultimate glutaminyl residues is cyclized to produce Onconase with an N-terminal pyroglutamate residue, and hence the same structure and function as native Onconase.

Abstract: A humanized form of an antiidiotype antibody to CEA, e.g., hWI2, has conserved immunoreactivity. The clinical benefits of antiCEA antibodies are maximized by using the humanized antiidiotype as a clearing agent for antiCEA antibodies or antibody fragments. The humanized antiidiotype also can be used as an immunogenic vaccine.

Abstract: A novel approach, named framework (FR)-patching, to re-engineer immunoglobulin so as to reduce the potential immunogenicity, when used in the intended species, in particular, humans, without significant alterations in the specificity and affinity of the resultant immunoglobulin is described. The method differs from previously reported approaches of chimerization, CDR-grafting and/or humanization in that, the variable region sequence of the immunoglobulin to be re-engineered is compartmentalized into FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4, according to the Kabat's method, or any other conventional classification, and each individual FR sequence is dealt with separately and independently, and replaced by the corresponding FR selected from a particular host species, for example human, without modifying the CDR sequences, using a set of criteria described in this invention.

Abstract: A humanized specific monoclonal antibody or antibody fragment, especially a B-cell specific antibody or antibody fragment, is engineered to contain a glyxosylation site in the non-Fc constant region. The glycosylated antibody is useful for diagnosis and/or therapy whenever a targeting antibody or fragment is used, especially for B-cell malignancies. The carbohydrate moiety allows conjugation of labeling or therapeutic agents of increased size, without affecting the binding affinity or specificity of the antibody.

Abstract: A method of making a glycosylated antibody or antibody fragment having a reactive ketone group on the glycosylated site is provided. The method comprises expressing a cell transfected with a vector encoding an antibody having one or more glycosylation sites in a culture medium comprising a ketone derivative of a saccharide or saccharide precursor and, in the case of an antibody fragment, fragmenting the resulting antibody into an antigen-binding antibody fragment. Methods of making immunoconjugates comprising the glycosylated antibodies or antibody fragments also are provided, wherein the antibody or antibody fragment is reacted with an agent comprising a ketone-reactive group. Glycosylated antibodies and antibody fragments having a reactive ketone group on the glycosylated site, immunoconjugates comprising such antibodies and antibody fragments and in vivo targeting methods using such antibodies, antibody fragments and immunoconjugates also are provided.

Abstract: Humoral and cellular immune responses against tumor cells and infectious agents are induced in a mammal using an antibody that binds with an epitope of an antigen that is associated with a tumor or an infectious agent, and that contains at least one &agr;-galactosyl epitope. Such an antibody is capable of forming a complex with cells that express the target epitope and with antibodies that bind &agr;-galactosyl epitopes. Suitable antibodies include molecules that contain at least one engineered glycosylation site in the constant region of the heavy chain.