Abstract: Disclosed herein are multimeric molecular complexes and compounds that are multivalent, i.e., they have two or more targeting elements directed to a ligand that confers paracellular transporting properties and/or transcytotic properties to complexes and compounds to which it is bound. The complexes and compounds have properties that are different from the properties of monomers, complexes and compounds having only one targeting element directed to a paracellular and/or transcytotic ligand. The complexes and compounds of the invention undergo endocytosis, transcytosis and exocytosis; following endocytosis, the complexes or compounds may be transported into the cytosol or an organelle of a cell. In polarized cells, transcytosis can proceed in a “forward” or “reverse” direction. Reverse transcytosis is used for the non-invasive delivery of biologically active agents from the lumen of, e.g., the gastrointestinal tract or the airways of lungs, to the circulatory system.

Abstract: The invention provides compositions and methods, including screening assays, for obtaining ligands (targeting elements) directed to a target molecule that undergoes apical endocytosis, reverse transcytosis, and/or basolateral exocytosis. Further provided are methods of identifying molecules that specifically bind a transcytotic molecule. Further provided are methods of identifying phage displaying a polypeptide, and determining the sequence of the polypeptide, that gives phage the ability to penetrate a layer of epithelial cells. Such polypeptides may confer paracellular transporting properties and/or transcytotic properties.

Abstract: Disclosed herein are multimeric molecular complexes and compounds that are multivalent, i.e., they have two or more targeting elements directed to a ligand that confers paracellular transporting properties and/or transcytotic properties to complexes and compounds to which it is bound. The complexes and compounds have properties that are different from the properties of monomers, complexes and compounds having only one targeting element directed to a paracellular and/or transcytotic ligand. The complexes and compounds of the invention undergo endocytosis, transcytosis and exocytosis; following endocytosis, the complexes or compounds may be transported into the cytosol or an organelle of a cell. In polarized cells, transcytosis can proceed in a “forward” or “reverse” direction. Reverse transcytosis is used for the non-invasive delivery of biologically active agents from the lumen of, e.g., the gastrointestinal tract or the airways of lungs, to the circulatory system.

Abstract: Disclosed herein are complexes and compounds that pass through cellular barriers to deliver compounds into, through and out of cells, and methods of producing and using such complexes and compounds. The complexes and compounds of the invention comprise a biologically active portion and a targeting element directed to a ligand that confers transcellular, transcytotic or paracellular transporting properties to an agent specifically bound to the ligand, with the proviso that the targeting element is not an antibody. Also disclosed are complexes and compounds that comprise two or more targeting elements directed to a ligand that confers transcellular, transcytotic or paracellular transporting properties to an agent specifically bound to the ligand. Preferred ligands include but are not limited to the stalk of pIgR, a pIgR domain, an amino acid sequence that is conserved among pIgR's from different animals, and one of several regions of pIgR defined herein.

Abstract: The present invention relates to a method of enhancing the efficacy of one or more agents in a subject by administering the agent or agents and a context-dependent functional entity to the subject, wherein a context-dependent functional entity includes a substructure with thrombogenic potential operably linked to a selective recognition domain, and interacts with a function-forming context expressed by a cell or tissue in the subject. The invention also relates to a method of treating a pathologic condition in a subject by administering to the subject a therapeutic agent and a context-dependent functional entity. The invention further relates to a pharmaceutical composition, which contains an agent and a context-dependent functional entity in a pharmaceutically acceptable form. The invention further provides a peptide having the amino acid sequence Pro-Arg-Lys-Leu-Tyr-Asp (SEQ ID NO: 1).

Abstract: Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a said preselected antigen by the binding site of each said polypeptide chain when administered to said mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

Abstract: The present invention is directed toward compositions comprising one or more transportable complexes and one or more carriers and methods of making and using the same.

Abstract: Disclosed is DNA encoding a single-chain Fv (sFv) polypeptide defining a binding site which exhibits the immunological binding properties of an immunoglobulin molecule which binds c-erbB-2 or a c-erbB-2-related tumor antigen, the sFv includes at least two polypeptide domains connected by a polypeptide linker spanning the distance between the C-terminus of one domain and the N-terminus of the other, the amino acid sequence of each of the polypeptide domains includes a set of complementarity determining regions (CDRs) interposed between a set of framework regions (FRs), the CDRs conferring immunological binding to the c-erbB-2 or c-erbB-2-related tumor antigen.

Abstract: Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a said preselected antigen by the binding site of each said polypeptide chain when administered to said mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

Abstract: Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a preselected antigen by the binding site of each polypeptide chain when administered to a mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

Abstract: A method for controlling the overgrowth of hyperproliferating cells in the presence of non-proliferating cells by exposing the hyperproliferating cells to a toxin conjugate that has a binding region that binds to an internalizable element of the hyperproliferating cell and a toxic moiety bound thereto is provided. The toxin conjugate may be a monoclonal antibody to transferrin receptor. Such toxin conjugates will have use in controlling hyperproliferative diseases of the integument and the eye.

Abstract: Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a said preselected antigen by the binding site of each said polypeptide chain when administered to said mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

Abstract: Proteins are described that affect adhesion of white blood cells (WBCs) to endothelial cells (ECs). The proteins include inter-.alpha.-trypsin inhibitor, .alpha..sub.1 -M, and HI-30. When administered in therapeutically effective amounts, these proteins can alter adhesion between WBCs and ECs to ultimately prevent inflammatory-type diseases.

Abstract: Ricin B muteins, ricin and ricin precursors having at least one amino acid of at least one galactoside binding site altered to decrease the binding of ricin B to galactosides are claimed. DNA sequences encoding the ricin B muteins, ricin and ricin precursor in which the B chain thereof is the ricin B mutein are claimed. Recombinant expression vectors effective in expressing the DNA sequences of the ricin B muteins, ricin and ricin precursors are claimed. Host cells transformed with the foregoing expression vectors are also claimed. Conjugates comprising binding moieties such as antibodies, hormones, and lymphokines bound to the ricin B mutein and ricin wherein the B chain thereof is the mutein is also claimed.

Abstract: Heterobifunctional crosslinkers up to about 34 .ANG. in length consisting of a sulfhydryl reactive group linked to a spacer group, which in turn is linked to an activated carboxylate group, that are useful for making efficacious anticancer immunotoxin conjugates as shown preferably by reacting an antibody associated amino group with the activated carboxylate group to form an antibody crosslinker complex and reacting the antibody crosslinker complex with a cytotoxin having a reactive sulfhydryl group with the sulfhydryl reactive group of the crosslinker, and using the conjugates so produced to treat cancer patients.

Abstract: Anti-tumor activity in humans can be augmented by administering to the mammalian host a pharmacologically effective amount of mammalian IL-2 and at least one immunotoxin that binds selectively to human tumor cells. The IL-2 and immunotoxin are preferably administered separately to the host. The composition is useful for prophylactic or therapeutic treatment of such cancers as ovarian and breast cancer.

Abstract: Anti-tumor activity in humans can be augmented by administering to the mammalian host a pharmacologically effective amount of mammalian IL-2 and at least one immunotoxin that binds selectively to human tumor cells. The IL-2 and immunotoxin are preferably administered separately to the host. The composition is useful for prophylactic or therapeutic treatment of such cancers as ovarian and breast cancer.