Abstract: Antibodies having noncovalent, autophilic properties are disclosed. The autophilic antibodies are derived from antibodies conjugated with an autophilic peptide. Such autophilic antibodies can promote apoptosis of target cells and enhance therapeutic efficacies in the treatment of patients with diseases or disorders responsive to antibody therapy. Compositions containing the antibodies, and methods of making and using the antibodies are also disclosed.

Abstract: Cell suicide (apoptosis) is associated with pathogenesis, for example, it is the major cause for the loss of neurons in Alzheimer's disease. Caspase-3 is critically involved in the pathway of apoptosis. Superantibody (SAT)-trans-membrane technology has been used to produce antibodies against the caspase enzyme in an effort to inhibit apoptosis in living cells. The advantage of using trans-membrane antibodies as apoptosis inhibitors is their specific target recognition in the cell and their lower toxicity compared to conventional apoptosis inhibitors. It is shown that a MTS-transport-peptide modified monoclonal anti-caspase-3 antibody reduces actinomycin D-induced apoptosis and cleavage of spectrin in living cells. These results indicate that antibodies conjugated to a membrane transporter peptide have a therapeutic potential to inhibit apoptosis in a variety of diseases.

Abstract: There is disclosed anti-receptor and growth blocking agents to the vitamin B12/transcobalamin II receptor and binding sites. The anti-receptor and growth blocking agents antagonize or modulate the vitamin B12/transcobalamin II receptor or binding sites, causing cellular depletion of vitamin B12, thus inhibiting cell division or causing apoptosis. Anti-receptor and growth blocking agents of the present invention include proteins (such as antibodies and antibody derivatives), peptides and small organic molecules. In a preferred embodiment, the anti-receptor agent is an antibody to the vitamin B12/transcobalamin II receptor.

Abstract: Vitamin B.sub.12 receptor modulating agents capable of modulating cell surface receptors by affecting the cell surface receptor trafficking pathway are disclosed. The vitamin B.sub.12 receptor modulating agents are comprised of a covalently bound rerouting moiety and targeting moiety linked by a water-solublizing linker.

Abstract: Receptor modulating agents capable of modulating cell surface receptors by affecting the cell surface receptor trafficking pathway are utilized for the treatment and diagnosis of a variety of disorders in warm-blooded animals, including neoplastic disorders. The receptor modulating agents are comprised of a covalently bound rerouting moiety and targeting moiety.

Abstract: Receptor modulating agents capable of modulating cell surface receptors by affecting the cell surface receptor trafficking pathway. The receptor modulating agents are comprised of a covalently bound rerouting moiety and targeting moiety.

Abstract: Vitamin B.sub.12 receptor modulating agents capable of modulating cell surface receptors by affecting the cell surface receptor trafficking pathway are disclosed. The vitamin B.sub.12 receptor modulating agents are comprised of a covalently bound rerouting moiety and targeting moiety linked by a water-solublizing linker.

Abstract: A biotinylated cobalamin, formed from a vitamin B.sub.12 molecule coupled to a biotin molecule, is disclosed. In a preferred embodiment, the vitamin B.sub.12 molecule is cyanocobalamin. The biotin molecule can also be coupled to a rerouting moiety, optionally through a biotin binding protein such as avidin or streptavidin. The biotinylated cobalamin binds to a cell surface receptor, is invaginated, and once internalized affects the receptor trafficking pathway.

Abstract: There is disclosed anti-receptor and growth blocking agents to the vitamin B.sub.12 /transcobalamin II receptor and binding sites. The anti-receptor and growth blocking agents antagonize or modulate the vitamin B.sub.12 /transcobalamin II receptor or binding sites, causing cellular depletion of vitamin B.sub.12, thus preventing or inhibiting cell division or causing apoptosis. Anti-receptor and growth blocking agents of the present invention include proteins (such as antibodies and antibody derivatives), peptides and small organic molecules. In a preferred embodiment, the anti-receptor agent is an antibody to the vitamin B.sub.12 /transcobalamin II receptor.

Abstract: Targeting substance-diagnostic/therapeutic agent conjugates joined by stabilized Schiff base or hydrazone linkages are disclosed. In addition, slow release carrier-drug pharmaceuticals are described. The diagnostic and therapeutic conjugates and pharmaceuticals of the present invention provide certain advantages relating to in vivo administration, including controlled release of the active agent at a target site.

Abstract: The present invention involves a method of imaging tissue sites of inflammation which takes advantage of the up-regulation of surface antigenic markers on leukocytes upon activation thereof. A recognition agent selected from the group of chemotactic peptides, eosinophilic peptides and agents which are capable of selective interaction with a chemotactic receptor associated with activated leukocytes is radiolabeled. The radiolabeled recognition agent is infused into a patient and the patient's tissue sites are thereafter imaged in order to detect, evaluate or monitor tissue damage mediated by inflammation.

Abstract: Covalently-linked complexes (CLCs) for targeting a defined population of cells, comprising a targeting protein; a cytotoxic agent; and an enhancing moiety, wherein the enhancing moiety is capable of promoting CLC-target cell interaction are disclosed. Methods for using the claimed CLCs to obtain enhanced in vivo cytotoxicity and enhanced in vivo imaging are also described.

Abstract: Methods are disclosed for increasing the solubility of antibodies and their radioisotope, toxin, or drug immunoconjugates and for reducing the non-specific uptake of antibody, either conjugated or unconjugated, into the RES organs such as via Fc receptor-mediated mechanisms. The methods involve incubation of the reactive component with amphipathic molecules, such as an anionic detergent, to achieve the desired result. A preferred anionic detergent in this regard is sodium dodecylsulfate.

Abstract: Conjugates comprising a therapeutically effective proteinaceous active moiety linked to an albumin moiety which exhibit enhanced serum half-life and stability properties are disclosed. The conjugates may additionally comprise targeting moieties to facilitate selective localization of the active moiety at a target site. Conjugates of the present invention comprising an albumin moiety additionally exhibit reduced toxicity, yet maintain a high degree of selectivity and potency.

Abstract: The present invention involves methods of enhancing the amount of target site localization of lymphoid cells. Methods of the present invention take advantage of the up-regulation of surface antigenic markers on lymphoid cells upon activation thereof. Imaging and therapeutic applications of such enhancement are described.

Abstract: A method for enhancing production of antibodies through immunization with insolubilized immune complexes is disclosed. Purified antigen or heterogeneous antigen mixtures may be combined with polyclonal or monoclonal antibody and the resultant complex bound to an insolubilized matrix to form insolubilized immune complexes. Methods for improving the immunogenicity of a soluble antigen and for producing monoclonal anti-iodiotypic antibodies are also disclosed. Monoclonal antibodies that are specific for a distinct, as yet unrecognized epitope may be produced by another disclosed method . Insolubilized immune complexes, comprising antigen and antibody that is ether directly linked to Sepharose.RTM. or absorbed onto insolubilized protein A, and immunosorbents, comprising antibody absorbed onto insolubilized protein A, are also disclosed.

Abstract: An insecticide dispenser made up of one flexible compartment or a series of flexible compartments forming or making up a cow ear tag, a browband, or a collar and filled with saturated fabric, an outeredge of packing material extending to one or more dispensing orifices. When the dispenser has more than one compartment, there is a restricted flow control channel in a wall dividing each compartment from an adjoining compartment. One compartment may be a primary compartment and one or more others in a series of sequence on one or both sides of the primary compartment or extending downward from both ends of the primary compartment. Insecticide is dispensed to cows, horses and domestic animals when the animals turn their heads or shake their heads so that the insecticide in the packing material touches their hairy, furry or like coating. The insecticide dispensed is replaced by more insecticide flowing into the packing material which fills the one or more dispensing orifice.

Abstract: The present invention involves method of enhancing the amount of label accumulating at tissue sites of inflammation. Methods of the present invention take advantage of the up-regulation of surface antigenic markers on leukocytes upon activation thereof. A method of imaging utilizing a chemotactic peptide containing an affinity label and a radionuclide label conjugated to leukocytes is taught. Imaging applications of such enhancement are described.

Abstract: A livestock data indicator is made up of two parallel plastic members adapted to be folded together by plastic hinges disposed between and joining the two members, the plastic members being held together by studs on one of the members which fit into corresponding holes in the other so as to secure hairs, for example of the mane of a horse or the tail of a cow, therebetween and not be brushed off the animal on which used by switching of the tail against a fence or other obstructive object or rubbing the mane against a gate or the like. For additional security the inside of each of the two members, that is, the sides or surfaces which are folded and attached together, preferably have rows of teeth thereon which aid in holding or locking the hairs in place when the two members are snapped together.

Abstract: A plastic or like indicator for containing livestock treatment data has at one end thereof a flexible fastener of either an injury-proof snap-tight or lock-band type for encircling the tail near its bushy end. To prevent detachment the tag has a second fastener at its other end with parallel members thereof adapted to be bent and fastened together so as to hold tail hairs tightly therebetween. The indicator may contain a color-coded label adhered thereto to show, for example, dry and lactating milk cows. It may have thereon an insecticide compartment. These and other indicator components such as the label may be parts of a kit which may also contain a marker and can or syringe for putting insecticide into the compartment.