Abstract: Methods for the treatment of lymphoma by administration of a B cell-specific antibody are described. The invention encompasses providing to a patient both unlabeled antibodies and antibodies labeled with a radioisotope. A principal advantage of the method is that tumor responses can be obtained in a radiometric dose range that does not require hematopoietic stem cell replacement as an adjunct therapy.

Abstract: This invention relates to new macrocyclic chelants and metal chelates thereof, methods of preparing the chelants and metal chelates, and pharmaceutical compositions comprising the macrocyclic chelants and metal chelates. This invention relates particularly to the use of the new metal chelates as contrast agents in X-ray or CT, MRI imaging, and radiopharmaceuticals for the diagnosis of cardiovascular disorders, infectious disease and cancer. This invention also relates to new bifunctional chelants (BFCs) for attaching diagnostic metals and therapeutic isotopes to target-specific biomolecules such as proteins, peptides, peptidomimetics, and non-peptide receptor ligands. In addition, the macrocyclic chelants are useful for heavy metal detoxification.

Abstract: A lock unimolecular micelle includes at least one engineered acceptor specifically binding a ligand (or specifically a “key” unimolecular micelle) thereto. A key unimolecular micelle comprises a core molecule and a plurality of branches extending therefrom, at least one of the branches including a shank portion extending therefrom having a terminal moiety at an end thereof for binding to a complimentary acceptor of a lock unimolecular micelle. Together, the lock and key micelles form a unit, either irreversibly or reversibly bound wherein the lock micelles is a soluble receptor engineered to specifically bind to the specifically engineered key micelle.

Abstract: Novel therapeutic lipid constructs comprising a polymerized liposome, an anti-cell surface targeting agent, and a radiotherapeutic metal ion are disclosed.

Abstract: The present invention relates to a method for the preparation of a conjugate comprising a first and a second polypeptide, said method comprising the steps of (a) incubating said first polypeptide in the presence of a heterobifunctional crosslinker comprising an N-hydroxylsuccinimide ester group and a maleimide group linked via a polyethylene oxide spacer; (b) removing excess heterobifunctional crosslinker; and (c) incubating the reaction product of step (b) with said second polypeptide, wherein said second polypeptide comprises at least one sulfhydryl group. Furthermore, the present invention relates to a conjugate obtainable by the method of the present invention. Also described is a pharmaceutical composition comprising the conjugate of the present invention and, optionally, a pharmaceutically acceptable carrier and/or diluent, and the use of the conjugate for the preparation of a pharmaceutical composition for preventing and/or treating an allergic disease or an autoimmune disease.

Abstract: A 99mTc complex which contains the moiety Tc═NR, Tc—N═NY or Tc(—N═NY)2, and as a synthetic organic ligand which confers biological target-seeking properties on the technetium complex, where: R is an aryl group, a substituted or unsubstituted alkyl group or the group —NR1R2; Y is an aryl group or a substituted or unsubstituted alkyl group; R1 and R2 are H, aryl groups or substituted or unsubstituted aliphatic or cyclic alkyl groups, and are the same or different provided that both are not hydrogen; where at least one of the R or Y groups comprises an aryl group which chelates the 99mTc.

Abstract: A radiation delivery system and method are described. The system includes a treatment configuration such as a stent, balloon catheter, wire, ribbon, or the like, a portion of which is covered with a gold layer. Chemisorbed to the gold layer is a radiation-emitting self-assembled monolayer or a radiation-emitting polymer. The radiation delivery system is compatible with medical catheter-based technologies to provide a therapeutic dose of radiation to a lesion following an angioplasty procedure.

Abstract: Novel composite and humanized anti-TAG-72 monoclonal antibodies, antibody fragments, and derivatives thereof using human subgroup IV kappa light chain framework regions.

Abstract: A radiotherapeutic agent comprising a 32P or 33P radiolabeled protein selected from the group consisting of: wherein X is an targeting peptide, Y is a phosphorylation peptide, L is a flexible linker, preferably a peptide linker, and SH2 represents an SH2 domain; whereby said phosphorylation peptide is radiolabeled with 32P or 33P

Abstract: Antibody binding assays and radiolabeling kits are disclosed for radiolabeling and testing therapeutic antibodies in the commercial setting. In particular, the kits are designed for making and evaluating radiolabeled anti-CD20 conjugates to be used for the treatment and imaging of B cell lymphoma tumors. All kit reagents are sterile and are designed to achieve a high level of antibody radiolabeling and product stability with results which are highly reproducible.

Abstract: Antibodies to cell surface ligands such as EGFRvIII can be used to therapeutically or diagnostically deliver a radiolabel to tumor cells with high selectivity. The utility of radioconjugated internalizing antibodies is limited, however, by release of the label and its reuptake into normal cells. The invention provides new technology for radioconjugation of internalizing antibodies which reduces the release of label and improves retention of radioconjugated antibodies in lysosomes, where radiation is more effectively and selectively delivered to the nucleus of tumor cells.

Abstract: Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity. The present invention thus provides new antibody-based compositions, methods and combined protocols for treating cancer and other angiogenic diseases. Advantageous immunoconjugate and prodrug compositions.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, three-step pretargeting methods are described.

Abstract: This invention provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention also provides an immunoconjugate which comprises 1) a gamma radiation-emitting radionuclide of low to moderate cytotoxicity and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention further provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a heterotetramer comprising two heavy chains and two light chains, both heavy chains being either 1) IgG2 heavy chains or b) chimeric CD4-IgG2 heavy chains, and both light chains being either a) kappa light chains or b) chimeric CD4-kappa light chains.

Abstract: Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity. The present invention thus provides new antibody-based compositions, methods and combined protocols for treating cancer and other angiogenic diseases. Advantageous immunoconjugate and prodrug compositions and methods using the new VEGF-specific antibodies are also provided.

Abstract: The invention relates to compositions and methods for delivering a virus vector to an animal. The compositions include compositions which comprise a hydrogel matrix (e.g. a collagen matrix which can comprise a poloxamer or an alginate) containing a virus vector therein in a transfectious form. The invention also includes methods of making such hydrogel precursor mixtures and hydrogel matrices, including particles, devices, bulk materials, and other objects which comprise, consist of, or are coated with such mixtures or matrices. The invention further relates to compositions comprising a hydrogel precursor mixture having a virus vector suspended therein, which, when administered to an animal, gel to form a hydrogel matrix containing a virus vector therein in a transfectious form. Methods of delivering a virus vector to an animal tissue are also described.

Abstract: A 99mTc complex which contains the moiety Tc═NR, Tc—N═NY or Tc(—N═NY)2, and as a synthetic organic ligand which confers biological target-seeking properties on the technetium complex, where: R is an aryl group, a substituted or unsubstituted alkyl group or the group —NR1R2; Y is an aryl group or a substituted or unsubstituted alkyl group; R1 and R2 are H, aryl groups or substituted or unsubstituted aliphatic or cyclic alkyl groups, and are the same or different provided that both are not hydrogen; where at least one of the R or Y groups comprises an aryl group which chelates the 99mTc.

Abstract: The present invention relates to bioconjugates and the delivery of bioactive agents which are preferably targeted for site-specific release in cells, tissues or organs. More particularly, this invention relates to bioconjugates which comprise of bioactive agent and an organocobalt complex. The bioactive agent is covalently bonded directly or indirectly to the cobalt atom of the organocobalt complex. The bioactive agent is released from the bioconjugate by the cleavage of the covalent bond between the bioactive agent and the cobalt atom in the organocobalt complex. The cleavage may occur as a result of normal displacement by cellular nucleophiles or enzymatic action, but is preferably caused to occur selectively at a predetermined release site by application of an external signal. The external signal may be light or photoexcitation, i.e. photolysis, or it may be ultrasound, i.e. sonolysis.

Abstract: Starburst conjugates which are composed of at least one dendrimer in association with at least one unit of a carried agricultural, pharmaceutical, or other material have been prepared. These conjugates have particularly advantageous properties due to the unique characteristics of the dendrimer.

Abstract: Methods are provided for in vivo detection of tissue associated with a disease state in a subject, such as tissue located in a body opening. In the invention method, the subject is administered a biologically compatible fluorescing targeting construct, the construct is allowed to bind to any target tissue present in the subject, a body part of the subject suspected of containing the target tissue is irradiated with UV light while extraneous light to the body part is substantially eliminated, and fluorescence emanating from the fluorescing targeting construct bound to the target tissue is detected and visualized by the observer with or without the aid of an endoscope, so as to determine the location and size of the target tissue. The invention methods offer the advantage that diseased or abnormal tissue can be detected at interior body sites with or without the aid of an endoscopic device.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.

Abstract: Methods for the treatment of lymphoma by adminstration of a B cell-specific antibody are described. The invention encompasses providing to a patient both unlabeled antibodies and antibodies labeled with a radioisotope. A principal advantage of the method is that tumor responses can be obtained in a radiometric dose range that does not require hematopoietic stem cell replacement as an adjunct therapy.

Abstract: Methods are provided for in vivo detection of tumor tissue associated with a disease state in a subject, such as tumor tissue located in body opening. In the invention method, the subject is administered a biologically compatible fluorescing targeting construct, the construct is allowed to bind to and/or be taken up by tumor tissue present in the subject, a body part of the subject suspected of containing the tumor tissue is irradiated with UV light while extraneous light to the body part is substantially eliminated, and fluorescence emanating from the fluorescing targeting construct bound to and/or taken up by the tumor tissue is directly viewed by the observer with or without the aid of an endoscope, so as to determine the location and size of the tumor tissue.

Abstract: A diagnostic agent for angiopathic diseases containing a monoclonal antibody against human smooth muscle myosin or active fragments of the antibody labeled with a radioactive isotope; a kit thereof; and a method of diagnostic imaging for angiopathic diseases by using the same. The invention permits the diagnostic imaging of angiopathic diseases such as dissecting aortic aneurysm and angiitis and the specification of the region affected by these diseases.

Abstract: The subject invention relates to the use of ascorbic acid and derivatives thereof in stabilizing radiolabeled proteins and peptides against oxidation loss of radiolabel and autoradiolysis. Ascorbic acid is added after radiolabeling, including any required incubation period, but prior to patient administration.

Abstract: Methods are provided for close-range intraoperative, endoscopic and intravascular detection and treatment of lesions, including tumors and non-malignant lesions. The methods use antibody fragments or subfragments labeled with isotopic and non-isotopic agents. Also provided are methods for detection and treatment of lesions with photodynamic agents and methods of treating lesions with a protein conjugated to an agent capable of being activated to emit Auger electron or other ionizing radiation. Compositions and kits useful in the above methods are also provided.

Abstract: The present invention relates to non-lethal methods of conditioning a recipient for bone marrow transplantation. In particular, it relates to the use of nonlethal doses of total body irradiation, total lymphoid irradiation, cell type-specific or cell marker-specific antibodies, especially antibodies directed to bone marrow stromal cell markers, NK cells, or the CD8 cell marker, cytotoxic drugs, or a combination thereof. The methods of the invention have a wide range of applications, including, but not limited to, the conditioning of an individual for hematopoietic reconstitution by bone marrow transplantation for the treatment of hematologic malignancies, hematologic disorders, autoimmunity, infectious diseases such as acquired immunodeficiency syndrome, and the engraftment of bone marrow cells to induce tolerance for solid organ, tissue and cellular transplantation.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed.

Abstract: An implantable medical device is used to deliver a dosage of radiation to a localized site within a patient. The device is coated with a chelator selected for its bonding affinity with a specific radioisotope. A base layer and optionally a spacer layer is first applied to the device to provide a proper foundation for the chelator. Just prior to implantation, the device is immersed in a solution of the radioisotope which enables a preselected amount of such radioisotope to be adsorbed.

Abstract: The present invention relates to a series of nanospheres, having diameters of less than about 50 nm, and having probe ion cores surrounded by layers of surfactant and by a polymer shell. The surface of the shell is functionalized with acid compounds, at least one of which includes a spacer between the nanosphere surface and the acid functionality. In some alternative embodiments, the surface is also functionalized with long-chain ester and alcohol groups. The probe ion core improves the sensitivity and reproducibility of immunoassay procedures. The acid compounds on the surface minimize self-agglomeration of the nanospheres and improve the coupling of the nanosphere with antibodies. The ester and alcohol groups enhance the aqueous suspension characteristics and the shelf life of the nanospheres.