Neorx Corporation

Poniard Pharmaceuticals, Inc.

Mark D Hylarides

Alan R Fritzberg

Lauren Marie Tatalick

James Kyle Bryan

Elizabeth K John

Kent R Thoelke

Paul G Abrams

Ananthachari Srinivasan

Jeffrey N Fitzner

Vivekananda M Vrudhula

Robert W Mallett

John M Reno

Donald B Axworthy

Daniel S Wilbur

Scott Stoll Graves

Stephen M J Searle

Anthony R Rees

Andrew H Henry

Jan T Pedersen

The present invention relates to a method of suppressing bone marrow (BM) and treating conditions that arise in or near bone such as cancer, myeloproliferative diseases, autoimmune diseases, infectious diseases, metabolic diseases or genetic diseases, with compositions having as their active ingredient a radionuclide complexed with a chelating agent such as macrocyclic aminophosphonic acid.

High dose radionuclide complexes for bone marrow treatment

Treatment of bone-associated cancers

High dose radionuclide complexes for bone marrow suppression

Humanized antibodies which bind the NR-LU-13 antigen, conjugates containing such antibodies, and their use in pretargeting methods and conventional antibody therapy and immunodiagnosis are provided.

Humanized antibodies that bind to the antigen bound by antibody NR-LU-13

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.

Pretargeting protocols for enhanced localization of active agents to

The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of a target cell an agent free of its targeting molecule carrier. A diagnostically/therapeutically effective dose of a cleavable conjugate is administered to a warm-blooded animal such as man.

Cleavable conjugates for the delivery and release of agents in native

The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of a target cell an agent free of its targeting molecule carrier. A diagnostically/therapeutically effective dose of a cleavable conjugate is administered to a warm-blooded animal such as man. Another aspect of the invention provides methods for isolating a compound. The compound binds covalently to a solid phase which has been derivatized with the linkers described above and is released in native form by a variety of mild conditions. An additional aspect of the invention provides methods for introducing into a compound a free sulfhydryl, amino, or hydroxyl group by use of reagents structurally related to the linkers described above. Preferred uses of the method are to add a free amino or a free sulfhydryl group to a protein, such as an antibody, or a drug.

Methods for isolating compounds using cleavable linker bound matrices

Modified cellular substrates are used as linking groups that are recognized as cellular substrates by intracellular metabolic enzymes. The linking groups function to attach a ligand, such as a drug or radionuclide, to a targeting protein, such as an antibody or antibody fragment. The false substrate structure of the linking groups causes increased cellular retention of the linking group/ligand conjugate because the enzymes used for catabolism of the substrate are inhibited by the false substrate structure of the linking group.

Modified cellular substrates used as linkers for increased cell

The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of target cell an agent free of its targeting molecular carrier. A diagnostically therapeutically effective dose of a cleavable conjugate is administered to a warm-blooded animal such as man. Another aspect of the invention provides methods for isolating a compound. The compound binds covalently to a solid phase which has been derivatized with the linkers described above and is released in native form by a variety of mild conditions. An additional aspect of the invention provides methods for introducing into a compound a free sulfhydryl, amino, or hydroxyl group by use of reagents structurally related to the linkers described above. Preferred uses of the method are to add a free amino or a free sulfhydryl group to a protein, such as an antibody, or a drug.

Methods for introducing a sulfhydryl amino or hydroxyl groups to a

Growing community of inventors

Stanwood, WA, United States of America

Mark D Hylarides