Neorx Corporation

Poniard Pharmaceuticals, Inc.

Other

Kasina Laila Innova Pharmaceuticals Private Limited

Paul G Abrams

Alan R Fritzberg

Mark D Hylarides

Lauren Marie Tatalick

Elizabeth K John

Kent R Thoelke

James Kyle Bryan

Alton C Morgan, Jr

Sudhakar Kasina

John M Reno

David C Anderson

Gowsala P Sivam

Ananthachari Srinivasan

A Charles Morgan, Jr

Rama Raju Gokaraju

Louis J Theodore

Venkateswarlu Somepalli

Everett J Nichols

Donald B Axworthy

Vivekananda M Vrudhula

James A Sanderson

Robert F McIntyre

Robert W Schroff

Scott Stoll Graves

Clive S Woodhouse

The invention relates toF-labeled compounds of formula (I), hydrates, isomers, or pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions. The invention relates to the methods of diagnosing kidney function in humans by PET imaging. 

F-18 radiolabeled compounds for diagnosing and monitoring kidney function

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

Methods for targeting cytotoxins to target sites by administration of a combination of conjugates are provided. Novel cytotoxic combinations for use in such methods are also provided.

Pretargeting protocols for the enhanced localization of cytotoxins to

There is disclosed charge-modified conjugates comprising a targeting protein bound to a therapeutic or diagnostic agent. Charge-modifying a conjugate to cause an acidic shift in the isoelectric point results in prolonged serum half-life upon in vivo administration and is useful to accumulate a therapeutic agent at the target site. Conversely, charge-modification to cause a basic shift in the isoelectric point of the conjugate reduces serum half-life upon in vivo use for diagnostic imaging purposes and results in higher target-to-background ratios.

Alteration of pharmacokinetics of proteins by charge modification

Conjugates of trichothecenes and agents that bind to a defined population of cells are disclosed. Preferred are conjugates of trichothecene molecules with polyclonal or monoclonal antibodies or fragments thereof that recognize antigens that are present only on tumor cells or are augmented in their expression on tumor cells as compared to normal tissues. Trichothecene molecules are coupled to the agent through non-covalent and covalent linkages, such as peptide bonds, disulfide bonds, thioester bonds, or thioether bonds. A method for inhibiting the growth and metabolism of antigen-positive cells is also disclosed. Derivatized trichothecene compounds prepared for conjugation to targeting agents are also disclosed.

Trichothecene conjugates

A process for reducing the non-target organ accumulation of immunoconjugates administered in vivo during therapeutic or diagnostic procedures involves the use of immunoconjugates comprising linkers that are cleavable at the non-target organs. The linkers are cleavable under conditions present, or induced, at one or more non-target organs, which include the kidneys or the liver.

Cleavable linkers for the reduction of non-target organ retention of

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.

Covalently-linked complexes and methods for enhanced cytotoxicity and

Conjugates of trichothecenes and agents that bind to a defined population of cells are disclosed. Preferred are conjugates of trichothecene molecules with polyclonal or monoclonal antibodies or fragments thereof that recognize antigens that are present only on tumor cells or are augmented in their expression on tumor cells as compared to normal tissues. Trichothecene molecules are coupled to the agent through non-covalent and covalent linkages, such as peptide bonds, disulfide bonds, thioester bonds, or thioether bonds. A method for inhibiting the growth and metabolism of antigen-positive cells is also disclosed.

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

The activity of cytotoxic agents on target cells is enhanced through administration of a sensitizing agent to a patient prior to or simultaneously with administration of the cytotoxic agent. One or both of the two types of agents are attached to antibodies specific for the desired target cells, thereby enhancing the cytotoxic effect on target cells compared to non-target cells. The sensitizer and/or the cytotoxic agent may be attached to monoclonal antibodies specific for cancer cells to selectively eradicate the cancer cells while minimizing toxicity toward normal tissues.

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Seattle, WA, United States of America

Paul G Abrams