Scios Inc.

Scios Nova, Inc.

The Beth Israel Hospital Association

R Tyler White

Lawrence W Stanton

Deborah Damm

George Frederic Schreiner

Alison Joly

David D Lesikar

Brett L Garrick

Kathleen McFadden

John A Lewicki

Bruce M Spiegelman

Jeffrey S Flier

Barry M Rosen

The invention concerns new secreted factors encoded by clones P00184_D11 (SEQ ID NO: 1), P00185_D11 (SEQ ID NO: 3), P00188_D12 (SEQ ID NO: 5), P00188_E01 (SEQ ID NO: 7), P00194_G01 (SEQ ID NO: 9), P00194_G05 (SEQ ID NO: 11), P00194_H10 (SEQ ID NO: 13), P00199_D08 (SEQ ID NO: 15), P00203_D04 (SEQ ID NO: 17), P00203_E06 (SEQ ID NO: 19), P00209_F06 (SEQ ID NO: 21), P00219_D02 (SEQ ID NO: 23), P00219_F06 (SEQ ID NO: 25), P00220_H05 (SEQ ID NO: 27), P00222_G03 (SEQ ID NO: 29), P00225_C01 (SEQ ID NO: 32), P00227_D11 (SEQ ID NO: 34), P00228_F03 (SEQ ID NO: 36), P00233_H08 (SEQ ID NO: 38), P00235_G08 (SEQ ID NO: 40), P00239_C11 (SEQ ID NO: 42), P00240_E05 (SEQ ID NO: 45), P00247_A04 (SEQ ID NO: 50), P00248_B04 (SEQ ID NO: 52), P00249_F09 (SEQ ID NO: 54), P00258_A10 (SEQ ID NO: 56), P00262_C10 (SEQ ID NO: 58), P00269_H08 (SEQ ID NO: 62), P00628_H02 (SEQ ID NO: 66), P00629_C08 (SEQ ID NO: 68), P00641_G11 (SEQ ID NO: 71), P00648_E12 (SEQ ID NO: 73), P00697_C03 (SEQ ID NO: 75), and other mammalian homologues and variants of such factor, as well as polynucleotides encoding them. The invention further concerns methods and means for producing such factors and their use in the diagnosis and treatment of various cardiac, renal or inflammatory diseases.

Secreted factors

Analogues of the Kunitz Protease Inhibitor (KPI) domain of amyloid precursor protein bind to and inhibit activity of serine proteases, including kallikrein, plasmin and coagulation factors such as factors VIIa, IXa, Xa, XIa, and XIIa. Pharmaceutical compositions containing the KPI analogues, along with methods for using such compositions, are useful for ameliorating and treating clinical conditions associated with increased serine protease activity, such as blood loss related to cardiopulmonary bypass surgery. Nucleic acid sequences encoding these analogues and systems for expression of the peptides of the invention are provided.

Protease inhibitor peptides

The invention concerns new secreted factors encoded by clones P00184_D11 (SEQ ID NO:1), P00185_D11 (SEQ ID NO:3), P00188_D12 (SEQ ID NO:5), P00188_E01 (SEQ ID NO:7), P00194_G01 (SEQ ID NO:9), P00194_G05 (SEQ ID NO:11), P00194_H10 (SEQ ID NO:13), P00199_D08 (SEQ ID NO:15), P00203_D04 (SEQ ID NO:17), P00203_E06 (SEQ ID NO:19), P00209_F06 (SEQ ID NO:21), P00219_D02 (SEQ ID NO:23), P00219_F06 (SEQ ID NO:25), P00220_H05 (SEQ ID NO:27), P00222_G03 (SEQ ID NO:29), P00225_C01 (SEQ ID NO:32), P00227_D11 (SEQ ID NO:34), P00228_F03 (SEQ ID NO:36), P00233_H08 (SEQ ID NO:38), P00235_G08 (SEQ ID NO:40), P00239_C11 (SEQ ID NO:42), P00240_E05 (SEQ ID NO:45), P00247_A04 (SEQ ID NO:50), P00248_B04 (SEQ ID NO:52), P00249_F09 (SEQ ID NO:54), P00258_A10 (SEQ ID NO:56), P00262_C10 (SEQ ID NO:58), P00269_H08 (SEQ ID NO:62), P00628_H02 (SEQ ID NO:66), P00629_C08 (SEQ ID NO:68), P00641_G11 (SEQ ID NO:71), P00648_E12 (SEQ ID NO:73), P00697_C03 (SEQ ID NO:75), and other mammalian homologues and variants of such factor, as well as polynucleotides encoding them. The invention further concerns methods and means for producing such factors and their use in the diagnosis and treatment of various cardiac, renal or inflammatory diseases.

The present invention relates to methods and compositions for the detection, diagnosis, prevention and treatment of a disease, specifically cardiac, kidney or inflammatory disease, and related disorders. The present invention also relates to compositions and methods useful in the diagnosis, prevention and therapeutic treatment of a disease, specifically cardiac, kidney or inflammatory disease. Specifically, methods and compositions are provided for the diagnostic evaluation and prognosis of conditions involving a disease, specifically cardiac, kidney or inflammatory disease, for the identification of subjects exhibiting a predisposition to such conditions, for modulating the effect of these differentially expressed genes, for monitoring patients undergoing clinical evaluation for the prevention and treatment of a disease, specifically cardiac, kidney or inflammatory disease, and its disorders, and for monitoring the efficacy of compounds used in clinical trials.

Methods for detection and use of differentially expressed genes in disease states

The invention concerns the use of agonists and antagonists of peripheral-type benzodiazepine receptors (PTBR) in the diagnosis and treatment of cardiac hypertrophy and other circulatory conditions. The invention specifically concerns the use of PTBR antagonists in the prevention or treatment of decompensated cardiac hypertrophy and, eventually, heart failure. The invention also concerns the use of PTBR agonists in the management of conditions calling for increased blood flow or cardiac output, including injury or functional compromise of the heart, increased demand for physical exercise, or an acquired or inherited predisposition to cardiac contractile disfunction. Pharmaceutical compositions for the treatment of such conditions and screening methods to identify PTBR agonists and antagonists are also included.

Agonists and antagonists of peripheral-type benzodiazepine receptors

The invention concerns the use of ligands of peripheral-type benzodiazepine receptors (PTBR) in the diagnosis and treatment of diseases involving cyst formation and in particular polycystic kidney disease. The invention further concerns the treatment of hypertension accompanying polycystic kidney disease, and pharmaceutical compositions and articles of manufacture for the treatment or diagnosis of the target disease or condition.

Treatment of diseases involving cyst formation

The invention concerns the use of agonists and antagonists of peripheral-type benzodiazcpine receptors (PTBR) in the diagnosis and treatment of cardiac hypertrophy and other circulatory conditions. The invention specifically concerns the use of PTBR antagonists in the prevention or treatment of decompensated cardiac hypertrophy and, eventually, heart failure. The invention also concerns the use of PTBR agonists in the management of conditions calling for increased blood flow or cardiac output, including injury or functional compromise of the heart, increased demand for physical exercise, or an acquired or inherited predisposition to cardiac contractile disfunction. Pharmaceutical compositions for the treatment of such conditions and screening methods to identify PTBR agonists and antagonists are also included.

The invention provides a recombinant purified human protein in substantial quantities which has both adipsin and complement D activity. The invention also provides materials and methods to produce the protein. In addition, antibodies immunoreactive with this protein are useful to diagnose metabolic defects attributable to adipsin deficiency or complement D deficiency. The protein can be used to treat obesity caused by adipsin deficiency or to treat subjects for infection.

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Fremont, CA, United States of America

R Tyler White