Smithkline Beecham Corporation

Glaxosmithkline LLC

Smithkline Beechum P.l.c.

Robert B Kirkpatrick

Martin M Rosenberg

Kyung Oh Johanson

Zdenka Ludmila Jonak

Narendra B Bam

Xiayang Qiu

Cheryl Ann Janson

Allan R Shatzman

Ping Yeh

Xianyang Qiu

Jacob Bongers

Yen Sen Ho

Patrick McDevitt

Julie Adamou

Stephen D Holmes

David Robbins

Kyung O Johanson

Patrick Mcdevitt

Jacab S Bongers

Ping-Yang Yeh

Methods of treating cancer in patients in need thereof with human interleukin-18 (IL-18) polypeptides and substitution mutants thereof that are conjugated to water-soluble polymers at specific sites on the human IL-18 protein are disclosed.

Method of treating cancer by administering conjugates comprising human IL-18 and substitution mutants thereof

The present invention provides a method for producing physiologically active human Interleukin-18 ('IL-18').

Method for preparing a physiologically active IL-18 polypeptide

Human interleukin-18 (IL-18) polypeptides and substitution mutants thereof were conjugated to water-soluble polymers at specific sites on the human IL-18 protein. These conjugated human IL-18 and substitution mutants thereof retain biological activity. These conjugated cytokines demonstrate enhanced and unexpected biological properties when compared to the corresponding unconjugated cytokines.

Conjugates comprising human IL-18 and substitution mutants thereof

A method for producing a physiologically active polypeptide, comprising contacting a precursor polypeptide with an activating enzyme, or co-expressing the polypeptide with an activating protease.

Nucleic acid sequences for HC gp-39L are provided. Methods of detecting altered expression of tissue remodeling proteins and diagnosing tissue remodeling disorders are also provided.

Human cartilage glycoprotein

Nucleic acid sequences for HC gp-39L is provided. Methods of detecting altered expression of tissue remodeling proteins and diagnosing tissue remodeling disorders are also provided.

HC gp39-L polypeptides and DNA (RNA) encoding such HC gp39-L and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such HC gp39-L for the treatment of rheumatoid and osteoarthritis, osteoporosis, artherosclerosis, metastatic cancers, periodontia, chronic renal diseases, etc. Antagonists against such HC gp39-L and their use as a therapeutic to treat rheumatoid and osteoarthritis, osteoporosis, artherosclerosis, metastatic cancers, periodontia, chronic renal diseases, etc. are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to mutations in the nucleic acid sequences and altered concentrations of the polypeptides. Also disclosed are diagnostic assays for detecting mutations in the polynucleotides encoding the HC gp39-L and for detecting altered levels of the polypeptide in a host.

Human cartilege gp39-like gene

The invention relates to a method of diagnosing artherosclerosis by detecting mutation or altered expression of HC gp-39.

Tissue remodeling proteins

Methods of screening for colorectal cancer by measuring levels of HC gp-39 are provided. Methods of monitoring patients with colorectal cancer are also provided. In addition, kits for detection of HC gp-39 useful in screening for and monitoring of colorectal cancer in a patient are provided.

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King of Prussia, PA, United States of America

Robert B Kirkpatrick