Chiron Corporation

Novartis Vaccines & Diagnostics, Gmbh

Nansha Biologics (hong Kong) Limited

Nansha Biologies (hong Kong) Limited

Nansha Biologies (hk) Limited

Avalon Polytom (hk) Limited

Novartis Ag

Qui-lim Choo

George Kuo

Michael Houghton

Michael S. Urdea

Jang Han

Amy J. Weiner

Qui-Lim Choo

Jang Hyun Han

Johnson Yiu-Nam Lau

Kang-Sheng Wang

Amy Joan Weiner

Lacy Rasco Overby

Kuo-Ming Yu

Manson Fok

Kent B Thudium

John Andrew Hall

Frank I Marcus

Robert O Ralston

Barbara A Gervase

Kim M Berger

Joonho Choe

David Y Chien

Mark J Selby

Michael S Urdea

Amy J Weiner

Janice A Kolberg

Bruce D Irvine

Sergio Abrignani

Edward Glazer

Angelica Medina-Selby

Doris Guenzi Coit

Stephen R Coates

Sergio Pichuantes

Yiu-Lian Fong

Taewoo Kwon

Charles A Harrington

William Andrews

Stephen Coates

Susan Hilt

Pui Shi Pang

Yun Chung Leung

Yuk-Keung Yeung

Hyun Chul Song

Yifei Zhu

Charles Harrington

Methods are provided for producing a PEGylated interleukin 11 (IL-11) by treating a recombinant IL-11 PEGylated with an equimolar to low molar excess of PEG carrying an amine-reactive group to achieve a highly pure monoconjugate preparation, which provides improved half-life in serum while having desirable therapeutic activity and presenting fewer side-effects. Most preferably, the IL-11 is an N-terminally truncated human or humanized IL-11 and has a 20 Kd or 40 Kd branched PEG moiety, Y- or comb-shaped in particular, coupled to the N-terminal amino group. Such compounds are characterized by substantially increased stability in serum and sustained biological activity while exhibiting significantly reduced plasma expansion.

Methods of preparing a pegylated human IL-11 composition

Compositions and methods for the preparation of high purity arginase and high efficiency preparation of monosubstituted polyethylene glycol conjugation of arginase are provided, as are methods for using arginase in combination with asparaginase to inhibit cancer cells. High purity arginase is provided by applying an initial high temperature precipitation step, followed by ion exchange to provide arginase at a purity of 90% or greater. Conjugation with either linear or branched polyethylene glycol is performed using a maleimide-derivatized polyethylene glycol at low molar excess relative to arginase and at reduced temperature. Such polyethylene glycol-derivatized arginase is useful in combination with asparaginase in inhibiting the growth of cancer cells, particularly cells that have low endogenous asparaginase expression.

Compositions and methods for amino acid depletion therapy

Recombinant interleukin-11 (rhIL-11) is expressed in yeast, then isolated from aerobic fermentation media by precipitation, solubilization of the precipitate in the presence of a denaturant, and renaturation of the solubilized protein. Renatured rhIL-11 is further purified by cation exchange and hydrophobic interaction chromatography to provide a highly purified rhIL-11 with high biological activity and low rhIL-11 dimer and oxidized rhIL-11 content.

Systems and methods for production of recombinant IL-11 in yeast

Methods are provided for treating an individual with a pharmaceutical preparation that includes a recombinant IL-11 PEGylated at equimolar to low molar excess of PEG to achieve a highly pure monoconjugate preparation, which provides improved half-life in serum while having desirable therapeutic activity and presenting fewer side-effects. Most preferably, the IL-11 is an N-terminally truncated human or humanized IL-11 and has a 20 Kd or 40 Kd branched PEG moiety, Y- or comb-shaped in particular, coupled to the N-terminal amino group. Such compounds are characterized by substantially increased stability in serum and sustained biological activity while exhibiting significantly reduced plasma expansion.

Methods of treatment using a branched amino terminal pegylated Il-11 composition

Compositions are presented that include a recombinant IL-11 PEGylated at equimolar to low molar excess of PEG to achieve a highly pure monoconjugate preparation, which provides improved half-life in serum while having desirable therapeutic activity and presenting fewer side-effects. Most preferably, the IL-11 is an N-terminally truncated human or humanized IL-11 and has a 20 Kd or 40 Kd branched PEG moiety, Y- or comb-shaped in particular, coupled to the N-terminal amino group. Such compounds are characterized by substantially increased stability in serum and sustained biological activity while exhibiting significantly reduced plasma expansion.

Interleukin-11 PEGylation reaction intermediate composition

Compositions and methods are presented in which recombinant IL-11 is PEGylated to achieve improved half-life in serum while having desirable therapeutic activity and presenting less side-effects. Most preferably, the IL-11 is an N-terminally truncated human or humanized IL-11 and has a 20 Kd or 40 Kd branched PEG moiety, Y- or comb-shaped in particular, coupled to the N-terminal amino group. Such compounds are characterized by substantially increased stability in serum and sustained biological activity while exhibiting significantly reduced plasma expansion.

Increasing serum half-life of human IL-11 variants by N-terminal branched PEGylation

A tissue culture system for production of infectious hepatitis C virus is described. In particular, the invention provides recombinant monocistronic and bicistronic genomic constructs for production of virus, including constructs for production of wild-type HCV type 2a strain JFH1 and constructs for production of chimeric viruses comprising HCV proteins from strain JFH1 and a second HCV isolate. Constructs of the invention also include a reporter gene to facilitate measurement of RNA replication and viral infectivity in cultures. The cell culture system may also include various factors that improve viral replication or infectivity. In addition, a neutralization assay using HCV grown in cell culture is described.

Tissue culture system for production of hepatitis C virus

Recombinant production of immunogenic West Nile Virus (WNV) proteins is described. These proteins, heterodimers comprising the proteins, fusions thereof, polynucleotides encoding the proteins, and combinations thereof, as well as antibodies produced therefrom, can be used in immunogenic compositions for preventing, treating and diagnosing WNV infection. Also described are highly sensitive ELISA and strip immunoassay methods for detecting the presence of WNV in biological samples.

Immunogenic reagents from west nile virus

A family of cDNA sequences derived from hepatitis C virus (HCV) are provided. These sequences encode antigens which react immunologically with antibodies present in individuals with non-A non-B hepatitis (NANBH), but which are absent from individuals infected with hepatitis A virus, or hepatitis B virus, and also are absent in control individuals. The HCV cDNA sequences lack substantial homology to the sequences of hepatitis delta virus (HDV) and HBV. A comparison of the sequences of amino acids encoded in the HCV cDNA with the sequences of Flaviviruses indicates that HCV may be related to the Flaviviruses. The HCV cDNA sequences and the polypeptides encoded therein are useful as reagents for the detection and therapy of HCV. The reagents provided in the invention are also useful for the isolation of NANBH agent(s), for the propagation of these agents in tissue culture, and for the screening of antiviral agents for HCV.

NANBV diagnostics and vaccines

Methods for obtaining recombinantly produced, C-terminally truncated, E1 and E2 polypeptides from cell lysates are disclosed. The intracellularly expressed truncated molecules display improved biological properties as compared to their secreted counterparts.

Intracellular production of hepatitis C E1 and E2 truncated polypeptides

Two Hepatitis C Virus envelope proteins (E1 and E2) are expressed without sialylation. Recombinant expression of these proteins in lower eukaryotes, or in mammalian cells in which terminal glycosylation is blocked, results in recombinant proteins which are more similar to native HCV glycoproteins. When isolated by GNA lectin affinity, the E1 and E2 proteins aggregate into virus-like particles.

Antibodies to hepatitis C virus asialoglycoproteins

The Hepatitis C Virus (HCV) NS3 protein contains amino acid motifs of a serine proteinase, a nucleotide triphosphatase (NTPase), and an RNA helicase. A carboxy fragment of the HCV NS3 protein was purified and possessed RNA helicase activity. Detections from the amino terminus resulted in the protein becoming soluble. Deletions from the carboxy terminus do not result in a loss of helicase activity until at least 50 amino acids are deleted. The helicase activity requires ATP and divalent cations such as Mgand Mn. The helicase activity was blocked by monoclonal antibody specific to the HCV NS3 protein.

HCV NS3 protein fragments having helicase activity and improved solubility

Intracellular production of Hepatitis C E2 polypeptides

The Hepatitis C Virus (HCV) NS3 protein contains amino acid motifs of a serine proteinase, a nucleotide triphosphatase (NTPase), and an RNA helicase. A carboxy fragment of the HCV NS3 protein was purified and possessed RNA helicase activity. Detections from the amino terminus resulted in the protein becoming soluble. Deletions from the carboxy terminus do not result in a loss of helicase activity until at least 50 amino acids are deleted. The helicase activity requires ATP and divalent cations such as Mg and Mn . The helicase activity was blocked by monoclonal antibody specific to the HCV NS3 protein.

Growing community of inventors

El Cerrito, CA, United States of America

Qui-Lim Choo