Genentech, Inc.

Smithkline Beecham Corporation

Genetech, Inc.

Gerardo A Zapata

Zahra Shahrokh

Steven R Leong

Iphigenia Koumenis

Vanessa Hsei

Leonard G Presta

Ernst H Rinderknecht

Gregory Scott Blank

Daljit S Narindray

Robert D Van Reis

Haiyan Liu

Anthony S Lubiniecki

Shing H Mai

Amy A Murnane

Leonard T Olszewski

Described are conjugates formed by an antibody fragment covalently attached to a nonproteinaceous polymer, wherein the apparent size of the conjugate is at least about 500 kD. The conjugates exhibit substantially improved half-life, mean residence time, and/or clearance rate in circulation as compared to the underivatized parental antibody fragment. Also described are conjugates directed against human vascular endothelial growth factor (VEGF), human p185 receptor-like tyrosine kinase (HER2), human CD20, human CD18, human CD11a, human IgE, human apoptosis receptor-2 (Apo-2), human tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), human tissue factor (TF), human &#x3b1;&#x3b2;integrin, human GPIIb-IIIa integrin, human epidermal growth factor receptor (EGFR), human CD3, and human interleukin-2 receptor &#x3b1;-chain (TAC) for diagnostic and therapeutic applications.

Methods of binding TNF-&#x3b1; using anti-TNF-&#x3b1; antibody fragment-polymer conjugates

Described are conjugates formed by an antibody fragment covalently attached to a non-proteinaceous polymer, wherein the apparent size of the conjugate is at least about 500 kD. The conjugates exhibit substantially improved half-life, mean residence time, and/or clearance rate in circulation as compared to the underivatized parental antibody fragment. Also described are conjugates directed against human vascular endothelial growth factor (VEGF), human p185 receptor-like tyrosine kinase (HER2), human CD20, human CD18, human CD11a, human IgE, human apoptosis receptor-2 (Apo-2), human tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), human tissue factor (TF), human &#x3b1;&#x3b2;integrin, human GPIIb-IIIa integrin, human epidermal growth factor receptor (EGFR), human CD3, and human interleukin-2 receptor &#x3b1;-chain (TAC) for diagnostic and therapeutic applications.

Antibody fragment-polymer conjugates and uses of same

A process for purifying an antibody is provided. In this process, a mixture containing the antibody and a contaminant is subjected to low pH hydrophobic interaction chromatography (LPHIC) at low salt concentration. The antibody is eluted from the column in the fraction which does not bind thereto. This process can be preceded and followed by other purification steps.

Antibody compositions

Described are conjugates formed by an antibody fragment covalently attached to a non-proteinaceous polymer, wherein the apparent size of the conjugate is at least about 500 kD. The conjugates exhibit substantially improved half-life, mean residence time, and/or clearance rate in circulation as compared to the underivatized parental antibody fragment. Also described are conjugates directed against human vascular endothelial growth factor (VEGF), human p185 receptor-like tyrosine kinase (HER2), human CD20, human CD18, human CD11a, human IgE, human apoptosis receptor-2 (Apo-2), human tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), human tissue factor (TF), human &#x3b1;4&#x3b2;7 integrin, human GPIIb-IIIa integrin, human epidermal growth factor receptor (EGFR), human CD3, and human interleukin-2 receptor &#x3b1;-chain (TAC) for diagnostic and therapeutic applications.

Described are conjugates formed by an antibody fragment covalently attached to a non-proteinaceous polymer, wherein the apparent size of the conjugate is at least about 500 kD. The conjugates exhibit substantially improved half-life, mean residence time, and/or clearance rate in circulation as compared to the underivatized parental antibody fragment. Also described are conjugates directed against human vascular endothelial growth factor (VEGF), human p185 receptor-like tyrosine kinase (HER2), human CD20, human CD18, human CD11, human IgE, human apoptosis receptor-2 (Apo-2), human tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), human tissue factor (TF), human &#x3b1;4&#x3b2;7 integrin, human GPIIb-IIIa integrin, human epidermal growth factor receptor (EGFR), human CD3, and human interleukin-2 receptor &#x3b1;-chain (TAC) for diagnostic and therapeutic applications.

A quantitative PCR method has been developed for the simultaneous detection and quantitation of an agent in samples of biologically derived materials. Unlike conventional quantitative PCR detection methods, this assay allows for the detection of viable agents.

Detection of viable agents

Antibody purification

Humanized anti-IL-8 monoclonal antibodies and variants thereof are described for use in diagnostic applications and in the treatment of inflammatory disorders. Also described is a conjugate formed by an antibody fragment covalently attached to a non-proteinaceous polymer, wherein the apparent size of the conjugate is at least about 500 kD. The conjugate exhibits substantially improved half-life, mean residence time, and/or clearance rate in circulation as compared to the underivatized parental antibody fragment.

Antibody fragment-peg conjugates

The invention herein provides a method for recovering a polypeptide comprising exposing a composition comprising a polypeptide to a reagent which binds to, or modifies, the polypeptide, wherein the reagent is immobilized on a solid phase; and then passing the composition through a filter bearing a charge which is opposite to the charge of the reagent in the composition, so as to remove leached reagent from the composition.

Protein recovery

Provided are methods for treating inflammatory diseases in a patient comprising administering to the patient an effective amount of a conjugate consisting essentially of one or more antibody fragments covalently attached to one or more nonproteinaceous polymer molecules, wherein at least one antibody fragment comprises an antigen binding site that binds to human IL-8, and wherein the apparent size of the conjugate is at least about 500 kD.

Methods of treating inflammatory diseases with anti-IL-8 antibody fragment-polymer conjugates

Methods of treating inflammatory disease with anti-IL-8 antibody fragment-polymer conjugates

The present application describes nucleic acid encoding, and methods for preparing, an antibody comprising a linear V,&mdash;C,1&mdash;V,&mdash;C,1 heavy chain fragment associated with two light chains.

Growing community of inventors

Foster City, CA, United States of America

Gerardo A Zapata