Genentech, Inc.

Iphigenia Koumenis

Zahra Shahrokh

Steven R Leong

Vanessa Hsei

Gerardo A Zapata

Leonard G Presta

Avi J Ashkenazi

Robert F Kelley

Woon-Lam Susan Leung

Laura C Simmons

Roger Pai

Sarah G Hymowitz

Mark O'Connell

Gerarado A Zapata

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

Methods of making Apo-2 ligand and formulations of Apo-2 ligand using divalent metal ions are provided. Such divalent metal ions include zinc and cobalt which improve Apo-2 ligand trimer formation and stability. The crystal structure of Apo-2 ligand is also provided, along with Apo-2 ligand variant polypeptides identified using oligonucleotide-directed mutagenesis.

Methods for making Apo-2 ligand using divalent metal ions

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.

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

Antibody fragment-polymer conjugates and humanized anti-IL-8 monoclonal antibodies

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.

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Winston-Salem, NC, United States of America

Iphigenia Koumenis