Domantis Limited

Cephalon Australia Pty. Ltd.

Glaxo Group Limited

Other

Abbott Laboratories Corporation

Ian M Tomlinson

Carolyn Enever

Benjamin P Woolven

Malgorzata Pupecka

Steve Holmes

Jennifer A Lee

Gregory Paul Winter

Anthony Gerard Doyle

Jasper Clube

Chung-Ming Hsieh

Jonathan Henry Ellis

Laurent S Jespers

Philip Anthony Jennings

Armin Sepp

Justian Craig Fox

Mary Frances Fitzgerald

Rudolf M T De Wildt

Malgorzata Pupecka-Swider

Jennifer Luckett

Greg Winter

Lucy J Holt

Steven Grant

Michael Roguska

Olga Ignatovich

Yuliya Kutskova

Mihriban Tuna

John Memmott

Oliver Schon

Bradford L McRae

Michael Steward

Thil Dinuk Batuwangala

Amrik Basran

Ruud De Wildt

Neil D Brewis

Carrie Enever

Stanislas Blein

Kate Jones

Tejash Shah

Ahmed Yasin

Neil Brewis

Laurent Jespers

Lucy Holt

Michael J Molloy

Stanislas Charles Blein

The disclosure relates to a method for selecting, isolating and/or recovering a peptide or polypeptide from a library or a repertoire of peptides and polypeptides (e.g., a display system) that is resistant to degradation by a protease such as a protease found in the serum. Generally, the method comprises providing a library or repertoire of peptides or polypeptides, incubating the library or repertoire with a protease under conditions suitable for protease activity, and selecting, isolating and/or recovering a peptide or polypeptide that is resistant to degradation by the protease and has a desired biological activity. The selected peptides and polypeptides have utility as therapeutics, e.g., for treating disease in humans.

Methods for selecting protease resistant polypeptides

The invention relates to anti-TNFR1 polypeptides and antibody single variable domains (dAbs) that are resistant to degradation by a protease, as well as antagonists comprising these. The polypeptides, dAbs and antagonists are useful for as therapeutics and/or prophylactics that are likely to encounter proteases when administered to a patient, for example for pulmonary administration, oral administration, delivery to the lung and delivery to the GI tract of a patient, as well as for treating inflammatory disease, such as arthritis or COPD.

Polypeptides, antibody variable domains and antagonists

Disclosed is the use of an agent (e.g., antibody fragment, antagonist, ligand, dAb monomer) that binds a target in pulmonary tissue for the manufacture of a long action or long therapeutic window formulation for local delivery to pulmonary tissue, and methods for administering an agent that binds a target in pulmonary tissue to a subject to produce a long therapeutic window in pulmonary tissue. The formulation is for, and the method comprises, administering locally to pulmonary tissue. Also disclosed is the use of antagonists of TNFR1 for the manufacture of a formulation or medicament for treating, preventing or suppressing lung inflammation or a respiratory disease, and methods of treating such diseases. Also disclosed are the use of agents a for the manufacture of a delivery device (e.g., inhaler, intranasal delivery device) for the treatment or prevention of lung inflammation or a respiratory disease, and a delivery device for the treatment or prevention of lung inflammation or a respiratory disease that contains an agent as described herein.

Methods for targeting pulmonary diseases with agents that bind a target in pulmonary tissue

The invention provides a dual-specific ligand comprising a first immunoglobulin variable domain having a first binding specificity and a complementary or non-complementary immunoglobulin variable domain having a second binding specificity.

Ligand

The invention provides methods for treating inflammatory diseases (e.g., chronic inflammatory diseases) comprising administering an antagonist of Tumor Necrosis Factor Receptor 1. The invention also provides ligands that contain an immunoglobulin single variable domain (domain antibody, dAb) monomer that binds Tumor Necrosis Factor Receptor 1, and methods of using the ligands. Also provided are nucleic acids encoding the ligands, recombinant host cells and methods for preparing the ligands.

Antagonists against TNFR1 and methods of use therefor

Drug compositions, fusions and conjugates are provided. The drug fusions and conjugates contain a therapeutic or diagnostic agent that is fused or conjugated to an antigen-binding fragment of an antibody that binds serum albumin. The drug compositions, fusions and conjugates have a longer in vivo half-life in comparison with the unconjugated or unfused therapeutic or diagnostic agent.

Bispecific fusion antibodies with enhanced serum half-life

The invention relates to anti-VEGF polypeptides and antibody single variable domains (dAbs) that are resistant to degradation by a protease, as well as antagonists comprising these. The polypeptides, dAbs and antagonists are useful for pulmonary administration, oral administration, delivery to the lung and delivery to the GI tract of a patient, as well as for treating cancer and inflammatory disease, such as arthritis.

The invention relates to anti-IL-1R1 polypeptides and antibody single variable domains (dAbs) that are resistant to degradation by a protease, as well as antagonists comprising these. The polypeptides, dAbs and antagonists are useful for as therapeutics and/or prophylactics that are likely to encounter proteases when administered to a patient, for example for pulmonary administration, oral administration, delivery to the lung and delivery to the GI tract of a patient, as well as for treating inflammatory disease, such as arthritis or COPD.

Polypeptides, antibody variable domains and antagonists methods for

The invention provides an isolated, dual-specific antibody, or an antigen-binding portion thereof, which is specific for human IL-1&#x3b1; and human IL-1&#x3b2;. The dual specific antibodies of the invention also neutralize both human IL-1&#x3b1; and human IL-1&#x3b2;. The invention also provides domain antibodies (dAbs) specific for human IL-1&#x3b1; and human IL-1&#x3b2;.

Dual-specific IL-1&#x3b1;/IL-1&#x3b2; antibodies

The present invention provides a recombinant domain antibody (dAb) which binds to human TNF&#x3b1;, the dAb comprising an immunoglobulin heavy or light chain variable domain comprising at least one complementarity determining region (CDR) having a sequence derived from a New World primate.

Anti-inflammatory dAb

Growing community of inventors

Cambridgeshire, United Kingdom

Ian M Tomlinson