Biotest Ag

Immunogen, Inc.

Dana-farber-cancer Institute Inc.

Astellas Pharma Gmbh

Ganymed Pharmaceuticals Ag

Tron—translationale Onkologie An Der Universitátsmedizin Der Johannes Gutenberg—universitÄt Mainz Gemeinnützige Gmbh

Johannes Gutenberg-universität Mainz, Vertreten Durch Den Präsidenten

Christoph Uherek

Ugur Sahin

Özlem Türeci

Christoph Bruecher

Frank Osterroth

Andrea Wartenberg-Demand

Steffen Zeng

Juergen Lindner

Kenneth Carl Anderson

Dirk Usener

Benjamin Daelken

Chantal Zuber

Matthias Germer

Peter Röttgen

Daniele Wolf

Judith Wessels-Kranz

Teru Hideshima

Harald-Gerhard Geppert

Stefan Fritz

Gunda Brandenburg

Gregor Schulz

Silke Aigner

Elmar Kraus

Anja Kristina Schröder

Niklas Czeloth

André Engling

Philippe Thiel

Marcus Gutscher

Sibylle Kaiser

Thomas Haeder

Gabriele Niemann

Holger Wallmeier

Markus Ruehle

Martin Koenig

Kirsten Völp

Katrin Bernoester

Michael Soldan

Anatoly Rudnev

Disclosed is a method and composition for treating a disease associated with target cells expressing CD138 in a multiple dose regimen. An immunoconjugate comprising an engineered targeting antibody targeting CD138 expressing cells and an effector molecule is administered in a multiple dose regimen. The multiple dose regimen comprises at least two doses and the aggregate dose administered within an active treatment cycle is an aggregate maximum tolerable dose (AMTD) or a fraction of the AMTD. The AMTD and/or said fraction exceeds the dose resulting in dose limiting toxicity (DLT) and/or exceeds the maximum tolerable dose (MTD) when the immunoconjugate is administered as a single dose, including as part of a multiple single dose regimen within said active treatment cycle.

Uses of immunoconjugates targeting CD138

Provided are methods of screening to identify molecules capable of binding to CD4 and capable of activating CD4+CD25+ regulatory T cells. Further provided are antibodies and antibody fragments capable of activating CD4+CD25+ regulatory T cells and methods and uses involving the antibodies and fragments thereof.

Agents for treating disease

Provided is a humanized or chimeric antibody or fragment thereof capable of binding to interleukin-10 (IL-10), wherein said antibody or fragment thereof is capable of being administered to a subject in the absence of an intolerable increase in the level of pro-inflammatory cytokines. Further provided are methods of treatment involving the use of the antibody or fragment thereof.

Humanized anti-IL-10 antibodies for the treatment of systemic lupus erythematosus (SLE)

The present invention provides pharmaceutical composition for treating an autoimmune disease comprising a pharmaceutically acceptable carrier and an agent capable of activating CD4+CD25+ regulatory T cells, wherein the composition is to be administered to a subject at most every 3 days.

Method for treating psoriasis

Provided is a humanized or chimeric antibody or fragment thereof capable of binding to interleukin-10 (IL-10), wherein said antibody or fragment thereof: (i) binds to the same region of IL-10 as the IL-10 receptor &#x3b1; (IL-I10Ra) and is not capable of binding IL-10 when the IL-10 is bound to the IL-10 receptor; and (ii) binds to IL-10 in homodimeric form by binding a discontinuous epitope comprising residues of both monomers. Further provided are related products and methods involving the use of the antibody or fragment thereof.

Use of antibodies for detection of IL-10

The present invention provides a pharmaceutical composition for treating an autoimmune disease comprising a pharmaceutically acceptable carrier and an agent capable of activating CD4+CD25+ regulatory T cells, wherein the composition is to be administered to a subject in a dose of the agent from 10 mg to 200 mg.

Agent for treating disease

Disclosed are immunoconjugates having specificity for CD138 that diminish adhesion of CD138 expressing tumor cells to stroma cells and methods of using the same. This diminished adhesion renders the tumor cells not only susceptible to the immunoconjugate, but also to other agents, in particular cytotoxic agents.

Methods and agents for improving targeting of CD138 expressing tumor cells

Disclosed are immunoconjugates having in particular specificity for CD138 expressed on target cells and which display homogenous targeting. The immunoconjugates may be sterially hindered and/or contain a cleavable linker.

Immunoconjugates targeting CD138 and uses thereof

The present invention provides a pharmaceutical composition for treating an autoimmune disease comprising a pharmaceutically acceptable carrier and an agent capable of activating CD4+CD25+ regulatory T cells, wherein the composition is to be administered to a subject in a dose of the agent from 0.2 mg to 30 mg.

Disclosed are methods and treatment regimes that include the administration of immunconjugates targeting CD138 to combat diseases. The immunoconjugate is either used as the sole active ingredient, as part of a treatment regime or as part of an anticancer combination.

Disclosed is a human murine chimeric antibody targeting CD138 which substantially retains the antigen binding region of its murine counterpart. The engineered antibody displays improved binding affinities to the antigen and/or more homogenous binding to target cells relative to its murine counterpart. A constant region of the immunoglobulin heavy chain is preferably an IgG4 isotype constant region.

Agents targeting CD138 and uses thereof

Disclosed are methods, compositions and kits for improving targeting, in particular tumor targeting, of immunoconjugates. The method and composition relies on the sequestration of non-target cells that also express the antigen the immunoconjugate targets. Sequestration of those non-target cells in a variety of ways is disclosed. The methods, compositions and kits allow appropriate sequestration of non-target cells while maintaining a high degree of effectiveness of the immunoconjugates against target cells.

Method of decreasing cytotoxic side-effects and improving efficacy of  immunoconjugates

Provided is a humanized or chimeric antibody or fragment thereof capable of binding to interleukin-10 (IL-10), wherein said antibody or fragment thereof: (i) binds to the same region of IL-10 as the IL-10 receptor &#x3b1;(IL-I10Ra) and is not capable of binding IL-10 when the IL-10 is bound to the IL- 10 receptor; and (ii) binds to IL-10 in homodimeric form by binding a discontinuous epitope comprising residues of both monomers. Further provided are related products and methods involving the use of the antibody or fragment thereof.

Humanized anti-IL 10 antibodies for the treatment of systemic lupus erythematosus (SLE)

Provided is a humanized or chimeric antibody or fragment thereof capable of binding to interleukin-10 (Th-10), wherein said antibody or fragment thereof is capable of being administered to a subject in the absence of an intolerable increase in the level of pro-inflammatory cytokines. Further provided are methods of treatment involving the use of the antibody or fragment thereof.

Growing community of inventors

Seligenstadt, Germany

Christoph Uherek