Hoffmann-la Roche Inc.

Boehringer Mannheim Gmbh

Roche Palo Alto LLC

Scil Proteins Gmbh

Roche Diagnostics Gmbh

Maxygen, Inc.

F. Hoffmann-la Roche Ag

Adelbert Grossmann

Erhard Kopetzki

Rainer Rudolph

Friederike Hesse

Sascha Lutz

Norbert Oranth

Monika Baehner

Ulrich Tibes

Tim Sattelkau

Nadine Losleben

Stefan Hepbildikler

Guy Georges

Stefan Seeber

Olaf Mundigl

Wolfgang Von Der Saal

Ralf Schumacher

Christian Schantz

Wilma Lau

Elisabeth Schwarz

Anke Rattenholl

Paul Parren

Phillip A Patten

Wolfgang Schaefer

Joerg Thomas Regula

Jan Van De Winkel

Stephan Fischer

Kay-Gunnar Stubenrauch

Anja Limberg

Matthias Koerner

Roberto Falkenstein

Torben Lauesgaard Nissen

Yvo Graus

Klaus-Peter Kuenkele

Andreas Schaubmar

Martine Van Vugt

Frank Rebers

Frank Herting

Sridhar Viswanathan

Josef Endl

Anne Vogt

Harald Kropshofer

Jan Olaf Stracke

Sebastian Neumann

Maria Elena Fuentes

Claudia Giessel

Marc Pompiati

Birgit Weydanz

Nicole Fuehrler

Sybille Gabel

Brigitte Kraemer

Sandra Vereecken-Verploegen

Sybille Greithanner

Maria Fuentes

Jan Stracke

Herein is reported a method for obtaining a polypeptide in monomeric form comprising the steps of a) providing a solution comprising the polypeptide in monomeric form and in aggregated form, wherein the ratio of monomeric to aggregated form is 4:1 or less as determined by size exclusion chromatography, b) performing a mixed-mode chromatography in bind-and-elute mode, or a hydrophobic interaction chromatography in flow-through mode, or a size-exclusion chromatography, and c) performing a weak cation exchange chromatography in bind-and-elute mode or flow-through mode, and thereby obtaining the polypeptide in monomeric form.

Method for separation of monomeric polypeptides from aggregated polypeptides

A micro fluid filtration system () preferably for increasing the concentration of components contained in a fluid sample has a fluid circuitry (). The fluid circuitry () comprises the following elements: A tangential flow filtration element () capable for separating the fluid sample into a retentate stream and a permeate stream upon passage of the fluid, an element for pumping () for creating and driving a fluid flow through the fluid circuitry () and at least one element for obtaining information about the properties of the fluid sample within the circuitry. The circuitry further comprises a plurality of conduits () connecting the elements of the fluid circuitry () through which a fluid stream of the fluid sample is conducted. The circuitry () has a minimal working volume of at most 5 ml, which is the minimal fluid volume retained in the elements and the conduits () of the circuitry () such that the fluid can be recirculated in the circuitry () without pumping air through the circuitry (). An integrated microfluidic element () of the circuitry () contains the functionality of at least two elements of the group of elements of the circuitry ().

Micro flow filtration system and integrated microfluidic element

A micro flow filtration system comprises a fluid circuitry () and a first reservoir () outside the circuitry () suitable for containing a fluid. The fluid circuitry () comprises a tangential flow filtration module () capable of separating the fluid sample into a retentate stream and a permeate stream upon passage of the fluid sample into the tangential flow filtration module () through an inlet feed (). The fluid circuitry () further comprises a second reservoir () integrated in the fluid circuitry (), a pump () for creating and driving a fluid flow, optionally at least one pressure sensor (or) for acquiring and detecting data about the fluid sample, optionally a pressure regulator () for regulating the flow in the fluid circuitry () and a plurality of conduits () forming the fluid circuitry () together with the second reservoir (), the TFF-module (), the pump (), the pressure sensor (or) (if present) and the pressure regulator () (if present). The volume of the first reservoir () outside the circuitry () is significantly larger than the volume of the second reservoir (). The first reservoir () outside the fluid circuitry () is connected to the circuitry () via a connection conduit () such that the fluid flows unidirectionally into the circuitry () until the first reservoir () is empty so that a continuous fluid flow from the first reservoir () to the circuitry () is established.

Micro flow filtration system and flow filtration method

Herein is reported a method for obtaining a polypeptide in monomeric form comprising the steps of a) providing a solution comprising the polypeptide m monomeric form and m aggregated form, wherein the ratio of monomeric to aggregated form is 4:1 or less as determined by size exclusion chromatography, b) performing a mixed-mode chromatography in bind-and-elute mode, or a hydrophobic interaction chromatography in flow-through mode, or a size-exclusion chromatography, and c) performing a weak cation exchange chromatography in bind-and-elute mode or flow-through mode, and thereby obtaining the polypeptide m monomeric form.

A flow filtration system () for concentration of components contained in a fluid sample comprises a fluid channel () being formed by two conduits () allowing a bidirectional flow of the fluid sample through the fluid channel (), a tangential flow filtration module () and at least two pairs () of piston pumps () each having two piston pumps (), wherein the piston pumps () having a piston swept volume forming a reservoir being able to contain the fluid for volumes of up to 100 ml. The tangential flow filtration module () is located in the fluid channel () so that a fluid flowing through the channel () passes through the filtration module (). At each end () of the channel () one piston pump () of each pair () of piston pumps () is located in such a manner that the piston pumps are fluidically connected in parallel. The system () is arranged and adapted such that during the concentration process at least for a predetermined period of time only one of the pairs () of piston pumps () is used to drive the fluid through the tangential flow filtration module ().

Micro flow filtration system and flow filtration method for a fluid sample

Herein is reported a method for the recombinant production of a polypeptide, which comprises the dipeptide AR, characterized in that the method comprises the recovering of the polypeptide from the cells or the cultivation medium of a cultivation of a cell comprising a nucleic acid encoding the polypeptide and thereby producing the polypeptide, whereby the dipeptide AR comprised in the polypeptide is encoded by the oligonucleotide gca cgt, or the oligonucleotide gcg cgt, or the oligonucleotide gcc cgt.

Method for reduction of 1-&#x3e;2 reading frame shifts

The current invention reports a method for the purification of a not-glycosylated, heterologous polypeptide, which has been recombinantly produced in a prokaryotic cell, wherein the method comprises three chromatography steps of which the first chromatography step selected from i) hydrophobic charge induction chromatography, or ii) hydrophobic interaction chromatography, or iii) affinity chromatography, or iv) ion exchange chromatography, the second chromatography step is selected from i) anion exchange chromatography, or ii) cation exchange chromatography, or iii) hydroxylapatite chromatography, or iv) hydrophobic interaction chromatography, and the a third chromatography step is selected from i) hydrophobic charge induction chromatography, or ii) anion exchange chromatography, or iii) cation exchange chromatography, or iv) hydrophobic interaction chromatography, whereby the first chromatography step is an affinity chromatography in case of polypeptides capable of interacting with metal ligands, the second chromatography step is not a hydroxylapatite chromatography step in case of polypeptides with an isoelectric point below 6.0, and the third chromatography step can be performed in flow-through mode with polypeptides having a low or high isoelectric point.

Purification of non-glycosylated polypeptides

A pro-polypeptide which is useful for the expression of a polypeptide of interest in a prokaryotic cell. Therefore the pro-polypeptide is fused to the N-terminus of the polypeptide of interest. The pro-polypeptide as reported herein provides for improved expression yields and improves the handling of the fusion polypeptide (downstream processing, purification). For example, efficient endotoxin removal is effected while the protein of interest comprising the pro-polypeptide is bound e.g. to an affinity chromatography material. Thereafter the pro-polypeptide can efficiently be cleaved from the polypeptide of interest by the incorporated protease cleavage site with the cognate protease.

Prokaryotic expression construct

The invention relates to a method for producing biologically active &#x3b2;-NGF from the proform proNGF. After expressing the proform of the &#x3b2;-NGF in a prokaryotic host cell, the recombinant protein is isolated in the form of insoluble inactive aggregates (inclusion bodies). After the solubilization thereof in a strong denaturing agent and the subsequent conversion thereof into the natural conformation, which is determined by the disulfide bridges present in the natural &#x3b2;-NGF, biologically active &#x3b2;-NGF is obtained by subsequently splitting-off the prosequence.

Method for obtaining active pro-NGF and beta-NGF

Pharmaceutical preparations comprising human proNGF

The instant specification discloses an antibody binding to IL-13R&#x3b1;1, inhibiting IL-13 bioactivity and comprising a variable heavy and a variable light chain, characterized in that the variable heavy chain amino acid sequence CDR3 of this antibody is selected from the group consisting of the heavy chain CDR3 sequences of SEQ ID NO: 1, 3, 5, 7 or 9, and this antibody is useful in the treatment of asthma and allergic diseases.

Antibodies against IL-13 receptor alpha1 and uses thereof

The present invention provides interferon-alpha polypeptides and conjugates, and nucleic acids encoding the polypeptides. The invention also includes compositions comprising these polypeptides, conjugates, and nucleic acids; cells containing or expressing the polypeptides, conjugates, and nucleic acids; methods of making the polypeptides, conjugates, and nucleic acids; and methods of using the polypeptides, conjugates, and nucleic acids.

Interferon-alpha polypeptides and conjugates

The (R) and (S) enantiomers of a compound of formula I are novel antiproliferative therapeutic agents. These compounds have HDAC inhibitor activity and are useful in the treatment of cancer. Also disclosed are methods of making and using compounds of formula (I), as well as pharmaceutical compositions containing compounds of formula (I).

Thiophene hydroxamic acid derivatives

A compound of formula (I) wherein A and B are optionally substituted cyclohexenyl or phenyl groups, X is carbonyl or sulfonyl, and Y is 5&#x2013;7 atoms-linker, is useful as histone deacetylase inhibitors, particularly for inhibiting cell proliferation.

Tricyclic lactam and sultam derivatives and their use as histone deacetylase inhibitors

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Eglfing, Germany

Adelbert Grossmann