Hoffmann-la Roche Inc.

F. Hoffmann-la Roche Ag

Friedrich Metzger

Joerg Thomas Regula

Kurt Lang

Andreas Schaubmar

Friederike Hesse

Stephan Fischer

Christian Schantz

Hendrik Knoetgen

Martin Ebeling

Manaswini Sivaramakrishnan

Hans-Joachim Schoenfeld

Hasane Ratni

Klaus-Peter Kuenkele

Martin Lanzendoerfer

Stefan Foser

Michael Sendtner

Beat Amrein

Bettina Holtmann

Jörg Regula

Hans Joachim Schoenfeld

The present invention relates to a FoxM1 gene splicing modifier selected from a compound of formula (I) or of formula (VI) 

Compounds for the treatment of cancer

The invention discloses a screening method for the identification of new compounds for use in the treatment of cancer.

Screening method

A conjugate consisting of an insulin-like growth factor-1 (IGF-I) variant and one or two poly(ethylene glycol) group(s), characterized in that said IGF-I variant has an amino acid alteration at up to three amino acid positions 27, 37, 65, 68 of the wild-type IGF-I amino acid sequence so that one or two of said amino acids is/are lysine and amino acid 27 is a polar amino acid but not lysine, is conjugated via the primary amino group(s) of said lysine(s) and said poly(ethylene glycol) group(s) have an overall molecular weight of from 20 to 100 kDa is disclosed. This conjugate is useful for the treatment of neurodegenerative disorders like Alzheimer's Disease.

Conjugates of insulin-like growth factor-1 and poly(ethylene glycol)

The present invention relates to a fusion protein comprising IGF-I or an IGF-I variant N-terminally linked to the C-terminus of a propeptide. The invention relates also to a method involving the use of the aforementioned fusion protein in the production of a lysine-PEGylated IGF-I or IGF-I variant. The method comprises the steps of cultivating a prokaryotic host cell comprising an expression vector containing a nucleic acid encoding the fusion protein and causing the cell to express the fusion protein, recovering and PEGylating said fusion protein, cleaving said PEGylated fusion protein with IgA protease, and recovering lysine-PEGylated IGF-I or IGF-I variant. The invention relates also to a lysine-PEGylated IGF-I or IGF-I variant produced using the above method. In addition, the invention relates to a method for treating a neurodegenerative disorders like Alzheimer's Disease using the lysine-PEGylated IGF-I or IGF-I variant and a composition comprising the lysine-PEGylated IGF-I or IGF-I variant.

Method for the production of conjugates of insulin-like growth factor-1 and poly(ethylene glycol)

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Freiburg, Germany

Friedrich Metzger