Hoechst Aktiengesellschaft

Aventis Pharma Deutschland, Gmbh

Sanofi-a Ventis Deutschland Gmbh

Gerhard Seipke

Paul Habermann

Johann Ertl

Karl Geisen

Georg Tschank

Norbert Tennagels

Ulrich Werner

Dominique Tripier

Gunter Muller

Mark Sommerfeld

Gerd Johnscher

Roland Kurrle

Eugen Uhlmann

Axel Walch

Rainer Obermeier

Johannes Meiwes

Michael Ahlers

Michael Dorschug

Jurgen Ludwig

Richard Bicker

Günter Müller

Michael Dörschug

Axel Wollmer

Gregory Russell-Jones

The invention relates to novel insulin analogs having a basal time-action profile, which are characterized by the following features: a) the B chain end consists of an amidated basic amino acid residue such as lysine or arginine amide; b) the N-terminal amino acid residue of the insulin A chain is a lysine or arginine radical; c) the amino acid position A8 is occupied by a histidine radical; d) the amino acid position A21 is occupied by a glycine radical; and e) one or more substitutions and/or additions of negatively charged amino acid residues are carried out in the positions A5, A15, A18, B-1, B0, B1, B2, B3 and B4.

Insulin derivatives having an extremely delayed time-action profile

The invention relates to novel insulin analogs having a basal time-action profile, which are characterized by the addition and/or substitution of negatively and positively charged amino acid residues and by an amidation of the C-terminal carboxy group of the B chain and histidine in position 8 of the insulin A chain. The invention also relates to the production and use thereof.

A mini-proinsulin, in which the amino acid Arg bridges the A and the B chain instead of the C chain, shows insulin activity and is suitable for the preparation of pharmaceuticals for the treatment of diabetes mellitus. It can furthermore be converted into an insulin derivative simply using trypsin, the B chain of which is lengthened by Arg. This can be converted into insulin using carboxypeptidase B. Advantageously, however, the mini-proinsulin can also be converted to insulin directly in a one-pot process.

Mini-proinsulin, its preparation and use

The invention relates to insulin analogs exhibiting enhanced zinc binding capacity and to stable zinc complexes thereof having a retarded activity in comparison with human insulin. The invention further relates to a method for the production of said insulin analogs and to their use, particularly in pharmaceutical preparations for therapy of type I and type II diabetes mellitus.

Insulin analogs with enhanced zinc binding

C peptide for improved preparation of insulin and insulin analogs

The present invention relates to insulin derivatives which in comparison to human insulin, have an accelerated onset of action, to a process for their preparation and to their use, in particular in pharmaceutical preparations for the treatment of diabetes mellitus. In particular, the present invention relates to insulin derivatives or physiologically tolerable salts thereof in which asparagine (Asn) in position B3 of the B chain is replaced by a naturally occurring basic amino acid residue and at least one amino acid residue in the positions B27, B28 or B29 of the B chain is replaced by another naturally occurring amino acid residue, it optionally being possible for asparagine (Asn) in position 21 of the A chain to be replaced by Asp, Gly, Ser, Thr or Ala and for phenylalanine (Phe) in position B1 of the B chain and the amino acid residue in position B30 of the B chain to be absent.

Insulin derivatives having a rapid onset of action

Insulin derivatives with increased zinc binding

Nanoparticles containing an active substance and a ketalized polytartramidic acid, process for their preparation, and use thereof. Nanoparticles containing an active substance and a ketalized polytartramidic acid are suitable as vehicles for active substances, in particular for peptides and proteins. Processes for the preparation of the nanoparticles are described.

Nanoparticles containing an active substance and a ketalized

The invention relates to a method for the preparation of polypeptides or proteins by enzymatic cleavage of the oligo- or polyglycine sequence of a fusion protein using an endoprotease.

Method for the selective cleavage of fusion proteins with lysostaphin

The invention relates to a process for the cleavage of peptides and proteins at the methionyl bond using cyanogen chloride.

Process for the cleavage of peptides and proteins at the methionyl bond

What is disclosed is a method for making human insulin or modified human insulin from pig insulin or modified pig insulin by reacting the pig insulin starting material at a pH below its isoelectric point with an excess of a threonine ester in the presence of trypsin or a trypsin-like enzyme.

Process for the preparation of human or the derivatives thereof from pig

The invention relates to a polypeptide which can be isolated from thymus glands and has an action on the immunological system, and which has a molecular weight of 3,480, a UV absorption with a maximum at 205 to 210 nm and an isoelectric point of 3.95+0.15 and a specific aminoacid composition, the N-terminal, if appropriate, carrying an acyl group or an acylglycyl group, processes for its isolation and purification, its use, agents containing this polypeptide, and its cleavage products, their use and agents containing them.

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Frankfurt am Main, Germany

Gerhard Seipke