Novozymes Biopharma Dk A/s

Delta Biotechnology Limited

Albumedix A/s

Albumedix Limited

Human Genome Sciences, Inc.

Hauser, Hans-peter

Dickneite, Gerhard

Weimer, Thomas

Kröz, Monika

Darrell Sleep

Esben Peter Friis

Richard A Johnson

Gerhard Dickneite

Hans-Peter Hauser

David James Ballance

Christopher John Arthur Finnis

Jason Cameron

Andrew Robert Goodey

Inger Sandlie

Andrew J Turner

Jan Terje Andersen

John Rodney Woodrow

Christopher P Prior

Homayoun Sadeghi

Stephen Berezenko

Andrew Plumridge

Hendrik Van Urk

Alan Victor Quirk

Patricia Carol Wood

Philip Harvey Morton

Andrew John Cartwright

David John Mead

Joanna Mary Hay

Gillian Shuttleworth

Mark J Wilson

Steven James Burton

David J Ballance

Stephen James Burton

David St Coghlan

Jean-Luc Bernard Veron

Christopher J A Finnis

Michael G Courtney

Graham P Belfield

Dina Vakeria

Leslie Evans

Steven Athwal

Elizabeth Allan

Michel Gaston Joseph Grandgeorge

Leslie Robert Evans

Joanne Patricia Waters

David John Tooth

Malcolm John Saxton

Neil Dodsworth

Joanna Hay

Miranda Hughes

Gurdeep Singh Athwal

Monika Kröz

Thomas Weimer

Based on the three-dimensional structure of albumin, the inventors have designed variant polypeptides (muteins) which have one or more cysteine residues with a free thiol group (hereinafter referred to as 'thio-albumin'). The variant polypeptide may be conjugated through the sulphur atom of the cysteine residue to a conjugation partner such as a bioactive compound.

Albumin variants and conjugates

The present invention relates to variants of a parent albumin having altered plasma half-life compared with the parent albumin. The present invention also relates to fusion polypeptides and conjugates comprising said variant albumin.

Albumin variants

The application discloses albumin derivatives comprising or consisting of domain III and at least one further domain wherein the derivative or variant is not a naturally occurring albumin derivative or variant. The derivatives may be used in conjugates and fusion polypeptides.

Albumin derivatives and variants

The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Albumin fusion proteins

Treatment with factor VII-albumin fusion protein

The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acid vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Treatment with factor ix-albumin fusion protein

A process is provided for the preparation of a highly pure albumin solution the process comprising subjecting albumin (preferably expressed and secreted by transformed yeast) to a series of chromatographic steps. Preferably, the process comprises the steps of positive mode cation exchange chromatography, positive mode anion exchange chromatography, positive mode affinity chromatography, negative mode affinity chromatography (preferably using immobilized aminophenylboronic acid), negative mode cation exchange chromatography, and negative or positive mode anion exchange chromatography. A process for reducing the level of nickel in an albumin solution is also disclosed, as is a recombinant albumin coding sequence comprising two or more in-frame translation stop codons. Also disclosed is a process for producing recombinant albumin, the process comprising culturing a fungal cell expressing a recombinant albumin coding sequence, wherein the cell has a reduced capacity of mannosylation of the recombinantly-expressed albumin.

Process for the purification of recombinant albumin

The present invention provides a polypeptide comprising (i) a leader sequence, the leader sequence comprising a (a) secretion pre sequence, and (b) the following motif: where Xis phenylalanine, tryptophan, or tyrosine, Xis isoleucine, leucine, valine, alanine or methionine, Xis leucine, valine, alanine or methionine, Xis serine or threonine and Xis isoleucine, valine, alanine or methionine; and (ii) a desired protein heterologous to the leader sequence. A polypeptide of the invention may additionally comprise, as part of the leader sequence, a secretion pro sequence. The invention also provides a polynucleotide comprising a sequence that encodes a polypeptide of the invention and a cell, preferably a yeast cell, comprising said polynucleotide.

Gene and polypeptide sequences

The present invention provides a method for producing a desired protein (such as a desired heterologous protein) comprising: (a) providing a host cell comprising a first recombinant gene encoding a protein comprising the sequence of a first chaperone protein, a second recombinant gene encoding a protein comprising the sequence of a second chaperone protein and a third gene, such as a third recombinant gene, encoding a desired protein (such as a desired heterologous protein), wherein the first and second chaperones are different; and (b) culturing the host cell in a culture medium to obtain expression of the first, second and third genes.

Gene expression technique

The present invention provides a method for producing a desired protein (such as a desired heterologous protein) comprising:

Albumin Fusion Proteins

The present invention provides a polypeptide comprising (i) a leader sequence, the leader sequence comprising a (a) secretion pre sequence, and (b) the following motif: -X-X-X-X-X- where Xis phenylalanine, tryptophan, or tyrosine, Xis isoleucine, leucine, valine, alanine or methionine, Xis leucine, valine, alanine or methionine, Xis serine or threonine and Xis isoleucine, valine, alanine or methionine; and (ii) a desired protein heterologous to the leader sequence. A polypeptide of the invention may additionally comprise, as part of the leader sequence, a secretion pro sequence. The invention also provides a polynucleotide comprising a sequence that encodes a polypeptide of the invention and a cell, preferably a yeast cell, comprising said polynucleotide.

Growing community of inventors

Nottingham, United Kingdom

Darrell Sleep