Zymogenetics, Inc.

Ppl Therapeutics (scotland) Limited

Pharmaceutical Proteins Limited

Ppl Therapeutics

Pharming Intellectual Property Bv

Profactor Pharma Ltd.

Ian Garner

Ian Robert Cottingham

Donald C Foster

Donna E Prunkard

Cindy A Sprecher

Bruce Vernon

Michael L Dalrymple

Simon M Temperley

John Henderson Mcvey

Adele Dale

Michael A Dalrymple

Peptides can be produced in and purified from the milk of transgenic animals. The peptides are made as fusion proteins with a suitable fusion partner such as &agr;-lactalbumin, which is a natural milk protein. The fusion partner protein acts to promote secretion of the peptides and, at least in the case of &agr;-lactalbumin, allows a single-step purification based on specific affinity. The peptide is released from the purified fusion protein by a simple cleavage step and purified away from the now liberated &agr;-lactalbumin by repeating the same affinity purification method. A particular advantage of producing peptides via this route, in addition to the obvious advantages of high yield and biocompatibility, is that specific post-translational modifications, such as carboxy terminal amidation, can be performed in the mammary gland.

Peptide production as fusion protein in transgenic mammal milk

Methods for producing protein C in transgenic non-human mammals are disclosed. The protein C is modified at the two-chain cleavage site between the light and heavy chains of protein C from Lys-Arg to R.sub.1 -R.sub.2 -R.sub.3 -R.sub.4 where R.sub.1 through R.sub.4 are individually Arg or Lys. DNA segments encoding modified protein C are introduced into the germ line of a non-human mammals, and the mammal or its female progeny produces milk containing protein C expressed from the introduced DNA segments. The protein C expressed from the introduced DNA segments has anticoagulant activity when activated. Non-human mammalian embryos and transgenic non-human mammals carrying DNA segments encoding heterologous protein C are also disclosed.

Protein C production in non-human transgenic mammals

Materials and methods for producing fibrinogen in transgenic non-human mammals are disclosed. DNA segments encoding A.alpha., B.beta. and .gamma. chains of fibrinogen are introduced into the germ line of a non-human mammal, and the mammal or its female progeny produces milk containing fibrinogen expressed from the introduced DNA segments. Non-human mammalian embryos and transgenic non-human mammals carrying DNA segments encoding heterologous fibrinogen polypeptide chains are also disclosed.

Production of fibrinogen in transgenic animals

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Edinburgh, United Kingdom

Ian Garner