Transgenic non human mammal milk

• US 5,750,172 A
• Filed: 06/05/1995
• Issued: 05/12/1998
• Est. Priority Date: 06/23/1987
• Status: Expired due to Term

• Current Assignee: Pharming Intellectual Property B.V. (Pharming Group N.V.)
• Original Assignee: Pharming BV (Pharming Group N.V.)
• Inventors: Lonberg, Nils, Meade, Harry
• Primary Examiner(s): Crouch, Deborah
• Application Number:
  US08/460,959
• Time in Patent Office: 1,072 Days
• Field of Search: 800/2, 800/DIG. 1, 800/3, 800/4, 435/172.1, 435/69.1, 435/69.4, 435/69.51, 435/69.52, 435/69.6, 435/215, 435/183, 935/63, 935/9, 935/11, 935/13, 935/14, 935/53, 530/832, 530/833, 426/580
• US Class Current: 426/580
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2227/103 Ovine
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A01K 67/0278 Knock-in vertebrates, e.g. humanised vertebrates
• CPC Class Codes: C07K 14/4732 Casein in foodstuffs A23J
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 2830/008 cell type or tissue specific enhancer/promoter combination
• CPC Class Codes: C12N 2830/85 mammalian
• CPC Class Codes: C12N 2840/44 being a specific part of the splice mechanism, e.g. donor, acceptor
• CPC Class Codes: C12N 9/6456 Plasminogen activators

Abstract

This invention relates to the production of recombinant proteins, such as coagulation factors VIII and IX, tissue plasminogen activator (TPA), urokinase, growth hormone, insulin, interferons, interleukins, peptide hormones and immunoglobulins, in mammals'"'"' milk. Particularly, this invention relates to an expression system which when transgenically incorporated into a mammal permits the female species of that mammal to produce the desired recombinant protein in or along with its milk. This invention also relates to the transgenic mammal that produces the desired recombinant product in its milk.

Claims

1. Nonhuman mammal'"'"'s milk comprising detectable levels of a recombinant polypeptide chain, wherein the recombinant polypeptide chain is produced by a nonhuman transgenic mammal whose somatic and germ cells contain an expression system comprising a DNA sequence coding for the recombinant polypeptide chain operably linked to a casein promoter and a signal peptide sequence, wherein the recombinant polypeptide chain is selected from the group consisting of coagulation factors VIII and IX, tissue plasminogen activator (TPA), urokinase, growth hormone, insulin, interferons, interleukins, peptide hormones, immunoglobulins and biologically active fragments thereof.

2. The milk of claim 1, wherein the non-human mammal is selected from the group consisting of sheep, goats, pigs and mice.

3. The milk of claim 1, wherein the expression system further comprises a 3'"'"' untranslated region downstream of the DNA sequence coding for the recombinant polypeptide.

4. The milk of claim 1, wherein the expression system further comprises a 5'"'"' untranslated region between said promoter and the DNA sequence coding for the signal peptide.

5. The milk of claim 1, wherein the promoter is an α

s1 casein promoter.