Methods and products related to the transfer of molecules from blood to the mammary gland

• US 20080063780A1
• Filed: 04/20/2007
• Published: 03/13/2008
• Est. Priority Date: 04/21/2006
• Status: Active Grant

• Current Assignee: LFB USA, Inc. (Agence des Participations de l’Etat)
• Original Assignee: GTC Biotherapeutics, Inc.
• Inventors: Pollock, Daniel, Meade, Harry
• Granted Patent: US 8,173,860 B2
• Time in Patent Office: Days
• US Class Current: 426/580
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/01 Animal expressing industrially exogenous proteins
• CPC Class Codes: A01K 67/0275 Genetically modified vertebrates, e.g. transgenic
• CPC Class Codes: C07K 14/70535 Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 2510/02 Cells for production
• CPC Class Codes: C12N 2517/04 Cells produced using nuclear transfer
• CPC Class Codes: C12N 2830/008 cell type or tissue specific enhancer/promoter combination

Abstract

The invention provides, in part, methods for the production of proteins in a transgenic non-human mammal, wherein the proteins are transported from the blood to the mammary gland for secretion in milk. The transport of the protein to the mammary gland and/or milk is facilitated by binding to a transport receptor in the mammary gland.

Claims

1. A non-human mammal that expresses a functional transport receptor in the mammary gland during lactation and a transgenic protein in the blood.

2. The non-human mammal of claim 1, wherein the functional transport receptor is functional FcRn.

3. The non-human mammal of claim 2, wherein the non-human mammal comprises a transgenic nucleic acid encoding FcRn and a transgenic nucleic acid encoding the transgenic protein.

5. The non-human mammal of claim 3, wherein the transgenic nucleic acid encoding FcRn also encodes beta-microglobulin.

6. The non-human mammal of claim 3, wherein the transgenic nucleic acid encoding FcRn also encodes a mammary gland-specific promoter.

8. The non-human mammal of claim 3, wherein the transgenic nucleic acid encoding the transgenic protein also encodes a non-mammary gland-specific promoter.

9. The non-human mammal of claim 8, wherein the non-mammary gland-specific promoter is a liver-specific promoter.

10. The non-human mammal of claim 9, wherein the liver-specific promoter is an albumin promoter.

11. The non-human mammal of claim 1, wherein the transgenic protein can bind functional FcRn.

12. The non-human mammal of claim 11, wherein the transgenic protein comprises a Fc-domain.

13. The non-human mammal of claim 11, wherein the transgenic protein is fused to a Fc-domain or a molecule comprising a Fc-domain and can bind the functional FcRn via the Fc-domain or molecule comprising the Fc-domain.

14. The non-human mammal of claim 1, wherein the transgenic protein is an antibody.

21. A composition comprising milk obtained from the non-human mammal of claim 1.

23. A method for obtaining a transgenic protein, comprising:

collecting milk from the non-human mammal of claim 1, and separating the transgenic protein from the milk.

35. The method of claim 23, wherein the glycosylation pattern of the transgenic protein is different from the glycosylation pattern of the protein when expressed in the mammary gland of the non-human mammal.

47. A composition comprising the collected milk of the method of claim 23.

4. (canceled)

7. (canceled)

15-20. -20. (canceled)

22. (canceled)

24. A method for obtaining a transgenic protein present in the milk of a non-human mammal, comprising:

generating a non-human mammal that expresses a functional transport receptor in the mammary gland during lactation and a transgenic protein in the blood, wherein the transgenic protein binds the functional transport receptor, and

collecting milk from the non-human mammal.

25. The method of claim 24, wherein the functional transport receptor is functional FcRn.

27. The method of claim 25, wherein the non-human mammal comprises a transgenic nucleic acid encoding FcRn under the control of a mammary gland-specific promoter and a transgenic nucleic acid encoding the transgenic protein under the control of a non-mammary gland-specific promoter.

28. The method of claim 27, wherein the transgenic nucleic acid encoding FcRn also encodes beta-microglobulin.

29. The method of claim 27, wherein the non-human mammal further comprises a transgenic nucleic acid encoding beta-microglobulin under the control of a mammary gland-specific promoter.

31. The method of claim 27, wherein the non-mammary gland-specific promoter is a liver-specific promoter.

32. The method of claim 31, wherein the liver-specific promoter is an albumin promoter.

39. The method of claim 25, wherein the transgenic protein comprises a Fc-domain.

40. The method of claim 25, wherein the transgenic protein is fused to a Fc-domain or a molecule comprising a Fc-domain and binds the functional FcRn via the Fc-domain or the molecule comprising the Fc-domain.

41. The method of claim 24, wherein the transgenic protein is an antibody.

26. (canceled)

30. (canceled)

33-34. -34. (canceled)

36-38. -38. (canceled)

42-46. -46. (canceled)

48. (canceled)

49. A composition comprising milk from a non-human mammal, wherein the milk contains a transgenic protein that binds a functional transport receptor, wherein the transgenic protein is not expressed in the mammary gland of the non-human mammal.

50. The composition of claim 49, wherein the functional transport receptor is FcRn.

51. The composition of claim 49, wherein the glycosylation pattern of the transgenic protein is different from the glycosylation pattern of the protein when expressed in the mammary gland of the non-human mammal.

52-63. -63. (canceled)