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Last Updated: March 29, 2024

Claims for Patent: 9,051,356


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Summary for Patent: 9,051,356
Title:Use of human cells of myeloid leukaemia origin for expression of antibodies
Abstract: The invention relates to a method for producing a protein molecule composition having a defined glycosylation pattern, comprising (a) introducing in a host cell which is an immortalized human blood cell at least one nucleic acid encoding at least a part of said protein; and (b) culturing said host cell under conditions which permit the production of said protein molecule composition; and (c) isolating said protein molecule composition.
Inventor(s): Goletz; Steffen (Glienicke-Nordbahn, DE), Danielczyk; Antje (Panketal, DE), Baumeister; Hans (Berlin, DE), Stahn; Renate (Berlin, DE), Loffler; Anja (Eichhorst, DE), Stockl; Lars (Berlin, DE)
Assignee: Glycotope GmbH (Berlin, DE)
Application Number:12/440,562
Patent Claims:1. A method for producing a protein molecule composition, comprising (a) introducing in a host cell which is an immortalized human blood cell at least one nucleic acid encoding said protein; and (b) culturing said host cell under conditions which permit the production of said protein molecule composition; and (c) isolating said protein molecule composition; wherein the host cell is selected from the group consisting of GT-2.times.[DSM ACC 2858], NM-H9D8 [DSM ACC 2806], NM-H9D8-E6 [DSM ACC 2807], and NM H9D8-E6Q 12 [DSM ACC 2856].

2. The method according to claim 1, wherein the host cell grows and produces the protein molecule composition under serum-free conditions.

3. The method according to claim 1, wherein a nucleic acid is introduced in the host cell, encoding an antifolate resistant dihydrofolate reductase (DHFR)-variant.

4. The method according to claim 3, wherein the nucleic acid encoding said antifolate resistant DHFR variant is introduced via a separate vector in addition to a vector comprising the nucleic acid encoding said protein to be expressed or wherein a vector is used, comprising at least the nucleic acid encoding said protein to be expressed and the nucleic acid encoding the antifolate resistant DHFR variant.

5. The method according to claim 3, wherein the host cell is cultured with said antifolate.

6. The method according to claim 3, wherein the nucleic acid sequence encoding said protein molecule to be expressed is amplified by stepwise increasing the antifolate concentration in the culture.

7. The method according to claim 3, wherein at least one of the following characteristics is fulfilled (a) the antifolate is methotrexate (b) the nucleic acid encoding said antifolate resistant DHFR variant encodes a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to 9.

8. The method according to claim 1, wherein said protein is an antibody.

9. The method according to claim 8, wherein the antibody is selected from the group consisting of an antibody against MUC 1, an antibody against HER2, and an antibody against EGFR.

10. The method according to claim 8, wherein the antibody is chosen from antibodies against ganglioside GD3, antibodies against human interleukin-5 receptor alpha-chain, antibodies against HER2, antibodies against CC chemokine receptor 4, antibodies against CD20, antibodies against CD22, antibodies against neuroblastoma, antibodies against MUC1, and antibodies against epidermal growth factor receptor.

11. The method according to claim 8, wherein the antibody is Cetuximab.

12. The method according to claim 8, wherein the antibody is Herceptin.

13. The method according to claim 8, wherein the antibody is Panko 1 or Panko 2.

14. The method according to claim 8, wherein the antibody is Rituximab.

15. The method according to claim 8, wherein the antibody has at least one N-glycosylation site having the amino acid sequence Asn-Xaa-Ser/Thr, wherein Xaa can be any amino acid except Pro, and/or at least one O-glycosylation site in the sequence of the Fab region.

16. The method according to claim 10, wherein the antibody is chosen from Pankomab, Muromomab, Daclizumab, Basiliximab, Abciximab, Rituximab, Herceptin, Gemtuzumab, Alemtuzumab, Ibritumomab, Cetuximab, Bevacizumab, Tositumomab, Pavlizumab, Infliximab, Eculizumab, Epratuzumab, Omalizumab, Efalizumab, Adalimumab, Campath-1H, C2B8, Panorex, BrevaRex, Simulect, Antova, OKT3, Zenapax, ReoPro, Synagis, Ostavir, Protovir, OvaRex, Vitaxin, anti-CC chemokine receptor 4 antibody KM2160, and anti-neuroblastoma antibody chCE7.

17. The method according to claim 1, for producing an antibody molecule composition, comprising: (a) introducing in a host cell of human myeloid leukaemia origin at least one nucleic acid encoding an antibody molecule, and at least one nucleic acid comprising at least one nucleic acid sequence encoding at least one polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to 9; and (b) amplifying the nucleic acid sequence encoding said antibody molecule by culturing said host cell with methotrexate; and (c) culturing said host cell under conditions which permits the production of said antibody molecule composition, and (d) isolating said antibody molecule composition.

18. The method according to claim 1 for producing an antibody molecule composition having increased activity and/or increased yield and/or improved homogeneity, comprising: (a) introducing in a host cell of human myeloid leukaemia origin at least one nucleic acid encoding an antibody molecule; and (b) culturing said host cell under conditions which permits the production of said antibody molecule compositions; and (c) isolating said antibody molecule composition having increased activity and/or increased yield and/or improved homogeneity.

19. The method according to claim 1 for producing an antibody molecule composition having increased activity and/or increased yield and/or improved homogeneity, comprising: (a) introducing in a host cell of human myeloid leukaemia origin at least one nucleic acid encoding an antibody molecule, and at least one nucleic acid comprising at least one nucleic acid sequence encoding at least one polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to 9; and (b) amplifying the nucleic acid sequence encoding said antibody molecule by culturing said host cell with methotrexate; and (c) culturing said host cell under conditions which permits the production of said antibody molecule composition, and (d) isolating said antibody molecule composition having increased activity and/or increased yield and/or improved homogeneity.

20. The method according to claim 1, wherein the host cell is NM-H9D8 [DSM ACC 2806].

21. The method according to claim 1, wherein the host cell is NM-H9D8 [DSM ACC 2807].

22. The method according to claim 1, wherein the host cell is NM-H9D8 [DSM ACC 2856].

23. The method according to claim 1, wherein the protein is chosen from cytokines and their receptors; renin; human growth hormone and bovine growth hormone; growth hormone releasing factor; parathyroid hormone; thyroid stimulating hormone; lipoproteins; alpha-1-antitrypsin; insulin A-chain and B-chain; gonadotrophins; calcitonin; glucagon; clotting factors; anti-clotting factors; atrial natriuretic factor; lung surfactant; plasminogen activators; bombesin; thrombin; hemopoietic growth factor; enkephalinase; human macrophage inflammatory protein; a serum albumin; mullerian-inhibiting substance; relaxin A-chain and B-chain; prorelaxin; mouse gonadotropin-associated peptide; vascular endothelial growth factor; receptors for hormones or growth factors; integrin; protein A and D; rheumatoid factors; neurotrophic factors; platelet-derived growth factor; fibroblast growth factors; epidermal growth factor; transforming growth factor; insulin-like growth factor-I and -II; insulin-like growth factor binding proteins; CD proteins; erythropoietin (EPO); osteoinductive factors; immunotoxins; bone morphogenetic proteins; interferons; colony stimulating factors (CSFs); interleukins (IL's); superoxide dismutase; T-cell receptors; surface membrane proteins; decay accelerating factor; antibodies and immunoadhesins; glycophorin A; MUC1.

24. The method according to claim 23, wherein the protein is chosen from tumor necrosis factors TNF-alpha and TNF-beta, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyrotrophin, human chorionic gonadotrophin (hCG), factor VIIIC, factor IX, factor VII, tissue factor, von Willebrands factor, protein C, urokinase, human urine plasminogen activator, tissue-type plasminogen activator, human serum albumin, bone-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, neurotrophin-5, neurotrophin-6, nerve growth factor-beta, TGF-alpha, TGF-beta, CD-3, CD-4, CD-8, CD-19, interferon-alpha, interferon-beta, interferon-gamma, M-CSF, GMCSF, G-CSF, and IL-1 to IL-12.

25. The method according to claim 1, wherein the protein is FSH.

26. The method according to claim 1, wherein the protein is Factor VII.

27. The method according to claim 1, wherein the protein is encoded by a single nucleic acid molecule.

28. The method according to claim 1, wherein the protein is encoded by multiple nucleic acid molecules.

29. An immortalized human blood cell selected from the group consisting of GT-2.times.[DSM ACC 2858], NM-H9D8 [DSM ACC 2806], NM-H9D8-E6 [DSM ACC 2807], and NM-H9D8-E6Q12 [DSM ACC 2856].

30. The cell according to claim 29, comprising at least one nucleic acid encoding a protein molecule, and at least one nucleic acid comprising at least one nucleic acid sequence encoding at least one polypeptide having the amino acid sequence selected from the group of consisting of SEQ ID NO: 1 to 9.

31. The cell according to claim 29, wherein the cell is NM-H9D8 [DSM ACC 2806].

32. The cell according to claim 29, wherein the cell is NM-H9D8-E6 [DSM ACC 2807].

33. The cell according to claim 29, wherein the cell is NM-H9D8-E6Q12 [DSM ACC 2856].

34. The cell according to claim 29, comprising at least one nucleic acid encoding a protein molecule in an appropriate expression vector.

35. The cell according to claim 34, wherein the protein is encoded by a single nucleic acid molecule.

36. The cell according to claim 34, wherein the protein is encoded by multiple nucleic acid molecules.

37. The cell according to claim 34, where in the protein molecule is an antibody molecule.

38. The cell according to claim 37, wherein the antibody molecule encoded is PankoMab, Panko 1, Panko 2 or Cetuximab, or a variant thereof, binding the same epitope.

39. The cell according to claim 37, which grows and produces the antibody molecule composition under serum-free conditions.

40. A method for producing a protein, comprising expressing a nucleic acid encoding the protein in an immortalized human blood cell according to claim 29.

41. The method according to claim 40, wherein the protein molecule is an antibody molecule.

42. The method according to claim 40, wherein the protein is encoded by a single nucleic acid molecule.

43. The method according to claim 40, wherein the protein is encoded by multiple nucleic acid molecules.

44. A method for producing an antibody molecule composition comprising (a) introducing at least one nucleic acid encoding said antibody into a host cell; wherein the host cell is an immortalized human blood cell; (b) culturing said host cell under conditions which permit the production of said antibody molecule composition; and (c) isolating said antibody molecule composition; wherein the antibody is selected from the group consisting of an antibody which binds a MUC1 epitope comprising the amino acid sequence DTR of the extracellular tandem repeat region; Cetuximab or a variant thereof, binding the same epitope as Cetuximab; and a fragment of anyone of these antibodies comprising the binding region of said antibody; and wherein the host cell is selected from the group consisting of K562, NM-F9 [DSM ACC 2606], NM-D4 [DSM ACC 2605], GT-2.times.[DSM ACC 2858], NM-H9D8 [DSM ACC 2806], NM-H9D8-E6 [DSM ACC 2807], and NM-H9D8-E6Q12 [DSM ACC 2856].

45. The method according to claim 44, wherein the antibody is encoded by a single nucleic acid molecule.

46. The method according to claim 44, wherein the antibody is encoded by multiple nucleic acid molecules.

Details for Patent 9,051,356

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Microbix Biosystems Inc. KINLYTIC urokinase For Injection 021846 01/16/1978 ⤷  Try a Trial 2026-09-10
Janssen Biotech, Inc. REOPRO abciximab Injection 103575 12/22/1994 ⤷  Try a Trial 2026-09-10
Genentech, Inc. RITUXAN rituximab Injection 103705 11/26/1997 ⤷  Try a Trial 2026-09-10
Idec Pharmaceuticals Corp. RITUXAN rituximab Injection 103737 02/19/2002 ⤷  Try a Trial 2026-09-10
Hoffmann-la Roche Inc. ZENAPAX daclizumab Injection 103749 12/10/1997 ⤷  Try a Trial 2026-09-10
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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