TWI456062B - 細胞培養改良 - Google Patents

細胞培養改良 Download PDF

Info

Publication number
TWI456062B
TWI456062B TW96134338A TW96134338A TWI456062B TW I456062 B TWI456062 B TW I456062B TW 96134338 A TW96134338 A TW 96134338A TW 96134338 A TW96134338 A TW 96134338A TW I456062 B TWI456062 B TW I456062B
Authority
TW
Taiwan
Prior art keywords
cell culture
hydrolysate
fragment
solution
plant
Prior art date
Application number
TW96134338A
Other languages
English (en)
Other versions
TW200831669A (en
Inventor
Itzcoatl A Pla
Joseph C Matuck
John C Fann
Christof Schulz
Nichole A Roy
David F Bruton
James Mcintire
Yu-Hsiang David Chang
Thomas Seewoester
Original Assignee
Abbvie Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=39184386&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=TWI456062(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Abbvie Inc filed Critical Abbvie Inc
Publication of TW200831669A publication Critical patent/TW200831669A/zh
Application granted granted Critical
Publication of TWI456062B publication Critical patent/TWI456062B/zh

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0018—Culture media for cell or tissue culture
    • C12N5/0037—Serum-free medium, which may still contain naturally-sourced components
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/244—Interleukins [IL]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2869—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against hormone receptors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/0018—Culture media for cell or tissue culture
    • C12N5/0031—Serum-free culture media
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0603—Embryonic cells ; Embryoid bodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/05—Inorganic components
    • C12N2500/10—Metals; Metal chelators
    • C12N2500/20—Transition metals
    • C12N2500/24—Iron; Fe chelators; Transferrin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/05—Inorganic components
    • C12N2500/10—Metals; Metal chelators
    • C12N2500/20—Transition metals
    • C12N2500/24—Iron; Fe chelators; Transferrin
    • C12N2500/25—Insulin-transferrin; Insulin-transferrin-selenium
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/30—Organic components
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/30—Organic components
    • C12N2500/32—Amino acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/30—Organic components
    • C12N2500/34—Sugars
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/30—Organic components
    • C12N2500/38—Vitamins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/50—Soluble polymers, e.g. polyethyleneglycol [PEG]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/60—Buffer, e.g. pH regulation, osmotic pressure
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/70—Undefined extracts
    • C12N2500/74—Undefined extracts from fungi, e.g. yeasts
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/70—Undefined extracts
    • C12N2500/76—Undefined extracts from plants
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2500/00—Specific components of cell culture medium
    • C12N2500/90—Serum-free medium, which may still contain naturally-sourced components
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/30—Hormones
    • C12N2501/33—Insulin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2510/00—Genetically modified cells
    • C12N2510/02—Cells for production
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2511/00—Cells for large scale production

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Endocrinology (AREA)
  • Neurology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (70)

  1. 一種用於產生蛋白之分批饋料(fed batch)方法，其包含：a)在包含細胞培養產生培養基之細胞培養物中培養包含編碼該蛋白之核酸的哺乳動物細胞；及b)藉由在一時段內向該細胞培養物中添加水解產物強化(enrichment)溶液及基本強化溶液而對該等哺乳動物細胞饋料，其中該水解產物強化溶液包含以植物為主之水解產物及75-300g/L之以酵母為主之水解產物，以產生該蛋白。
  2. 如請求項1之方法，其中該基本強化溶液包含濃縮之基本培養基。
  3. 如請求項1之方法，其中該基本強化溶液包含基本培養基、天冬醯胺酸及葡萄糖。
  4. 如請求項1之方法，其中該基本強化溶液包含PF CHO基本培養基。
  5. 如請求項1之方法，其中該哺乳動物細胞為中國倉鼠卵巢(CHO)細胞。
  6. 如請求項1之方法，其中該蛋白為抗體或其片段。
  7. 如請求項6之方法，其中該抗體或其片段係抗IL-18抗體或其片段或抗EPO受體(EPO-R)抗體或其片段。
  8. 一種用於產生抗TNFα抗體或其片段之分批饋料方法，其包含： a)在包含細胞培養產生培養基之細胞培養物中培養包含編碼該抗TNFα抗體或其片段之核酸的中國倉鼠卵巢(CHO)細胞；及b)藉由在一時段內向該細胞培養物中添加水解產物強化溶液及基本強化溶液而對該等CHO細胞饋料，其中該基本強化溶液包含以植物為主之水解產物及75-300g/L之以酵母為主之水解產物，以產生該抗TNFα抗體或其片段。
  9. 一種用於產生抗TNFα抗體或其片段之分批饋料方法，其包含：a)在包含細胞培養產生培養基之細胞培養物中培養包含編碼該抗TNFα抗體或其片段之核酸的CHO細胞；b)藉由在一時段內向該細胞培養物中添加水解產物強化溶液及基本強化溶液而對該等CHO細胞饋料，及c)根據pH線性斜坡(ramp)來調節該細胞培養產生培養基之pH；其中該基本強化溶液包含基本培養基、天冬醯胺酸及葡萄糖，且其中該水解產物強化溶液包含至少兩種不同的基於非動物之水解產物，以產生該抗TNFα抗體或其片段，其中該細胞培養物係在介於約32至38℃範圍內之溫度培養。
  10. 如請求項8之方法，其進一步包含回收該抗TNFα抗體或 其片段。
  11. 如請求項10之方法，其中該培養溫度為約35℃。
  12. 如請求項8之方法，其中該細胞培養產生培養基維持20與65%之間之溶氧。
  13. 如請求項12之方法，其中該細胞培養產生培養基維持約30%之溶氧。
  14. 如請求項8之方法，其中在整個培養期間該細胞培養產生培養基之滲透壓維持不超過500 mOsm。
  15. 如請求項9之方法，其中該水解產物強化溶液包含非源自植物或動物之第一水解產物及基於植物之第二水解產物。
  16. 如請求項15之方法，其中該非源自植物或動物且非基於植物之水解產物為基於酵母之水解產物。
  17. 如請求項8之方法，其中該基於植物之水解產物為基於大豆之水解產物。
  18. 如請求項8或9之方法，其中該水解產物強化溶液基本上由下列組成：約50至280g/kg基於大豆之水解產物；及約75至300g/kg基於酵母之水解產物。
  19. 如請求項8之方法，其中該基本培養基為PF CHO。
  20. 如請求項8之方法，其中該基本強化溶液具有約9.0至10.5之pH。
  21. 如請求項8之方法，其中該時段在約9至15天之間。
  22. 如請求項21之方法，其中該時段為約12天。
  23. 如請求項8之方法，其中在該時段以下各日之至少一日 將該基本強化溶液添加至該細胞培養產生培養基中：第4日、第6日、第9日及第11日。
  24. 如請求項8之方法，其中在該時段之第4日、第7日、或第4日及第7日將該水解產物強化溶液添加至該細胞培養產生培養基中。
  25. 如請求項8之方法，其進一步包含根據pH線性斜坡(ramp)來調節該細胞培養產生培養基之pH，其中該pH線性斜坡包含自約7.1至7.2之pH起始且產生約6.9之最終pH。
  26. 如請求項25之方法，其中該pH線性斜坡係於至少約24小時之時期中調節。
  27. 如請求項25之方法，其中該pH線性斜坡係於至少約48小時之時期中調節。
  28. 如請求項25之方法，其中該pH線性斜坡係於約72小時之時期中調節。
  29. 如請求項8之方法，其中該細胞培養產生培養基包含：a)排除下列組份之經修飾之基本培養基：碳酸氫鈉、緩衝液、磷酸二氫鈉、磷酸二鈉、滲透壓調節劑、界面活性劑及單醣葡萄糖；b)約8至10ml/kg或110至130mg/L檸檬酸鐵；c)約4至8mL/kg或10至14mg/kg重組人類胰島素；d)約5至9g/kg無水葡萄糖；e)約0.1至1g/kg L-麩醯胺酸；f)約1至3g/kg碳酸氫鈉； g)約1至3g/kg HEPES；h)約2至3g/kg NaCl；i)約0.1至2g/kg Pluronic F-68；j)約0.01至0.1g/kg NaH2 PO4 ˙H2 O；k)約0.1至0.1g/kg Na2 HPO4 ˙7H2 O；l)約8至12g/kg基於酵母之水解產物；及m)約6至8g/kg基於植物之水解產物。
  30. 如請求項29之方法，其中該細胞培養產生培養基包含：a)約10.0ml/kg或122.45mg/L檸檬酸鐵；b)約6.0mL/kg或12mg/kg重組人類胰島素；c)約7.0g/kg無水葡萄糖；d)約0.58至0.59g/kg L-麩醯胺酸；e)約1.6g/kg碳酸氫鈉；f)約1.8g/kg HEPES；g)約2.45g/kg NaCl；h)約1.0g/kg Pluronic F-68；i)約0.03至0.04g/kg NaH2 PO4 ˙H2 O；j)約0.43至0.44g/kg Na2 HPO4 ˙7H2 O；k)約10.7g/kg基於酵母之水解產物；及l)約6.9至7.0g/kg基於植物之水解產物。
  31. 如請求項8-17及19至30中任一項之方法，其中該哺乳動物細胞為CHO細胞。
  32. 如請求項8之方法，其中該細胞培養物為大規模細胞培養物。
  33. 如請求項32之方法，其中該大規模細胞培養物大於約10L。
  34. 如請求項32之方法，其中該大規模細胞培養物為13L。
  35. 如請求項8之方法，其中該抗TNFα抗體或其片段為完全人類。
  36. 如請求項35之方法，其中該抗TNFα抗體為阿達木單抗(adalimumab)或其片段。
  37. 一種用於產生抗IL12或其片段抗體之分批饋料方法，其包含：a)在包含細胞培養產生培養基之細胞培養物中培養包含編碼該抗體或其片段之核酸的CHO細胞，b)藉由在一時段內向該細胞培養物中添加水解產物強化溶液及基本強化溶液而對該等CHO細胞饋料，其中該基本強化溶液包含基本培養基、天冬醯胺酸及葡萄糖，其中該水解產物強化溶液包含以植物為主之水解產物及75-300g/L之以酵母為主之水解產物，以產生該抗IL12抗體或其片段。
  38. 如請求項37之方法，其中該水解產物強化溶液進一步包含葡萄糖。
  39. 如請求項37之方法，其進一步包含回收該抗IL12抗體或其片段。
  40. 如請求項37之方法，其中該細胞培養物係在介於約32至38℃範圍內之溫度培養。
  41. 如請求項37之方法，其中該培養溫度為約33℃。
  42. 如請求項37之方法，其中該細胞培養產生培養基維持20-65%之間之溶氧。
  43. 如請求項42之方法，其中該細胞培養產生培養基維持約40%之溶氧。
  44. 如請求項37之方法，其中該細胞培養產生培養基具有約6.7至7.2之pH。
  45. 如請求項37之方法，其中該基於植物之水解產物為基於大豆之水解產物。
  46. 如請求項37之方法，其中該水解產物強化溶液基本上由下列組成：約50至225g/kg基於大豆之水解產物、約75至300g/kg基於酵母之水解產物及約2至3g/L葡萄糖。
  47. 如請求項37之方法，其中該基本強化溶液包含基本培養基、天冬醯胺酸及葡萄糖。
  48. 如請求項37之方法，其中該基本強化溶液具有約9.7之pH及約1400至1500 mOsm之滲透壓。
  49. 如請求項37之方法，其中該基本強化溶液中之基本培養基為PF CHO。
  50. 如請求項8之方法，其中該時段在14-15天之間。
  51. 如請求項37之方法，其中自該時段中之第5日起始，每隔一天將該基本強化溶液添加至該細胞培養產生培養基中。
  52. 如請求項37之方法，其中自該時段中之第5日或第6日起始，每天將該水解產物強化溶液添加至該細胞培養產生 培養基中。
  53. 如請求項8之方法，其中自該時段中之第5日起始，每天將該基本強化溶液及該水解產物強化溶液添加至該細胞培養產生培養基中。
  54. 如請求項37之方法，其中該細胞培養產生培養基包含：a)排除下列組份之經修飾之基本培養基：碳酸氫鈉、緩衝液、磷酸二氫鈉、磷酸二鈉、滲透壓調節劑、界面活性劑及單醣葡萄糖；b)約8至12ml/kg或110至130mg/L檸檬酸鐵；c)約5至8mL/kg或11至15mg/kg重組人類胰島素；d)約5至9g/kg無水葡萄糖；e)約0.1至1g/kg L-麩醯胺酸；f)約1至2g/kg碳酸氫鈉；g)約1至2g/kg HEPES；h)約2至3g/kg NaCl；i)約0.1至2g/kg Pluronic F-68；j)約0.01至0.1g/kg NaH2 PO4 ˙H2 O；k)約0.1至1g/kg Na2 HPO4 ˙7H2 O；l)約6至12g/kg基於酵母之水解產物；及m)約6至8g/kg基於植物之水解產物。
  55. 如請求項54之方法，其中該細胞培養產生培養基包含：a)約10ml/kg或122.45mg/L檸檬酸鐵；b)約6.5mL/kg或13mg/kg重組人類胰島素；c)約7.0g/kg無水葡萄糖； d)約0.58至0.59g/kg L-麩醯胺酸；e)約1.6g/kg碳酸氫鈉；f)約1.8g/kg HEPES；g)約2.45g/kg NaCl；h)約1.0g/kg Pluronic F-68；i)約0.03至0.04g/kg NaH2 PO4 ˙H2 O；j)約0.43至0.44g/kg Na2 HPO4 ˙7H2 O；k)約10.7g/kg基於酵母之水解產物；及l)約6.9至7.0g/kg基於植物之水解產物。
  56. 如請求項37之方法，其中該細胞培養物為大規模細胞培養物。
  57. 如請求項56之方法，其中該大規模細胞培養物大於10L。
  58. 如請求項56之方法，其中該大規模細胞培養物為約13L。
  59. 如請求項37之方法，其中該抗IL12抗體或其片段為完全人類。
  60. 如請求項59之方法，其中該完全人類抗IL-12抗體為ABT-874或其片段。
  61. 一種產生阿達木單抗或其片段之分批饋料方法，其包含：a)在細胞培養物中培養表現阿達木單抗或其片段的哺乳動物細胞，其中於32-38℃之間的恆定溫度培養該該哺乳動物細胞；及b)藉由添加水解產物強化溶液及基本強化溶液至該細胞培養物而對該等哺乳動物細胞饋料， 其中該水解產物強化溶液包含基於植物之水解產物及75-300g/L之非源自至植物或動物之水解產物，以產生該阿達木單抗或其片段。
  62. 如請求項61之方法，其中該基本強化溶液包含基本培養基、天冬醯胺酸及葡萄糖。
  63. 如請求項62之方法，其中該基本培養基為PF CH0。
  64. 如請求項61-63中任一項之方法，其中該哺乳動物細胞為中國倉鼠卵巢(CHO)細胞。
  65. 如請求項61之方法，其中該非源自植物或動物之水解產物為基於酵母之水解產物。
  66. 如請求項61之方法，其中該基於植物之水解產物為基於大豆之水解產物。
  67. 如請求項61至63中任一項之方法，其中該溫度為35℃。
  68. 如請求項6之方法，其中該抗體或其片段為抗IL-12抗體或其片段。
  69. 如請求項17之方法，其中該基於大豆之水解產物的濃度為50-280g/L。
  70. 如請求項45之方法，其中該基於大豆之水解產物的濃度為50-280g/L。
TW96134338A 2006-09-13 2007-09-13 細胞培養改良 TWI456062B (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US84515806P 2006-09-13 2006-09-13
US87637406P 2006-12-21 2006-12-21

Publications (2)

Publication Number Publication Date
TW200831669A TW200831669A (en) 2008-08-01
TWI456062B true TWI456062B (zh) 2014-10-11

Family

ID=39184386

Family Applications (4)

Application Number Title Priority Date Filing Date
TW102127154A TWI548747B (zh) 2006-09-13 2007-09-13 細胞培養改良
TW105116479A TW201708537A (zh) 2006-09-13 2007-09-13 細胞培養改良
TW96134338A TWI456062B (zh) 2006-09-13 2007-09-13 細胞培養改良
TW103124010A TW201516149A (zh) 2006-09-13 2007-09-13 細胞培養改良

Family Applications Before (2)

Application Number Title Priority Date Filing Date
TW102127154A TWI548747B (zh) 2006-09-13 2007-09-13 細胞培養改良
TW105116479A TW201708537A (zh) 2006-09-13 2007-09-13 細胞培養改良

Family Applications After (1)

Application Number Title Priority Date Filing Date
TW103124010A TW201516149A (zh) 2006-09-13 2007-09-13 細胞培養改良

Country Status (17)

Country Link
US (11) US8093045B2 (zh)
EP (4) EP2064314A4 (zh)
JP (3) JP5878682B2 (zh)
KR (2) KR20140132017A (zh)
CN (6) CN102337243A (zh)
AU (1) AU2007294731B2 (zh)
BR (1) BRPI0716762A2 (zh)
CA (5) CA2842964A1 (zh)
IL (1) IL197444A0 (zh)
MX (4) MX353340B (zh)
MY (4) MY161866A (zh)
NO (1) NO20091439L (zh)
NZ (2) NZ597334A (zh)
RU (2) RU2518289C2 (zh)
SG (3) SG10201510384UA (zh)
TW (4) TWI548747B (zh)
WO (1) WO2008033517A2 (zh)

Families Citing this family (136)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6090382A (en) 1996-02-09 2000-07-18 Basf Aktiengesellschaft Human antibodies that bind human TNFα
NZ512006A (en) * 1996-02-09 2005-05-27 Abbott Biotech Ltd Medical treatment with human TNF-alpha antibodies
US20090280065A1 (en) * 2006-04-10 2009-11-12 Willian Mary K Uses and Compositions for Treatment of Psoriasis
EP2371859A3 (en) * 2002-07-19 2011-12-28 Abbott Biotechnology Ltd Treatment of TNF alpha related disorders
US20040033228A1 (en) * 2002-08-16 2004-02-19 Hans-Juergen Krause Formulation of human antibodies for treating TNF-alpha associated disorders
MY150740A (en) * 2002-10-24 2014-02-28 Abbvie Biotechnology Ltd Low dose methods for treating disorders in which tnf? activity is detrimental
TWI556829B (zh) * 2004-04-09 2016-11-11 艾伯維生物技術有限責任公司 用於治療ＴＮＦα相關失調症之多重可變劑量療法
GB0414054D0 (en) 2004-06-23 2004-07-28 Owen Mumford Ltd Improvements relating to automatic injection devices
US20060083741A1 (en) * 2004-10-08 2006-04-20 Hoffman Rebecca S Treatment of respiratory syncytial virus (RSV) infection
AU2006246721B2 (en) 2005-05-16 2012-12-13 Abbvie Biotechnology Ltd Use of TNF inhibitor for treatment of erosive polyarthritis
US7919264B2 (en) * 2005-11-01 2011-04-05 Abbott Biotechnology Ltd. Methods and compositions for determining the efficacy of a treatment for ankylosing spondylitis using biomarkers
KR20150006085A (ko) 2006-04-05 2015-01-15 애브비 바이오테크놀로지 리미티드 항체 정제
US9624295B2 (en) 2006-04-10 2017-04-18 Abbvie Biotechnology Ltd. Uses and compositions for treatment of psoriatic arthritis
US20080118496A1 (en) * 2006-04-10 2008-05-22 Medich John R Uses and compositions for treatment of juvenile rheumatoid arthritis
US9399061B2 (en) * 2006-04-10 2016-07-26 Abbvie Biotechnology Ltd Methods for determining efficacy of TNF-α inhibitors for treatment of rheumatoid arthritis
US9605064B2 (en) * 2006-04-10 2017-03-28 Abbvie Biotechnology Ltd Methods and compositions for treatment of skin disorders
US20090317399A1 (en) * 2006-04-10 2009-12-24 Pollack Paul F Uses and compositions for treatment of CROHN'S disease
WO2007120626A2 (en) 2006-04-10 2007-10-25 Abbott Biotechnology Ltd. Uses and compositions for treatment of ankylosing spondylitis
US20080131374A1 (en) * 2006-04-19 2008-06-05 Medich John R Uses and compositions for treatment of rheumatoid arthritis
US20080311043A1 (en) * 2006-06-08 2008-12-18 Hoffman Rebecca S Uses and compositions for treatment of psoriatic arthritis
US20100021451A1 (en) 2006-06-08 2010-01-28 Wong Robert L Uses and compositions for treatment of ankylosing spondylitis
CN101484199B (zh) 2006-06-30 2014-06-25 艾伯维生物技术有限公司 自动注射装置
SG10201510384UA (en) 2006-09-13 2016-01-28 Abbvie Inc Cell culture improvements
BRPI0717335A2 (pt) 2006-10-27 2013-12-10 Abbott Biotech Ltd Anticorpos anti-htnfalfa cristalinos
JP2010524467A (ja) * 2007-04-16 2010-07-22 モメンタ ファーマシューティカルズ インコーポレイテッド 規定の糖タンパク質産物および関連の方法
DK2154244T3 (en) 2007-04-26 2017-06-12 Chugai Pharmaceutical Co Ltd CELL CULTIVATION PROCEDURE WHEN AN ACID-ENRICHED MEDIUM IS USED
EP2679996A1 (en) * 2007-05-31 2014-01-01 AbbVie Inc. Biomarkers predictive of the responsiveness to TNF-alfa inhibitors in autoimmune disorders
WO2008154543A2 (en) 2007-06-11 2008-12-18 Abbott Biotechnology Ltd. Methods for treating juvenile idiopathic arthritis
US20090053786A1 (en) 2007-07-09 2009-02-26 Yung-Hsiang Kao Prevention of disulfide bond reduction during recombinant production of polypeptides
WO2009011782A2 (en) * 2007-07-13 2009-01-22 Abbott Biotechnology Ltd. METHODS AND COMPOSITIONS FOR PULMONARY ADMINISTRATION OF A TNFa INHIBITOR
CA2697163A1 (en) 2007-08-08 2009-02-12 Abbott Laboratories Compositions and methods for crystallizing antibodies
CN101969971A (zh) 2007-11-30 2011-02-09 雅培制药有限公司 蛋白制剂及其制备方法
US8883146B2 (en) 2007-11-30 2014-11-11 Abbvie Inc. Protein formulations and methods of making same
US8415094B2 (en) * 2007-12-21 2013-04-09 Jaffar Ali bin M. Abdullah Protein-free gamete and embryo handling and culture media products
EP4269443A3 (en) 2007-12-26 2023-12-27 Xencor, Inc. Fc variants with altered binding to fcrn
CA2710333A1 (en) * 2008-01-03 2009-07-09 Abbott Biotechnology Ltd. Predicting long-term efficacy of a compound in the treatment of psoriasis
US8637312B2 (en) 2008-01-09 2014-01-28 Cellca Gmbh Mammalian culture media with polyamine and iron
NZ601913A (en) 2008-01-15 2014-02-28 Abbott Gmbh & Co Kg Powdered protein compositions and methods of making same
US8318416B2 (en) * 2008-08-08 2012-11-27 Biogen Idec Ma Inc. Nutrient monitoring and feedback control for increased bioproduct production
JP4883067B2 (ja) 2008-09-29 2012-02-22 株式会社日立プラントテクノロジー 培養装置及び培養方法
MX2011004200A (es) * 2008-10-20 2011-05-24 Abbott Lab Aislamento y purificacion de anticuerpos usando la cromatografia de afinidad de proteina a.
KR101737645B1 (ko) 2008-12-30 2017-05-18 박스알타 인코퍼레이티드 알킬-아민-ｎ-옥시드 (ａａｎｏｘ)를 사용하는 세포 성장 증진 방법
CN102458517B (zh) 2009-04-29 2014-07-23 阿布维生物技术有限公司 自动注射装置
WO2010128159A1 (en) 2009-05-07 2010-11-11 Hemarina Novel heamoglobin and uses thereof
US8969043B2 (en) 2009-05-28 2015-03-03 Boehringer Ingelheim International Gmbh Method for a rational cell culturing process
BRPI1010068A2 (pt) * 2009-07-24 2016-03-15 Hoffmann La Roche "sistema agitador, dispositivo, método para cultivo de células animais, método para produzir um polipeptídeo, uso de um sistema agitador e dispositivos para cultivar células animais"
LT2464725T (lt) 2009-08-11 2020-06-10 F. Hoffmann-La Roche Ag Baltymų gamyba ląstelių mitybinėje terpėje, kurioje nėra glutamino
EP2512558A4 (en) 2009-12-15 2014-08-13 Abbvie Biotechnology Ltd IMPROVED TRIP KNOB FOR AUTOMATIC INJECTION DEVICE
MX2012011648A (es) * 2010-04-07 2012-11-29 Momenta Pharmaceuticals Inc Glicanos de alta manosa.
US20110262965A1 (en) * 2010-04-23 2011-10-27 Life Technologies Corporation Cell culture medium comprising small peptides
CN107254499B (zh) * 2010-04-26 2021-09-17 诺华股份有限公司 改进的细胞培养方法
MX2012014080A (es) 2010-06-03 2013-05-01 Abbvie Biotechnology Ltd Usos y composiciones para el tratamiento de hidradenitis superativa (hs).
IL286298B (en) * 2010-07-08 2022-08-01 Baxalta Inc A method to generate high molecular weight substituted vwf in cell culture
KR20130101034A (ko) * 2010-08-31 2013-09-12 프리슬랜드 브랜즈 비브이 진핵 세포를 위한 배양 배지
CN105854016A (zh) 2010-11-11 2016-08-17 艾伯维生物技术有限公司 改进的高浓度抗TNFα抗体液体制剂
EP2749305B1 (en) 2011-01-24 2017-11-01 AbbVie Biotechnology Ltd Automatic injection devices having overmolded gripping surfaces
WO2012110435A1 (en) * 2011-02-14 2012-08-23 Basf Se Bio process additives
US9062106B2 (en) 2011-04-27 2015-06-23 Abbvie Inc. Methods for controlling the galactosylation profile of recombinantly-expressed proteins
SG11201401220SA (en) * 2011-10-21 2014-07-30 Pfizer Addition of iron to improve cell culture
WO2013158279A1 (en) 2012-04-20 2013-10-24 Abbvie Inc. Protein purification methods to reduce acidic species
US9067990B2 (en) 2013-03-14 2015-06-30 Abbvie, Inc. Protein purification using displacement chromatography
WO2013158273A1 (en) 2012-04-20 2013-10-24 Abbvie Inc. Methods to modulate c-terminal lysine variant distribution
US20130281355A1 (en) * 2012-04-24 2013-10-24 Genentech, Inc. Cell culture compositions and methods for polypeptide production
KR102136698B1 (ko) 2012-05-02 2020-07-22 라이프 테크놀로지스 코포레이션 고밀도 성장 및 형질감염 배지 및 발현 인핸서의 독특한 페어링을 사용하는 포유동물 세포들 내의 고수율의 일시적 발현
US9249182B2 (en) 2012-05-24 2016-02-02 Abbvie, Inc. Purification of antibodies using hydrophobic interaction chromatography
US9512214B2 (en) 2012-09-02 2016-12-06 Abbvie, Inc. Methods to control protein heterogeneity
BR112015004467A2 (pt) 2012-09-02 2017-03-21 Abbvie Inc método para controlar a heterogeneidade de proteínas
AR093460A1 (es) * 2012-11-14 2015-06-10 Merck Patent Ges Mit Beschränkter Haftung Medios de cultivo celular
US10717965B2 (en) 2013-01-10 2020-07-21 Gloriana Therapeutics, Inc. Mammalian cell culture-produced neublastin antibodies
WO2014109858A1 (en) * 2013-01-14 2014-07-17 Amgen Inc. Methods of using cell-cycle inhibitors to modulate one or more properties of a cell culture
AU2013381687A1 (en) * 2013-03-12 2015-09-24 Abbvie Inc. Human antibodies that bind human TNF-alpha and methods of preparing the same
EP2970916B1 (en) 2013-03-13 2021-04-14 Merck Sharp & Dohme Corp. Adapted lepidopteran insect cells for the production of recombinant proteins
WO2014159579A1 (en) 2013-03-14 2014-10-02 Abbvie Inc. MUTATED ANTI-TNFα ANTIBODIES AND METHODS OF THEIR USE
US9217168B2 (en) 2013-03-14 2015-12-22 Momenta Pharmaceuticals, Inc. Methods of cell culture
AU2014240431A1 (en) 2013-03-14 2015-08-27 Abbvie Inc. Low acidic species compositions and methods for producing the same using displacement chromatography
WO2014151878A2 (en) 2013-03-14 2014-09-25 Abbvie Inc. Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosacharides
US20140271633A1 (en) * 2013-03-14 2014-09-18 Abbvie Inc. Mammalian cell culture performance through surfactant supplementation of feed media
WO2014158231A1 (en) 2013-03-14 2014-10-02 Abbvie Inc. Low acidic species compositions and methods for producing and using the same
US9017687B1 (en) 2013-10-18 2015-04-28 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same using displacement chromatography
WO2015051293A2 (en) * 2013-10-04 2015-04-09 Abbvie, Inc. Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins
US11390663B2 (en) 2013-10-11 2022-07-19 Regeneron Pharmaceuticals, Inc. Metabolically optimized cell culture
KR102418824B1 (ko) * 2013-10-14 2022-07-11 아레스 트레이딩 에스.아. 포유동물의 고성능 유가식 배양을 위한 신규 배지
WO2015057910A1 (en) 2013-10-16 2015-04-23 Oncobiologics, Inc. Buffer formulations for enhanced antibody stability
US9085618B2 (en) 2013-10-18 2015-07-21 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
US8946395B1 (en) 2013-10-18 2015-02-03 Abbvie Inc. Purification of proteins using hydrophobic interaction chromatography
US9181337B2 (en) 2013-10-18 2015-11-10 Abbvie, Inc. Modulated lysine variant species compositions and methods for producing and using the same
US20150139988A1 (en) 2013-11-15 2015-05-21 Abbvie, Inc. Glycoengineered binding protein compositions
EP3083933A1 (en) * 2013-12-20 2016-10-26 Biogen MA Inc. Use of perfusion seed cultures to improve biopharmaceutical fed-batch production capacity and product quality
EP2923707A1 (en) 2014-03-28 2015-09-30 Hemarina Blood substitute with respiratory pigment
CA2945390A1 (en) 2014-04-10 2015-10-15 Bayer Healthcare Llc Compounded media powder formulation and method of preparation of liquid medium for cell culture
KR101699761B1 (ko) * 2014-05-23 2017-01-25 주식회사 비비에이치씨 플로로탄닌 분획물을 이용한 중간엽 줄기세포로부터 유도만능 줄기세포를 제조하는 방법
US11384378B2 (en) 2014-06-04 2022-07-12 Amgen Inc. Methods for harvesting mammalian cell cultures
CA2952241A1 (en) * 2014-06-18 2015-12-23 Medimmune, Llc Cell culture methods and media comprising n-acetylcysteine
WO2016004197A1 (en) 2014-07-03 2016-01-07 Abbvie Inc. Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using cobalt
WO2016007764A1 (en) 2014-07-09 2016-01-14 Abbvie Inc. Methods for modulating the glycosylation profile of recombinant proteins using non-commonly used sugars
US10435464B1 (en) * 2014-09-05 2019-10-08 Coherus Biosciences, Inc. Methods for making recombinant proteins
KR102007930B1 (ko) 2014-12-31 2019-08-06 주식회사 엘지화학 재조합 당단백질의 글리코실화 조절 방법
CN105820246A (zh) * 2015-01-07 2016-08-03 上海张江生物技术有限公司 一种新型重组抗TNFα嵌合单克隆抗体制备方法及用途
WO2016118707A1 (en) 2015-01-21 2016-07-28 Oncobiologics, Inc. Modulation of charge variants in a monoclonal antibody composition
JP6812967B2 (ja) * 2015-03-30 2021-01-13 味の素株式会社 キレート化鉄を含む神経幹細胞用培地
CN106190948B (zh) * 2015-05-07 2020-09-25 上海津曼特生物科技有限公司 一种cho-s细胞半固体培养基及其配制方法与应用
CN105018425B (zh) * 2015-07-09 2018-09-28 广州白云山拜迪生物医药有限公司 一种无动物来源成分的外周血淋巴细胞培养基
WO2017011598A1 (en) * 2015-07-13 2017-01-19 Life Technologies Corporation System and method for improved transient protein expression in cho cells
CN105441378A (zh) * 2015-12-22 2016-03-30 肇庆大华农生物药品有限公司 一种培养Vero细胞用的无血清培养基及其制备方法
US11285210B2 (en) 2016-02-03 2022-03-29 Outlook Therapeutics, Inc. Buffer formulations for enhanced antibody stability
US20190055513A1 (en) * 2016-02-22 2019-02-21 Agency For Science, Technology And Research Cell culture medium
JP6997079B2 (ja) * 2016-05-10 2022-01-17 三菱商事ライフサイエンス株式会社 培地用組成物
CN105794772A (zh) * 2016-05-16 2016-07-27 天津市中奥天元科技发展有限公司 一种无血清细胞冻存液
WO2018018613A1 (zh) 2016-07-29 2018-02-01 广东东阳光药业有限公司 一种提高抗体纯度的细胞培养基和培养方法
CN106635974B (zh) * 2016-10-19 2020-10-27 浙江译美生物科技有限公司 一种人脐带间充质干细胞的分离和培养方法
PE20191436A1 (es) 2016-12-23 2019-10-14 Serum Institute Of India Pvt Ltd Metodos mejorados para estimular la productividad de anticuerpos en el cultivo de celulas de mamiferos y reducir la agregacion durante los procesos de formulacion post-tratamiento (downstream) y formulaciones de anticuerpos estables obtenidas a partir de los mismos
WO2018178069A1 (en) * 2017-03-31 2018-10-04 Boehringer Ingelheim International Gmbh Perfusion medium
US10280217B2 (en) * 2017-09-19 2019-05-07 American Air Liquide, Inc. Cell culture additives and their use for increased bioprotein production from cells
CN107904200B (zh) * 2017-10-20 2018-10-16 通化东宝生物科技有限公司 一种表达阿达木单抗的联合培养基及其应用
CA3079053A1 (en) * 2017-11-01 2019-05-09 Chugai Seiyaku Kabushiki Kaisha Antibody variant and isoform with lowered biological activity
US20210171901A1 (en) * 2017-11-16 2021-06-10 Life Technologies Corporation Streamlined methods for making liquid media
JP7471220B2 (ja) 2017-11-30 2024-04-19 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 哺乳動物細胞の培養方法
EP3492582A1 (en) * 2017-12-01 2019-06-05 UCB Biopharma SPRL Cell culture methods
US11391725B2 (en) * 2018-03-16 2022-07-19 Genzyme Corporation Methods for improving cell viability in a production bioreactor
WO2019224333A1 (en) * 2018-05-24 2019-11-28 Ares Trading S.A. Method for controlling the afucosylation level of a glycoprotein composition
PT3818078T (pt) * 2018-07-03 2024-04-18 Bristol Myers Squibb Co Métodos de produção de proteínas recombinantes
CN112469814A (zh) * 2018-07-27 2021-03-09 味之素株式会社 动物细胞的悬浮培养用添加物、悬浮培养用培养基和悬浮培养方法
CN109337861B (zh) * 2018-11-12 2021-06-25 友康恒业生物科技（北京）有限公司 一种支持产物高表达的cho细胞无血清培养基
WO2020132583A1 (en) * 2018-12-21 2020-06-25 Gloriana Therapeutics Sarl Mammalian cell culture-produced neublastin antibodies
JOP20200214A1 (ar) 2019-09-03 2021-03-03 Serum Institute Of India Pvt Ltd تركيبات مولدة للمناعة ضد الأمراض المعوية وطرق لتحضيرها
KR20220097421A (ko) * 2019-11-05 2022-07-07 아지노모토 가부시키가이샤 단백질의 제조 방법
IL302538A (en) 2019-12-06 2023-07-01 Regeneron Pharma Anti-VEGF protein preparations and methods for their production
CN111233996A (zh) * 2020-01-20 2020-06-05 北京交通大学 一种将丁酸钠用于促进工程细胞株分泌表达rhIL-24的方法
EP4155389A3 (en) * 2020-03-31 2023-07-12 Cell Exosome Therapeutics Inc. Method of producing proliferated cells, method of producing cell product, mesenchymal stem cell population and method of producing same, culture supernatant of stem cells and method of producing same, and therapeutic agent
JP7521738B2 (ja) * 2020-05-18 2024-07-24 キヤノン株式会社 目的細胞の生産方法、目的細胞による生産物の生産方法、および無血清培地
CN112592948B (zh) * 2020-12-16 2023-05-09 广州汉腾生物科技有限公司 动物细胞的灌流培养方法
WO2022154762A1 (en) * 2021-01-18 2022-07-21 Turgut İlaçlari A.Ş. Method of producing adalimumab
KR20230170728A (ko) * 2021-04-14 2023-12-19 젠자임 코포레이션 포유류 세포의 관류 배양 방법
CN114230669B (zh) * 2021-12-24 2024-01-30 天士力生物医药股份有限公司 一种双特异性抗体的生产方法
CN118742652A (zh) * 2022-02-21 2024-10-01 中外制药株式会社 灌流培养方法
WO2024096506A1 (ko) * 2022-10-31 2024-05-10 삼성바이오에피스 주식회사 고농도 액체 배지 제조 방법

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004058944A2 (en) * 2002-12-23 2004-07-15 Bristol-Myers Squibb Company Product quality enhancement in mammalian cell culture processes for protein production
US20040171152A1 (en) * 1996-10-10 2004-09-02 Invitrogen Corporation Animal cell culture media comprising non-animal or plant-derived nutrients

Family Cites Families (215)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4657866A (en) 1982-12-21 1987-04-14 Sudhir Kumar Serum-free, synthetic, completely chemically defined tissue culture media
GB8308235D0 (en) 1983-03-25 1983-05-05 Celltech Ltd Polypeptides
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
GB8422238D0 (en) 1984-09-03 1984-10-10 Neuberger M S Chimeric proteins
US5672502A (en) 1985-06-28 1997-09-30 Celltech Therapeutics Limited Animal cell culture
US5681718A (en) 1986-03-14 1997-10-28 Celltech Limited Methods for enhanced production of tissue plasminogen activator in cell culture using alkanoic acids or salts thereof
GB8607679D0 (en) 1986-03-27 1986-04-30 Winter G P Recombinant dna product
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US5045468A (en) 1986-12-12 1991-09-03 Cell Enterprises, Inc. Protein-free culture medium which promotes hybridoma growth
US4965195A (en) 1987-10-26 1990-10-23 Immunex Corp. Interleukin-7
US4968607A (en) 1987-11-25 1990-11-06 Immunex Corporation Interleukin-1 receptors
US6048728A (en) 1988-09-23 2000-04-11 Chiron Corporation Cell culture medium for enhanced cell growth, culture longevity, and product expression
WO1990005183A1 (en) 1988-10-31 1990-05-17 Immunex Corporation Interleukin-4 receptors
IL162181A (en) 1988-12-28 2006-04-10 Pdl Biopharma Inc A method of producing humanized immunoglubulin, and polynucleotides encoding the same
US6451983B2 (en) 1989-08-07 2002-09-17 Peptech Limited Tumor necrosis factor antibodies
US5272071A (en) 1989-12-22 1993-12-21 Applied Research Systems Ars Holding N.V. Method for the modification of the expression characteristics of an endogenous gene of a given cell line
US5110913A (en) 1990-05-25 1992-05-05 Miles Inc. Antibody purification method
US5096816A (en) 1990-06-05 1992-03-17 Cetus Corporation In vitro management of ammonia's effect on glycosylation of cell products through pH control
AU651596B2 (en) 1990-06-05 1994-07-28 Immunex Corporation Type II interleukin-1 receptors
US5122469A (en) 1990-10-03 1992-06-16 Genentech, Inc. Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins
GB9022543D0 (en) 1990-10-17 1990-11-28 Wellcome Found Antibody production
GB9022545D0 (en) * 1990-10-17 1990-11-28 Wellcome Found Culture medium
US20060246073A1 (en) 1991-03-18 2006-11-02 Knight David M Anti-TNF antibodies and peptides of human tumor necrosis factor
US20040120952A1 (en) 2000-08-07 2004-06-24 Centocor, Inc Anti-TNF antibodies and peptides of human tumor necrosis factor
US5656272A (en) 1991-03-18 1997-08-12 New York University Medical Center Methods of treating TNF-α-mediated Crohn's disease using chimeric anti-TNF antibodies
US7192584B2 (en) 1991-03-18 2007-03-20 Centocor, Inc. Methods of treating psoriasis with anti-TNF antibodies
US20070298040A1 (en) 1991-03-18 2007-12-27 Centocor, Inc. Methods of treating seronegative arthropathy with anti-TNF antibodies
US6277969B1 (en) 1991-03-18 2001-08-21 New York University Anti-TNF antibodies and peptides of human tumor necrosis factor
EP1681305A3 (en) 1991-03-18 2008-02-27 New York University Monoclonal and chimeric antibodies specific for human tumor necrosis factor
DE69233482T2 (de) 1991-05-17 2006-01-12 Merck & Co., Inc. Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen
AU662752B2 (en) 1991-07-15 1995-09-14 Wellcome Foundation Limited, The Production of antibodies
DK0667901T4 (da) 1991-10-25 2008-11-10 Immunex Corp Hidtil ukendt cytokin
EP0666312A1 (en) 1994-02-08 1995-08-09 Wolfgang A. Renner Process for the improvement of mammalian cell growth
US5429746A (en) 1994-02-22 1995-07-04 Smith Kline Beecham Corporation Antibody purification
US5856179A (en) 1994-03-10 1999-01-05 Genentech, Inc. Polypeptide production in animal cell culture
US5741705A (en) 1995-02-23 1998-04-21 Quest International Flavors & Food Ingredients Company, Division Of Indopco, Inc. Method for in vitro cell growth of eucaryotic cells using low molecular weight peptides
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
US5705364A (en) 1995-06-06 1998-01-06 Genentech, Inc. Mammalian cell culture process
US6656466B1 (en) 1995-06-06 2003-12-02 Genetech, Inc. Human tumor necrosis factor—immunoglobulin(TNFR1-IgG1) chimera composition
US5721121A (en) 1995-06-06 1998-02-24 Genentech, Inc. Mammalian cell culture process for producing a tumor necrosis factor receptor immunoglobulin chimeric protein
IL122174A (en) 1995-06-07 2004-07-25 Immunex Corp DNA encoding the CD40L mutine and CD40L polypeptide encoded by the above DNA
JP4306813B2 (ja) 1995-09-19 2009-08-05 アスビオファーマ株式会社 動物細胞の新規培養方法
US6090382A (en) 1996-02-09 2000-07-18 Basf Aktiengesellschaft Human antibodies that bind human TNFα
AR005035A1 (es) 1995-12-11 1999-04-07 Merck Patent Ges Mit Beschränkter Haftung Procedimiento para preparar proteinas recombinantes en e. coli, mediante fermentacion con gran concentracion de celulas.
JP3495375B2 (ja) 1996-01-11 2004-02-09 イミュネックス・コーポレーション 真核生物発現システムの発現増大配列エレメント（ｅａｓｅ）
NZ512006A (en) 1996-02-09 2005-05-27 Abbott Biotech Ltd Medical treatment with human TNF-alpha antibodies
EP0802257B1 (fr) 1996-04-19 2002-08-21 Societe Des Produits Nestle S.A. Lignée immortalisée de cellules épithéliales du colon humain
AU4751697A (en) 1996-10-10 1998-05-05 Douglas Danner Animal cell culture media comprising plant-derived nutrients
SI0950067T1 (sl) 1996-11-27 2007-12-31 Genentech Inc Afinitetno čiščenje polipeptida na proteinskemA matriksu
US20020045207A1 (en) 1997-10-31 2002-04-18 Lynne A. Krummen Glycoprotein production process
AU1663599A (en) 1997-12-19 1999-07-12 Novo Nordisk A/S Method for producing heterologous proteins in eukaryotic cells on an industrial scale using nucleotide-manipulating agents
US20030175884A1 (en) 2001-08-03 2003-09-18 Pablo Umana Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
WO1999057246A1 (en) * 1998-05-01 1999-11-11 Life Technologies, Inc. Animal cell culture media comprising non-animal or plant-derived nutrients
DK1308456T3 (da) 1998-05-06 2007-12-27 Genentech Inc Antistofoprensning ved ionbytterkromatografi
US6528286B1 (en) 1998-05-29 2003-03-04 Genentech, Inc. Mammalian cell culture process for producing glycoproteins
KR100608154B1 (ko) 1998-07-01 2006-08-04 다카라 바이오 가부시키가이샤 유전자 도입 방법
US6406909B1 (en) 1998-07-10 2002-06-18 Chugai Seiyaku Kabushiki Kaisha Serum-free medium for culturing animal cells
US6210924B1 (en) 1998-08-11 2001-04-03 Amgen Inc. Overexpressing cyclin D 1 in a eukaryotic cell line
US7883704B2 (en) 1999-03-25 2011-02-08 Abbott Gmbh & Co. Kg Methods for inhibiting the activity of the P40 subunit of human IL-12
US6914128B1 (en) 1999-03-25 2005-07-05 Abbott Gmbh & Co. Kg Human antibodies that bind human IL-12 and methods for producing
AT409379B (de) 1999-06-02 2002-07-25 Baxter Ag Medium zur protein- und serumfreien kultivierung von zellen
US6190523B1 (en) 1999-07-20 2001-02-20 Basf Corporation Electrocoat coating composition and process for electrocoating a substrate
PT1650307E (pt) 1999-09-27 2010-10-21 Genentech Inc Métodos para preparação de proteínas recombinantes utilizando inibidores de apoptose
ATE312186T1 (de) 1999-10-13 2005-12-15 Immunex Corp Vektoren und verfahren für rekombinante proteinexpression
AR026743A1 (es) 1999-12-09 2003-02-26 Pharmacia Ab Produccion de peptidos
US20030211573A1 (en) 2000-02-08 2003-11-13 Thomas Ryll Galactosylation of recombinant glycoproteins
EP1257585A2 (en) 2000-02-10 2002-11-20 Basf Aktiengesellschaft Antibodies that bind human interleukin-18 and methods of making and using
WO2001077362A1 (fr) * 2000-04-06 2001-10-18 Chugai Seiyaku Kabushiki Kaisha Dosage immunologique d'anticorps anti hm1 . 24
US7598055B2 (en) 2000-06-28 2009-10-06 Glycofi, Inc. N-acetylglucosaminyltransferase III expression in lower eukaryotes
EP1175931A1 (en) 2000-07-25 2002-01-30 Computer Cell Culture Center S.A. Integration of high cell density bioreactor operation with ultra fast on-line downstream processing
UA81743C2 (uk) 2000-08-07 2008-02-11 Центокор, Инк. МОНОКЛОНАЛЬНЕ АНТИТІЛО ЛЮДИНИ, ЩО СПЕЦИФІЧНО ЗВ'ЯЗУЄТЬСЯ З ФАКТОРОМ НЕКРОЗУ ПУХЛИН АЛЬФА (ФНПα), ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЙОГО МІСТИТЬ, ТА СПОСІБ ЛІКУВАННЯ РЕВМАТОЇДНОГО АРТРИТУ
US7288390B2 (en) 2000-08-07 2007-10-30 Centocor, Inc. Anti-dual integrin antibodies, compositions, methods and uses
US20050249735A1 (en) 2000-08-07 2005-11-10 Centocor, Inc. Methods of treating ankylosing spondylitis using anti-TNF antibodies and peptides of human tumor necrosis factor
US20060018907A1 (en) 2000-08-07 2006-01-26 Centocor, Inc. Anti-TNF antibodies and peptides of human tumor necrosis factor
AU2001294520A1 (en) 2000-08-21 2002-03-04 Clonex Development, Inc. Methods and compositions for increasing protein yield from a cell culture
US6693173B2 (en) 2000-12-26 2004-02-17 Alpha Therapeutic Corporation Method to remove citrate and aluminum from proteins
US20030096414A1 (en) 2001-03-27 2003-05-22 Invitrogen Corporation Culture medium for cell growth and transfection
EP1401870A4 (en) * 2001-05-24 2006-04-19 Human Genome Sciences ANTIBODIES AGAINST TUMOR NECROSIS FACTOR DELTA (APRIL)
CA2448788C (en) 2001-06-05 2010-08-24 Genetics Institute, Llc. Methods for purifying highly anionic proteins
CA2447791A1 (en) 2001-06-13 2002-12-19 Neslihan Delacruz Methods of culturing animal cells and polypeptide production in animal cells
EP1434857B1 (en) 2001-10-02 2007-08-01 Novo Nordisk Health Care AG Method for production of recombinant proteins in eukaryote cells
HUP0600342A3 (en) 2001-10-25 2011-03-28 Genentech Inc Glycoprotein compositions
WO2003046162A2 (en) 2001-11-28 2003-06-05 Polymun Scientific Immunbiologische Forschung Gmbh Process for the production of polypeptides in mammalian cell cultures
WO2003045995A2 (en) 2001-11-28 2003-06-05 Sandoz Gmbh Cell culture process
WO2003059935A2 (en) 2001-12-21 2003-07-24 Immunex Corporation Methods for purifying protein
US20030201229A1 (en) 2002-02-04 2003-10-30 Martin Siwak Process for prefiltration of a protein solution
AU2003210802B2 (en) 2002-02-05 2009-09-10 Genentech Inc. Protein purification
CA2417689C (en) 2002-03-05 2006-05-09 F. Hoffmann-La Roche Ag Improved methods for growing mammalian cells in vitro
ES2557741T3 (es) 2002-03-27 2016-01-28 Immunex Corporation Procedimientos para incrementar la producción de polipéptidos
US20030190710A1 (en) 2002-03-28 2003-10-09 Devries Ruth L. Control of glycoforms in IgG
WO2003085118A1 (fr) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Procede de production de composition anticorps
US20040029229A1 (en) 2002-05-20 2004-02-12 Reeves Philip J. High level protein expression system
PT1543106E (pt) 2002-07-15 2007-05-31 Immunex Corp Métodos e meios para controlar a sialilação de proteínas produzidas por células de mamíferos
US6974681B1 (en) 2002-08-23 2005-12-13 Immunex Corporation Cell culture performance with vanadate
US6924124B1 (en) 2002-08-23 2005-08-02 Immunex Corporation Feeding strategies for cell culture
US7067279B1 (en) 2002-08-23 2006-06-27 Immunex Corporation Cell culture performance with betaine
US7208585B2 (en) 2002-09-18 2007-04-24 Genencor International, Inc. Protein purification
US6890736B1 (en) * 2002-09-20 2005-05-10 Immunex Corporation Methods for producing proteins in cultured cells
US20040071694A1 (en) 2002-10-14 2004-04-15 Devries Peter J. Erythropoietin receptor binding antibodies
JP4541157B2 (ja) 2002-12-23 2010-09-08 ブリストル−マイヤーズ スクイブ カンパニー タンパク質を製造するための哺乳類細胞培養法
AU2004215653B2 (en) 2003-02-28 2011-03-17 Lonza Biologics Plc. Antibody purification by protein A and ion exchange chromatography
US20060104968A1 (en) * 2003-03-05 2006-05-18 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases
ES2344789T5 (es) 2003-05-15 2017-06-14 Wyeth Llc Alimentación restringida de glucosa para el cultivo de células animales
EP1648940B1 (en) 2003-07-28 2016-04-27 Genentech, Inc. Reducing protein a leaching during protein a affinity chromatography
GB2404665B (en) 2003-08-08 2005-07-06 Cambridge Antibody Tech Cell culture
WO2005014800A1 (en) * 2003-08-08 2005-02-17 Cambridge Antibody Technology Limited Myeloma cell culture in transferrin-free low iron medium
ES2565077T3 (es) 2003-10-10 2016-03-31 Novo Nordisk Health Care Ag Método para producción en gran escala de un polipéptido en células eucariotas
DK1678208T3 (da) 2003-10-27 2013-07-08 Wyeth Llc Fjernelse af aggregater med høj molekylvægt under anvendelse af hydroxyapatitchromatografi
US7968684B2 (en) 2003-11-12 2011-06-28 Abbott Laboratories IL-18 binding proteins
US20050100965A1 (en) 2003-11-12 2005-05-12 Tariq Ghayur IL-18 binding proteins
WO2005063813A2 (en) 2003-12-23 2005-07-14 Applied Research Systems Ars Holding N.V. Process for the production of tumor necrosis factor-binding proteins
US8084032B2 (en) 2004-01-21 2011-12-27 Ajinomoto Co., Inc. Purification method which prevents denaturation of an antibody
CN1238498C (zh) * 2004-02-12 2006-01-25 陈志南 动物细胞无血清悬浮培养工艺过程控制参数的方法
WO2005087915A2 (en) 2004-03-08 2005-09-22 Biovest International, Inc. Use of ethanolamine for enhancing cell growth in membrane systems
SE0400886D0 (sv) 2004-04-02 2004-04-02 Amersham Biosciences Ab Process of purification
US20060018902A1 (en) 2004-04-09 2006-01-26 Reilly Edward B Antibodies to erythropoietin receptor and uses thereof
US20060127950A1 (en) 2004-04-15 2006-06-15 Massachusetts Institute Of Technology Methods and products related to the improved analysis of carbohydrates
RU2006138181A (ru) 2004-05-04 2008-06-10 Ново Нордиск Хелс Кеа Аг (Ch) О-связанные гликоформы полипептидов и способ их изготовления
US20060001890A1 (en) * 2004-07-02 2006-01-05 Asml Holding N.V. Spatial light modulator as source module for DUV wavefront sensor
TWI384069B (zh) 2004-08-27 2013-02-01 Pfizer Ireland Pharmaceuticals 多胜肽之製法
WO2006039588A2 (en) 2004-09-30 2006-04-13 Bayer Healthcare Llc Devices and methods for integrated continuous manufacturing of biological molecules
US20060094104A1 (en) 2004-10-29 2006-05-04 Leopold Grillberger Animal protein-free media for cultivation of cells
EP1812557A4 (en) 2004-10-29 2009-11-04 Centocor Ortho Biotech Inc COMPOSITIONS OF CHEMICALLY DEFINED MEDIA
JP2006143601A (ja) 2004-11-16 2006-06-08 Yamato Yakuhin Kk 血液粘度低下剤
EP1851305B1 (en) 2005-02-11 2012-01-18 Novo Nordisk Health Care AG Production of a polypeptide in a serum-free cell culture liquid containing plant protein hydrolysate
ES2797480T3 (es) 2005-03-11 2020-12-02 Wyeth Llc Un procedimiento de cromatografía de reparto débil
US20090203055A1 (en) 2005-04-18 2009-08-13 Massachusetts Institute Of Technology Compositions and methods for RNA interference with sialidase expression and uses thereof
US7247457B2 (en) 2005-04-26 2007-07-24 United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention Detection and identification of enteroviruses by semi-nested amplification of the enterovirus VP1 protein
EP1888638A2 (en) 2005-06-03 2008-02-20 Genentech, Inc. Method of producing antibodies with modified fucosylation level
AU2006254217A1 (en) 2005-06-03 2006-12-07 Biovitrum Ab (Publ) Process for cultivating animal cells comprising the feeding of plant-derived peptones
BRPI0611901A2 (pt) 2005-06-14 2012-08-28 Amgen, Inc composição, liofilizado, kit, e, processo para preparar uma composição
AR053633A1 (es) 2005-06-17 2007-05-09 Wyeth Corp Metodos para purificar proteinas que contienen una region fc
HUE038947T2 (hu) 2005-08-26 2018-12-28 Ares Trading Sa Eljárás glikozilált béta-interferon elõállítására
DE102005046225B4 (de) * 2005-09-28 2012-01-05 Cellca Gmbh Verbessertes Zellkulturmedium
AR058140A1 (es) 2005-10-24 2008-01-23 Wyeth Corp Metodo de produccion proteica utilizando compuestos anti-senescencia
EP2495308A1 (en) 2005-12-08 2012-09-05 Amgen Inc. Improved production of glycoproteins using manganese
US20070190057A1 (en) 2006-01-23 2007-08-16 Jian Wu Methods for modulating mannose content of recombinant proteins
JP5406710B2 (ja) 2006-05-19 2014-02-05 グライコフィ， インコーポレイテッド エリスロポエチン組成物
JP2010510963A (ja) 2006-06-14 2010-04-08 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー セラミックヒドロキシアパタイトを使用する抗体の精製方法
ES2668212T3 (es) 2006-07-13 2018-05-17 Wyeth Llc Producción de factor de coagulación IX con patrón de glucosilación mejorado
ES2764222T3 (es) 2006-09-08 2020-06-02 Wyeth Llc Lavado con arginina en la purificación de proteínas mediante el uso de cromatografía de afinidad
SG10201510384UA (en) 2006-09-13 2016-01-28 Abbvie Inc Cell culture improvements
US8911964B2 (en) 2006-09-13 2014-12-16 Abbvie Inc. Fed-batch method of making human anti-TNF-alpha antibody
WO2008036600A2 (en) 2006-09-18 2008-03-27 Genentech, Inc. Methods of protein production
CA2666317C (en) 2006-11-03 2013-08-06 Wyeth Glycolysis-inhibiting substances in cell culture
JP5065391B2 (ja) 2006-12-06 2012-10-31 日本ケミカルリサーチ株式会社 ヒトエリスロポエチンの製造方法
RU2009132986A (ru) 2007-03-02 2011-04-10 Уайт (Us) Применение меди и глутамата в культуре клеток для производства полипептидов
US20110130544A1 (en) 2007-03-30 2011-06-02 Medimmune, Llc Antibodies with decreased deamidation profiles
SG177941A1 (en) 2007-04-03 2012-02-28 Oxyrane Uk Ltd Glycosylation of molecules
JP2010524467A (ja) 2007-04-16 2010-07-22 モメンタ ファーマシューティカルズ インコーポレイテッド 規定の糖タンパク質産物および関連の方法
TW200902708A (en) 2007-04-23 2009-01-16 Wyeth Corp Methods of protein production using anti-senescence compounds
WO2008135498A2 (en) 2007-05-04 2008-11-13 Novo Nordisk A/S Prevention of protein degradation in mammalian cell cultures
EP1988101A1 (en) 2007-05-04 2008-11-05 Novo Nordisk A/S Improvement of factor VIII polypeptide titers in cell cultures
EP2152856B1 (en) 2007-05-11 2012-08-29 Amgen Inc. Improved feed media
US20100221823A1 (en) 2007-06-11 2010-09-02 Amgen Inc. Method for culturing mammalian cells to improve recombinant protein production
US20090053786A1 (en) 2007-07-09 2009-02-26 Yung-Hsiang Kao Prevention of disulfide bond reduction during recombinant production of polypeptides
US20090042253A1 (en) 2007-08-09 2009-02-12 Wyeth Use of perfusion to enhance production of fed-batch cell culture in bioreactors
SI2215117T2 (en) 2007-10-30 2018-04-30 Genentech, Inc. Purification of the antibody by cation exchange chromatography
CN101969971A (zh) 2007-11-30 2011-02-09 雅培制药有限公司 蛋白制剂及其制备方法
PT2235197T (pt) 2007-12-27 2017-10-11 Baxalta Inc Processos para cultura de células
WO2009092014A1 (en) 2008-01-18 2009-07-23 Gagnon Peter S Enhanced purification of antibodies and antibody fragments by apatite chromatography
JP2011512875A (ja) 2008-03-11 2011-04-28 ジェネンテック， インコーポレイテッド 増強されたａｄｃｃ機能を有する抗体
WO2009129226A1 (en) 2008-04-15 2009-10-22 Talecris Biotherapeutics, Inc. Two-stage ultrafiltration/diafiltration
CA2723197C (en) 2008-05-02 2017-09-19 Seattle Genetics, Inc. Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation
US8318416B2 (en) 2008-08-08 2012-11-27 Biogen Idec Ma Inc. Nutrient monitoring and feedback control for increased bioproduct production
DK2848625T3 (da) 2008-08-14 2019-10-07 Genentech Inc Fremgangsmåder til fjernelse af en kontaminant under anvendelse af ion bytningsmembrankromatografi med forskydning af naturligt forekommende proteiner
JP2012503656A (ja) 2008-09-26 2012-02-09 エウレカ セラピューティクス，インコーポレイテッド 変異体グリコシル化パターンを有する細胞株およびタンパク質
WO2010051360A1 (en) 2008-10-31 2010-05-06 Wyeth Llc Purification of acidic proteins using ceramic hydroxyapatite chromatography
JP2012511531A (ja) 2008-12-09 2012-05-24 エフ．ホフマン−ラ ロシュ アーゲー 賦形剤不含抗体溶液を得るための方法
US9631008B2 (en) 2008-12-22 2017-04-25 Hoffmann-La Roche Inc. Immunoglobulin purification
CN102272144B (zh) 2009-01-08 2014-09-17 通用电气健康护理生物科学股份公司 采用单一聚合物相系统的分离方法
CA2752393C (en) 2009-03-05 2020-01-14 Biogen Idec Ma Inc. Purification of immunoglobulins
US9056896B2 (en) 2009-03-27 2015-06-16 Asahi Kasei Medical Co., Ltd. Method for removing viruses from high concentration monoclonal antibody solution
TW201041899A (en) 2009-04-13 2010-12-01 Bristol Myers Squibb Co Protein purification by citrate precipitation
AU2010240569A1 (en) 2009-04-20 2011-10-20 Pfizer Inc. Control of protein glycosylation and compositions and methods relating thereto
US8969043B2 (en) 2009-05-28 2015-03-03 Boehringer Ingelheim International Gmbh Method for a rational cell culturing process
CA2763164A1 (en) 2009-06-05 2010-12-09 Momenta Pharmaceuticals, Inc. Methods of modulating fucosylation of glycoproteins
EP2451936B1 (en) 2009-07-06 2019-08-28 F.Hoffmann-La Roche Ag Method of culturing eukaryotic cells
AU2010275774B2 (en) 2009-07-24 2016-03-31 F. Hoffmann-La Roche Ag Optimizing the production of antibodies
WO2011015926A1 (en) 2009-08-03 2011-02-10 Avesthagen Limited A process of fermentation, purification and production of recombinant soluble tumour necrosis factor alfa receptor (tnfr) - human igg fc fusion protein
NZ597809A (en) 2009-08-06 2014-05-30 Genentech Inc Method to improve virus removal in protein purification
WO2011019622A1 (en) 2009-08-14 2011-02-17 Genentech, Inc. Cell culture methods to make antibodies with enhanced adcc function
WO2011024025A1 (en) 2009-08-28 2011-03-03 Avesthagen Limited An erythropoietin analogue and a method thereof
WO2011028753A1 (en) 2009-09-01 2011-03-10 Genentech, Inc. Enhanced protein purification through a modified protein a elution
US9540426B2 (en) 2009-10-06 2017-01-10 Bristol-Myers Squibb Company Mammalian cell culture processes for protein production
US20120208986A1 (en) 2009-10-20 2012-08-16 Wenger Marc D Use of mixed mode chromatography for the capture and purification of basic antibody products
EP2499973A1 (en) 2009-11-10 2012-09-19 Hitachi Medical Corporation Ultrasonic diagnosis device
US9096879B2 (en) 2009-11-24 2015-08-04 Biogen Ma Inc. Method of supplementing culture media to prevent undesirable amino acid substitutions
WO2011069056A2 (en) 2009-12-04 2011-06-09 Momenta Pharmaceuticals, Inc. Antennary fucosylation in glycoproteins from cho cells
US8277649B2 (en) 2009-12-14 2012-10-02 General Electric Company Membranes and associated methods for purification of antibodies
SG10201408384PA (en) 2009-12-18 2015-01-29 Novartis Ag Wash solution and method for affinity chromatography
MX2012011648A (es) 2010-04-07 2012-11-29 Momenta Pharmaceuticals Inc Glicanos de alta manosa.
CN107254499B (zh) 2010-04-26 2021-09-17 诺华股份有限公司 改进的细胞培养方法
PL2563904T3 (pl) 2010-04-26 2015-06-30 Novartis Ag Udoskonalona pożywka do hodowli komórkowej
EP2576580B1 (en) 2010-05-28 2016-09-14 F.Hoffmann-La Roche Ag Decreasing lactate level and increasing polypeptide production by downregulating the expression of lactate dehydrogenase and pyruvate dehydrogenase kinase
EP2601287B1 (en) 2010-08-05 2015-01-07 Amgen Inc. Dipeptides to enhance yield and viability from cell cultures
WO2012030512A1 (en) 2010-09-03 2012-03-08 Percivia Llc. Flow-through protein purification process
JP5918697B2 (ja) 2010-10-15 2016-05-18 Ｊｃｒファーマ株式会社 糖鎖の非還元末端がマンノース残基である糖蛋白質の製造方法
EP2450375A1 (en) 2010-11-09 2012-05-09 Sandoz Gmbh Cell culture medium and process for protein expression, said medium and process comprising a PAM inhibitor
US20120149878A1 (en) 2010-12-08 2012-06-14 Gillespie Ronald Protein purification
JP5838221B2 (ja) 2010-12-21 2016-01-06 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト アイソフォーム濃縮抗体調製物及びこれを得る方法
TW201242976A (en) 2011-01-07 2012-11-01 Abbott Lab Anti-IL-12/IL-23 antibodies and uses thereof
US9574003B2 (en) 2011-03-06 2017-02-21 Merck Serono S.A. Low fucose cell lines and uses thereof
SG193564A1 (en) 2011-03-25 2013-10-30 Genentech Inc Novel protein purification methods
EP2511293A1 (en) 2011-04-13 2012-10-17 LEK Pharmaceuticals d.d. A method for controlling the main complex N-glycan structures and the acidic variants and variability in bioprocesses producing recombinant proteins
US9133493B2 (en) 2011-04-21 2015-09-15 Amgen Inc. Method for culturing mammalian cells to improve recombinant protein production
EP2702143B1 (en) 2011-04-29 2018-06-06 Biocon Research Limited Methods for reducing accumulation of lactate during culturing and method for producing polypeptide
US20120283419A1 (en) 2011-05-03 2012-11-08 Avantor Performance Materials, Inc. Separation of protein monomers from aggregates by solid weak anion exchange support functionalized with amine moieties
WO2012158551A1 (en) 2011-05-13 2012-11-22 Biogen Idec Ma Inc. Methods of preventing and removing trisulfide bonds
LT2837680T (lt) 2011-07-01 2020-07-10 Amgen Inc. Žinduolių ląstelių kultūra
WO2013006461A1 (en) 2011-07-01 2013-01-10 Biogen Idec Ma Inc. Cholesterol-based media supplementals for cell culture
US9475858B2 (en) 2011-07-08 2016-10-25 Momenta Pharmaceuticals, Inc. Cell culture process
WO2013013013A2 (en) 2011-07-21 2013-01-24 Alnylam Pharmaceuticals, Inc. Compositions and methods for producing modified glycoproteins
EP2768845B1 (en) 2011-10-19 2017-01-18 Roche Glycart AG Separation method for fucosylated antibodies
WO2013066707A1 (en) 2011-10-31 2013-05-10 Merck Sharp & Dohme Corp. Chromatography process for resolving heterogeneous antibody aggregates

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040171152A1 (en) * 1996-10-10 2004-09-02 Invitrogen Corporation Animal cell culture media comprising non-animal or plant-derived nutrients
WO2004058944A2 (en) * 2002-12-23 2004-07-15 Bristol-Myers Squibb Company Product quality enhancement in mammalian cell culture processes for protein production

Also Published As

Publication number Publication date
MY185872A (en) 2021-06-14
SG174804A1 (zh) 2011-10-28
CA2842959A1 (en) 2008-03-20
EP2532737A2 (en) 2012-12-12
TW201708537A (zh) 2017-03-01
CN101663390A (zh) 2010-03-03
KR20090074040A (ko) 2009-07-03
WO2008033517A3 (en) 2008-11-27
TW201346032A (zh) 2013-11-16
EP2500413A1 (en) 2012-09-19
CN101663390B (zh) 2013-10-23
CA2842964A1 (en) 2008-03-20
EP2064314A2 (en) 2009-06-03
JP2013230151A (ja) 2013-11-14
EP2064314A4 (en) 2009-12-30
US9284371B2 (en) 2016-03-15
US20160186130A1 (en) 2016-06-30
CN102337243A (zh) 2012-02-01
US20170130191A1 (en) 2017-05-11
SG10201510384UA (en) 2016-01-28
TW201516149A (zh) 2015-05-01
CA2842966A1 (en) 2008-03-20
NZ575328A (en) 2012-06-29
US20140134674A1 (en) 2014-05-15
CA2663442A1 (en) 2008-03-20
JP5878682B2 (ja) 2016-03-08
WO2008033517A9 (en) 2009-02-26
BRPI0716762A2 (pt) 2013-09-24
JP2010503397A (ja) 2010-02-04
CN103276033A (zh) 2013-09-04
CN103397065A (zh) 2013-11-20
US8906646B2 (en) 2014-12-09
MX345141B (es) 2017-01-18
US20190225934A1 (en) 2019-07-25
US20140206038A1 (en) 2014-07-24
US9234032B2 (en) 2016-01-12
RU2518289C2 (ru) 2014-06-10
MY161866A (en) 2017-05-15
RU2009113613A (ru) 2010-10-20
MX2009002748A (es) 2009-03-26
RU2014110141A (ru) 2015-09-27
US20080227136A1 (en) 2008-09-18
CA2910619A1 (en) 2008-03-20
US10119118B2 (en) 2018-11-06
US20150087024A1 (en) 2015-03-26
MY185887A (en) 2021-06-14
IL197444A0 (en) 2011-08-01
TWI548747B (zh) 2016-09-11
NO20091439L (no) 2009-05-28
MX353340B (es) 2018-01-09
US8663945B2 (en) 2014-03-04
JP2016000030A (ja) 2016-01-07
KR20140132017A (ko) 2014-11-14
US20160039927A1 (en) 2016-02-11
NZ597334A (en) 2014-02-28
US20150125905A1 (en) 2015-05-07
US20120077213A1 (en) 2012-03-29
AU2007294731B2 (en) 2014-04-17
MX346523B (es) 2017-03-23
CN103555651A (zh) 2014-02-05
US8093045B2 (en) 2012-01-10
EP2532737A3 (en) 2013-03-27
US9073988B2 (en) 2015-07-07
MY185040A (en) 2021-04-30
TW200831669A (en) 2008-08-01
CN103555652A (zh) 2014-02-05
SG192441A1 (zh) 2013-08-30
EP2527425A1 (en) 2012-11-28
US20140134675A1 (en) 2014-05-15
WO2008033517A2 (en) 2008-03-20
AU2007294731A1 (en) 2008-03-20

Similar Documents

Publication Publication Date Title
TWI456062B (zh) 細胞培養改良
JP2010503397A5 (zh)
US6406909B1 (en) Serum-free medium for culturing animal cells
RU2458988C2 (ru) ПОЛУЧЕНИЕ РЕКОМБИНАНТНОГО БЕЛКА pФНО-lg
CN102858953B (zh) 改进的细胞培养基
CN1187441C (zh) 用于培养动物细胞的培养基和使用该培养基生产蛋白质的方法
US20220010347A1 (en) Modification of rna-related enzymes for enhanced production
CN101195817A (zh) 一种杂交瘤细胞扩增培养基及其用途
CN103555658A (zh) 一种bhk-21细胞全悬浮培养的无血清培养基
CN105431454A (zh) 用于生产单克隆抗体的改进方法
RU2644246C2 (ru) Способ получения капсулярного полисахарида Haemophilus influenzae типа b, применение капсулярного полисахарида и способ получения вакцинной композиции
CN109207415A (zh) 一种生产胞二磷胆碱的重组微生物及生产胞二磷胆碱的方法
JPS61202694A (ja) 発酵法によるｌ−グルタミンの製造法
CN118086167B (zh) 一种生产l-色氨酸的基因工程菌及其构建方法与应用
WO2016153041A1 (ja) 銅イオン制御製造方法
CN109777765A (zh) 干细胞培养基及其应用和干细胞培养方法
CN101768560A (zh) 一种提高质粒dna在大肠杆菌工程菌中比含量的培养基
CN106318998B (zh) 用于提高重组人ⅱ型肿瘤坏死因子受体-抗体融合蛋白唾液酸化水平的组合物
CN101235356B (zh) 用于生物合成肝素酶的培养基
CN106754648A (zh) 一种无动物源培养基
KR101318498B1 (ko) 재조합 단백질의 생산성 향상을 위한 배양용 배지 첨가용 조성물
US3313710A (en) Process for producing tri-and diphosphates of adenosine and guanosine by fermentation
CN109880790A (zh) 适用于多种动物细胞规模培养的无血清培养基
SU992568A1 (ru) Питательна среда дл выращивани SеRRатIа маRсеSсеNS 24-продуцента нуклеазы
SU738398A1 (ru) Питательна среда дл выращивани чуМНОгО МиКРОбА