USRE30985EExpiredUtility

Serum-free cell culture media

70
Priority: Jan 1, 1978Filed: Feb 6, 1981Granted: Jun 29, 1982
Est. expiryJan 1, 1998(expired)· nominal 20-yr term from priority
A01N 1/122C12N 2501/33C12N 5/0037C12N 2501/39C12N 2501/395
70
PatentIndex Score
796
Cited by
1
References
13
Claims

Abstract

A serum-less medium for use in the growth of cells. The medium is an improved aqueous culture media of the MEM type comprising thyroxin, insulin, and Vitamin A. Hydrocortisone and essential fatty acids may also be advantageously used, as may effective quantities of Vitamin E. Surfactants are used to make the vitamins and any fatty acids available for cell growth. This aqueous media may also comprise cell-growth-enhancing quantities of biotin and folic acids.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. .[.An MEM zinc option.]. .Iadd.A cell culturing .Iaddend.medium wherein the amino acid profile is about as follows:   ______________________________________                                    
Item         Amount (milligrams per liter)                                
______________________________________                                    
L alanine    8.9                                                          
L asparagine 75.0                                                         
L aspartic acid                                                           
             13.0                                                         
L glutamic acid                                                           
             14.7                                                         
L glycine    7.5                                                          
L proline    11.5                                                         
L serine     52.5                                                         
L arginine HCl                                                            
             196.52                                                       
L cystine    37.2                                                         
L glutamine  584.0                                                        
L histidine HCl                                                           
             65.0                                                         
L isoleucine 80.88                                                        
L leucine    160.88                                                       
L lysine     112.38                                                       
L methionine 23.30                                                        
L phenyl-alanine                                                          
             50.15                                                        
L threonine  74.18                                                        
L tryptophan 15.61                                                        
L valine     71.4                                                         
L tyrosine   45.9                                                         
______________________________________                                    
     
     
     
       2. .[.An MEM zinc option.]. .Iadd.A .Iaddend.medium, as defined in claim 1, wherein said medium is augmented with cell growth promoting quantities of biotin and folic acid. 
     
     
       3. A culture media as defined in claim 1 further comprising   ______________________________________                                    
Thyroxine       0.01 to 0.03 micrograms per liter                         
Insulin         4 milligrams per liter                                    
Hydrocortisone  0.075 to 0.3 milligrams per liter                         
Essential Fatty Acids                                                     
                2.5 to 15 milligrams per liter                            
Vitamin A       0.1 to 0.4 milligrams per liter                           
Vitamin E       7.5 to 30 milligrams per liter                            
Surfactants     Sufficient quantity to disperse                           
                vitamins and fatty acids.                                 
______________________________________                                    
     
     
     
       4. A culture media as defined in claim 2 further comprising   ______________________________________                                    
Thyroxine       0.01 to 0.03 micrograms per liter                         
Insulin         4 milligrams per liter                                    
Hydrocortisone  0.075 to 0.3 milligrams per liter                         
Essential Fatty Acids                                                     
                2.5 to 15 milligrams per liter                            
Vitamin A       0.1 to 0.4 milligrams per liter                           
Vitamin E       7.5 to 30 milligrams per liter                            
Surfactants     Sufficient quantity to disperse                           
                vitamins and fatty acids.                                 
______________________________________                                    
     
     
     
       5. A culture media as defiined in claim 3 wherein said surfactant is a polysorbate 20. 
     
     
       6. A culture media as defined in claim 1 further comprising   ______________________________________                                    
Item              Amount                                                  
______________________________________                                    
thyroxine         0.02 micrograms per liter                               
insulin           4 milligrams per liter                                  
hydrocortisone    .[.1.5.]. .Iadd.0.15.Iaddend.                           
                  milligrams per liter                                    
linoleic acid     5.0 milligrams per liter                                
linolenic acid    5.0 milligrams per liter                                
arachidonic acid  5.0 milligrams per liter                                
surfactant, emulsifier                                                    
                  110 milligrams per liter                                
Vitamin E         20 milligrams per liter                                 
Vitamin A         0.25 milligrams per liter                               
______________________________________                                    
     
     
     
       7. An aqueous culture media for use in cell growth having about the following formula:   ______________________________________                                    
Item          Amount (milligrams per liter)                               
______________________________________                                    
L alanine     8.9                                                         
L asparagine  75.0                                                        
L aspartic acid                                                           
              13.0                                                        
L glutamic acid                                                           
              14.7                                                        
L glycine     7.5                                                         
L proline     11.5                                                        
L serine      52.5                                                        
L arginine HCl                                                            
              196.52                                                      
l cystine     37.2                                                        
L glutamine   584.0                                                       
L histidine HCl                                                           
              65.0                                                        
L isoleucine  80.88                                                       
L leucine     160.88                                                      
L lysine      112.38                                                      
L methionine  23.30                                                       
L phenyl-alanine                                                          
              50.15                                                       
L threonine   74.18                                                       
L tryptophan  15.61                                                       
L valine      71.4                                                        
L tyrosine    45.9                                                        
CaCl          200                                                         
KCl           400                                                         
.[.MgCl6H.sub.2 O.].                                                      
.Iadd.MgCl.sub.2 . 6H.sub.2 O.Iaddend.                                    
              183                                                         
MgSO.sub.4 7H.sub.2 O                                                     
              12                                                          
NaCl          6800                                                        
NaH.sub.2 PO.sub.4 H.sub.2 O                                              
              150                                                         
phenol red    10                                                          
glucose       2000                                                        
Na pyruvate   110                                                         
biotin        1.0                                                         
D-calcium pantothenate                                                    
              1.0                                                         
choline Cl    56.0                                                        
folic acid    1.0                                                         
inositol      36.0                                                        
nicotinamide  1.0                                                         
pyridoxal HCl 1.0                                                         
riboflavin    0.1                                                         
thiamine      1.0                                                         
B.sub.12      1.36                                                        
folinic acid  1.0                                                         
DL thioctic acid                                                          
              0.20                                                        
putrescine HCl                                                            
              0.16                                                        
linoleic      0.084                                                       
FeCl.sub.3 6H.sub.2 O                                                     
              0.54                                                        
ZnSO.sub.4 7H.sub.2 O                                                     
              0.14                                                        
insulin       4.00                                                        
HEPES buffer solution                                                     
              2380.0                                                      
NaHCO.sub.3   sufficient to adjust to a pH of                             
              about 7.4                                                   
______________________________________                                    
 Distilled water to make a total of 1 liter                               
     
     
     
       8. A culture media as defined in claim 7 further comprising   ______________________________________                                    
Thyroxine       0.01 to 0.03 micrograms per liter                         
Insulin         4 milligrams per liter                                    
Hydrocortisone  0.075 to 0.3 milligrams per liter                         
Essential Fatty Acids                                                     
                2.5 to 15 milligrams per liter                            
Vitamin A       0.1 to 0.4 milligrams per liter                           
Vitamin E       7.5 to 30 milligrams per liter                            
Surfactants     Sufficient quantity to disperse                           
                vitamins and fatty acids.                                 
______________________________________                                    
     
     
     
       9. A medium as defined in claims 3, 4, or 8 wherein said essential fatty acids are predominantly comprised of linoleic acid, linolenic acid and arachindonic acid. 
     
     
       10. A medium as defined in claims 1, 2, 7, 3, 4, 8, 5 or 6 wherein said medium is maintained substantially free of cell-damaging quantities of proteolytic enzymes. 
     
     
       11. An improved process for growing lines of living cells comprising the steps of growing said cells in a growth medium, through at least two passages, said medium .[.an.]. .Iadd.a modified .Iaddend.MEM .[.zinc option type.]. medium having about the following amino acid profile:   ______________________________________                                    
Item         Amount (milligrams per liter)                                
______________________________________                                    
L alanine    8.9                                                          
L asparagine 75.0                                                         
L aspartic acid                                                           
             13.0                                                         
L glutamic acid                                                           
             14.7                                                         
L glycine    7.5                                                          
L proline    11.5                                                         
L serine     52.5                                                         
L arginine HCl                                                            
             196.52                                                       
L cystine    37.2                                                         
L glutamine  584.0                                                        
L histidine HCl                                                           
             65.0                                                         
L isoleucine 80.88                                                        
L leucine    160.88                                                       
L lysine     112.38                                                       
L methionine 23.30                                                        
L phenyl-alanine                                                          
             50.15                                                        
L threonine  74.18                                                        
L tryptophan 15.61                                                        
L valine     71.4                                                         
L tyrosine   45.9                                                         
______________________________________                                    
     
     
     
       12. A process as defined in claim 11 wherein said medium comprises effective amounts of additional nutrients as follows: biotin   folic acid   Thyroxine   Insulin   Hydrocortisone   Essential Fatty Acids   Vitamin A   Vitamin E   Surfactants   
     
     
       13. A process as defined in claims 11 or 12, wherein transfer of cells from one passage to another is primarily effected by use of physical means and without use of cell-harming quantities of proteolytic enzymes.

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