Separative harvesting device

Abstract

A harvesting device for capturing a biological product directly by binding the secreted biological product with a resin, discarding the nutrient medium and eluting the biological product as a concentrated solution, eliminating the steps of sterile filtration and volume reduction, thus allowing one to combine the steps of recombinant expression and separation of a biological product. The method allows loading of resin for column-purification, eliminating all steps of perfusion process and maintaining a sink condition of a toxic product in nutrient medium to optimize productivity of host cells. The instant invention also allows harvesting of solubilized inclusion bodies after the cells have been lysed and refolding of proteins inside the bioreactor.

I claim: 
     
         1 . A harvesting device for capturing a biological product comprising at least one container with at least one external surface and an inner volume to hold at least one ligand or resin capable of binding a biological product and the surface having a plurality of pores. 
     
     
         2 . The harvesting device according to  claim 1 , wherein the container is a flexible pouch. 
     
     
         3 . The harvesting device according to  claim 1 , wherein the container comprises a plastic, nylon, metallic mesh, or a composite material. 
     
     
         4 . The harvesting device according to  claim 1 , wherein the size of pores is between 0.2 and 30 microns. 
     
     
         5 . The harvesting device according to  claim 1 , wherein the size of pores is between 1 and 5 microns. 
     
     
         6 . The harvesting device according to  claim 1 , wherein the resin or ligand is an ionic-exchange resin, a hydrophobic resin, a stimuli responsive polymer, an affinity resin, Protein A-coated magnetic beads, Protein-G magnetic beads, a dual affinity polypeptide, Q Hypercel sorbant, S Hypercel sorbent, 4-mercaptoethylpyridine (MEP), Protein G, countercurrent chromatography media, a peptide ligand, an Fe-receptor mimetic ligand, sn inorganic ligand, a synthetic dye, or a single-domain camel-derived anti-IgG antibody. 
     
     
         7 . The harvesting device according to  claim 1 , wherein the container comprises a plurality of resins. 
     
     
         8 . The harvesting device according to  claim 1 , wherein there is a plurality of containers. 
     
     
         9 . The harvesting device according to  claim 1 , wherein the harvesting device is disposed inside a bioreactor. 
     
     
         10 . The harvesting device according to  claim 9 , wherein the device is used at the end of a bioreactor operation cycle. 
     
     
         11 . The harvesting device according to  claim 9 , wherein the device is used during a bioreactor operation cycle. 
     
     
         12 . The harvesting device according to  claim 1 , wherein the device is used to capture a biological product from a nutrient media comprising a biological culture contained in a bioreactor. 
     
     
         13 . The harvesting device according to  claim 1 , wherein the biological product is produced using bacteria, yeast, hybrodomas, baculoviruses, animal cells, mammalian cells or plant cells. 
     
     
         14 . The harvesting device according to  claim 1 , wherein the biological product comprises solubilized inclusion bodies, small proteins, enamel matrix proteins, fusion proteins, tag proteins, hormones, parathyroid hormones, growth hormones, gonadotripins, insulin, ACTH, prolactin, placental lactogen, melanocyte stimulating hormone, thyrotropin, calcitonin, enkephalin, angiotensin, cytokines human serum albumin, bovine serum albumin, ovalbumin, glucose isomerase, α-amylase, endo-β-glucanase, growth hormone (GH), IGF-1, IGF-2, PTH, PGE 2 , TGF-β, TGF-α, bEGF, EGF, PDGF-AB, PDGF-BB, osteoprotegerin (OPG), osteopontin (OP), FGF-1, FGF-2, thyroid hormone, BMP-2, BMP-3, BMP-4, BMP-6, BMP-7, VEGF, L25(OH) 2 ,vitamin D 3 , caclitonin, IFN-alpha, IFN-beta, IFN-gamma, OCN (osteocalcin), ON (osteonectin), OP-1 (osteogenic protein-1), NGF, collagen, fibronectin, fibrinogen, thrombin, factor XIII, a recombinant protein, a recombinant antibody, or a recombinant peptide.