Claims for Patent: 8,852,435

Summary for Patent: 8,852,435

Title:	Purification and separation treatment assembly (PASTA) for biological products
Abstract:	An assembly capable of capturing and purifying expressed biological products during or at the end of a bioreaction cycle is disclosed wherein a binding resin is kept separated from the contents of the bioreactor allowing capturing, harvesting and purification of biological products in a bioreactor; the invention additionally provides means of removing undesirable metabolic products as well as provides for efficient loading of chromatography columns.
Inventor(s):	Niazi; Sarfaraz (Deerfield, IL)
Assignee:	Therapeutics Proteins International, LLC (Chicago, IL)
Application Number:	13/286,193
Patent Claims:	1. A method for harvesting and purifying a target biological product at the end of a production cycle comprising: a) Expressing a target biological product in a bioreactor; b) Disposing in the bioreactor at the end of the production cycle, an appropriate length of a purification and separation treatment assembly (PASTA) comprising: a flexible porous tube filled with a binding resin, wherein the porous tube comprises a plurality of pores smaller in size than the size of the binding resin and wherein the porous tube is sealed at both ends to provide a pre-determined quantity of resin; c) Capturing the target biological product by mixing the contents of the bioreactor to allow substantially complete binding of the target biological product to the resin in the PASTA; d) Removing the contents of the bioreactor except the PASTA from the bioreactor; e) Eluting the target biological product from the PASTA held in the bioreactor by adding to the bioreactor a buffer capable of removing the binding of the target biological product from the resin in the PASTA. 2. The method according to claim 1, wherein the flexible porous tube is made of plastic, nylon and a composite material. 3. The method according to claim 1, wherein the diameter of the flexible porous tube is less than 10 mm. 4. The method according to claim 1, wherein the size of the pores ranges from 1 micron to 50 microns. 5. The method according to claim 1, wherein the resin comprises an ionic-exchange resin, a hydrophobic resin, an affinity resin or a mixture thereof. 6. The method according to claim 1, wherein the resin comprises a protein or a peptide as a ligand. 7. The method according to claim 1, wherein the resin comprises a resin with specific affinity towards the target biological product. 8. The method according to claim 1, wherein the resin comprises a plurality of resins. 9. The method for harvesting and purifying a target biological product according to claim 1, wherein the step (e) is repeated using different buffers. 10. The method for harvesting and purifying a target biological product according to claim 1, wherein the PASTA is removed from the bioreactor after step (d) and packed in a chromatography column for purification. 11. A method for harvesting a target biological product during its production comprising: a) Starting an expression cycle of the target biological product in a bioreactor; b) Disposing in the bioreactor a purification and separation treatment assembly (PASTA) comprising: a flexible porous tube filled with a binding resin, wherein the porous tube comprises a plurality of pores smaller in size than the size of the binding resin and wherein the porous tube is sealed at both ends to provide a pre-determined quantity of resin at a pre-determined stage in the expression cycle and leaving one end of the PASTA accessible from the outside of the bioreactor; c) Allowing the resin in the PASTA to bind a pre-determined quantity of the target biological product; d) Removing the PASTA from the bioreactor by pulling on the end of PASTA accessible from the outside of the bioreactor and replacing it with fresh PASTA; e) Submerging the removed PASTA in a separate container holding a buffer capable of breaking the binding of the target biological product with the resin, removing the PASTA from the container to obtain a concentrated solution of purified target protein; f) Reusing the PASTA from step (e) in step (b). 12. The method for harvesting a target biological product according to claim 11, wherein the bioreactor is replenished with nutrient elements that are removed by the PASTA. 13. The method for harvesting and purifying a target biological product according to claim 1 or 11, wherein the target biological product is produced by an organism selected from the group consisting of bacteria, yeast, hybrodomas, baculoviruses, mammalian cells or plant cells. 14. The method for harvesting and purification of a target biological product according to claim 1 or 11, wherein the target biological product is selected from the group consisting of a solubilized inclusion body, small protein, enamel matrix protein, fusion protein, tag protein, hormone, parathyroid hormone, growth hormone, gonadotropin, insulin, ACTH, prolactin, placental lactogen, melanocyte stimulating hormone, thyrotropin, calcitonin, enkephalin, angiotensin, cytokines human serum albumin, bovine serum albumin, ovalbumin, glucose isomerase, .alpha.-amylase, endo-.beta., glucanase, growth hormone (GH), IGF-1, IGF-2, PTH, PGE.sub.2, TGF-.beta., TGF-.alpha., 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).sub.2, vitamin D.sub.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 and a recombinant peptide. 15. A method for removing undesirable metabolites in a production cycle of a target biological product comprising: a) Adding to a bioreactor a sufficient quantity of a purification and separation treatment assembly (PASTA) comprising: a flexible porous tube filled with a binding resin or a mixture of binding resins capable of binding one or more undesirable metabolic products in the bioreactor, wherein the porous tube comprises a plurality of pores smaller in size than the size of the binding resin and wherein the porous tube is sealed at both ends; b) Removing the PASTA from the bioreactor upon achieving a desired low level of undesirable metabolic products in the bioreactor; c) Reacting the removed PASTA with a buffer capable of removing undesirable metabolic products and re-using the PASTA in step (a). 16. The method for harvesting a target biological product according to claim 15, wherein a plurality of PASTA is used to remove any undesirable metabolic products of the production cycle separately from the target biological product. 17. A method for harvesting and purifying a target biological product comprising: a) Disposing in the bioreactor at the beginning or during the bioreaction cycle, an appropriate length of a purification and separation treatment assembly (PASTA) comprising: a flexible porous tube filled with a binding resin; wherein the porous tube comprises a plurality of pores smaller in size than the size of the binding resin; and wherein the porous tube is sealed at both ends; to provide a pre-determined quantity of resin; b) Expressing the target biological product in a bioreactor; c) Allowing the resin in the PASTA to bind a pre-determined quantity of the target biological product; d) Removing the contents of the bioreactor except the PASTA from the bioreactor; and e) Eluting the target biological product from the PASTA held in the bioreactor by: 1) adding to the bioreactor a buffer capable of removing the binding of the target biological product from the resin in the PASTA; or 2) removing the PASTA from the bioreactor and submerging the removed PASTA in a separate container holding a buffer capable of breaking the binding of the target biological product with the resin and removing the PASTA from the container to obtain a concentrated solution of purified target protein. 18. The method of any one of claims 1, 11, 15, or 17, wherein the porous tube is further sealed along the porous tube into regularly spaced segments. 19. The method according to claim 18, wherein the segments range in size from 10 mm to 100 mm.

Details for Patent 8,852,435

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2039-03-29