# US 6,294,656 B1 · Transforming growth factor β crystals > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,294,656 B1 - Document ID: US6294656B1 - Status: Granted - Kind: B1 - Application number: 09/000,069 - Filed: 1998-01-22 - Granted: 2001-09-25 - Earliest claimed: 1995-07-25 - Assignees: Novartis AG - Inventors: Peer Mittl; Markus Grütter; Tudor Arvinte - Web page: https://patentgrep.com/patent/US6294656B1 ## CPC - C07K 14/495: Transforming growth factor [TGF] - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract The invention concerns TGF-β in a crystalline form which shows no adsorption or less adsorption to the walls of vials than the soluted TGF-β and which is more stable towards oxidative agents than the soluted form. TGF-β crystals of the invention can be used for structure determination and for drug design and for the production of a slow release pharmaceutical preparation. ## Claims ### Claim 1 A composition consisting essentially of Transforming Growth Factor-β3 (TGF-β3) crystals and a carrier, wherein said crystals belong to a triagonal or hexagonal space group. ### Claim 2 (depends on 1) A composition according to claim 1, in which the hexagonal space group is hexagonal crystal form H. ### Claim 3 (depends on 1) A composition according to claim 1, in which the trigonal space group is trigonal crystal form T. ### Claim 4 A method for preparing Transforming Growth Factor β3 (TGF-β3) in crystalline form comprising: (a) combining a crystallization buffer solution comprising soluted TGF-β3 with a precipitating agent selected from a water-miscible organic solvent and polyethylene glycol to form a mixture, wherein the concentration of said precipitating agent is initially lower than that required for crystal formation; (b) increasing the concentration of the precipitating agent in the mixture to a level such that crystal formation will occur; (c) incubating the mixture of step (b) for a time and under conditions effective to produce crystals of TGF-β3; and (d) recovering the resulting TGF-β3 crystals from the mixture of step (c). ### Claim 5 (depends on 4) The method of claim 4 characterized in that the water miscible organic solvent is dioxane. ### Claim 6 (depends on 4) The method of claim 4 characterized in that the precipitating agent is polyethylene glycol. ### Claim 7 A method for preparing Transforming Growth Factor β3 (TGF-β3) in crystalline form comprising (a) combining a crystallization buffer solution comprising soluted TGF-β3 with a precipitating agent selected from a water-miscible organic solvent and polyethylene glycol to form a mixture, wherein the concentration of said precipitating agent is initially lower than that required for crystal formation; (b) increasing the concentration of the precipitating agent in the mixture to a level such that crystal formation will occur; (c) adding seed crystals of TGF-β3 to facilitate TGF-β3 crystal formation in the mixture of step (b) (d) incubating the mixture of step (c) for a time and under conditions effective to produce crystals of TGF-β3; and (e) recovering the resulting TGF-β3 crystals from the mixture of step (d). ### Claim 8 (depends on 7) The method of claim 7 in which the crystallization buffer solution is seeded with microcrystal seeds of TGF-β3. ### Claim 9 (depends on 7) The method of claim 7 in which the crystallization buffer solution is seeded with macrocrystal seeds of TGF-β3.