Isolation Or Purification Patents (Class 530/305)
  • Patent number: 5070186
    Abstract: Insulin preparations with improved properties for parenteral administration can be prepared at pH values of about 3 to 8.5 by presence of magnesium ions in concentration of about 0.005 to 0.5M, a preferred range is 0.02M to 0.5M.
    Type: Grant
    Filed: April 19, 1989
    Date of Patent: December 3, 1991
    Assignee: Novo Industri A/S
    Inventor: Klaus Joergensen
  • Patent number: 5070075
    Abstract: The invention provides DNA sequences encoding a human preproinsulin-like growth factor I protein and novel extension peptides. A novel preproinsulin-like growth factor I protein and novel extension peptides are also provided. The present invention further provides a human IGF-I gene which has been sequenced and which encodes at least two preproinsulin-like growth factor-I proteins. Various genes and DNA sequences useful in producing essentially pure mature IGF-I, preproinsulin-like growth factor I proteins and IGF-I gene related proteins are also provided.
    Type: Grant
    Filed: March 15, 1990
    Date of Patent: December 3, 1991
    Assignee: Washington University
    Inventors: Peter S. Rotwein, Gwen G. Krivi
  • Patent number: 5059329
    Abstract: A process for purifying dithiochrome from a natural source is disclosed. The process comprises: (i) contacting a eukaryotic cell mass with a mixture of water and an alcohol; (ii) separating the alcohol phase from the water phase and obtaining a water phase extract; (iii) subjecting the water phase extract to a sulfhydryl exchange chromatography matrix; (iv) washing said chromatography matrix; and (v) treating said chromatrography matrix with an active thiol to obtain dithiochromate; a material capable of binding with insulin. Dithiochromate may be used to treat patients suffering from elevated blood glucose or suboptimal glucose kinetics. An adduct of this compound with insulin may be used to treat patients for type I diabetes.
    Type: Grant
    Filed: September 19, 1989
    Date of Patent: October 22, 1991
    Assignee: Thymax Corporation
    Inventor: Scott King
  • Patent number: 5049545
    Abstract: Insulin derivatives of the general formulae I and IIX--(Y.sub.1 --S--S--Y.sub.2 --Z--"Insulin").sub.m IA--S--Y.sub.3 --Z--"Insulin" IIin whichX is a radical of a physiologically tolerated carbon compound,Y.sub.1, Y.sub.2 and Y.sub.3 are, independently of one another, a chemical bond or an organic chemical bridge,S is a sulfur atom,"Insulin" denotes the biologically active peptidic portion of a natural, semisynthetic or synthetic insulin or an insulin which has been prepared by genetic engineering, or one of its biologically active analogs without the inessential amino group,Z is an amino group which is inessential for the biological activity of insulin,A is a hydrogen atom or the radical of a mercapto-containing, physiologically tolerated hydrocarbon compound, andm is an integer from 1 to 20,agents containing these derivatives, a process for the preparation of these derivatives, and their use for the treatment of metabolic disorders, are described.
    Type: Grant
    Filed: March 15, 1989
    Date of Patent: September 17, 1991
    Assignee: Behringwerke Aktiengesellschaft
    Inventors: Hartmut Lobermann, Eric P. Paques, Norbert Heimburger
  • Patent number: 5015728
    Abstract: The invention relates to a process for the preparation of an insulin derivative of the formula I ##STR1## in which R.sup.1 denotes H or H-Phe, R.sup.30 represents the radical of a naturally occurring L-aminoacid and R.sup.31 represents a physiologically acceptable organic group of neutral or basic character consisting of 1 to 3 .alpha.-aminoacids in which the terminal carboxyl function is present in the free form and which insulin derivative has an isoelectric point above 5.8, which comprises reacting an insulin of the formula I in which R.sup.30 denotes the radical of a genetically codable L-aminoacid and R.sup.31 represents OH or a protective group of the carboxyl function, with a peptide or aminoacid derivatives of the formula R-R.sup.30 -R.sup.31 consisting of 2 to 4 .alpha.-aminocacids, in which the terminal carboxyl function is in free form, in the presence of a trypsin-like endopeptidase at a pH value below the isoelectric point of the starting insulin.
    Type: Grant
    Filed: March 23, 1988
    Date of Patent: May 14, 1991
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Rainer Obermeier, Rolf Geiger, Ulrich Grau
  • Patent number: 4909941
    Abstract: There is described a mobile phase for use in the purification of proteins using reversed phase HPLC on a preparative scale. The mobile phase is an aqueous solution containing 0.005 to 1M of a physiologicially acceptable acid of the general formula YCOOH where Y is a polar electron withdrawing group capable of hydrogen bonding silanol groups. The solution also contains up to 95% by volume of a physilogically acceptable organic solvent. A preparative method of purifying proteins such as HSA or BSA and recombinant deoxyribonucleic proteins using reversed phased PHLC is also described.
    Type: Grant
    Filed: December 8, 1988
    Date of Patent: March 20, 1990
    Inventors: Dick J. Poll, David R. K. Harding, William S. Hancock
  • Patent number: 4801684
    Abstract: A process for the preparation of insulin precursors of the formula (I) ##STR1## in which R is hydrogen or the presequence P.sub.m --Q.sub.n --, in which P is a sequence of naturally occurring amino acids with m being from 0 to 50, Q are basic natural amino acids, and n is an integer from 1 to 4, Y represents --Lys.sup.B29 --Z.sup.B30 --, in which Z denotes Ala, Thr or Ser, and the bridge extending from A-1 to A-21 is an insulin A-chain, the bridge extending from B-1 to B-30 represents an insulin B-chain, and X is a bridge which is bonded to the insulin A-chain at the amino group of A-1 and is bonded to the insulin B-chain at the .epsilon.-amino group of B-29-- in which case it is bonded to the free bond of Z.sup.
    Type: Grant
    Filed: September 2, 1986
    Date of Patent: January 31, 1989
    Assignee: Hoechst Aktiengesellschaft
    Inventor: Ulrich Grau
  • Patent number: 4801691
    Abstract: Guanidine hydrochloride (GCl) is used to remove excess sodium dodecyl sulfate (SDS) from SDS-solubilized protein solutions, and particularly from SDS-solubilized inclusion body solutions, GCl is added to the solution containing SDS to induce the formation of a GCl-SDS complex (GDS) which, when allowed to precipitate, can easily be removed by centrifugation, filtration, or other suitable means.
    Type: Grant
    Filed: May 15, 1987
    Date of Patent: January 31, 1989
    Assignee: International Minerals & Chemical Corp.
    Inventor: Henry E. Auer
  • Patent number: 4789660
    Abstract: A therapeutic composition for trans-mucosal administration in the treatment of diabetes including insulin, as an adjuvant a water-soluble fusidic acid salt and as a co-adjuvant methylparaben and/or propylparaben.
    Type: Grant
    Filed: September 10, 1987
    Date of Patent: December 6, 1988
    Assignee: American Home Products Corporation
    Inventors: Robin P. Enever, Thomas W. Leonard, Karol K. Mikula
  • Patent number: 4764592
    Abstract: This disclosure provides a crystalline human proinsulin, the preparation of which comprises(a) preparing an aqueous mixture containing from about 5 to about 50 mg/ml human proinsulin, from about 0.1 to about 5 mg/ml of a phenolic substance, from about 0.03 to about 0.6 milliequivalents/ml of a salt of a cation selected from the group consisting of lithium, calcium, sodium, potassium, ammonium, magnesium, and barium, and from about 0.2 to about 5 milliequivalents of Zn.sup.+2 cation;(b) adjusting the aqueous mixture to a pH in the range of from about 5.4 to about 6.5;(c) allowing crystal formation to occur; and(d) recovering crystalline human proinsulin from the aqueous mixture.
    Type: Grant
    Filed: April 23, 1987
    Date of Patent: August 16, 1988
    Assignee: Eli Lilly and Company
    Inventors: Eddie H. Massey, Richard L. Jackson
  • Patent number: 4705845
    Abstract: A process for sulphation and phosphorylation of a protein or peptide comprising contacting said protein or peptide with sulphuric or phosphoric acid in the presence of a non-aqeuous apolar organic solvent and contacting the resultant solution with a dehydrating agent is disclosed. Non-aggregating insulin products with bioactivity may be prepared by this process.
    Type: Grant
    Filed: September 5, 1986
    Date of Patent: November 10, 1987
    Assignee: Rockefeller University
    Inventors: Anthony Cerami, Sandor Pongor, Michael Brownlee
  • Patent number: 4677192
    Abstract: A method for separating insulin or certain insulin derivatives from mixtures containing the same by chromatography of the mixture on a column filled with silica gel having a particle size between 40 and 500 microns with an eluant mixture comprising chloroform, methanol, water and triethylamine.
    Type: Grant
    Filed: December 4, 1985
    Date of Patent: June 30, 1987
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Rainer Obermeier, Volker Teetz, Jurgen Ludwig
  • Patent number: 4663087
    Abstract: A method of comminuting frozen blocks of animal organs or animal tissue, such as for example pancreas glands, lungs, liver, thyroid glands and intestinal mucosa, from which hormones and other physiologically active substances are to be extracted. The blocks are comminuted by a chip-forming treatment whereby they are transformed into a snow-like mass having an extremely large surface. For the said comminution a machine of the planing machine type can e.g. be used.
    Type: Grant
    Filed: July 10, 1985
    Date of Patent: May 5, 1987
    Assignee: Laboratorios Leo S.A.
    Inventor: Willy H. Jensen
  • Patent number: 4639333
    Abstract: The invention relates to a process for the preparation of insulins from analogs of preproinsulins, which comprises reacting preproinsulin analogs, at a pH below the isoelectric point of the insulins in the presence of trypsin or a trypsin-like endopeptidase, with an ester of natural amino acids or their derivatives and then cleaving off the ester group and other protective groups which may optionally be present.
    Type: Grant
    Filed: October 12, 1984
    Date of Patent: January 27, 1987
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Rainer Obermeier, Rolf Geiger, Ulrich Grau
  • Patent number: 4616078
    Abstract: This specification describes a process for separating impurities from an impure mixture containing proinsulin-like material with substantially complete recovery of said proinsulin-like material, which comprises:(1) applying said mixture to a reverse phase macroporous acrylate ester copolymer resin support at a pH of from about 7 to about 10; and(2) eluting said proinsulin-like material from said support with an aqueous eluant having a pH of from about 8 to about 11 and containing from about 10% to about 30% by volume of an organic diluent selected from the group consisting of acetone, acetonitrile, and a combination of acetone and acetonitrile.
    Type: Grant
    Filed: April 8, 1985
    Date of Patent: October 7, 1986
    Assignee: Eli Lilly and Company
    Inventor: Richard D. DiMarchi