Patents Represented by Attorney William C. Martens, Jr.
  • Patent number: 4654324
    Abstract: A pharmaceutical composition which comprises human proinsulin in association with a pharmaceutically acceptable carrier is useful in controlling a diabetic condition and in promoting attainment of natural hormonal homeostasis, thereby preventing or substantially diminishing or retarding diabetic complications.
    Type: Grant
    Filed: December 17, 1984
    Date of Patent: March 31, 1987
    Assignee: Eli Lilly and Company
    Inventors: Ronald E. Chance, Bruce H. Frank, John A. Galloway
  • Patent number: 4652547
    Abstract: A pharmaceutical composition which comprises, in association with a pharmaceutically acceptable carrier, human insulin and human proinsulin in a weight ratio, human insulin to human proinsulin, of from about 1:100 to about 100:1, is useful in treating diabetics and in promoting attainment of natural hormonal homeostasis, thereby preventing or substantially diminishing or retarding diabetic complications.
    Type: Grant
    Filed: December 17, 1984
    Date of Patent: March 24, 1987
    Assignee: Eli Lilly and Company
    Inventors: Ronald E. Chance, Bruce H. Frank, John A. Galloway
  • Patent number: 4652548
    Abstract: A pharmaceutical composition which comprises, in association with a pharmaceutically acceptable carrier, human insulin, human C-peptide, and human proinsulin, said human C-peptide being present in a molar ratio, human insulin to human C-peptide, of from about 1:4 to about 4:1, and said human proinsulin being present in a weight ratio, human insulin to human proinsulin, of from about 1:100 to about 100:1, is useful in treating diabetics and in promoting attainment of natural hormonal homeostasis, thereby preventing or substantially diminishing or retarding diabetic complications.
    Type: Grant
    Filed: December 17, 1984
    Date of Patent: March 24, 1987
    Assignee: Eli Lilly and Company
    Inventors: Ronald E. Chance, Bruce H. Frank, John A. Galloway
  • Patent number: 4617376
    Abstract: There is disclosed herein a process for the purification of glucagon from a glucagon salt cake containing pancreas gland-sourced glucagon, which comprises(1) dissolving said glucagon salt cake in an aqueous medium containing a water-miscible organic solvent;(2) contacting the glucagon salt cake solution with a hydrophobic adsorption support at a pH less than about 4 or greater than about 7.5 and at conditions under which the glucagon is adsorbed on said hydrophobic adsorption support;(3) eluting glucagon from said hydrophobic adsorption support with an aqueous solution containing a water-miscible organic solvent to obtain a first glucagon-containing solution;(4) contacting a solution containing glucagon eluted from said hydrophobic adsorption support, said solution having a pH of from about 7.5 to about 10.
    Type: Grant
    Filed: February 24, 1986
    Date of Patent: October 14, 1986
    Assignee: Eli Lilly and Company
    Inventors: David G. Maskalick, Marie T. Anderson
  • 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
  • Patent number: 4605513
    Abstract: There is disclosed herein a process for inhibiting carbamylation of peptides during treatment of said peptides, which comprises carrying out said treatment in the presence of a carbamylation-inhibiting amount of an agent selected from the group consisting of 1,2-ethylene diamine and 1,2-ethylene diamine-like materials.
    Type: Grant
    Filed: August 8, 1984
    Date of Patent: August 12, 1986
    Assignee: Eli Lilly and Company
    Inventor: Richard D. DiMarchi
  • Patent number: 4581165
    Abstract: A class of compounds having insulin-like activity is described. These compounds have the formula ##STR1## in which X is --OH, -Arg-Arg-OH, or -Arg-Arg-Glu-Ala-Glu-Asp-Leu-Gln-Val-Gly-Gln-Val-Glu-Leu-Gly-Gly-Gly-Pro-G ly-Ala-Gly-Ser-Leu-Gln-Pro-Leu-OH.
    Type: Grant
    Filed: June 14, 1984
    Date of Patent: April 8, 1986
    Assignee: Eli Lilly and Company
    Inventors: Bruce H. Frank, Allen H. Pekar
  • Patent number: 4569791
    Abstract: A class of compounds having insulin-like activity is described. These compounds have the formula ##STR1## in which n is zero or one.
    Type: Grant
    Filed: June 14, 1984
    Date of Patent: February 11, 1986
    Assignee: Eli Lilly and Company
    Inventors: Bruce H. Frank, Allen H. Pekar
  • Patent number: 4569792
    Abstract: A class of compounds having insulin-like activity is described. These compounds have the formula ##STR1## in which X is --OH, -Ala-Leu-Glu-Gly-Ser-Leu-Gln-OH, or -Ala-Leu-Glu-Gly-Ser-Leu-Gln-Lys-Arg-OH.
    Type: Grant
    Filed: June 14, 1984
    Date of Patent: February 11, 1986
    Assignee: Eli Lilly and Company
    Inventors: Bruce H. Frank, Allen H. Pekar
  • Patent number: 4522750
    Abstract: There is provided by this invention cell-targeting cytotoxic compositions comprising transferrin covalently coupled to vinca alkaloid.
    Type: Grant
    Filed: February 21, 1984
    Date of Patent: June 11, 1985
    Assignee: Eli Lilly and Company
    Inventors: Edwin W. Ades, George J. Cullinan
  • Patent number: 4510082
    Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in whichR is hydrogen, methyl, ethyl, cyclopropylmethyl, or allyl;A is a residue of a D-amino acid selected from the goup consisting of Ala, Abu, Nva, Val, Nle, Leu, Ile, Gly(Al), Gly(Cp) Met, Cys(Me), Met(O), Cys(Me) (O), Ser, Ser(Me), Thr, and Hse;R.sub.1 is hydrogen, C.sub.1 -C.sub.3 primary alkyl, cyclopropylmethyl, allyl, ethylthiomethyl, 2-fluoroethyl, or propargyl; andX is hydrogen, fluoro, bromo, iodo, chloro, hydroxy, C.sub.1 -C.sub.3 alkyl, trifluoromethyl, or C.sub.1 -C.sub.2 alkoxy; are useful analgesic agents.
    Type: Grant
    Filed: March 7, 1983
    Date of Patent: April 9, 1985
    Assignee: Eli Lilly and Company
    Inventors: Paul D. Gesellchen, Robert T. Shuman
  • Patent number: 4451396
    Abstract: The discovery of this invention is a process for inhibiting undesired irreversible thiol reactions of thiol-containing peptides while preforming desirable thiol intermediates during methionyl cleavage of said peptides using CNBr by carrying out said cleavage in the presence of thiosulfate ion.
    Type: Grant
    Filed: August 1, 1983
    Date of Patent: May 29, 1984
    Assignee: Eli Lilly and Company
    Inventor: Richard D. Di Marchi
  • Patent number: 4430266
    Abstract: A proinsulin-like disulfide insulin precursor is produced from its corresponding linear chain S-sulfonate insulin precursor by reacting the S-sulfonate with a mercaptan in an amount which provides from about 1 to about 5 --SH moieties per --SSO.sub.3.sup.- moiety in an aqueous medium at a pH of from about 7 to about 11.5 and at an S-sulfonate concentration of up to about 10 mg. per ml. of aqueous medium.
    Type: Grant
    Filed: February 16, 1982
    Date of Patent: February 7, 1984
    Assignee: Eli Lilly and Company
    Inventor: Bruce H. Frank
  • Patent number: 4430327
    Abstract: A method is described for preventing or minimizing the effects of a drug on an embryo or a fetus by placental transport while alleviating pain and anxiety of the pregnant female by administering a pharmaceutically effective amount of a compound of the formulaH-L-Tyr-D-Ala-Gly-L-Phe-L-(N-CH.sub.3)Met-NH.sub.2or a pharmaceutically acceptable salt thereof.
    Type: Grant
    Filed: May 18, 1982
    Date of Patent: February 7, 1984
    Assignee: Eli Lilly and Company
    Inventor: Robert C. A. Frederickson
  • Patent number: 4426517
    Abstract: A .beta.-cyanoethyl blocking group is selectively removed from the phosphate moiety of a nucleotide or polynucleotide by treatment with diethyl amine.
    Type: Grant
    Filed: August 24, 1981
    Date of Patent: January 17, 1984
    Assignee: Eli Lilly and Company
    Inventor: Hansen M. Hsiung
  • Patent number: 4419509
    Abstract: A .beta.-cyanoethyl blocking group is selectively removed from the phosphate moiety of a nucleotide or polynucleotide by treatment with a primary amine having from 3 to 5 carbon atoms.
    Type: Grant
    Filed: August 24, 1981
    Date of Patent: December 6, 1983
    Assignee: Eli Lilly and Company
    Inventor: Hansen M. Hsiung
  • Patent number: 4415493
    Abstract: A class of 23 or 24 amino acid peptides available by chemical synthesis or by enzymatic and chemical cleavage of IgG is described. The compounds are useful in modulating the immune response.
    Type: Grant
    Filed: May 11, 1982
    Date of Patent: November 15, 1983
    Assignee: Scripps Clinic and Research Foundation
    Inventors: William O. Weigle, Edward L. Morgan
  • Patent number: 4351763
    Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in whichL and D define the chirality;R.sub.1 is hydrogen or C.sub.1 -C.sub.3 primary alkyl;R.sub.2 is C.sub.1 -C.sub.4 primary or secondary alkyl, allyl, cyclopropylmethyl, C.sub.1 -C.sub.2 hydroxyalkyl, or --(CH.sub.2).sub.m -U-CH.sub.3 in which U is --S-- or ##STR2## and m is 1 or 2; R.sub.3 is hydrogen, C.sub.1 -C.sub.4 primary or secondary alkyl, cyclopropylmethyl, or allyl;R.sub.4 is hydrogen, C.sub.1 -C.sub.5 primary or secondary alkyl, --(CH.sub.2).sub.n --X--(CH.sub.2).sub.p --CH.sub.3 in which X is --O--, --S--, ##STR3## n is 1 or 2, and p is 0 or 1, phenyl, or monosubstituted phenyl in which the substituent is halo, hydroxy, C.sub.1 -C.sub.3 alkoxy, nitro, C.sub.1 -C.sub.3 alkyl, or trifluoromethyl;R.sub.5 is hydrogen or C.sub.1 -C.sub.4 primary alkyl; andZ is --CH.sub.2 OR.sub.6, ##STR4## in which R.sub.6 is hydrogen or C.sub.1 -C.sub.3 alkyl and R.sub.7 is C.sub.1 -C.sub.
    Type: Grant
    Filed: April 24, 1981
    Date of Patent: September 28, 1982
    Assignee: Eli Lilly and Company
    Inventors: Paul D. Gesellchen, Robert T. Shuman
  • Patent number: 4333873
    Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D define the chirality;R.sub.1 is hydrogen or C.sub.1 -C.sub.3 primary alkyl;R.sub.2 is C.sub.1 -C.sub.4 primary or secondary alkyl, allyl, cyclopropylmethyl, C.sub.1 -C.sub.2 hydroxyalkyl, or --(CH.sub.2).sub.m --U--CH.sub.3 in which U is --S-- or >S--O and m is 1 or 2,R.sub.3 is cyclopropylmethyl or allyl; and ##STR2## in which R.sub.4 is hydrogen, acetyl, or acetoxymethyl and R.sub.5 is C.sub.1 -C.sub.3 alkyl; are useful analgesic agents.
    Type: Grant
    Filed: April 24, 1981
    Date of Patent: June 8, 1982
    Assignee: Eli Lilly and Company
    Inventor: Robert T. Shuman
  • Patent number: 4331593
    Abstract: Compounds of the formula ##STR1## and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D, when applicable, define the chirality;R.sub.1 and R.sub.2 independently are hydrogen or C.sub.1 -C.sub.3 primary alkyl;R.sub.3 is C.sub.1 -C.sub.4 primary or secondary alkyl or --CH.sub.2 CH.sub.2 --S--CH.sub.3 ;R.sub.4 is hydrogen or C.sub.1 -C.sub.3 primary alkyl;R.sub.5 is hydrogen or C.sub.1 -C.sub.3 primary alkyl;Y is hydrogen or acetyl; andZ is ##STR2## --CH.sub.2 OH, or --CN; subject to the limitation that no more than one of R.sub.4 and R.sub.5 is C.sub.1 -C.sub.3 primary alkyl; are useful analgesic agents.
    Type: Grant
    Filed: October 31, 1980
    Date of Patent: May 25, 1982
    Inventors: Edward L. Smithwick, Jr., Robert C. A. Frederickson, Robert T. Shuman