Patents Represented by Attorney Nancy J. Harrison
  • Patent number: 5063155
    Abstract: The present invention discloses a method for producing a novel antibiotic, 2"'-O-demethyltylosin. The novel antibiotic, utilizing recombinant DNA technology, can be produced from a transformed mutant of a tylosin producing microorganism. By transforming for example Streptomyces fradiae GS 16 with plasmid pHJL284, the transformant can produce 2"'-O-demethyltylosin. Streytomyces fradiae GS16 is a tylosin producing species that contain a mutation in the tylE gene found in the tylosin biosynthetic pathway. The tylE gene codes for demethylmacrocin 2"'-O-methyltransferase enzyme (DMOMT), the enzyme that methylates the 2-hydroxyl position of the 6-deoxyallose moiety. Plasmid pHJL284 contains the cloned tylF gene which codes for the macrocin 3"'-O-methyltransferase enzxyme (MOMT), the enzyme that methylates the 3"'-hydroxyl position, but it does not contain the tylE gene. Transformation of S.
    Type: Grant
    Filed: March 28, 1988
    Date of Patent: November 5, 1991
    Assignee: Eli Lilly and Company
    Inventors: Karen L. Cox, Eugene T. Seno, Gene M. Wild
  • Patent number: 5039789
    Abstract: A new group of cyclic peptides, the A54145 cyclic peptides, which have the general formula: ##STR1## wherein: R is selected from the group consisting of hydrogen, an amino-protecting group, 8-methylnonanoyl, 8-methyldecanoyl and n-decanoyl;(Lys-R.sup.1) represents --NH(CH.sub.2).sub.4 CH(NHR.sup.1)CO--;R.sup.1 is hydrogen or an amino-protecting group;X is Ile or Val: andY is Glu or 3-MG; provided that R.sup.1 cannot be hydrogen when R is 8-methylnonanoyl, 8-methyldecanoyl or n-decanoyl;and their salts are useful intermediates in the preparation of anitbacterial agents.
    Type: Grant
    Filed: April 11, 1988
    Date of Patent: August 13, 1991
    Assignee: Eli Lilly and Company
    Inventors: David S. Fukuda, Jon S. Mynderse
  • Patent number: 5028590
    Abstract: A new group of cyclic peptide derivatives, the A54145 cyclic peptide derivatives, which have the general formula: ##STR1## wherein: R is C.sub.8 -C.sub.18 -alkyl, optionally substituted C.sub.8 -C.sub.18 -alkanoyl or C.sub.8 -C.sub.18 -alkenoyl;(R,R.sup.2)-Trp represents a group of formula ##STR2## (Lys-R.sup.1) represents --NH(CH.sub.2).sub.4 CH(NHR.sup.1)CO--; R.sup.1 is hydrogen or an amino-protecting group; andR.sup.2 is hydrogen; orR and R.sup.2, taken together, represent a C.sub.8 -C.sub.18 -alkylidene group;X is Ile or Val; andY is Glu or 3-MG;provided that: 1) when R.sup.1 =H, X=Ile and Y=Glu or 3-MG, R cannot be 8-methylnonanoyl, 8-methyldecanoyl or n-decanoyl; 2) when R.sup.1 =H, X=Val and Y=3-MG, R cannot be 8-methyldecanoyl; and 3) when R.sup.1 =H, X=Val and Y=Glu, R cannot be 8-methylnonanoyl; and 4) when R.sup.1 is an amino protecting group, R cannot be 8-methylnonanoyl, 8-methyldecanoyl, or n-decanoyl; and their salts are antibacterial agents or intermediates to such agents.
    Type: Grant
    Filed: April 11, 1988
    Date of Patent: July 2, 1991
    Assignee: Eli Lilly and Company
    Inventors: David S. Fukuda, Jon S. Mynderse
  • Patent number: 4996148
    Abstract: New glycopeptide antibiotic A80407, comprising A80407A and A80407B, is produced by Kibdelosporangium philippinensis strains NRRL 18198, and NRRL 18199 or A80407-producing mutants of these strains. The A80407 antibiotics have excellent activity against Gram-positive bacteria, increase feed-utilization efficiency in monogastric and ruminant animals and improve weight gains in animals.
    Type: Grant
    Filed: July 13, 1987
    Date of Patent: February 26, 1991
    Assignee: Eli Lilly and Company
    Inventors: Lawrence E. Doolin, Richard M. Gale, Otis W. Godfrey, Robert L. Hamill, David F. Mahoney, Raymond C. Yao
  • Patent number: 4996229
    Abstract: Scytophycins A, B, C, D and E, an aldehyde and alcohol derivative of scytophycin B and the specified alkanoyl and benzoyl esters of scytophycins A, B, C, D and E and the B derivatives (scytophycin compounds) are novel antineoplastic and antifungal agents. Antifungal compositions containing a scytophycin compound and methods of inhibiting fungi, especially plant pathogenic fungi, using these compositions are included. A method for producing the scytophycin complex, comprising scytophycins A, B, C, D and E, using a new strain of the blue-green alga Scytonema pseudohofmanni, and a biologically purified culture of the alga are also provided.
    Type: Grant
    Filed: August 31, 1989
    Date of Patent: February 26, 1991
    Assignees: University of Hawaii, Eli Lilly and Company
    Inventors: Richard E. Moore, Eiichi Furusawa, Ted R. Norton, Gregory M. L. Patterson, Jon S. Mynderse
  • Patent number: 4994270
    Abstract: New peptide antibiotic A54145, individual A54145 components A, A.sub.1, B, B.sub.1, C, D, E and F and their pharmaceutically acceptable salts, are useful antibacterial agents which also improve growth performance in animals, especially poultry. Biologically pure cultures of the A54145-producing Streptomyces fradiae cultures NRRL 18158, NRRL 18159 and NRRL 18160 cultures and methods of making antibiotic A54145 using those cultures are also provided.
    Type: Grant
    Filed: April 11, 1988
    Date of Patent: February 19, 1991
    Assignee: Eli Lilly and Company
    Inventors: LaVerne D. Boeck, David S. Fukuda, Jon S. Mynderse, Marvin M. Hoehn, Ralph E. Kastner, Harold R. Papiska
  • Patent number: 4981468
    Abstract: An improved device for containing and administering orally active therapeutic agents is described. A unit dose of a therapeutic agent in free-flowing form is retained and positioned for oral administration in a tube adapted to deliver the dose with a flow of liquid drawn through the tube by normal sipping action of a patient. The combination of small particle size and high flow rates into the alimentary canal allow dosage administration with minimal sensed contact with the oral cavity. The invention is particularly advantageous for the administration of orally active therapeutic agents to pediatric and geriatric patients.
    Type: Grant
    Filed: January 12, 1990
    Date of Patent: January 1, 1991
    Assignee: Eli Lilly and Company
    Inventors: Robert L. Benefiel, John W. Clarke, Dale C. Harris, Robert J. Morff, Peter L. Oren
  • Patent number: 4977083
    Abstract: Improved processes for preparing A54145 components and cyclic peptide derivatives (A54145 compounds) comprising: (1) feeding alkanoic or alkenoic acids or alcohols, or esters or salts thereof, (2) feeding glucose at a rate from about 6-9 g/L/day, or (3) feeding enzymatic soy digest at a rate from about 2-4 g/L/day to an A54145-producing culture during its fermentation and recovering the A54145 compound, are provided.
    Type: Grant
    Filed: April 11, 1988
    Date of Patent: December 11, 1990
    Assignee: Eli Lilly and Company
    Inventor: LaVerne D. Boeck
  • Patent number: 4945080
    Abstract: Novel macrolide, AS-E 136 metabolite, is obtained from the body fluids of animals receiving AS-E 136 or erythromycylamine. Methods for treating infections caused by pathogenic bacteria, especially Gram-positive bacteria, and pharmaceutical compositions containing the metabolite are provided.
    Type: Grant
    Filed: May 26, 1987
    Date of Patent: July 31, 1990
    Assignee: Eli Lilly and Company
    Inventors: Terry D. Lindstrom, Gary W. Whitaker
  • Patent number: 4921947
    Abstract: This invention provides an improvement in the process for preparing C-20-amino-substituted derivatives of the macrolide antibiotics of the tylosin type by reductively aminating the C-20 aldehyde group in the parent antibiotic. The improvement comprises using formic acid as the reducing agent. The new process is less expensive and more amenable to scale-up than previously used processes, but is still selective.
    Type: Grant
    Filed: March 31, 1986
    Date of Patent: May 1, 1990
    Assignee: Eli Lilly and Company
    Inventors: Eddie V. P. Tao, Jeffrey T. Vicenzi
  • Patent number: 4920103
    Abstract: New 4'"-O-modified-20-modified tylosin and 4"-O-modified-20-modified-desmycosin and 4'-deoxydesmycosin derivatives of formula 1 have significant oral antibacterial activity. Compositions containing and methods of using these compounds are also provided.
    Type: Grant
    Filed: September 29, 1986
    Date of Patent: April 24, 1990
    Assignee: Eli Lilly and Company
    Inventors: Herbert A. Kirst, James P. Leeds
  • Patent number: 4920102
    Abstract: Novel ring-contracted macrolides which enhance gastrointestinal motility and novel methods and compositions for treating gtastrointestinal disorders in animals with these macrolides and with certain other previously known ring-contracted macrolides are provided.
    Type: Grant
    Filed: April 18, 1988
    Date of Patent: April 24, 1990
    Assignee: Eli Lilly and Company
    Inventors: Jaswant S. Gidda, Herbert A. Kirst, David W. Robertson
  • Patent number: 4885243
    Abstract: An improved process for producing A-21978C cyclic peptide derivatives having a C.sub.2 -C.sub.14 alkanoyl side chain which comprises feeding a C.sub.2 -C.sub.14 alkanoic acid, or an ester or salt thereof, to the A-21978C-producing culture during the production stages of the fermentation.
    Type: Grant
    Filed: September 9, 1985
    Date of Patent: December 5, 1989
    Assignee: Eli Lilly and Company
    Inventors: Floyd M. Huber, Richard L. Pieper, Anthony J. Tietz
  • Patent number: 4885170
    Abstract: New antibiotic A80509, its C.sub.1 -C.sub.7 -alkyl ester derivatives and salts are useful antibacterial and anticoccidial agents and improve feed efficiency and growth in animals. Methods of making A80509 by fermentation of, and a biologically pure culture of, Streptomyces mutabilis NRRL 18269 are also provided.
    Type: Grant
    Filed: March 24, 1988
    Date of Patent: December 5, 1989
    Assignee: Eli Lilly and Company
    Inventors: Robert L. Hamill, Raymond C. Yao
  • Patent number: 4880735
    Abstract: Improved fermentation process for producing the Gram-positive antibiotic A47934 which comprises cultivating a new strain of Streptomyces toyocaensis, NRRL 18112, and a biologically purified culture of this microorganism are provided.
    Type: Grant
    Filed: September 24, 1986
    Date of Patent: November 14, 1989
    Assignee: Eli Lilly and Company
    Inventors: Jeffrey T. Fayerman, Michael D. Jones, Karl H. Michel, Raymond C. Yao, Milton J. Zmijewski
  • Patent number: 4870021
    Abstract: Antibiotic A42125, which is produced by a new strain of Nocardia aerocolonigenes, NRRL 18049, is a useful inhibitor of Gram-positive and methane-generating microorganisms. A42125 also increases feed utilization efficiency in ruminants. A biologically purified culture of N. aerocolonigenes NRRL 18049 and a method for producing A42125 by fermentation of this culture are provided.
    Type: Grant
    Filed: March 9, 1987
    Date of Patent: September 26, 1989
    Assignee: Eli Lilly and Company
    Inventors: Robert L. Hamill, Ralph E. Kastner
  • Patent number: 4870185
    Abstract: New alkaloids called hapalindoles J-Q and T-V, which are antibacterial and antifungal agents, and methods of preparing these alkaloids by culturing the blue-green alga Hapalosiphon fontinalis ATCC 39694, are provided.
    Type: Grant
    Filed: September 18, 1986
    Date of Patent: September 26, 1989
    Assignees: Eli Lilly and Company, University of Hawaii
    Inventors: Rosanne Bonjouklian, Richard E. Moore, Jon S. Mynderse, Gregory M. L. Patterson, Tim A. Smitka
  • Patent number: 4863955
    Abstract: Scytophycins A, B, C, D and E, an aldehyde and alcohol derivative of scytophycin B and the specified alkanoyl and benzoyl esters of scytophycins A, B, C, D and E and the B derivatives (scytophycin compounds) are novel antineoplastic and antifungal agents. Antifungal compositions containing a scytophycin compound and methods of inhibiting fungi, especially plant pathogenic fungi, using these compositions are included. A method for producing the scytophycin complex, comprising scytophycins A, B, C, D and E, using a new strain of the blue-green alga Scytonema pseudohofmanni, and a biologically purified culture of the alga are also provided.
    Type: Grant
    Filed: May 21, 1986
    Date of Patent: September 5, 1989
    Assignees: Eli Lilly and Company, University of Hawaii
    Inventors: Richard E. Moore, Eiichi Furusawa, Ted R. Norton, Gregory M. L. Patterson, Jon S. Mynderse
  • Patent number: 4845194
    Abstract: An improvement in the large-scale recovery of vancomycin-type glycopeptide antibiotics which comprises (1) commingling the fermentation medium in which the antibiotic is produced with a polystyrene divinylbenzene resin such as Dow XFS-43278.00, (2) separating the resin from the medium and (3) eluting the antibiotic from the resin. This improvement avoids preliminary filtration and pH adjustment of the broth, simplifies waste-disposal problems and eliminates antibiotic losses due to mycelial adsorption and filtration.
    Type: Grant
    Filed: February 27, 1987
    Date of Patent: July 4, 1989
    Assignee: Eli Lilly and Company
    Inventors: Suzanne L. E. Glass, Charles W. Johnson, John L. Spencer
  • Patent number: 4830967
    Abstract: A new strain of Streptomyces pactum, NRRL 15970, and an improved fermentation process for producing the polyether antibiotic A80438 using this microorganism are provided.
    Type: Grant
    Filed: May 28, 1985
    Date of Patent: May 16, 1989
    Assignee: Eli Lilly and Company
    Inventors: Robert L. Hamill, Raymond C. Yao