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Title: |
US5591821:
Omega-conotoxin peptides
[ Derwent Title ]

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Country: |
US United States of America

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Inventor: |
Olivera, Baldomero M.; Salt Lake City, UT
Hillyard, David R.; Salt Lake City, UT
Imperial, Julita S.; Salt Lake City, UT
Monje, Virginia D.; Quezon City, Philippines

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Assignee: |
The University of Utah, Salt Lake City, UT
other patents from UNIVERSITY OF UTAH (600055) (approx. 249)
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Published / Filed: |
1997-01-07
/ 1993-07-16

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Application Number: |
US1993000092215

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IPC Code: |
Advanced:
C07K 14/435;
Core:
more...
IPC-7:
A61K 38/00;
C07K 7/00;
C07K 14/00;

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ECLA Code: |
C07K14/435;

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U.S. Class: |
Current:
530/324;
Original:
530/324;

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Field of Search: |
514/012,13
530/324,327

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Government Interest: |
This invention was made with Government support under Grant No. GM-22737 awarded by the National Institutes of Health, Bethesda, Md. The United States Government has certain rights in the invention.

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Priority Number: |
| 1993-07-16 |
US1993000092215 |

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Abstract: |
The present invention is directed to ω-conotoxin peptides having 24-30 amino acids, six cysteines which form disulfide bonds between the first and fourth, second and fifth, and third and sixth cysteines, respectively, and an internal sequence of Cys-Arg-Lys-Thr-Xaa1 -Tyr-Xaa2 -Cys-Cys-Ser-Gly-Ser-Cys (SEQ ID NO:1). The invention is further directed to ω-conotoxin peptides of the generic formula Cys-Xaa1 -Gly-Xaa2 -Gly-Ala-Xaa3 -Cys-Arg-Lys-Thr-Xaa4 -Tyr-Xaa5 -Cys-Cys-Ser-Gly-Ser-Cys-Xaa6 -Arg-Gly-Xaa7 -Cys (SEQ ID NO:2). Preferably, the C-terminus is amidated. These peptides also contain three disulfide bonds. Examples of ω-conotoxin peptides within the generic formula are MVIIC having the formula Cys-Cys-Gly-Lys-Gly-Ala-Xaa1 -Cys-Arg-Lys-Thr-Xaa2 -Tyr-Asp-Cys-Cys-Ser-Gly-Ser-Cys-Gly-Arg-Arg-Gly-Lys-Cys (SEQ ID NO:3), wherein Xaa is preferably Pro or Hyp (4-hydroxyproline) and Xaa2 is preferably Met or Nle (norleucine) and wherein preferably the C-terminus is amidated, and MVIID having the formula Cys-Gln-Gly-Arg-Gly-Ala-Ser-Cys-Arg-Lys-Thr-Xaa-Tyr-Asn-Cys-Cys-Ser-Gly-Ser-Cys-Asn-Arg-Gly-Arg-Cys (SEQ ID NO:4), wherein Xaa is preferably Met or Nle (norleucine), and wherein preferably the C-terminus is amidated. These peptides target the P-like subtypes of Ca2+ channels as well as the N-type Ca2+ channels.

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Attorney, Agent or Firm: |
Venable, Baetjer, Howard & Civiletti, LLP ;

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Primary / Asst. Examiners: |
Weimar, Elizabeth C.; Marshall, S. G.

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INPADOC Legal Status: |
Show legal status actions

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Family: |
None

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First Claim:
Show all 20 claims |
What is claimed is:
1. A substantially pure ω-conotoxin peptide having the formula Cys-Xaa1 -Gly-Xaa2 -Gly-Ala-Xaa3 -Cys-Arg-Lys-Thr-Xaa4 -Tyr-Xaa5 -Cys-Cys-Ser-Gly-Ser-Cys-Xaa6 -Arg-Gly-Xaa7 -Cys (SEQ ID NO:2), wherein Xaa1 is Lys or Gln, Xaa2 is Lys or Arg, Xaa3 is Pro, Ser or 4-hydroxyproline, Xaa4 is Met, Ser or norleucine, Xaa5 is Asp or Asn, Xaa6 is Gly-Arg or Asn and Xaa7 is Lys or Arg.

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Background / Summary: |
Show background / summary

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Drawing Descriptions: |
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Description: |
Show description

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Forward References: |
Show 4 U.S. patent(s) that reference this one

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Foreign References: |

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Other Abstract Info: |
CHEMABS 126(12)154222F
CAN126(12)154222F
DERABS C97-086679
DERC97-086679

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Other References: |
Monje, et al, Neuropharmacology vol. 32, No. 11, pp. 1141-1149, 1993.
(9 pages)
Cited by 10 patents
[ISI abstract]
Olivera, et al, J. Biol. Chem., 266(33), 22067-71.
Olivera, et al, Biochemistry, 26, 2086-2090, 1987.
(5 pages)
Cited by 19 patents
McIntosh, M. et al. (1982). Isolation and Structure of a Peptide Toxin from the Marine Snail Conus magus. Arch. Biochem. Biophys. 218: 329-334.
(6 pages)
Cited by 8 patents
Olivera, B. M. et al. (1984). Purification and Sequence of a Presynaptic Peptide Toxin from Conus geographus Venom. Biochemistry 23:5087-5090.
(4 pages)
Cited by 13 patents
Olivera, B. M. et al. (1985). Peptide Neurotoxins from Fish-Hunting Cone Snails. Science 230: 1338-1343.
(6 pages)
Cited by 25 patents
Cruz, L. J. et al. (1986). Calcium Channel Antagonists. J. Biol. Chem. 261:6230-6233.
(4 pages)
Cited by 4 patents
McCleskey, E. W. et al. (1987). w-Conotoxin: Direct and Persistent Blockade of Specific Types of Calcium Channels in Neurons But Not Muscle. Proc. Natl. Acad. Sci. USA 84:4327-4331.
(5 pages)
Cited by 8 patents
Olivera, B. M. et al. (1987). Neuronal Calcium Channel Antagonists. Discrimination Between Calcium Channel Subtypes Using w-Conotoxin from Conus magus Venom. Biochemistry 26: 2086-2090.
(5 pages)
Cited by 19 patents
Rivier, J. P. et al. (1987). Neuronal Calcium Channel Inhibitors. J. Biol. Chem. 262:1194-1198.
(5 pages)
Cited by 11 patents
Yoshikami, D. et al. (1989). The Inhibitory Effects of Omega-Conotoxins on Ca Channels and Synapses. Ann. NY Acad. Sci. 560:230-248.
(19 pages)
Cited by 4 patents
Olivera, B. M. et al. (1990). Diversity of Conus Neoropeptides. Science 249:257-263.
(7 pages)
Cited by 36 patents
Olivera, B. M. et al. (1991). Conotoxins. J. Biol. Chem. 266:22067-22070.
(4 pages)
Cited by 30 patents
[ISI abstract]
Lundy, P. M. et al. (1991). Pharmacological evidence for an w-conotoxin, dihydropyridine-insensitive neuronal Ca2+ channel. Eur. J. Pharmacol. 206: 61-68.
(8 pages)
Cited by 4 patents
[ISI abstract]
Regan, L. J. et al. (1991). Ca2+ Channels in Rat Central and Peripheral Neurons: High-Threshold Current Resistant to Dihydropyridine Blockers and w-Conotoxin. Neuron 9:69-77.
Hillyard, D. R. et al. (1992). A New Conus Peptide Ligand for Mammalian Presynaptic Ca2+ Channels. Neuron 9:69-77.
(9 pages)
Cited by 4 patents
[ISI abstract]
Ramilo, C. A. et al. (1992). Novel a--and w-Conotoxins from Conus striatus Venom. Biochemistry 31:9919-9926.
(8 pages)
Cited by 5 patents
[ISI abstract]

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