Patent US4795740A successfully refreshed from Google Patents.
US4795740A
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Antiviral peptides and means for treating herpes infections
Assignee: Individual
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Filing: 1987-05-07
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Granted: 1989-01-03
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Expires: 2007-05-07
Abstract
Abstract Disclosed herein are antiviral peptides of the formula A-R 8 -R 9 -R 10 -R 11 -R 12 -R 13 -R 14 -R 15 -B wherein A is from zero up to seven amino acid residues and includes a terminal hydrogen or a terminal N-acyl, or A is a phenylacetyl with optional substitution of the para position of the phenyl, R 8 , R 9 , R 10 , R 13 , R 14 and R 15 are various amino acid residues with the stipulation that one or more of the four amino acid residues immediately preceding R 11 may optionally be deleted, R 11 and R 12 are independently Val, D-Val, Nva, D-Nva, Leu, D-Leu, Nle, D-Nle, Ile or D-Ile, and B is hydroxy, amino or lower alkylamino. The antiviral activity of the peptides can be enhanced by combining them with a protease inhibitor. The peptides and the combination are useful for the treatment of herpes viral infections in mammals.
Inventors
- 👤 Eric A. Cohen
- 👤 Pierrette Gaudreau
- 👤 Jacques Michaud
- 👤 Paul Brazeau
- 👤 Yves Langelier
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-31 17:03
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/005; A; A61; A61K; A61K38/00; C12; C12N; C12N2710/00; C12N2710/00011; C12N2710/16011; C12N2710/16611; C12N2710/16622; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/19; Y10S930/22; Y10S930/224
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
351 words
A pharmaceutical composition for treating herpes infection in a mammal, comprising an effective amount of a peptide represented by the formula: A-R.sup.8 -R.sup.9 -R.sup.10 -R.sup.11 -R.sup.12 -R.sup.13 -R.sup.14 -R.sup.15 -B, (I) or a therapeutically acceptable salt of said peptide, and a pharmaceutically or veterinarily acceptable carrier, wherein A denotes (1) L-(aa) 0-6 R 7 , wherein L is hydrogen or lower acyl, aa is an amino acid residue derived from an amino acid selected from the group consisting of ##STR11## norleucine, norvaline, β-alanine, the natural amino acids excluding cystine, and any of the enantiomorphic forms thereof, where (i) Y denotes lower alkyl, lower alkoxy, amino, nitro, azido or halo, (ii) each of the aa in the radical aa 2-6 is the same or a different amino acid residue in relation to aa1, and (iii) R7 is an amino acid residue derived from an amino acid selected from the group consisting of ##STR12## His and Trp, and any of enantiomorphic forms thereof, Z being hydrogen, lower alkyl, lower alkoxy, amino, nitro, azido, halo or hydroxy, or (2) ##STR13## wherein X is hydrogen, lower alkyl, lower alkoxy, amino, nitro, azido, halo or hydroxy; and R 8 , R 9 , R 10 , R 13 , R 14 and R 15 are independently an amino acid residue (aa) as defined hereinabove; R 11 and R 12 are independently Val, D-Val, Nva, D-Nva, Leu, D-Leu, Nle, D-Nle, Ile or D-Ile; and B is hydroxy, amino or lower alkyl amino, provided that when A is L-(aa) O -R 7 , L, aa and R 7 being defined as above, then one or more of R 7 , R 8 , R 9 and R 10 may be deleted, but when the deletion is only one of R 8 , R 9 or R 10 , then R 7 , R 11 , R 12 , R 13 , R 14 and R 15 are not Tyr, Val, VAl, Asn, Asp and Leu, respectively, and the remaining two amino acid residues of R 8 , R 9 and R 10 are not Gly and Ala, respectively.
Claim 2
Dependent Claim
351 words
A pharmaceutical composition for treating herpes infection in a mammal, comprising an effective amount of a peptide represented by the formula: A-R.sup.8 -R.sup.9 -R.sup.10 -R.sup.11 -R.sup.12 -R.sup.13 -R.sup.14 -R.sup.15 -B, (I) or a therapeutically acceptable salt of said peptide, and a pharmaceutically or veterinarily acceptable carrier, wherein A denotes (1) L-(aa) 0-6 R 7 , wherein L is hydrogen or lower acyl, aa is an amino acid residue derived from an amino acid selected from the group consisting of ##STR11## norleucine, norvaline, β-alanine, the natural amino acids excluding cystine, and any of the enantiomorphic forms thereof, where (i) Y denotes lower alkyl, lower alkoxy, amino, nitro, azido or halo, (ii) each of the aa in the radical aa 2-6 is the same or a different amino acid residue in relation to aa1, and (iii) R7 is an amino acid residue derived from an amino acid selected from the group consisting of ##STR12## His and Trp, and any of enantiomorphic forms thereof, Z being hydrogen, lower alkyl, lower alkoxy, amino, nitro, azido, halo or hydroxy, or (2) ##STR13## wherein X is hydrogen, lower alkyl, lower alkoxy, amino, nitro, azido, halo or hydroxy; and R 8 , R 9 , R 10 , R 13 , R 14 and R 15 are independently an amino acid residue (aa) as defined hereinabove; R 11 and R 12 are independently Val, D-Val, Nva, D-Nva, Leu, D-Leu, Nle, D-Nle, Ile or D-Ile; and B is hydroxy, amino or lower alkyl amino, provided that when A is L-(aa) O -R 7 , L, aa and R 7 being defined as above, then one or more of R 7 , R 8 , R 9 and R 10 may be deleted, but when the deletion is only one of R 8 , R 9 or R 10 , then R 7 , R 11 , R 12 , R 13 , R 14 and R 15 are not Tyr, Val, VAl, Asn, Asp and Leu, respectively, and the remaining two amino acid residues of R 8 , R 9 and R 10 are not Gly and Ala, respectively.
Claim 3
Dependent Claim
177 words
A pharmaceutical composition of claim 1, wherein A is L-(aa) 0-6 -R 7 , L being hydrogen or lower acyl; aa is an amino acid residue derived from an amino acid selected from the group of ##STR14## norleucine, norvaline, the natural amino acids excluding cystine, and any of the enantiomorphic forms thereof, Y being halo and each of the aa in the radical aa 2-6 being the same or a different amino acid residue in relation to aa 1 ; and R 7 is an amino acid residue derived from an amino acid selected from the group of ##STR15## His and Trp, and any of the enantiomorphic forms thereof, Z being hydrogen, halo or hydroxy, or A is ##STR16## wherein X is hydrogen, halo or hydroxy; and R 8 , R 9 , R 10 , R 13 , R 14 and R 15 are independently an amino acid residue (aa) as defined in this claim; R 11 and R 12 are independently Val, D-Val, Nva, or D-Nva; and B is hydroxy, amino or lower alkyl amino.
Claim 4
Dependent Claim
11 words
A pharmaceutical composition of claim 2, further comprising a protease inhibitor.
Claim 5
Dependent Claim
10 words
A pharmaceutical composition of claim 1, further comprising a protease
Claim 6
Dependent Claim
30 words
A pharmaceutical composition of claim 4, wherein the protease inhibitor is selected from the group of bacitracin, or a therapeutically acceptable salt thereof, amastatin, antipain, epiamastatin, aprotinin, chymostatin and leupeptin.
Claim 7
Dependent Claim
37 words
A pharmaceutical composition of claim 4, wherein the protease inhibitor is bacitracin or zinc bacitracin; and each of the amount of the peptide and protease inhibit range from 0.01 to 0.2 percent by weight of the composition.
Claim 8
Dependent Claim
26 words
A cosmetic composition comprising a peptide as recited in claim 1, or a therapeutically acceptable salt thereof, and a physiologically acceptable carrier suitable for topical application.
Claim 9
Dependent Claim
30 words
A method of treating herpes viral infection in a mammal, comprising administering thereto an effective amount of a peptide as recited in claim 1, or a therapeutically acceptable salt thereof.
Claim 10
Dependent Claim
39 words
A method of treating herpes viral infection in a mammal, comprising administering thereto an effective amount of a composition comprising a protease inhibitor and a peptide as recited in claim 1 or a therapeutically acceptable salt of said peptide.
Claim 11
Dependent Claim
27 words
A pharmaceutical composition of claim 1 wherein the peptide of formula 1 is selected from the group consisting of H-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Gly-Cys-Arg-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Tyr-Thr-Met-Leu-Val-Val-Asp-Asp-Leu-OH, H-Val-Ser-Arg-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Tyr-Ala-Gly-Thr-Val-Ile-Asn-Asp-Leu-OH, and ##STR17##
Claim 12
Dependent Claim
11 words
A pharmaceutical composition of claim 10, wherein said peptide is H-Tyr-Ala-Gly-Thr-Val-Ile-Asn-Asp-Leu-OH.
Claim 13
Dependent Claim
11 words
A pharmaceutical composition of claim 3, wherein said peptide is H-Tyr-Ala-Gly-Thr-Val-Ile-Asn-Asp-Leu-OH.
Claim 14
Dependent Claim
15 words
A pharmaceutical composition of claim 12, wherein said protease inhibitor is bacitracin or zinc bacitracin.
Claim 15
Dependent Claim
175 words
A cosmetic composition of claim 7, wherein A is L-(aa)0-6-R 7 , L being hydrogen or lower acyl; aa is an amino acid residue derived from an amino acid selected from the group of ##STR18## norleucine, norvaline, the natural amino acids excluding cystine, and any of the enantiomorphic forms thereof, Y being halo and each of the aa in the radical aa 2-6 being the same or a different amino acid residue in relation to aa 1 ; and R 7 is an amino acid residue derived from an amino acid selected from the group of ##STR19## His and Trp, and any of the enantiomorphic forms thereof, Z being hydrogen, halo or hydroxy, or A is ##STR20## wherein X is hydrogen, halo or hydroxy; and R 8 , R 9 , R 10 , R 13 , R 14 and R 15 are independently an amino acid residue (aa) as defined in this claim; R 11 and R 12 are independently Val, D-Val, Nva, or D-Nva; and B is hydroxy, amino or lowe alkyl amino.
Claim 16
Dependent Claim
24 words
A cosmetic composition of claim 14, wherein said peptide is selected from the group consisting of H-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Glu-Cys-Arg-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Vall-Val-Asn-Asp-Leu-OH, H-Tyr-Thr-Met-Leu-Val-Val-Asp-Asp-Leu-OH, H-Val-Ser-Arg-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Tyr-Ala-Gly-Thr-Val-Ile-Asn-Asp-Leu-OH, and ##STR21##
Claim 17
Dependent Claim
11 words
A cosmetic composition of claim 15, wherein said peptide is H-Tyr-Ala-Gly-Thr-Val-Ile-Asn-Asp-Leu-OH.
Claim 18
Dependent Claim
176 words
A method of claim 8, wherein A is L-(aa) 0-6 -R 7 , L being hydrogen or lower acyl; aa is an amino acid residue derived from an amino acid selected from the group of ##STR22## norleucine, norvaline, the natural amino acids excluding cystine, and any of the enantiomorphic forms thereof, Y being halo and each of the aa in the radical aa 2-6 being the same or a different amino acid residue in relation to aa 1 ; and R 7 is an amino acid residue derived from an amino acid selected from the group of ##STR23## His and Trp, and any of the enantiomorphic forms thereof, Z being hydrogen, halo or hydroxy, or A is ##STR24## wherein X is hydrogen, halo or hydroxy; and R 8 , R 9 , R 10 , R 13 , R 14 and R 15 are independently an amino acid residue (aa) as defined in this claim; R 11 and R 12 are independently Val, D-Val, Nva, or D-Nva; and B is hydroxy, amino or lower alkyl amino.
Claim 19
Dependent Claim
10 words
A method of claim 17, wherein said peptide is H-Tyr-Ala-Gly-Thr-Val-Ile-Asn-Asp-Leu-OH.
Claim 20
Independent Claim
42 words
A method of treating a herpes viral infection in a mammal, comprising administering thereto an effective amount of a composition comprising bacitrazin or zinc bacitracin and a peptide selected from the group consisting of H-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Glu-Cys-Arg-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Tyr-Thr-Met-Leu-Val-Val-Asp-Asp-Leu-OH, H-Val-Ser-Arg-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Tyr-Ala-Gly-Thr-Val-Ile-Asn-Asp-Leu-OH, and ##STR25##
Claim 21
Independent Claim
42 words
A method of treating a herpes viral infection in a mammal, comprising administering thereto an effective amount of a composition comprising bacitrazin or zinc bacitracin and a peptide selected from the group consisting of H-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Glu-Cys-Arg-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Tyr-Thr-Met-Leu-Val-Val-Asp-Asp-Leu-OH, H-Val-Ser-Arg-Ser-Thr-Ser-Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu-OH, H-Tyr-Ala-Gly-Thr-Val-Ile-Asn-Asp-Leu-OH, and ##STR25##
Claim 22
Dependent Claim
11 words
A method of claim 19, wherein said peptide is H-Tyr-Ala-Gly-Thr-Val-Ile-Asn-Asp-Leu-OH. inhibitor.
References Cited (Backward Citations)
CA1098850A
Cited
GB2167296A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-01-03 | 1992-07-04 | 1993-01-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-01-03 | 1996-07-04 | 1997-01-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-01-03 | 2000-07-04 | 2001-01-03 | $7700.00 | Window Closed / Lapsed |