Processing

Please wait...

Settings

Settings

Goto Application

1. WO1996040770 - ANTI-FUNGAL D-AMINO ACID HISTATIN-BASED PEPTIDES

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]
CLAIMS
What is claimed is :

1. A composition for treating a fungal or bacterial
infection comprising a peptide having an amino acid sequence, of at least 8 amino acids, selected from the group consisting of :
a) a human histatin;
b) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18;
c) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where the glycine at
position 6 is replaced by lysine, arginine or
another basic amino acid;
d) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where the lysine at
position 8 is replaced by histidine,
phenylalanine or another hydrophobic amino acid; e) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where at least one of the histidines at positions 4, 5 and 12 is replaced
by phenylalanine, tyrosine, leucine or another
hydrophobic amino acid;
f) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where at least one of the lysines at positions 2 and 10 is replaced by
glutamine, arginine or by another basic amino
acid;
g) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where at least one of the arginines at positions 3 and 9 is replaced by
glutamine, lysine or by another basic amino acid;
and
h) any combination of the amino acid replacements of preceding sections c) - g) with the exception that glutamine or any other non-basic amino acid cannot simultaneously occupy positions 2, 3, 9
and 10 of the amino acid sequence,
wherein said peptide contains one or more D-amino acids .

2. A composition of Claim 1 wherein said peptide is
selected from the group consisting of:
a) the amino acid sequence of histatin 1 as set
forth in SEQ ID NO: 1;
b) the amino acid sequence of histatin 3 as set
forth in SEQ ID NO: 3;
c) the amino acid sequence of histatin 5 as set
forth in SEQ ID NO: 5;
d) the amino acid sequence of histatin 9 as set
forth in SEQ ID NO: 9;
e) the amino acid sequence of peptide 101 as set
forth in SEQ ID NO: 13;
f) the amino acid sequence of peptide 102 as set
forth in SEQ ID NO: 14;
g) the amino acid sequence of peptide 103 as set
forth in SEQ ID NO: 15;
h) the amino acid sequence of peptide 104 as set
forth in SEQ ID NO: 16;
i) the amino acid sequence of peptide 105 as set
forth in SEQ ID NO: 17;
j ) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18;
k) the amino acid sequence of histatin 11 as set
forth in SEQ ID NO: 11;
1) the amino acid sequence of peptide 129 as set
forth in SEQ ID NO: 23;
m) the amino acid sequence of peptide 117 as set
forth in SEQ ID NO: 19;

n) the amino acid sequence of peptide 118 as set forth in SEQ ID NO: 20;
o) the amino acid sequence of peptide 119 as set forth in SEQ ID NO: 21;
p) the amino acid sequence of peptide 120 as set forth in SEQ ID NO: 22;
q) the amino acid sequence of peptide 113 -F4 as set forth in SEQ ID NO: 24;
r) the amino acid sequence of peptide 113-F5 as set forth in SEQ ID NO: 25;
s) the amino acid sequence of peptide 113-F12 as set forth in SEQ ID NO: 26;
t) the amino acid sequence of peptide 113-F4.5 as set forth in SEQ ID NO: 27;
u) the amino acid sequence of peptide 113-F4.5.12 as set forth in SEQ ID NO: 28;
v) the amino acid sequence of peptide 113 -K6 as set forth in SEQ ID NO: 29;
w) the amino acid sequence of peptide 113 -H8 as set forth in SEQ ID NO: 30;
x) the amino acid sequence of peptide 113-K6H8 as set forth in SEQ ID NO: 31;
y) the amino acid sequence of peptide 113 -F8 as set forth in SEQ ID NO: 32;
z) the amino acid sequence of peptide 113-L4.5.12 as set forth in SEQ ID NO: 33;
aa) the amino acid sequence of peptide 113 -Y4.5.12 as set forth in SEQ ID NO: 34;
bb) the amino acid sequence of peptide 113-Q2.10 as set forth in SEQ ID NO: 35; 44
cc) the amino acid sequence of peptide 113-Q3.9 as set forth in SEQ ID NO: 36; and
dd) combinations of two or more of the above with the exception of peptide 113-Q2.3.9.10 as set forth in SEQ ID NO: 37.

3. A composition of Claim 1 wherein the peptide has a
modification comprising a substituent addition to
either the N-terminus, the C-terminus, or to both the N-terminus and C-terminus of said peptide.

4. A composition of Claim 3 wherein the peptide has at least one of said modifications selected from the
group consisting of :
a) an acetyl or a carbamyl addition at the N- terminus ; and
b) an amide addition at the C-terminus.

5. A peptide having an amino acid sequence, of at least 8 amino acids, selected from the group consisting of:
a) a human histatin;
b) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18.
c) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where the glycine at
position 6 is replaced by lysine, arginine or
another basic amino acid;
d) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where the lysine at
position 8 is replaced by histidine,
phenylalanine or another hydrophobic amino acid; e) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where at least one of the histidines at positions 4, 5 and 12 is replaced
by phenylalanine, tyrosine, leucine or another
hydrophobic amino acid;
f) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where at least one of the lysines at positions 2 and 10 is replaced by
glutamine, arginine or by another basic amino
acid;

g) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where at least one of the arginines at positions 3 and 9 is replaced by
glutamine, lysine or by another basic amino acid;
and
h) any combination of the amino acid replacements of preceding sections c) - g) with the exception
that glutamine or any other non-basic amino acid cannot simultaneously occupy positions 2, 3, 9
and 10 of the amino acid sequence.
wherein said peptide contains one or more D-amino
acids .

6. A peptide of Claim 5 wherein said human histatin or said peptide is selected from the group consisting of: a) the amino acid sequence of histatin 1 as set
forth in SEQ ID NO: 1;
b) the amino acid sequence of histatin 3 as set
forth in SEQ ID NO: 3;
c) the amino acid sequence of histatin 5 as set
forth in SEQ ID NO: 5;
d) the amino acid sequence of histatin 9 as set
forth in SEQ ID NO: 9;
e) the amino acid sequence of peptide 101 as set
forth in SEQ ID NO: 13;
f) the amino acid sequence of peptide 102 as set
forth in SEQ ID NO: 14;
g) the amino acid sequence of peptide 103 as set
forth in SEQ ID NO: 15;
h) the amino acid sequence of peptide 104 as set
forth in SEQ ID NO: 16;
i) the amino acid sequence of peptide 105 as set
forth in SEQ ID NO: 17;
j ) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18;

k) the amino acid sequence of histatin 11 as set
forth in SEQ ID NO: 11;
1) the amino acid sequence of peptide 129 as set
forth in SEQ ID NO: 23;
m) the amino acid sequence of peptide 117 as set
forth in SEQ ID NO: 19;
n) the amino acid sequence of peptide 118 as set
forth in SEQ ID NO: 20;
o) the amino acid sequence of peptide 119 as set
forth in SEQ ID NO: 21;
p) the amino acid sequence of peptide 120 as set
forth in SEQ ID NO: 22;
q) the amino acid sequence of peptide 113-F4 as set forth in SEQ ID NO: 24;
r) the amino acid sequence of peptide 113 -F5 as set forth in SEQ ID NO: 25;
s) the amino acid sequence of peptide 113-F12 as set forth in SEQ ID NO: 26;
t) the amino acid sequence of peptide 113-F4.5 as set forth in SEQ ID NO: 27;
u) the amino acid sequence of peptide 113-F4.5.12 as set forth in SEQ ID NO: 28;
v) the amino acid sequence of peptide 113 -K6 as set forth in SEQ ID NO: 29;
w) the amino acid sequence of peptide 113 -H8 as set forth in SEQ ID NO: 30;
x) the amino acid sequence of peptide 113-K6H8 as set forth in SEQ ID NO: 31;
y) the amino acid sequence of peptide 113 -F8 as set forth in SEQ ID NO: 32;
z) the amino acid sequence of peptide 113-L4.5.12 as set forth in SEQ ID NO: 33;
aa) the amino acid sequence of peptide 113 -Y4.5.12 as set forth in SEQ ID NO: 34;

bb) the amino acid sequence of peptide 113-Q2.10 as
set forth in SEQ ID NO: 35; and
cc) the amino acid sequence of peptide 113-Q3.9 as
set forth in SEQ ID NO: 36.

7. A peptide of Claim 5 wherein the peptide has a
modification comprising a substituent addition to
either the N-terminus, the C-terminus, or to both the N-terminus and C-terminus of said peptide.

8. A peptide of Claim 7 wherein the peptide has at least one of said modifications selected from the group
consisting of:
a) an acetyl or a carbamyl addition at the N- terminus ; and
b) an amide addition at the C-terminus.

9. A method for treating a fungal or bacterial infection in an individual comprising administering to said
individual a therapeutically effective amount of at least one peptide having an amino acid sequence, of at least 8 amino acids, selected from the group
consisting of:
a) a human histatin;
b) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18;
c) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where the glycine at
position 6 is replaced by lysine, arginine or
another basic amino acid;
d) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where the lysine at
position 8 is replaced by histidine,
phenylalanine or another hydrophobic amino acid;

e) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where at least one of the histidines at positions 4, 5 and 12 is replaced
by phenylalanine, tyrosine, leucine or another
hydrophobic amino acid;
f) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where at least one of the lysines at positions 2 and 10 is replaced by
glutamine, arginine or by another basic amino
acid;
g) the amino acid sequence of peptide 113 as set
forth in SEQ ID NO: 18 where at least one of the arginines at positions 3 and 9 is replaced by
glutamine, lysine or by another basic amino acid; h) any combination of the amino acid replacements of preceding sections c) - g) with the exception
that glutamine or any other non-basic amino acid cannot simultaneously occupy positions 2, 3, 9
and 10 of the amino acid sequence.
wherein said human histatin and said peptide contain one or more D-amino acids.

10. A method for treating a fungal or bacterial infection of Claim 9 wherein said human histatin or said peptide is selected from the group consisting of:
a) the amino acid sequence of histatin 1 as set
forth in SEQ ID NO: 1;
b) the amino acid sequence of histatin 3 as set
forth in SEQ ID NO: 3;
c) the amino acid sequence of histatin 5 as set
forth in SEQ ID NO: 5;
d) the amino acid sequence of histatin 9 as set
forth in SEQ ID NO: 9;
e) the amino acid sequence of peptide 101 as set
forth in SEQ ID NO: 13;

f) the amino acid sequence of peptide 102 as set forth in SEQ ID NO: 14;
g) the amino acid sequence of peptide 103 as set forth in SEQ ID NO: 15;
h) the amino acid sequence of peptide 104 as set forth in SEQ ID NO: 16;
i) the amino acid sequence of peptide 105 as set forth in SEQ ID NO: 17;
j) the amino acid sequence of peptide 113 as set forth in SEQ ID NO: 18;
k) the amino acid sequence of histatin 11 as set forth in SEQ ID NO: 11;
1) the amino acid sequence of peptide 129 as set forth in SEQ ID NO: 23;
m) the amino acid sequence of peptide 117 as set forth in SEQ ID NO: 19;
n) the amino acid sequence of peptide 118 as set
forth in SEQ ID NO: 20;
o) the amino acid sequence of peptide 119 as set forth in SEQ ID NO : 21;
p) the amino acid sequence of peptide 120 as set forth in SEQ ID NO: 22.
q) the amino acid sequence of peptide 113 -F4 as set forth in SEQ ID NO: 24;
r) the amino acid sequence of peptide 113 -F5 as set forth in SEQ ID NO: 25;
s) the amino acid sequence of peptide 113-F12 as set forth in SEQ ID NO: 26;
t) the amino acid sequence of peptide 113-F4.5 as set forth in SEQ ID NO: 27;
u) the amino acid sequence of peptide 113-F4.5.12 as set forth in SEQ ID NO: 28;
v) the amino acid sequence of peptide 113 -K6 as set forth in SEQ ID NO: 29;

w) the amino acid sequence of peptide 113-H8 as set forth in SEQ ID NO: 30;
x) the amino acid sequence of peptide 113-K6H8 as
set forth in SEQ ID NO: 31;
y) the amino acid sequence of peptide 113-F8 as set forth in SEQ ID NO: 32;
z) the amino acid sequence of peptide 113-L4.5.12 as set forth in SEQ ID NO: 33;
aa) the amino acid sequence of peptide 113 -Y4.5.12 as set forth in SEQ ID NO: 34;
bb) the amino acid sequence of peptide 113-Q2.10 as
set forth in SEQ ID NO: 35; and
cc) the amino acid sequence of peptide 113-Q3.9 as
set forth in SEQ ID NO: 36.

11. A method for treating a fungal or bacterial infection of Claim 9 wherein the peptide has a modification
comprising a substituent addition to either the N- terminus, the C-terminus, or to both the N-terminus and C-terminus of said peptide.

12. A method for treating a fungal or bacterial infection of Claim 11 wherein the peptide has at least one of said modifications selected from the group consisting of:
a) an acetyl or a carbamyl addition at the N- terminus; and
b) an amide addition at the C-terminus.

13. A method for treating a fungal or bacterial infection of Claim 9 wherein said fungal or bacterial infection is selected from the group consisting of:
a) an infection of the oral cavity;
b) an infection of the vagina;
c) an infection of the urethra;

d) an infection of the ear;
e) an infection of the skin;
f) a respiratory infection;
g) a mucosal infection;
h) an ophthalmic infection; and
i) a systemic infection.

14. A method for treating a fungal or bacterial infection of Claim 13 wherein the fungus or bacterium is
selected from the group consisting of :
a Candida albicans ;
b Actinomyces actinomycetemcomi tans ;
c Actinomyces viscosus;
d Bacteroides forsythus;
e Bacteriodes fragilis;
f Bacteriodes gracilis;
g Bacteriodes ureolyticus ;
h Campylobacter concisus;
i Campylobacter rectus ;
j Campylobacter showae;
k Campy 1 oba cter sput orum ;
1 Capnocytophaga gingivalis;
m Capnocytophaga ochracea;
n Capnocytophaga sputigena;
o Clostridium histolyticum;
P Eikenella corrodens;
q Eubacterium nodatum;
r Fusobacterium nucleatum;
s Fusobacterium periodonticum;
t Peptostreptococcus micros;
u Porphyromona s endodontalis ;
v Porphyromonas gingivalis;
w Prevotella intermedia ;
X Prevotella nigrescens;
y Propionibacterium acnes;

z) Pseudomonas aeruginosa; aa) Selenomonas noxia;
bb) Staphylococcus aureus;
cc) Streptococcus constellatus ; dd) Streptococcus gordonii ; ee) Streptococcus intermedius; ff) Streptococcus mutans;
gg) Streptococcus oralis;
hh) Streptococcus pneumonia; ii) Streptococcus sanguis;
kk) Treponema denticola;
11) Treponema pectinovorum; mm) Treponema socranskii ;
nn) Veϋloneϋa parvula; and oo) Wolinella succinogenes.