WO1997031019B1 - Antipathogenic peptides and compositions comprising them - Google Patents
Antipathogenic peptides and compositions comprising themInfo
- Publication number
- WO1997031019B1 WO1997031019B1 PCT/IL1997/000066 IL9700066W WO9731019B1 WO 1997031019 B1 WO1997031019 B1 WO 1997031019B1 IL 9700066 W IL9700066 W IL 9700066W WO 9731019 B1 WO9731019 B1 WO 9731019B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- leu
- lys
- amino acid
- ile
- ser
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract 16
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract 16
- 239000000203 mixture Substances 0.000 title claims 5
- 230000001775 anti-pathogenic Effects 0.000 title 1
- 230000001461 cytolytic Effects 0.000 claims abstract 25
- 150000001413 amino acids Chemical class 0.000 claims abstract 15
- 230000002949 hemolytic Effects 0.000 claims abstract 14
- 150000008574 D-amino acids Chemical group 0.000 claims abstract 10
- 230000001717 pathogenic Effects 0.000 claims abstract 10
- 150000008575 L-amino acids Chemical group 0.000 claims abstract 6
- 230000002209 hydrophobic Effects 0.000 claims abstract 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 6
- CTVQQQPWNOVEAG-QDOPKCMFSA-N Pardaxin Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O)[C@@H](C)CC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CN)C1=CC=CC=C1 CTVQQQPWNOVEAG-QDOPKCMFSA-N 0.000 claims abstract 4
- 125000000539 amino acid group Chemical group 0.000 claims abstract 4
- 125000004122 cyclic group Chemical group 0.000 claims abstract 4
- 108010036176 Melitten Proteins 0.000 claims abstract 3
- 201000011510 cancer Diseases 0.000 claims abstract 2
- 230000000875 corresponding Effects 0.000 claims abstract 2
- 235000001014 amino acid Nutrition 0.000 claims 11
- 210000004027 cells Anatomy 0.000 claims 9
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 4
- 239000004472 Lysine Substances 0.000 claims 4
- 229960003136 leucine Drugs 0.000 claims 4
- 241000894006 Bacteria Species 0.000 claims 3
- 206010057248 Cell death Diseases 0.000 claims 3
- 210000003743 Erythrocytes Anatomy 0.000 claims 3
- 210000003324 RBC Anatomy 0.000 claims 3
- 230000009089 cytolysis Effects 0.000 claims 3
- 229920005604 random copolymer Polymers 0.000 claims 3
- 229960003767 Alanine Drugs 0.000 claims 2
- 241000233866 Fungi Species 0.000 claims 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 2
- 241000700605 Viruses Species 0.000 claims 2
- 235000004279 alanine Nutrition 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 125000003636 chemical group Chemical group 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 2
- VDXZNPDIRNWWCW-JFTDCZMZSA-N melittin Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-JFTDCZMZSA-N 0.000 claims 2
- 229960004295 valine Drugs 0.000 claims 2
- 239000004474 valine Substances 0.000 claims 2
- 239000004475 Arginine Substances 0.000 claims 1
- 229960001230 Asparagine Drugs 0.000 claims 1
- 210000000170 Cell Membrane Anatomy 0.000 claims 1
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 claims 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims 1
- QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 claims 1
- 229960002449 Glycine Drugs 0.000 claims 1
- 239000004471 Glycine Substances 0.000 claims 1
- 229960000310 ISOLEUCINE Drugs 0.000 claims 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims 1
- 125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 claims 1
- 125000001176 L-lysyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 claims 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 1
- 241000204031 Mycoplasma Species 0.000 claims 1
- 229960005190 Phenylalanine Drugs 0.000 claims 1
- 229960002429 Proline Drugs 0.000 claims 1
- 239000004473 Threonine Substances 0.000 claims 1
- 229960004799 Tryptophan Drugs 0.000 claims 1
- 229960004441 Tyrosine Drugs 0.000 claims 1
- -1 aminoethylamino groups Chemical group 0.000 claims 1
- 235000009582 asparagine Nutrition 0.000 claims 1
- 230000005591 charge neutralization Effects 0.000 claims 1
- 235000018417 cysteine Nutrition 0.000 claims 1
- 230000003247 decreasing Effects 0.000 claims 1
- 201000009910 diseases by infectious agent Diseases 0.000 claims 1
- 235000004554 glutamine Nutrition 0.000 claims 1
- 230000003211 malignant Effects 0.000 claims 1
- 235000006109 methionine Nutrition 0.000 claims 1
- 230000001264 neutralization Effects 0.000 claims 1
- 238000006386 neutralization reaction Methods 0.000 claims 1
- 235000004400 serine Nutrition 0.000 claims 1
- 235000008521 threonine Nutrition 0.000 claims 1
- 206010017533 Fungal infection Diseases 0.000 abstract 1
- VDXZNPDIRNWWCW-UHFFFAOYSA-N Melitten Chemical compound NCC(=O)NC(C(C)CC)C(=O)NCC(=O)NC(C)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCCCN)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(C(C)O)C(=O)NCC(=O)NC(CC(C)C)C(=O)N1CCCC1C(=O)NC(C)C(=O)NC(CC(C)C)C(=O)NC(C(C)CC)C(=O)NC(CO)C(=O)NC(C(=O)NC(C(C)CC)C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCCCN)C(=O)NC(CCCNC(N)=N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(N)=O)CC1=CNC2=CC=CC=C12 VDXZNPDIRNWWCW-UHFFFAOYSA-N 0.000 abstract 1
- 206010028470 Mycoplasma infection Diseases 0.000 abstract 1
- 208000010362 Protozoan Infections Diseases 0.000 abstract 1
- 206010047461 Viral infection Diseases 0.000 abstract 1
- 208000001756 Virus Disease Diseases 0.000 abstract 1
- 230000000844 anti-bacterial Effects 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 244000052769 pathogens Species 0.000 abstract 1
Abstract
Peptides which have a net positive charge and none or only a partial α-helix configuration were found to have a non-hemolytic selective cytolytic activity. The peptides may be derived from natural peptides such as pardaxin and mellitin and fragments thereof in which L-amino acid residues are replaced by corresponding D-amino acid residues, and cyclic derivatives of the foregoing, or are diastereomers of linear peptides composed of varying ratios of at least one positively charged amino acid and at least one hydrophobic amino acid, and in which at least one of the amino acid residues is a D-amino acid, and preferably at least one third of the sequence is composed of D-amino acid residues. Pharmaceutical compositions comprising the non-hemolytic cytolytic peptides can be used for the treatment of several diseases caused by pathogens including antibacterial, fungal, viral, mycoplasma and protozoan infections and for the treatment of cancer.
Claims
AMENDED CLAIMS
[received by the International Bureau on 1 September 1997 (01.09.97); original claims 1-32 replaced by amended claims 1-31 (6 pages)]
1. A peptide having a selective cytolytic activity manifested in that it has a cytolytic activity on pathogenic cells, being cells which are non-naturally occurring within the body including pathogenic organisms and malignant cells; and it is non-hemolytic, namely it has no cytolytic effect on red blood cells or has a cytolytic effect on red blood cells at concentrations which are substantially higher than that in which it manifests said cytolytic activity, said non-hemolytic cytolytic peptide having the following characteristics:
(a) it is derived from a non-selective cytolytic natural peptide being
(aa) a peptide comprising both L-amino acid residues and D-amino acid residues, or
(ab) a peptide comprising one or both of L-amino acid residues and D-amino acid residues, and comprising an α-helix breaker moiety;
(b) the peptide has a net positive charge which is greater than +1 ; and
(c) the peptide is amphipathic.
2. A peptide according to claim 1 , which has either (i) no α-helix structure,
(ii) a non-terminal α-helix structure of a length which is insufficient to span the width of a cell membrane, or (iii) a terminal α-helix structure which has a length which is less than half of the length ofthe α-helix structure defined under (ii).
3. A peptide according to of claim lor 2, having a selective cytolytic activity on pathogenic cells, the selectivity being manifested in that the peptide induces cytolysis of the pathogenic cells at a much lower concentration than that in which it induces cytolysis of normal, non-pathogenic cells.
4. A peptide according to any one of claims 1-3, possessing a cytolytic activity against pathogenic cells of bacteria, virus, fungi, protozoans and mycroplasma.
66
5. A peptide according to claim 4 having a cytolytic activity against bacteria.
6. A peptide according to any one of claims 1-5, comprising both D- and L-amino acid residues having a sequence such that a homogeneous peptide comprising only L- or only D-amino acid residues and having the same amino acid sequence as said peptide, has an α- helix configuration and has a broad spectrum cytolytic activity manifested on a variety of cells.
7. A peptide according to any one of claims 1 -6, which is a diastereomer derived from pardaxin or from fragments thereof and cyclic derivatives ofthe foregoing.
8. A peptide according to claim 7, in which the net positive charge greater than +1 is due to the native amino acid composition, or is attained by neutralization of free carboxyl groups or by the addition of positively charged amino acid residues and/or positively charged chemical groups.
9. A peptide according to claim 8, which is selected from a diastereomer of pardaxin or of a fragment thereof to which Lys residues have been added to the N-terminus and/or aminoethylamino groups have been added to the C-terminus.
10. A peptide according to claim 9, selected from pardaxin-derived peptides herein designated peptides 1-7, ofthe sequence:
1. Gly-Phe-Phe-Ala-Leu-Ile-Em-Lys-lle-Ile-Ser- Ser-Pro-Leu-Phe-Lys-Thr-Leu-Leu-Ser-Ala-Val- Gly-Ser-Ala-Leu-Ser-Ser-Ser-Gly-Gly-Gln-Glu-(NH-CH2-CH2-NH2)2
2. Gly-Phe-Phe-Ala-Leu-Ile-Em-Lys-Ile-Ile-Ser- Ser-Pro-Leu-Phe-Lys-Thr-L£iιdUιι-Ser-Ala-Val-NH-CH2-CH2-NH2
3. Gly-Phe-Phe-Ala-Leu-Ile-Elβ-Lys-Ile-Ile-Ser- Ser-Pro-I.eu-Phe-Lys-Thr-Leu-Leu-Ser-Ala-Val
67
4. Lys-Gly-Phe-Phe-Ala-Leu-Ile-Pro-Lys-Ile-Ile-Ser- Ser-Pro-Leu-Phe-Lys-Thr-yai=Lejι-Ser-Ala-Val-NH-CH2-CH2-NH2
5. Lys-Lys-Gly-Phe-Phe-Ala-Leu-Ile-Em-Lys-Ile-Ile-Ser- Ser-Pro-Leu-Phe-Lys-Thr-Lejι=Lejι-Ser-Ala-Val-NH-CH2-CH2-NH2
6. Lys-Lys-Gly-Phe-Phe-Ala-Leu-Ile-Em-Lys-Ile-Ile-Ser- Ser-Pro-Leu-Phe-Lys-Thr-Leu-Leu-Ser-Ala-Val
7. Gly-Phe-Phe-Ala-Leu-Ile-Em-Lys-Ile-Ile-Ser-NH-CH2-CH2-NH2
11. A peptide according to any one of claims 1- 6, which is a diastereomer derived from melittin or from fragments thereof and cyclic derivatives ofthe foregoing.
12. A peptide according to claim 1 1, selected from melittin-derived peptides herein designated peptides 18-21, ofthe sequence:
18. Gly-Ile-Gly-Ala-Yal-Leu-Lys-Val-Leu-Thr-Thr-Gly-Leu- Pro-Ala-Leu-Il£-Ser-Tφ-Ile-Lys-Arg-Lys-Arg-Gln-Gln-NH2
19. Gly-Ile-Gly-Ala-Yal-Leu-Lys- Val-Leu-Thr-Thr-Gly-Leu- Pro-Ala-Leu-Ik-Ser-Trp-Ile-Lys-Arg-Lyj-Arg-Gln-Gln-COOH
20. Gly-Ile-Gly-Ala-YalzLeu-Lys-Yal-Leu-Thr-Thr-Gly-Leu- Pro-Ala-Leu-Ik-Ser-Tφ-Ile-Lys-Arg-NH-CH2-CH2-NH2
21. Ala-VaLLeu-Lys-YaLLeu-Thr-Thr-Gly-Leu- Pro-Ala-Leu-lle:Ser-Trp-Ile-Ly^-Arg-NH-CH2-CH2-NH2
13. A non-hemolytic cytolytic peptide according to claim 1 comprising both L-amino acid residues and D-amino acid residues, having a sequence of amino acids such that a corresponding amino acid sequence comprising only L-amino acid residues is not found in nature. 68
14. A peptide according to claim 13. which has a net positive charge and no α-helix structure.
15. A non-hemolytic cytolytic peptide according to claim 13 or 14, having the following characteristics:
(a) it is a non-natural synthetic peptide composed of varying ratios of at least one hydrophobic amino acid and at least one positively charged amino acid, and in which sequence at least one ofthe amino acid residues is a D-amino acid;
(b) the peptide has a net positive charge which is greater than +1 ; and
(c) the ratio of hydrophobic to positively charged amino acids is such that the peptide is cytolytic to pathogenic cells but does not cause cytolysis of red blood cells.
16. A peptide according to claim 15, wherein the positively charged amino acid is selected from lysine, arginine and histidine, and the hydrophobic amino acid is selected from leucine, isoleucine, glycine, alanine, valine, phenylalanine, proline, tyrosine and tryptophan.
17. A peptide according to claim 16, wherein the net positive charge greater than +1 is due to the amino acid composition or to the addition of positively charged chemical groups, or which hydrophobicity may be decreased by the addition of polar amino acids such as serine, threonine, methionine, asparagine, glutamine and cysteine.
18. A peptide according to claim 17 of at least 6 amino acid residues, in which the hydrophobic amino acid is leucine, alanine or valine, and the positively charged amino acid is lysine.
19. A peptide according to claim 18, being a diastereomer of a 6-mer. 8-mer or 12- mer peptide composed of leucine and lysine, in which at least one third of the sequence is composed of D-amino acids.
69
20. A Leu/Lys diastereomer according to claim 19 selected from the peptides herein designated 23 to 29, ofthe sequence:
23. Lys-Leu-Leu-Leu-Lys-Leu-Leu-Leu -Lys-Leu-Leu-Lys-NH2
24. Lys-Leu-Leu-Leu-Lys-Leu-Lys-Leu -Lys-Leu-Leu-Lys-NH2
25. Lys-Lys-Leu-Leu-Lys-Leu-Lys-Leu -Lys-Leu-Lys-Lys-NH2
26. Lys-Leu-Leu-Leu-Lvs-Leu-Leu-Leu
27. Lys-Leu-Leu-Leu-Lys-Leu-Lys-Leu-Lys-Leu-Leu-Lys-NH2
28. Lys-Leu-Leu- Leu -Leu-Lys
29. Lys-Leu-Leu- Leu - Lys-Leu-Leu-Lys
21. A non-hemolytic cytolytic peptide according to claim 1 , which is a cyclic diastereomer of a peptide derived from a non-selective cytolytic natural peptide or of a non- natural synthetic peptide.
22. A non-hemolytic cytolytic complex consisting of a plurality of 2 or more non- hemolytic cytolytic peptides according to any one of claims 1-21, said peptides being bundled together by the use of a linker molecule covalently bound to each ofthe peptides.
23. A complex according to claim 22, wherein the bundle is composed of 2 or more, preferably 5, molecules of the same peptide or of different peptides, and the linker is a peptide according to any one ofthe preceding claims or a commonly used linker.
24. A non-hemolytic cytolytic mixture of hydrophilic diastereomers according to any one of claims 1 to 21.
25. A non-hemolytic cytolytic random copolymer consisting of different ratios of a hydrophobic, a positively charged and a D-amino acid.
26. A non-hemolytic cytolytic random copolymer according to claim 25, composed of lysine, leucine and D-leucine in the ratio 1 : 1 : 1 , 2 : 1 : 1 or 3 : 1 : 1 (Mol).
70
27. A pharmaceutical composition comprising a non-hemolytic cytolytic peptide according to any one of claims 1-21, and a pharmaceutically acceptable carrier.
28. A pharmaceutical composition comprising a non-hemolytic cytolytic complex according to claims 22-23, a mixture of hydrophilic peptides according to claim 24 or a random copolymer according to claims 25-26, and a pharmaceutically acceptable carrier.
29. A pharmaceutical composition according to claim 27 or 28, for use in the treatment of infections caused by pathogenic organisms.
30. A pharmaceutical composition according to claim 29, wherein the pathogenic organism is selected from bacteria, fungi, protozoa, mycoplasma and virus.
31. A pharmaceutical composition according to claim 27 or 28, for use in the treatment of cancer.
71
Priority Applications (19)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EA199800754A EA199800754A1 (en) | 1996-02-22 | 1997-02-20 | ANTIPATOGENIC PEPTIDES AND COMPOSITIONS INCLUDING THEM |
| AU17319/97A AU730069B2 (en) | 1996-02-22 | 1997-02-20 | Antipathogenic peptides and compositions comprising them |
| JP9529954A JP2000506128A (en) | 1996-02-22 | 1997-02-20 | Antipathogenic peptides and compositions containing them |
| BR9707691A BR9707691A (en) | 1996-02-22 | 1997-02-20 | Antipathogenic peptides and compositions comprising the same |
| NZ331219A NZ331219A (en) | 1996-02-22 | 1997-02-20 | Antipathogenic peptides having a non-hemolytic selective cytolytic activity and compositions comprising them |
| IL12573497A IL125734A (en) | 1996-02-22 | 1997-02-20 | Antipathogenic peptides and compositions comprising them |
| EP97904561A EP0904291A2 (en) | 1996-02-22 | 1997-02-20 | Antipathogenic peptides and compositions comprising them |
| US09/125,605 US6172038B1 (en) | 1996-02-22 | 1997-02-20 | Antipathogenic peptides and compositions comprising them |
| IL13136898A IL131368A0 (en) | 1997-02-20 | 1998-02-19 | Antipathogenic synthetic peptides and compositions comprising them |
| PCT/IL1998/000081 WO1998037090A1 (en) | 1997-02-20 | 1998-02-19 | Antipathogenic synthetic peptides and compositions comprising them |
| BR9807456-3A BR9807456A (en) | 1997-02-20 | 1998-02-19 | Synthetic antipathogenic peptides and compositions comprising the same |
| US09/367,714 US7001983B1 (en) | 1997-02-20 | 1998-02-19 | Antipathogenic synthetic peptides and compositions comprising them |
| EA199900752A EA199900752A1 (en) | 1997-02-20 | 1998-02-19 | ANTIPATOGENIC SYNTHETIC PEPTIDES AND COMPOSITIONS INCLUDING THEM |
| KR1019997007477A KR20000071187A (en) | 1996-02-22 | 1998-02-19 | Antipathogenic synthetic peptides and compositions comprising them |
| JP53645398A JP2001512475A (en) | 1997-02-20 | 1998-02-19 | Antipathogenic synthetic peptides and compositions containing them |
| CA002281204A CA2281204A1 (en) | 1997-02-20 | 1998-02-19 | Antipathogenic synthetic peptides and compositions comprising them |
| EP98903286A EP0977774A1 (en) | 1997-02-20 | 1998-02-19 | Antipathogenic synthetic peptides and compositions comprising them |
| AU60056/98A AU6005698A (en) | 1997-02-20 | 1998-02-19 | Antipathogenic synthetic peptides and compositions comprising them |
| CN98804347A CN1252808A (en) | 1997-02-20 | 1998-02-19 | Antipathogenic synthetic piptides and compositions comprising them |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL11722396A IL117223A0 (en) | 1996-02-22 | 1996-02-22 | Antipathogenic polypeptides and compositions comprising them |
| IL117223 | 1996-02-22 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO1997031019A2 WO1997031019A2 (en) | 1997-08-28 |
| WO1997031019B1 true WO1997031019B1 (en) | 1997-10-23 |
| WO1997031019A3 WO1997031019A3 (en) | 1997-10-23 |
Family
ID=11068576
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IL1997/000066 WO1997031019A2 (en) | 1996-02-22 | 1997-02-20 | Antipathogenic peptides and compositions comprising them |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US6172038B1 (en) |
| EP (1) | EP0904291A2 (en) |
| JP (1) | JP2000506128A (en) |
| KR (2) | KR19990087100A (en) |
| CN (1) | CN1216549A (en) |
| AU (1) | AU730069B2 (en) |
| BR (1) | BR9707691A (en) |
| CA (1) | CA2247025A1 (en) |
| CZ (1) | CZ264398A3 (en) |
| EA (1) | EA199800754A1 (en) |
| IL (2) | IL117223A0 (en) |
| NZ (1) | NZ331219A (en) |
| WO (1) | WO1997031019A2 (en) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1252808A (en) * | 1997-02-20 | 2000-05-10 | 耶达研究及发展有限公司 | Antipathogenic synthetic piptides and compositions comprising them |
| US6818213B1 (en) * | 1998-07-13 | 2004-11-16 | Board Of Regents, The University Of Texas System | Cancer treatment compositions comprising therapeutic conjugates that bind to aminophospholipids |
| BR9912053A (en) | 1998-07-13 | 2001-04-03 | Univ Texas | Cancer treatment processes using therapeutic conjugates that bind to aminophospholipids |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| MEP42108A (en) | 1998-10-23 | 2011-02-10 | Kiren Amgen Inc | Dimeric thrombopoietin peptide mimetics binding to mp1 receptor and having thrombopoietic activity |
| US7488590B2 (en) | 1998-10-23 | 2009-02-10 | Amgen Inc. | Modified peptides as therapeutic agents |
| GB0005703D0 (en) | 2000-03-09 | 2000-05-03 | Alpharma As | Compounds |
| IL139720A0 (en) * | 2000-11-16 | 2002-02-10 | Yeda Res & Dev | Diastereomeric peptides and pharmaceutical compositions comprising them |
| CA2529125A1 (en) * | 2003-06-19 | 2004-12-23 | Yeda Research & Development Co. Ltd. | Antimicrobial and anticancer lipopeptides |
| EP1773400A2 (en) | 2004-07-08 | 2007-04-18 | Amgen Inc. | Therapeutic peptides |
| AU2005319578A1 (en) * | 2004-11-24 | 2006-06-29 | Neopro Labs, Llc | Methods and compositions for treating conditions |
| WO2006128289A1 (en) * | 2005-06-02 | 2006-12-07 | University Of Manitoba | Use of brevinin-2r in the treatment of cancer |
| US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
| WO2007074457A2 (en) * | 2005-12-27 | 2007-07-05 | Yeda Research And Development Co. Ltd. | Histidine-containing diastereomeric peptides and uses thereof |
| CA2637221A1 (en) | 2006-02-10 | 2007-08-16 | Dermagen Ab | Novel antimicrobial peptides and use thereof |
| US9283260B2 (en) | 2006-04-21 | 2016-03-15 | Amgen Inc. | Lyophilized therapeutic peptibody formulations |
| JP6205364B2 (en) * | 2012-09-05 | 2017-09-27 | 株式会社メニコン | Drug sustained release ophthalmic lens and method for producing the same |
| JP6093528B2 (en) * | 2012-09-19 | 2017-03-08 | 株式会社ミルボン | Screening method |
| US11103547B2 (en) | 2016-02-04 | 2021-08-31 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Methods for disrupting biofilms |
| GB2557654A (en) * | 2016-12-14 | 2018-06-27 | Uea Enterprises Ltd | Method for nucleic acid depletion |
| CN113528600A (en) * | 2021-07-08 | 2021-10-22 | 石河子大学 | Method for preparing antibacterial peptide by inducing fly maggots with salmonella |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5258454A (en) * | 1988-09-01 | 1993-11-02 | Riso National Laboratory | Peptide synthesis method and solid support for use in the method |
-
1996
- 1996-02-22 IL IL11722396A patent/IL117223A0/en unknown
-
1997
- 1997-02-20 EP EP97904561A patent/EP0904291A2/en not_active Ceased
- 1997-02-20 WO PCT/IL1997/000066 patent/WO1997031019A2/en not_active Application Discontinuation
- 1997-02-20 JP JP9529954A patent/JP2000506128A/en not_active Ceased
- 1997-02-20 CA CA002247025A patent/CA2247025A1/en not_active Abandoned
- 1997-02-20 CN CN97194000A patent/CN1216549A/en active Pending
- 1997-02-20 BR BR9707691A patent/BR9707691A/en unknown
- 1997-02-20 NZ NZ331219A patent/NZ331219A/en unknown
- 1997-02-20 KR KR1019980706488A patent/KR19990087100A/en not_active Application Discontinuation
- 1997-02-20 US US09/125,605 patent/US6172038B1/en not_active Expired - Fee Related
- 1997-02-20 AU AU17319/97A patent/AU730069B2/en not_active Ceased
- 1997-02-20 IL IL12573497A patent/IL125734A/en not_active IP Right Cessation
- 1997-02-20 CZ CZ982643A patent/CZ264398A3/en unknown
- 1997-02-20 EA EA199800754A patent/EA199800754A1/en unknown
-
1998
- 1998-02-19 KR KR1019997007477A patent/KR20000071187A/en not_active Application Discontinuation
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