1. A self-assembling peptide nanoparticle consisting of aggregates of a multitude of building blocks of formula (I) consisting of a continuous chain comprising a peptidic oligomerization domain D1, a linker segment L, and a peptidic oligomerization domain D2
D1-L-D2\u2003\u2003(I)
wherein D1 is a peptide having a tendency to form oligomers (D1)m of m subunits D1, D2 is a peptide having a tendency to form oligomers (D2)n of n subunits D2, m and n each is a figure between 2 and 10, with the proviso that m is not equal n and not a multiple of n, and n is not a multiple of m, L is a bond or a short linker segment, either D1 or D2 or both D1 and D2 is a coiled-coil oligomerization domain that incorporates one or more T- andor B-cell epitopes within the oligomerization domain, and wherein D1, D2 and L are optionally further substituted.
2. The peptide nanoparticle according to claim 1 wherein the coiled-coil oligomerization domain is consisting of heptad andor undecad repeats.
3. The peptide nanoparticle according to claim 1 wherein the peptidic oligomerization domain D1 at its N-terminal end andor the peptidic oligomerization domain D2 at its C-terminal end is substituted by one or more additional B- andor T-cell epitope, one or more other functional peptide or protein, or one or more additional hapten or other functional molecule.
4. The peptide nanoparticle according to claim 3 of the formulae S1-D1-L-D2, D1-L-D2-S2, or S1-D1-L-D2-S2, wherein S1 and S2 are peptidic substituents.
5. The peptide nanoparticle according to claim 3, consisting of identical building blocks D1-L-D2, wherein at least one of the identical building blocks carries one or more different substituent at the N-terminal end of D1 andor the C-terminal end of D2.
6. The peptide nanoparticle according to claim 1 wherein one of the oligomerization domains D1 and D2 is the pentamerization domain of the tryptophane zipper or a derivative thereof.
7. The peptide nanoparticle according to claim 1 wherein one of the oligomerization domains D1 and D2 is the tetramerization domain of tetrabrachion or a derivative thereof.
8. The peptide nanoparticle according to claim 1 wherein at least one of the epitopes is a CTL epitope.
9. The peptide nanoparticle according to claim 1 wherein at least one of the epitopes is a HTL epitope.
10. The peptide nanoparticle according claim 1 wherein at least one of the epitopes is a B-cell epitope.
11. The peptide nanoparticle according to claim 1 wherein the sequence D1-L-D2 comprises a series of optionally overlapping T- andor B-cell epitopes.
12. A composition comprising a peptide nanoparticle according to claim 1.
13. The composition of claim 12, wherein at least one of the B- or T-cell epitopes is selected from the group consisting of:
(a) an antigen suited to induce an immune response against bacteria;
(b) an antigen suited to induce an immune response against viruses;
(c) an antigen suited to induce an immune response against parasites;
(d) an antigen suited to induce an immune response against cancer cells;
(e) an antigen suited to induce an immune response against allergens;
(f) an antigen suited to induce an immune response against addictions;
(g) an antigen suited to induce an immune response against diseases and metabolic disorders;
(h) an antigen suited to induce an immune response in a farm animals; and
(i) an antigen suited to induce an immune response in a pet.
14. The composition of claim 12, wherein at least one of the B- or T-cell epitopes is selected from a protein of the pathogens causing diseases selected from the group consisting of Amoebiasis, Anthrax, Campylobacter infection, Chickenpox, Cholera, Dengue, Diphtheria, Encephalitis, Ebola, Influenza, Japanese Encephalitis, Leishmaniasis, Malaria, Measles, Meningococcal Disease, Mumps, Nosocomial infections, Pertussis, Pneumococcal Disease, Polio (Poliomyelitis), Rubella, Shingles, Shistosomiasis, Tetanus, Tick-Borne Encephalitis, Trichomoniasis, Trypanosomiasis, Tuberculosis, Typhoid, Varicella, and Yellow Fever.
15. The composition of claim 12, wherein at least one of the B- or T-cell epitopes is selected from a protein of the pathogens causing diseases selected from the group consisting of Campylobacter, Cytomegalovirus, Epstein-Barr Virus, FMDV, Haemophilus influenzae Type b, Helicobacter pylori, Hepatitis B Virus, Hepatitis C Virus, Hepatitis E Virus, Herpes Simplex Virus, Human Immunodeficiency Virus, Human Papillomavirus, Neisseria meningitidis, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, Respiratory Syncytial Virus, Rotavirus, Roundworm, Hookworm, and West Nile Virus.
16. The composition of claim 12, wherein at least one of the B- or T-cell epitopes is selected from the influenza proteins hemagglutinin andor M2.
17. The composition of claim 16, wherein the M2 B-cell epitope is the tetrameric form of the extracellular portion of this protein M2e attached to the N-terminal end of a tetrameric coiled-coil oligomerization domain D1.
18. The composition of claim 17, wherein the tetrameric oligomerization domain D1 is the tetrameric coiled-coil domain of tetrabrachion or a derivative thereof.
19-20. (canceled)
21. The composition of claim 12, wherein at least one of the B-cell epitopes is a sequence of between 8 and 48 residues that constitute a B cell epitope of the Plasmodium falciparum circumsporozoite (CS) protein said B cell epitope being comprised of two to about 12 repeats of the amino acid residue sequence Asn-Ala-Asn-Pro or permutations thereof.
22-25. (canceled)
26. The composition of claim 12, wherein at least one of the B-cell epitopes is a protein of HIV selected from the proteins gp41, gp120 or gp160.
27. The composition of claim 12, wherein at least one of the B-cell epitopes is a peptide of HIV selected from the binding sites of the neutralizing antibodies 2F5 andor 4E10 of gp41.
28. The composition of claim 12, wherein at least one of the B-cell epitopes is a peptide of HIV selected from the V3-loop of gp120 of HIV.
29-30. (canceled)
31. The composition of claim 12 wherein the B-cell epitope is an antigen suited to induce an immune response against addictions selected from the group consisting of opiates, marijuana, amphetamines, cocaine, barbiturates, glutethimide, methyprylon, chloral hydrate, methaqualone, benzodiazepines, LSD, nicotine, anticholinergic drugs, antipsychotic drugs, tryptamine, other psychomimetic drugs, sedatives, phencyclidine, psilocybine, volatile nitrite, and other drugs inducing physical dependence andor psychological dependence.
32-33. (canceled)
34. The composition of claim 12, wherein at least one of the B- or T-cell epitopes is selected from an antigen suited to induce an immune response against cancer cells of a type of cancer selected from Brain Cancer, Breast Cancer, Cervical Cancer, Colorectal Cancer, Esophageal Cancer, Glioblastoma, Leukemia (acute Myelogenous and chronic Myeloid), Liver cancer, Lung Cancer (Non-Small-Cell Lung Cancer, Small-Cell Lung Cancer), Lymphoma (Non-Hodgkin’s Lymphoma), Melanoma, Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, and Renal Cancer.
35-36. (canceled)
37. The composition of claim 12, wherein at least one of the B-cell epitopes is the A\u03b2-peptide or a fragment thereof comprising at least the sequence of 6 amino acids starting with the N-terminal amino acids.
38. The composition of claim 12, wherein at least one of the B-cell epitopes is angiotensin I or angiotensin II.
39. The composition of claim 12, wherein at least one of the B-cell epitopes is grehlin.
40. The composition of claim 12, wherein at least one of the B-cell epitopes is TNF\u03b1 or a fragment thereof comprising at least the sequence of 20 amino acids starting with the 4th N-terminal amino acid of TNF\u03b1.
41. A method of vaccinating a human or non-human animal, which comprises administering an effective amount of a peptide nanoparticle according to claim 1 to a subject in need of such vaccination.
42. A monomeric building block of formula (I) consisting of a continuous chain comprising a peptidic oligomerization domain D1, a linker segment L, and a peptidic oligomerization domain D2
D1-L-D2\u2003\u2003(I)
wherein D1 is a peptide having a tendency to form oligomers (D1)m of m subunits D1, D2 is a peptide having a tendency to form oligomers (D2)n of n subunits D2, m and n each is a figure between 2 and 10, with the proviso that m is not equal n and not a multiple of n, and n is not a multiple of m, L is a bond or a short linker segment, either D1 or D2 or both D1 and D2 is a coiled-coil oligomerization domain that incorporates one or more T- andor B-cell epitopes within the oligomerization domain, and wherein D1, D2 and L are optionally further substituted.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A laboratory autography phosphorescent marking pen capable of delivering a low viscosity phosphorescent marking ink comprising a suspension of phosphor particles having an average particle size of between 10 and 40 microns, and whose afterglow half-life is less than 5 minutes, wherein said marking pen further comprises a high porosity nib whose ink flow channels are of a sufficient size to allow said phosphor particles suspended in said ink to flow by capillary transport through said channels onto an ink receiving substrate material.
2. The phosphorescent marking pen of claim 1 wherein the phosphorescent marking ink has a viscosity of between 10 and 200 centipoise at 25\xb0 C.
3. The phosphorescent marking pen of claim 2 wherein the phosphorescent marking ink has a viscosity of between 35 and 50 centipoise at 25\xb0 C.
4. The phosphorescent marking pen of claim 1 wherein said marking pen comprises a reservoir that contains said marking ink together with at least one agitator element that allows said phosphor particles to be resuspended in said marking ink upon manual shaking of said marking pen.
5. The phosphorescent marking pen of claim 1 wherein said ink further comprises an amount of colorant that is sufficient for said ink to be visible while writing, said colorant being a white or colored pigment or dye.
6. The phosphorescent marking pen of claim 5 wherein said colorant is one or more materials selected from the group consisting of green dye, yellow dye, green pigment and yellow pigment.
7. The phosphorescent marking pen of claim 1 wherein the afterglow half-life of said phosphorescent marking ink, after drying on said substrate material, is less than 3 minutes.
8. The phosphorescent marking pen of claim 1 wherein said phosphor particles having an average particle size of between 10 and 25 microns.
9. The phosphorescent marking pen of claim 1 wherein said phosphor particles are zinc sulfide-based particles.
10. The phosphorescent marking pen of claim 9 wherein said zinc sulfide-based particles are copper-doped zinc sulfide-based particles.
11. The phosphorescent marking pen of claim 1 wherein said phosphor particles are a hexagonal Wurtzite crystalline form of zinc sulfide doped with various trace metals.
12. The phosphorescent marking pen of claim 1 wherein said a high porosity fiber-type writing nib is fabricated from fibers selected from the group consisting of polyethylene fibers, polypropylene fibers, acrylic fibers, polyester fibers and nylon fibers.
13. The phosphorescent marking pen of claim 1, wherein said writing nib is formed into a point.
14. The phosphorescent marking pen of claim 13, wherein the point of said writing nib is approximately 0.4-3 mm in diameter.
15. The phosphorescent marking pen of claim 14, wherein said writing nib is 0.6-1.5 mm in diameter.
16. The phosphorescent marking pen of claim 1 wherein the liquid vehicle in said low viscosity phosphorescent marking ink is selected from the group consisting of petroleum and water-based vehicles.
17. The phosphorescent marking ink of claim 1 wherein said ink contains between 5% and 30% by weight of said phosphor particles.
18. The phosphorescent marking pen of claim 1 wherein said marking pen comprises a reservoir that contains said marking ink, and further comprises an ink flow valve positioned between said reservoir and said writing nib.
19. A method of using a laboratory autography marking pen comprising the steps of:
writing notations on a substrate material using the laboratory autography marking pen and phosphorescent marking ink of claim 1;
exposing the annotated substrate material to visible or ultraviolet light to excite the phosphor particles in said marking ink;
placing said annotated substrate material into contact with X-ray film or other photo-detection surface for a period of time sufficient for the notations to be registered on said photo-detection surface; and
processing said photo-detection surface using a procedure suitable for visualizing said notations.
20. The method of claim 19, wherein said phosphorescent marking ink has a viscosity of between 10 and 200 centipoise at 25\xb0 C., said phosphor particles are zinc sulfide-based particles, and wherein said writing nib is formed into a point of approximately 0.4-3 mm in diameter.