DK2827899T3 - Polysaccharidantigen-glycolipid-konjugatvacciner - Google Patents
Polysaccharidantigen-glycolipid-konjugatvacciner Download PDFInfo
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- DK2827899T3 DK2827899T3 DK13710422.0T DK13710422T DK2827899T3 DK 2827899 T3 DK2827899 T3 DK 2827899T3 DK 13710422 T DK13710422 T DK 13710422T DK 2827899 T3 DK2827899 T3 DK 2827899T3
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Claims (15)
1. Forbindelse med den almene formel (I):
(l) hvor A betegner et kulhydratantigen med 1 til 10.000 kulhydratmonomerer, og kulhydratantigenet tilhører klassen af polysaccharider, hvor kulhydratmonomererne i kulhydratantigenet eventuelt er modificeret til at bære amid-, car-bonat-, carbamat-, carbonyl-, thiocarbonyl-, carboxy-, thiocarboxy-, ester-, thioester, ether-, epoxy-, hydroxyalkyl-, alkylenyl-, phenylen-, alkenyl-, imino-, imid-, isourea-, thiocarbamat-, thiourea- og/eller ureadele, p er antallet af rester -L-CH-CA, som er bundet til kulhydratantigen A, og p er et heltal defineret som følger: p er 1 eller 2 hvis u er 1 p er 1,2, 3 eller 4 hvis u er 2 p er 1,2, 3, 4, 5 eller 6 hvis u er 3 p er 1,2, 3, 4, 5, 6, 7 eller 8 hvis u er 4 1 ^ p ^ 10 hvis 5 ^ u ^ 10 2 ^ p ^ 50 hvis 11 < u ^ 100 20 ^ p ^ 200 hvis 101 < u ^ 1000 50 ^ p ^ 400 hvis 1001 < u ^ 10000 u er antallet af kulhydratmonomerer i kulhydratantigenet A L betegner -L1-L2-, -L2-, -L2-L3- eller -L1-L2-L3-; L1 betegner en af følgende rester:
hvor x er et heltal fra 1 til 60; S " s-s-· Y betegner en binding, -NH-,^ -CeHi2', -C7H14-, -CeHi6'» WHr.' CH(CH3)-C2H4-, -CH2-CH(CH3)-CHr, -C2H4-CH(CH3)-, -CH2-C[(CH3)2]-> C[(CH3)2]-CH2-, -CH(CH3)-CH(CH3)-, -0[(C2H5)(CH3)]-, -CH(C3H7)-, -(CH2-CH2-0)n-CH2-CH2-, -CO-CH2-, -CO-C2H4-, -CO-C3H6-, -CO-C4H8-, -CO-C5H10-, -CO-C6Hi2-, -CO-C7H14-, -CO-C8Hi6-, -CO-C9His-, -CO-Ci0H20-, -CO-CH(CH3)-, -CO-C[(CH3)2]-, -CO-CH2-CH(CH3)-, -CO-CH(CH3)-CH2-, -co-CH(CH3)-C2H4-, -CO-CH2-CH(CH3)-CH2-, -CO-C2H4-CH(CH3)-, -co-ch2-C[(CH3)2]-, -CO-C[(CH3)2]-CH2-, -CO-CH(CH3)-CH(CH3)-, -co- 0[(02Η5)(0Η3)]-, -CO-CH(C3H7)-, -C0-(CH2-CH2-0)n-CH2-CH2-; n betegner et heltal fra 1 til 60; L3 betegner -CO-, -O-CO-, -NH-CO-, -NH(C=NH)-, -S02-, -0-S02-, -NH-, -NH-CO-CH2-; CH betegner et monosaccharid, et disaccharid eller et trisaccharid; CA beteaner
R* og R# uafhængigt af hinanden betegner en lineær eller forgrenet eller cyklisk, substitueret eller usubstitueret, mættet eller umættet carbonrest bestående af 1 til 30 carbonatomer; og tautomerer og farmaceutisk acceptable salte deraf.
2. Forbindelse ifølge krav 1 med den almene formel (II):
(il) hvor A, L og p har de betydninger, der er defineret i krav 1; R1, R2, R3 uafhængigt af hinanden betegner: -H, -OH, -OCH3, -OC2H5, -OC3H7, -0-S02-CH3, -0-S02-C2H5, -O-SO2-C3H7, -0-C00CH3, -NHCOCHs, -NH2; R* og R# uafhængigt af hinanden betegner: -CH3, -(CH2)rCH3, -CH(OH)-(CH2)s-CH3, -CH=CH-CH3j -CH=CH-(CH2)t-CH3, -CH(OH)-(CH2)v-CH(CH3)2, -CH(OH)-(CH2)w-CH(CH3)-CH2-CH3, -(CH2)a- CH=CH-(CH2)b-CH3, -(CH2)c-CH=CH-(CH2)d-CH=CH-(CH2)e-CH3, -(CH2)r CH=CH-(CH2)g-CH=CH-(CH2)h-CH=CH-(CH2)rCH3, -(CH2)j-CH=CH-(CH2)k-CH=CH-(CH2)i-CH=CH-(CH2)o-CH=CH-(CH2)q-CH3, hvor a, b, c, d, e, f, g, h, i, j, k, I, o, q er heltal fra 1 til 26, forudsat at: (a+b) ^ 27; (c+d+e) ^ 25; (f+g+h+i) ^ 23; (j+k+l+o+q) < 21; og hvor r er et heltal fra 1 til 29, s er et heltal fra 1 til 28, t er et heltal fra 1 til 27, v er et heltal fra 1 til 26, w er et heltal fra 1 til 26.
3. Forbindelse ifølge krav 1 med den almene formel (XIV):
(XIV) hvor A, L, R*, R# og p har de betydninger, der er defineret i krav 1.
4. Forbindelse ifølge et hvilket som helst af kravene 1 - 3, hvor kulhydratmo nomererne i kulhydratantigenet tilhører gruppen af kulhydrater omfattende: a-D-ribopyranose, α-D-arabinopyranose, a-D-xylopyranose, a-D-lyxopyranose, α-D-allopyranose, a-D-altropyranose, α-D-glucopyranose, a-D-mannpyranose, a-D-glucopyranose, α-D-idopyranose, a-D-galactopyranose, α-D-talopyranose, a-D-psicopyranose, α-D-fructopyranose, a-D- sorbopyranose, α-D-tagatopyranose, a-D-ribofuranose, α-D-arabinofuranose, a-D-xylofuranose, α-D-lyxofuranose, a-D-Allofuranose, α-D-Altrofuranose, a-D-Glucofuranose, a-D-Mannofuranose, α-D-gulofuranose, a-D-idofuranose, α-D-galactof uranose, a-D-talof uranose, α-D-psicof uranose, a-D- fructofuranose, a-D-sorbofuranose, α-D-tagatofuranose, a-D-xylulofuranose, α-D-ribulofuranose, a-D-threofuranose, α-D-rhamnopyranose, a-D- erythrofuranose, α-D-glucosamin, a-D-glucopyranuronsyre, β-D-ribopyranose, β-D-arabinopyranose, β-D-xylopyranose, β-D-lyxopyranose, β-D-allopyranose, β-D-altropyranose, β-D-glucopyranose, β-D-mannpyranose, β-D-glucopyranose, β-D-idopyranose, β-D-galactopyranose, β-D- talopyranose, β-D-psicopyranose, β-D-fructopyranose, β-D-sorbopyranose, β-D-tagatopy ranose, β-D-ribofuranose, β-D-arabinofuranose, β-D- xylofuranose, β-D-lyxofuranose, β-D-rhamnopyranose, β-D-allofuranose, β-D-altrofuranose, β-D-glucofuranose, β-D-mannofuranose, β-D-gulofuranose, β-D-idofuranose, β-D-galactofuranose, β-D-talofuranose, β-D-psicofuranose, β-D-fructof uranose, β-D-sorbofuranose, β-D-tagatof uranose, β-D- xylulofuranose, β-D-ribulofuranose, β-D-threofuranose, β-D-erythrofuranose, β-D-glucosamin, β-D-glucopyranuronsyre, α-L-ribopyranose, a-L- arabinopyranose, a-L-xylopyranose, a-L-lyxopyranose, α-L-allopyranose, a-L-altropyranose, a-L-glucopyranose, α-L-mannpyranose, a-L-glucopyranose, α-L-idopyranose, a-L-galactopyranose, α-L-talopyranose, a-L-psicopyranose, α-L-fructopyranose, a-L-sorbopyranose, α-L-tagatopyranose, a-L- rhamnopyranose, a-L-ribofuranose, α-L-arabinofuranose, a-L-xylofuranose, α-L-lyxofuranose, a-L-Allofuranose, α-L-Altrofuranose, α-L-Glucofuranose, a-L-Mannofuranose, a-L-gulofuranose, α-L-idofuranose, a-L-galactofuranose, α-L-talofuranose, a-L-psicofuranose, α-L-fructofuranose, a-L-sorbofuranose, α-L-tagatofuranose, a-L-xylulofuranose, α-L-ribulofuranose, a-L- threofuranose, a-L-erythrofuranose, α-L-glucosamin, a-L- glucopyranuronsyre, β-L-ribopyranose, β-L-arabinopyranose, β-L- xylopyranose, β-L-lyxopyranose, β-L-allopyranose, β-L-altropyranose, β-L-glucopyranose, β-L-mannpyranose, β-L-glucopyranose, β-L-idopyranose, β-L-galactopyranose, β-L-talopyranose, β-L-psicopyranose, β-L- fructopyranose, β-L-sorbopyranose, β-L-tagatopyranose, β-L-ribofuranose, β-L-arabinofuranose, β-L-xylofuranose, β-L-lyxofuranose, β-L-allofuranose, β-L-altrofuranose, β-L-glucofuranose, β-L-mannofuranose, β-L-gulofuranose, β-L-idofuranose, β-L-galactofuranose, β-L-talofuranose, β-L-psicofuranose, β-L-fructofuranose, β-L-sorbofuranose, β-L-tagatofu ranose, β-L- xylulofuranose, β-L-ribulofuranose, β-L-threofuranose, β-L-erythrofuranose, β-L-glucosamin, β-L-glucopyranuronsyre, β-L-rhamnopyranose, eller N- eller O-substituerede derivater af neuraminsyre med følgende formel:
hvor Z betegner -NH2, -NHAc eller -OH. ;
5. Forbindelse ifølge et hvilket som helst af kravene 1 - 4, hvor kulhydratmonomererne i CH-delen tilhører gruppen af kulhydrater omfattende: a-D-ribopyranose, α-D-arabinopyranose, a-D-xylopyranose, a-D- lyxopyranose, α-D-allopyranose, a-D-altropyranose, α-D-glucopyranose, a-D-mannpyranose, a-D-glucopyranose, α-D-idopyranose, a-D-galactopyranose, α-D-talopyranose, a-D-psicopyranose, α-D-fructopyranose, a-D- sorbopyranose, α-D-tagatopyranose, a-D-ribofuranose, α-D-arabinofuranose, a-D-xylofuranose, α-D-lyxofuranose, a-D-Allofuranose, α-D-Altrofuranose, a-D-Glucofuranose, a-D-Mannofuranose, α-D-gulofuranose, a-D-idofuranose, α-D-galactof uranose, a-D-talof uranose, α-D-psicof uranose, a-D- fructofuranose, a-D-sorbofuranose, α-D-tagatofuranose, a-D-xylulofuranose, α-D-ribulofuranose, a-D-threofuranose, α-D-erythrofuranose, a-D-glucosamin, α-D-glucopyranuronsyre, a-D-rhamnopyranose, β-D-ribopyranose, β-D-arabinopyranose, β-D-xylopyranose, β-D-lyxopyranose, β-D-allopyranose, β-D-altropyranose, β-D-glucopyranose, β-D-mannpyranose, β-D-glucopyranose, β-D-idopyranose, β-D-galactopyranose, β-D-talopyranose, β-D-psicopyranose, β-D-fructopyranose, β-D-sorbopyranose, β-D- tagatopyranose, β-D-ribofuranose, β-D-arabinofuranose, β-D-xylofuranose, β-D-lyxofuranose, β-D-allofuranose, β-D-altrofuranose, β-D-glucofuranose, β-D-mannofuranose, β-D-gulofuranose, β-D-idofuranose, β-D-galactofuranose, β-D-talof uranose, β-D-psicofuranose, P-D-fructof uranose, β-D- sorbofuranose, β-D-tagatofuranose, β-D-xylulofuranose, β-D-ribulofuranose, β-D-threof uranose, β-D-eryth rof uranose, β-D-rhamnopyranose, β-D- glucosamin, β-D-glucopyranuronsyre, α-L-ribopyranose, a-L-arabinopyranose, a-L-xylopyranose, a-L-lyxopyranose, α-L-allopyranose, a-L-altropyranose, a-L-glucopyranose, α-L-mannpyranose, a-L-glucopyranose, α-L-idopyranose, a-L-galactopyranose, α-L-talopyranose, a-L-psicopyranose, α-L-fructopyranose, a-L-sorbopyranose, α-L-tagatopyranose, a-L- ribofuranose, α-L-arabinofuranose, a-L-xylofuranose, α-L-lyxofuranose, a-L-Allofuranose, α-L-Altrofuranose, a-L-Glucofuranose, α-L-Mannofuranose, a-L-gulofuranose, a-L-idofuranose, α-L-galactofuranose, a-L-talofuranose, a-L-psicofuranose, α-L-fructofuranose, a-L-sorbofuranose, α-L-tagatofuranose, a-L-xylulofuranose, a-L-ribulofuranose, α-L-rhamnopyranose a-L- threof uranose, α-L-eryth rof uranose, α-L-glucosamin, α-L- glucopyranuronsyre, β-L-ribopyranose, β-L-arabinopyranose, β-L-xylopyranose, β-L-lyxopyranose, β-L-allopyranose, β-L-altropyranose, β-L-glucopyranose, β-L-mannpyranose, β-L-glucopyranose, β-L-idopyranose, β-L-galactopyranose, β-L-talopyranose, β-L-psicopyranose, β-L- fructopyranose, β-L-sorbopyranose, β-L-tagatopyranose, β-L-ribofuranose, β-L-arabinofuranose, β-L-xylofuranose, β-L-lyxofuranose, β-L-allofuranose, β-L-altrofuranose, β-L-glucofuranose, β-L-mannofuranose, β-L-gulofuranose, β-L-idofuranose, β-L-galactofuranose, β-L-talofuranose, β-L-psicofuranose, β-L-fructofuranose, β-L-sorbofuranose, β-L-tagatof uranose, β-L- xylulofuranose, β-L-ribulofuranose, β-L-threofuranose, β-L-erythrofuranose, β-L-glucosamin, β-L-glucopyranuronsyre, β-L-rhamnopyranose.
6. Forbindelse ifølge et hvilket som helst af kravene 1 - 5, hvor saccharidan-tigenet A er et baterielt kapsel-saccharid, et saccharid af viralt glycoprotein, et saccharidantigen af sporozoer eller parasitter, et saccharidantigen af patogene svampe eller et saccharidantigen, som er specifikt for cancerceller.
7. Forbindelse ifølge et hvilket som helst af kravene 1 - 6 til anvendelse som farmaceutisk aktivt stof i medicin eller til anvendelse ved vaccination mod infektionssygdomme.
8. Forbindelse ifølge krav 7, hvor infektionssygdommen er forårsaget af et patogen valgt fra gruppen omfattende: Allochromatium vinosum, Acinetobacter baumanii, Bacillus anthracis, Campylobacter jejuni, Clostridium spp., Citrobacter spp., Escherichia coli, Entero-bacter spp., Enterococcus faecalis., Enterococcus faecium, Francisella tula-rensis, Haemophilus influenzae, Helicobacter pylori, Klebsiella spp., Listeria monocytogenes, Moraxella catharralis, Mycobacterium tuberculosis, Neisseria meningitidis, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella spp., Serratia spp., Shigella spp., Stenotrophomonas maltophilia, Staphylococcus aureus, Staphylococcus epi-dermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Yersinia pestis, Yersinia enterocolitica, influenzavirus, human immundefektvirus ("HIV"), herpes simplex virus ("HSV", type 1 eller 2), human papillomavirus ("HPV", type 16 eller 18), hu- man cytomegalovirus ("HCMV") eller human hepatitis B- eller C-virus ("HBV", type B; "HCV", type C).
9. Forbindelse ifølge krav 6, hvor det bakterielle kapsel-saccharid tilhører bakterier udvalgt blandt: Allochromatium vinosum, Acinetobacter baumanii, Bacillus anthracis, Campylobacter jejuni, Clostridium spp., Citrobacter spp., Escherichia coli, Entero-bacter spp., Enterococcus faecalis., Enterococcus faecium, Francisella tula-rensis, Haemophilus influenzae, Helicobacter pylori, Klebsiella spp., Listeria monocytogenes, Moraxella catharralis, Mycobacterium tuberculosis, Neisseria meningitidis, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella spp., Serratia spp., Shigella spp., Stenotrophomonas maltophilia, Staphylococcus aureus, Staphylococcus epi-dermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Yersinia pestis og Yersinia enterocolitica.
10. Forbindelse ifølge krav 6, hvor saccharidet af virale glycoproteiner tilhører vira udvalgt blandt: Adenovira, Ebolavirus, Epstein-Barr-virus, Flavivirus, FSME-virus, Influenzavirus, Hanta-virus, human immundefektvirus ("HIV"), herpes simplex virus ("HSV", type 1 eller 2), human herpes virus 6 (HHV-6), human papillomavirus ("HPV", type 16 eller 18), human cytomegalovirus ("HCMV"), human hepatitis B- eller C-virus ("HBV", type B; "HCV", type C), Lassavirus, Lyssavirus (EBL 1 eller EBL 2), Marburgvirus, Norovirus, Parvovirus B19, Pestvirus, Poliovirus, Rhinovirus, Rotavira, SARS-associeret Coronavirus, Varicella-Zoster-virus.
11. Forbindelse ifølge krav 6, hvor saccharidantigenet af sporozoer eller parasitter tilhører sporozoer eller parasitter udvalgt blandt: Babesia, Balantidium, Besnoitia, Blastocystis, Coccidia, Cryptosporidium, Cytauxzoon, Cyclospora, Dientamoeba, Eimeria, Entamoeba, Enterocyto-zoon, Enzephalitozoon, Eperythrozoon, Giardia, Hammondia, Isospora, Lei-shmania, Microsporidia, Naegleria, Plasmodium, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, Plasmodium knowlesi, Pneumocystis, Schistosoma, Sarcocystis, Theileria, Trichinella, Toxoplasma, Trichomonas, Trypanosoma, Unicaria, Cestoda, Dipylidium, Dranunculus, Echinococcus, Fasciola, Fasciolopsis, Taenia, Ancylostoma, Ascaris, Brugia, Enterobius, Loa loa, Mansonella, Necator, Oncocerca, Strongyloides, Strongylus, Toxocara, Toxascaris, Trichuris eller Wucheria.
12. Forbindelse ifølge krav 6, hvor saccharidantigenet af svampe tilhører svampe udvalgt blandt: Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton interdigi-tale, T. schonleinii, T. verrucosum, T. violaceum, T. tonsurans, Trichophyton spp., M. canis, Candida albicans, C. guillermondii, C. krusei, C. parapsilosis, C. tropicalis, C. glabrata, Candida spp., Microsporum spp., Microsporum canis, Microsporum audonii, Microsporum gypseum, M. ferrugineum, Trichos-porum beigelii, Trichosporum inkiin, Aspergillus niger, Alternaria, Acremoni-um, Fusarium eller Scopulariopsis.
13. Forbindelse ifølge krav 6, hvor saccharidantigenet, som er specifikt for cancerceller, tilhører gruppen af cancere udvalgt blandt: blærecancer, brystcancer, colon- og rektalcancer, endometriecancer, nyrecancer (renalcellecancer), leukæmi, lungecancermelanom, Non-Hodgkin lym-fom, pancreascancer, prostatacancer, cancer i skjoldbruskkirtlen.
14. Forbindelse ifølge et hvilket som helst af kravene 1 - 6, hvor det gennemsnitlige forhold mellem kulhydratantigenet A og glycolipid (L-CH-CA) er mellem 1:4 og 1:100 (n/n).
15. Vaccineformulering omfattende en forbindelse eller en blanding af forskellige forbindelser ifølge et hvilket som helst af kravene 1-14.
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AU2013237497A1 (en) | 2014-10-02 |
CA2866978A1 (en) | 2013-09-26 |
JP5933106B2 (ja) | 2016-06-08 |
US20150238597A1 (en) | 2015-08-27 |
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