US2016375120A1PendingUtilityA1
Synthetic oligosaccharides for moraxella vaccine
Est. expiryApr 27, 2030(~3.8 yrs left)· nominal 20-yr term from priority
C07H 15/26G01N 2333/212A61K 39/1045C07H 15/04G01N 33/56911C07H 3/06A61K 2039/6081C07K 2317/21C07K 2317/14C07K 19/00C07K 16/1203A61P 31/04C07K 2317/20
51
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present invention provides synthetic Moraxella catarrhalis lipooligosaccharide (LOS)-based oligosaccharides and conjugates containing various M. catarrhalis serotype-specific oligosaccharide antigens or various core M. catarrhalis oligosaccharide structures or motifs corresponding to one or more of the three major serotypes and/or members within a given serotype. The oligosaccharides may be synthesized by a chemical assembly methodology relying on a limited number of monosaccharide and disaccharide building blocks. The invention further provides M. catarrhalis LOS-based immunogenic and immunoprotective compositions and antibodies derived therefrom for diagnosing, treating, and preventing infections caused by M. catarrhalis.
Claims
exact text as granted — not AI-modified1 . A synthetic oligosaccharide 1a or 1b:
where each of R 1 and R 2 is independently H, a monosaccharide or a oligosaccharide, X is H or a protecting group, L is a linker, and Y is H or a carrier.
2 . The oligosaccharide of claim 1 , which is 1b.
3 . The oligosaccharide of claim 1 , where R 1 is H.
4 . The oligosaccharide of claim 1 , where R 2 is H.
5 . The oligosaccharide of claim 1 , where at least one of R 1 or R 2 is a mono-, di-, tri- or tetra-saccharide.
6 . The oligosaccharide of claim 1 , where at least one of R 1 and R 2 is a monosaccharide.
7 . The oligosaccharide of claim 1 , where each of R 1 and R 2 is independently a monosaccharide selected from the group consisting of Glc, Gal, and GlcNAc.
8 . The oligosaccharide of claim 1 , where the oligosaccharide comprises monosaccharide units selected from the group consisting of Glc, Gal, GlcNAc, and Neu5Ac.
9 . The oligosaccharide of claim 1 , where R 1 is α-Glc-(1→2).
10 . The oligosaccharide of claim 1 , where R 1 is β-Gal-(1→4)-α-Glc.
11 . The oligosaccharide of claim 1 , where R 1 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc.
12 . The oligosaccharide of claim 1 , where R 1 is H and R 2 is H.
13 . The oligosaccharide of claim 1 , where R 1 is H and R 2 is α-Glc(1→2).
14 . The oligosaccharide of claim 1 , where R 1 is H and R 2 is β-Gal-(1→4)-α-GlcNAc.
15 . The oligosaccharide of claim 1 , where R 1 is H and R 2 is α-Gal-(1→4)-β-Gal-(1→4)-α-GlcNAc.
16 . The oligosaccharide of claim 1 , where R 1 is H and R 2 is β-Gal-(1→4)-α-Glc(1→2).
17 . The oligosaccharide of claim 1 , where R 1 is H and R 2 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc(1→2).
18 . The oligosaccharide of claim 1 , where R 1 is H and R 2 is α-GlcNAc(1→2).
19 . The oligosaccharide of claim 1 , where R 1 is α-Glc-(1→2) and R 2 is H.
20 . The oligosaccharide of claim 1 , where R 1 is α-Glc-(1→2) and R 2 is α-GlcNAc.
21 . The oligosaccharide of claim 1 , where R 1 is α-Glc-(1→2) and R 2 is α-Glc-(1→2).
22 . The oligosaccharide of claim 1 , where R 1 is α-Glc-(1→2) and R 2 is β-Gal-(1→4)-α-Glc.
23 . The oligosaccharide of claim 1 , where R 1 is α-Glc-(1→2) and R 2 is β-Gal-(1→4)-α-GlcNAc.
24 . The oligosaccharide of claim 1 , where R 1 is α-Glc-(1→2) and R 2 is α-Gal(1→4)-β-Gal(1→4)-α-Glc(1→2).
25 . The oligosaccharide of claim 1 , where R 1 is α-Glc-(1→2) and R 2 is α-Gal(1→4)-β-Gal(1→4)-α-GlcNAc(1→2).
26 . The oligosaccharide of claim 1 , where R 1 is β-Gal-(1→4)-α-Glc and R 2 is H.
27 . The oligosaccharide of claim 1 , where R 1 is β-Gal-(1→4)-α-Glc and R 2 is α-Glc(1→2).
28 . The oligosaccharide of claim 1 , where R 1 is β-Gal-(1→4)-α-Glc and R 2 is β-Gal-(1→4)-α-Glc(1→2).
29 . The oligosaccharide of claim 1 , where R 1 is β-Gal-(1→4)-α-Glc and R 2 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc(1→2).
30 . The oligosaccharide of claim 1 , where R 1 is β-Gal-(1→4)-α-Glc and R 2 is α-GlcNAc(1→2).
31 . The oligosaccharide of claim 1 , where R 1 is β-Gal-(1→4)-α-Glc and R 2 is β-Gal-(1→4)-α-GlcNAc(1→2).
32 . The oligosaccharide of claim 1 , where R 1 is β-Gal-(1→4)-α-Glc and R 2 is α-Gal-(1→4)-β-Gal-(1→4)-α-GlcNAc (1→2).
33 . The oligosaccharide of claim 1 , where R 1 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc and R 2 is H.
34 . The oligosaccharide of claim 1 , where R 1 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc and R 2 is α-Glc(1→2).
35 . The oligosaccharide of claim 1 , where R 1 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc and R 2 is α-GlcNAc.
36 . The oligosaccharide of claim 1 , where R 1 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc and R 2 is β-Gal-(1→4)-α-Glc.
37 . The oligosaccharide of claim 1 , where R 1 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc and R 2 is β-Gal-(1→4)-α-GlcNAc.
38 . The oligosaccharide of claim 1 , where R 1 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc and R 2 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc.
39 . The oligosaccharide of claim 1 , where R 1 is α-Gal-(1→4)-β-Gal-(1→4)-α-Glc and R 2 is α-Gal-(1→4)-β-Gal-(1→4)-α-GlcNAc.
40 . The oligosaccharide of any one of claims 1 to 39 , where L is an alkylene thiol linker.
41 . The synthetic oligosaccharide of any one of claims 1 to 40 , where Y is a carrier selected from the group consisting of proteins, peptides, lipids, polymers, dendrimers, virosomes, and virus-like particles or combination thereof.
42 . The synthetic oligosaccharide of claim 41 , where the carrier is a carrier protein.
43 . The synthetic oligosaccharide of claim 42 , where the carrier protein is selected from the group consisting of bacterial toxoids, toxins, exotoxins, and nontoxic derivatives thereof.
44 . The synthetic oligosaccharide of claim 43 , wherein the carrier protein is selected from the group consisting of tetanus toxoid, tetanus toxin Fragment C, diphtheria toxoid, CRM, cholera toxoid, Staphylococcus aureus exotoxins or toxoids, Escherichia coli heat labile enterotoxin, Pseudomonas aeruginosa exotoxin A, genetically detoxified variants thereof; bacterial outer membrane proteins, serotype B outer membrane protein complex (OMPC), outer membrane class 3 porin (rPorB), porins; keyhole limpet hemocyanine (KLH), hepatitis B virus core protein, thyroglobulin, albumins, and ovalbumin; pneumococcal surface protein A (PspA), pneumococcal adhesin protein (PsaA); purified protein derivative of tuberculin (PPD); transferrin binding proteins, peptidyl agonists of TLR-5; and derivatives and/or combinations of the above carriers.
45 . The synthetic oligosaccharide of claim 44 , wherein the carrier protein is selected from the group consisting of CRM 197, Neisseria meningitidis , bovine serum albumin (BSA), human serum albumin (HSA), poly(lysine:glutamic acid), flagellin of motile bacteria, and derivatives and/or combinations thereof.
46 . The synthetic oligosaccharide of claim 44 , wherein the carrier protein is selected from the group consisting of tetanus toxoid, CRM 197, and OMPC.
47 . A pharmaceutical composition comprising a least one oligosaccharide of any one of claims 1 to 46 in an effective amount to stimulate an immune response, optionally further comprising a pharmaceutically acceptable carrier.
48 . The pharmaceutical composition of claim 47 , further comprising an adjuvant.
49 . The pharmaceutical composition of any one of claim 47 or 48 wherein the immune response is an antigen-specific immune response.
50 . A composition comprising a synthetic oligosaccharide of any one of claims 1 to 46 and a pharmaceutically acceptable vehicle.
51 . The composition of claim 50 , comprising a plurality of different oligosaccharides, where each oligosaccharide is an antigen 1b.
52 . A composition comprising at least two oligosaccharides, wherein a first is a M. catarrhalis serotype C antigen and a second is a M. catarrhalis core antigen.
53 . The composition of claim 52 , further comprising a third oligosaccharide which is a M. catarrhalis serotype A antigen.
54 . The composition of claim 52 , further comprising a fourth oligosaccharide which is a M. catarrhalis serotype B antigen.
55 . The composition of claim 54 , further comprising a fourth oligosaccharide which is a M. catarrhalis serotype B antigen.
56 . A composition comprising at least two oligosaccharides, wherein a first is a M. catarrhalis serotype B antigen and a second is a M. catarrhalis core antigen.
57 . The composition of claim 56 , further comprising a third oligosaccharide which is a M. catarrhalis serotype A antigen.
58 . A composition comprising at least two oligosaccharides, wherein a first is a M. catarrhalis serotype A antigen and a second is a M. catarrhalis core antigen.
59 . A composition comprising at least two oligosaccharides, wherein a first is a M. catarrhalis serotype B antigen and a second is a M. catarrhalis serotype C antigen.
60 . The composition of claim 59 , further comprising a third oligosaccharide which is a M. catarrhalis serotype A antigen.
61 . A composition comprising at least two oligosaccharides, wherein a first is a M. catarrhalis serotype A antigen and a second is a M. catarrhalis serotype C antigen.
62 . A composition comprising at least two oligosaccharides, wherein a first is a M. catarrhalis serotype A antigen and a second is a M. catarrhalis serotype B antigen.
63 . The composition of any of claims 51 to 62 , further comprising an adjuvant.
64 . The composition of claim 63 , where the adjuvant is selected from the group consisting of aluminum salts, RIBI, toll-like receptor agonists, AS01 AS02 AS03, AS04, AS05, CpG-oligodeoxynucleotide, MF-59, Montanide ISA-51 VG, Montanide ISA-720, Quil A, QS21, synthetic saponins, immunostimulating complexes, stearyl tyrosine, virus-like particles, reconstituted influenza virosomes, cytokines, mast cell activator compound 48/80, liposomes, muramyl dipeptides, SAF-1, and combinations thereof.
65 . The composition of any of claims 51 to 62 , comprising an amount of at least one oligosaccharide sufficient to confer immunity against Moraxella.
66 . A composition comprising an oligosaccharide of any one of claims 1 to 46 as a vaccine.
67 . An antibody preparation against an oligosaccharide according to any one of claims 1 to 41 .
68 . The antibody preparation of claim 67 , where the antibody preparation comprises at least one member from the group consisting of polyclonal antibody, monoclonal antibody, mouse monoclonal IgG antibody, humanized antibody, chimeric antibody, single chain antibodies, fragment thereof, or combination thereof.
69 . A method of treating a disease associated with M. catarrhalis infection, comprising administering effective amount for inducing an immune response against Moraxella of an oligosaccharide of any of claims 1 to 46 or antibody thereto.
70 . A method of treating a disease associated with M. catarrhalis infection, comprising administering to a patient in need thereof a composition of any of claims 1 to 46 .
71 . The method of claim 69 or 70 , wherein the disease is COPD.
72 . The method of claim 69 or 70 , wherein the disease is AOM.
73 . The method of claim 69 or 70 , wherein the patient is human.
74 . A method for producing antibodies comprising:
(a) administering to a subject an effective amount of at least one oligosaccharide of any one of claims 1 to 41 , for producing antibodies specific for Moraxella ; optionally further comprising an adjuvant. (b) isolating antibodies from the subject.
75 . A method for producing monoclonal antibodies comprising:
(a) administering to a subject an effective amount of at least one oligosaccharide of any one of claims 1 to 41 , for producing antibodies specific Moraxella; (b) isolating antibodies from the subject. (c) fusing antibody producing cells from the subject to myeloma cells, and (d) harvesting antibodies produced from a fusion subclone.
76 . The method of claims 74 and 75 , wherein the subject is a rabbit.
77 . The method of claims 74 and 75 , wherein the subject is a human.
78 . An antibody producing cell obtainable by performing steps (a) to (c) of claim 75 .
79 . An antibody obtainable by performing steps (a) to (d) of claim 75 .
80 . A method of diagnosing the presence of Moraxella in a sample, comprising contacting the sample with an antibody of claim 67 , 68 , 78 , or 79 .
81 . A compound selected from the group consisting of:
82 . A compound of the formula:
where R is allyl or R═(CH 2 ) 3 Sac.
83 . A compound of the formula:
84 . A compound of the formula:
85 . A compound of the formula:
86 . A compound of the formula:
87 . A compound of the formula:
88 . A compound of the formula:
89 . A compound of the formula:
90 . A compound of the formula:
91 . A compound of the formula:
where Y is a carrier.
92 . The compound of claim 91 , where the carrier is a carrier protein.
93 . The compound of claim 92 , where the carrier protein is selected from the group consisting of bacterial toxoids, toxins, exotoxins, and nontoxic derivatives thereof.
94 . The compound of claim 92 , wherein the carrier protein is selected from the group consisting of tetanus toxoid, tetanus toxin Fragment C, diphtheria toxoid, CRM, cholera toxoid, Staphylococcus aureus exotoxins or toxoids, Escherichia coli heat labile enterotoxin, Pseudomonas aeruginosa exotoxin A, genetically detoxified variants thereof; bacterial outer membrane proteins, serotype B outer membrane protein complex (OMPC), outer membrane class 3 porin (rPorB), porins; keyhole limpet hemocyanine (KLH), hepatitis B virus core protein, thyroglobulin, albumins, and ovalbumin; pneumococcal surface protein A (PspA), pneumococcal adhesin protein (PsaA); purified protein derivative of tuberculin (PPD); transferrin binding proteins, peptidyl agonists of TLR-5; and derivatives and/or combinations of the above carriers.
95 . The compound of claim 92 , wherein the carrier protein is selected from the group consisting of CRM 197, Neisseria meningitides , bovine serum albumin (BSA), human serum albumin (HSA), poly(lysine:glutamic acid), flagellin of motile bacteria, and derivatives and/or combinations thereof.
96 . The compound of claim 92 , wherein the carrier protein is selected from the group consisting of tetanus toxoid, CRM 197, and OMPC.
97 . A method of synthezing a compound of the formula:
comprising contacting a first intermediate of the formula:
with a second intermediate of the formula:
where R 7 is a Bn or is a monosaccharide or oligosaccharide;
R 8 is a Bn or is a monosaccharide or oligosaccharide; and
R 9 is a protecting group or linker consisting of —CH 2 CH═CH 2 , —CH 2 CCH, pentenyl, alkenylene, oligoalkyl thiol.
98 . The method of claim 97 , where the compound is:Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.