Carbocyclic derivatives and conjugated derivatives thereof, and their use in vaccines

1 . An oligomer of Formula (Ia) or (Ib):

wherein

n is ≥6;

R is H or —P(O)(OR″) 2 , wherein R″ is H or a pharmaceutically acceptable phosphate counterion;

R′ is H or a pharmaceutically acceptable phosphate counterion;

R x is H or —C(O)CH 3 and may be the same or different in each repeat unit;

R y is H or —C(O)CH 3 and may be the same or different in each repeat unit;

wherein at least one of R x or R y is —C(O)CH 3 in at least one repeat unit, wherein both of R x and R y are —C(O)CH 3 in at least one same repeat unit; and wherein taken together, about 50 to 90% of R x and R y in the oligomer is —C(O)CH 3 ;

Az is an aza substituent selected from the group consisting of —NH(CO)R 1 , —N(R 1 ) 2 and —N 3 , wherein R 1 is independently selected from the group consisting of H, a linear or branched C 1 -C 6 -alkyl and a linear or branched C 1 -C 6 -haloalkyl;

Z is (i) a protecting group,

(ii) a functional linker for conjugation to a protein,

or (iii) a linear or branched C 1 -C 6 alkyl, optionally substituted phenyl, —C(O) Y, or a linear or branched C 1 -C 6 -alkyl-X,

wherein Y is H, a linear or branched C 1 -C 6 -alkyl or a protecting group, and

wherein X is —NH 2 , —N 3 , —C≡CH, —CH═CH 2 , —SH or —S—C≡N.

2 . The oligomer of claim 1 , which is defined by Formula (Ia).

3 . The oligomer of claim 1 , wherein n is 8.

4 . The oligomer of claim 1 , wherein n is 8 to 15.

5 . The oligomer according claim 1 , wherein Az is —NHC (O)CH 3 .

6 . The oligomer according to claim 1 , wherein both of R x and R y are —C(O)CH 3 in 40 to 50% of the repeat units of the oligomer.

7 . The oligomer according to claim 6 , wherein in 10 to 30% of the remaining repeat units of the oligomer one of R x or R y is —C(O)CH 3 , the rest of the repeat units in the oligomer having R x ═R y ═H.

8 . An oligomer conjugate antigen of Formula (IIa) or (IIb):

wherein

n is ≥6;

R is H or —P(O)(OR″) 2 , wherein R″ is H or a pharmaceutically acceptable phosphate counterion;

R′ is H or a pharmaceutically acceptable phosphate counterion;

R x is H or —C(O)CH 3 and may be the same or different in each repeat unit;

R y is H or —C(O)CH 3 and may be the same or different in each repeat unit;

wherein at least one of R x or R y is —C(O)CH 3 in at least one repeat unit, wherein both of R x and R y are —C(O)CH 3 in at least one same repeat unit; and wherein taken together, about 50 to 90% of R x and R y in the oligomer is —C(O)CH 3 ;

Az is an aza substituent selected from the group consisting of —NH(CO)R 1 , —N(R 1 ) 2 and —N 3 , wherein R 1 is independently selected from the group consisting of H, a linear or branched C 1 -C 6 -alkyl and a linear or branched C 1 -C 6 -haloalkyl;

Z is a linker or a bond; and

P is a protein.

9 . The conjugate of claim 8 , wherein P is an inactivated bacterial toxin selected from diphtheria toxoid (DT), tetanus toxoid (TT), CRM 197 , E. coli ST and Pseudomonas aeruginosa exotoxin (rEPA), or P is a polyamino acid such as poly(lysine:glutamic acid) or P is hepatitis B virus core protein or SPR96-2021 or N. meningitidis serogroup B antigen fHbp-231.

10 . The conjugate of claim 8 , wherein P is CRM 197 .

11 . The conjugate of claim 8 , wherein Z is a linker having the following formula:

wherein * represents the point of attachment, and wherein

p is independently selected from 1 to 10; and

X is selected from —O—, —S— and —NH—; or

wherein Z is a linker having the following formula:

wherein m is independently selected from 1 to 10.

12 . A conjugate according to claim 8 having the following structure:

wherein n, R, R x and R y are as defined in any one of claims 1 to 8 .

13 . An immunogenic composition comprising (a) a conjugate according to claim 8 ; and (b) at least one pharmaceutically acceptable excipient.

14 . The immunogenic composition according to claim 13 , further comprising an adjuvant.

15 . The immunogenic composition according to claim 13 , further comprising at least one antigen derived from one of N. meningitidis serogroup C, W135, Y and optionally A.

16 . An immunogenic composition according to claim 13 for use in the treatment or prevention of Meningitis A, C, W135 or Y.

17 . An immunogenic composition according to claim 13 for use in inducing an immune response to Meningitis A, C, W135 or Y.

18 . A method for the treatment or prevention of Meningitidis A, C, W135 or Y in a subject, the method comprising administering to the subject a therapeutically or prophylactically effective amount of a conjugate according to claim 8 .

19 . A method of inducing an immune response to Meningitis A, C, W135 or Y in a subject, the method comprising administering to the subject an immunologically effective amount of an immunogenic composition according to claim 13 .

20 . The oligomer of claim 8 , wherein n is 7 to 14.

21 . The oligomer of claim 8 , wherein n is 8.

22 . The oligomer according to claim 8 , wherein Az is —NHC (O)CH 3 .

23 . The oligomer according to claim 8 , wherein both of Rx and Ry are —C(O)CH 3 in 40 to 50% of the repeat units of the oligomer.

24 . The oligomer according to claim 23 , wherein in 10 to 30% of the remaining repeat units of the oligomer one of R x or R y is —C(O)CH 3 , the rest of the repeat units in the oligomer having R x ═R y =H.