Login| Sign Up| Help| Contact|

Patent Searching and Data


Title:
NOVEL SEMI-SYNTHETIC MENINGOCOCCAL CONJUGATE VACCINE
Document Type and Number:
WIPO Patent Application WO/2015/181834
Kind Code:
A4
Abstract:
The present invention relates to novel semi-synthetic meningococcal conjugate vaccine comprising novel synthetic oligosaccharide conjugated to a carrier protein. The present invention also relates to novel synthetic meningococcal oligosaccharide and a process for its preparation.

Inventors:
GOEL, AKSHAY (Biological E. Ltd, 18/1 & 3 Azamabad,,Hyderabad - 0, Telangana, 500 02, IN)
RENUKUNTLA SANTOSH (Biological E. Ltd, 18/1 & 3 Azamabad,,Hyderabad - 0, Telangana, 500 02, IN)
KOWLAKUNTLA ESWARA (Biological E. Ltd, 18/1 & 3 Azamabad,,Hyderabad - 0, Telangana, 500 02, IN)
DETLA, MAHIMA (Biological E. Ltd, 18/1 & 3 Azamabad,,Hyderabad - 0, Telangana, 500 02, IN)
MANTENA, NARENDRA DEV (Biological E. Ltd, 18/1 & 3 Azamabad,,Hyderabad - 0, Telangana, 500 02, IN)
Application Number:
IN2015/000218
Publication Date:
March 10, 2016
Filing Date:
May 22, 2015
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
BIOLOGICAL E LIMITED (18/1 & 3, Azamabad,Hyderabad - 0, Telangana, 500 02, IN)
International Classes:
A61K39/095; A61P31/04; C07H1/00; C07H15/04; C07K1/107; C08B37/00
Attorney, Agent or Firm:
KAYSER, AVESH (KAYSER & COMPANY, 2nd floor 20, Raja Bahadur Mansion,,Ambalal Doshi Marg, Fort,,Mumbai - 1, Maharashtra, 400 00, IN)
Download PDF:
Claims:
AMENDED CLAIMS

received by the International Bureau on 15 January 2016 (15.01 .2016)

1. A novel synthetic meningococcal C oligosaccharide of formula (I)

(0

wherein m is an integer from 2-10 and n is an integer from 6-10;

Ri and R2 are same or different and independently represent H, Ci-6alkyl, acetyl;

R3 represents azide, NR5R6, wherein R5 and R6 are same or different and independently represent H, Ci-6 alkyl, aryl;

R4 represents H , Ci-6 alkyl, alkali metal cation selected from Li, Na, and Cs;

2. A novel semisynthetic meningococcal C vaccine of the formula (II)

(10

wherein m is an integer from 2-10 and n is an integer from 6-10;

Ri and R2 are same or different and independently represent H, Ci-6alkyl, acetyl;

R5 represent H, Ci-6 alkyl, aryl;

R4 represents H or Ci-6 alkyl;

CP represents a carrier protein;

Li is a bond, -O-, -S-, -NRs-, -C(-O)-, -NRsC(=O)-, -NR*C(=O)O-, -C(=0)NR8-, - OC(=O)NR8-, -SC(=O)-, -C(=O)S-, -OC(=O)-, -C(=O)O-, -NR8C(=S)-, -C(=S)NRs-, trans -CR9=CR9, 'tis -CR9=CR9 , -C≡C-, -OC(R9)2-, -C(R9)20-, -NR8C(R9)2-, - C(R9)2NR8- -SC(R9)2-, -C(R9)2S-, -S(=O)2O-, -OS(=O)2— , -S(=O)2NR8-, -NR8S(=O)2- , or an optionally substituted Ci-2ohydrocarbon chain, optionally wherein one or more carbon units of the hydrocarbon chain is replaced with -O-, -S-, -NRs-, -C(=O)-, NRsC(=O)-, -NRsC(=O)O-, -C(=O)NRs-, -OC(=O)NR8- -SC(=0)-, -C(=O)S- - OC(=O)-, -C(=O)O-, -NR8C(=S)-, -C(=S)NRs-, trans-CR9=CR9-, c«-CR9=CR9-, - C=C- -S(=O)2O-, -OS(=O)2-, -S(=O)2NRs-, or -NRsS(=0)2 , wherein Kg is hydrogen, optionally substituted Ci-6 alkyl, or a nitrogen protecting group, or R8 is joined with the adjacent carbon atom to form an optionally substituted heterocyclic ring, and wherein each occurrence of R is independently selected from the group consisting of hydrogen, halogen, optionally substituted Ci-10 alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl, or R9 is

6 joined with the adjacent carbon or nitrogen or oxygen atom to form an optionally substituted carbocyclic or heterocyclic ring, or two RLlb groups are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;

L2 is a moiety derived from a crosslinking reagent capable of crosslinking the carrier and Li and is selected from

R.7 is independently hydrogen, optionally substituted Ci-6 alkyl, optionally substituted acyl, or a nitrogen protecting group.

3. A process for the preparation of novel semisynthetic meningococcal conjugate vaccine as claimed in claim 2, which comprises the steps of:

a) Synthesising meningococcal oligosaccharide of formula (I) of claim 1, b) activation of oligosaccharide,

c) derivatization of carrier protein,

d) conjugation of meningococcal oligosaccharide obtained in step (b) with carrier protein and

e) purification of conjugate vaccine obtained in step (d).

4. The process as claimed in claim 3, wherein the activation of oligosaccharide is carried out using bromoacetic N-hydroxysuccinimide (NHS) ester, 6- Maleimidohexanoic acid NHS ester, 6-(iodoacetamido)caproic acid NHS ester, maleimidopropionoic acid NHS ester, maleimidoacetic acid NHS ester, maleimidobenzoic acid NHS ester.

5. The process as claimed in claim 3, wherein the derivatization of carrier protein is carried out using 6-3 -(acetyl thio) propionic acid N-hydroxysuccinimide ester, acetylthio-hexadecanoic acid NHS ester.

6. Semisynthetic meningococcal C conjugate vaccine of claim 2, wherein the carrier protein is selected from Tetanus toxoid, diphtheria toxoid or CRM 197.

7. Synthetic meningococcal oligosaccharides of claim 1, which are selected from:

7

8. An immunogenic composition comprising novel semisynthetic meningococcal C conjugate of claim 6 is selected from:

8

wherein CRM 197 is cross reacting moiety 197, DT is diphtheria toxoid and TT is tetanus toxoid.

9. A pharmaceutical composition comprising (a) a novel semisynthetic meningococcal C conjugate vaccine as claimed in claim 2 and (b) a pharmaceutically acceptable carrier.

10. The composition of claim 9, further comprising a saccharide antigen from one or more of serogroups A, W135 and Y of N. meningitidis, the saccharide being an oligosaccharide and being conjugated to a carrier protein.

11. The composition of claim 9 and 10, further comprising a vaccine adjuvant.

12. The composition of any one of claims 9 to 11, which is a vaccine against a disease caused by Neisseria meningitidis.

13. The use of a novel semisynthetic meningococcal C conjugate vaccine of formula (I), of any one of claims 9 to 12, in the manufacture of a medicament for preventing or treating a disease caused by one or more capsulate bacteria.

9

14. The composition of claim 9 further comprising 1 μg to 10 μg of each polysaccharide selected from Meningococcal serogroups A, Y and W-135, conjugated individually to 5 to 20 μg of carrier protein.

10