Novel compounds

• US 20060233839A1
• Filed: 02/24/2004
• Published: 10/19/2006
• Est. Priority Date: 02/26/2003
• Status: Abandoned Application

• Current Assignee: Glaxosmithkline Biologicals SA (GSK plc)
• Original Assignee: Glaxosmithkline Biologicals SA (GSK plc)
• Inventors: Jacquet, Alain
• Application Number:
  US10/547,206
• Publication Number:
  US 20060233839A1
• Time in Patent Office: Days
• US Class Current: 424/275.100
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 14/43531 from mites

Abstract

The present invention provides a novel treatment for allergy comprising the provision of a recombinant Der p 1/ProDer p 1/PreProDer p 1 allergen derivative, ProDer p 3 or a recombinant ProDer p 3/Der p 3/PreProDer p 3 allergen derivative with hypoallergenic activity. Pharmaceutical compositions comprising said mutant allergens which stimulate a Th1-type immune response in allergic or naïve individuals thereby reducing the potential for an allergic response upon contact with the wild-type allergen, are also provided.

Claims

1. A recombinant Dermatophagoides pteronyssinus Der p 1 protein allergen derivative wherein said allergen derivative has a significantly reduced allergenic activity compared to that the wild-type allergen in which said derivative has been genetically mutated and in which the mutant comprises the three following mutations:

a mutation of the cysteine 71 residue, a mutation of the cysteine 103 residue and a mutation of the cysteine 117 residue.

4. An isolated nucleic acid molecule encoding a mutated version of an allergen as claimed in claim 1.

5. A nucleic acid sequence according to claim 4 wherein the codon usage pattern resembles that of highly expressed mammalian genes.

6. An expression vector containing a nucleic acid of claim 4.

7. A host cell transformed with a nucleic acid sequence of claim 4 or with a vector as claimed in claim 6.

8. An immunogenic composition comprising a recombinant protein or mutant allergen as claimed in claim 1, or an encoding polynucleotide as claimed in claim 4, and, optionally, an adjuvant.

9. An immunogenic composition as claimed in claim 8, wherein the adjuvant is a preferential stimulator of Th1-type immune responses.

10. An immunogenic composition as claimed in claim 8 wherein the adjuvant comprises one or more of 3D-MPL, QS21, a CpG oligonucleotide, a polyethylene ether or ester or a combination of two or more of these adjuvants.

11. An immunogenic composition as claimed in claim 8 wherein the allergen is presented in an oil in water or a water in oil emulsion vehicle.

13. Use of a recombinant protein or mutant allergen as claimed in claim 1 in the manufacture of a medicament for the treatment of allergy.

14. A method of treating a patient suffering from or preventing a patient susceptible to allergic responses, comprising administering to said individual an immunogenic composition as claimed in claim 8.

20. An isolated nucleic acid molecule encoding a mutated version of an allergen as claimed in claim 1.

22. An expression vector containing a nucleic acid of claim 20.

23. A host cell transformed with a nucleic acid sequence of claim 20 or with a vector as claimed in claim 22.

2. A recombinant Dermatophagoides pteronyssinus Der p 1 protein allergen derivative wherein said allergen derivative has a significantly reduced allergenic activity compared to that the wild-type allergen in which said derivative has been genetically mutated and in which the mutant comprises a deletion of amino acid residues 147 to 160 of Der p 1 or residues 227-140 of ProDer p 1.

3. A recombinant mutant allergen having any of the sequences selected from the group consisting of:

, SEQ ID NO;

15, SEQ ID NO;

17.

12. A immunogenic composition as claimed herein for use in medicine.

15. A Dermatophagoides pteronyssinus ProDer p 3 or PreProDer p 3 protein allergen or derivative thereof, wherein said ProDer p 3, PreProDer p 3 or allergen derivative has a significantly reduced allergenic activity compared to Der p 3.

16. An allergen or derivative as claimed in claim 15, wherein said allergen or derivative has been thermally treated.

17. A allergen or derivative as claimed in claim 15, wherein said allergen or derivative has been genetically mutated.

18. A allergen or derivative as claimed in claim 17, wherein the mutation comprises a mutation of a cysteine residue.

24. An immunogenic composition comprising a recombinant protein or mutant allergen as claimed in claim 15, or an encoding polynucleotide as claimed in claim 20, and, optionally, an adjuvant.

25. An immunogenic composition as claimed in claim 24, wherein the adjuvant is a preferential stimulator of Th1-type immune responses.

26. An immunogenic composition as claimed in claim 24 wherein the adjuvant comprises one or more of 3D-MPL, QS21, a CpG oligonucleotide, a polyethylene ether or ester or a combination of two or more of these adjuvants.

27. An immunogenic composition as claimed in claim 24 wherein the allergen is presented in an oil in water or a water in oil emulsion vehicle.

29. Use of a recombinant protein or mutant allergen as claimed in claim 15 in the manufacture of a medicament for the treatment of allergy.

30. A method of treating a patient suffering from or preventing a patient susceptible to allergic responses, comprising administering to said individual an immunogenic composition as claimed in claim 24.

19. A recombinant allergen having the sequence of:

SEQ ID NO;

19.

21. An isolated nucleic acid molecule having the sequence of any of SEQ ID NOs.20 or 21.

28. A immunogenic composition as claimed herein for use in medicine.