RU2011152602A

RU2011152602A - SYNTHETIC Glucopyranosyl lipid adjuvants

Info

Publication number: RU2011152602A
Application number: RU2011152602/04A
Authority: RU
Inventors: Стивен Дж. Рид; Даррик КАРТЕР
Original assignee: Инфекшес Дизиз Рисерч Инститьют
Priority date: 2009-06-05
Filing date: 2010-06-04
Publication date: 2013-07-20

Claims

1. GLA compound having the following structure (I)

(I)

or its pharmaceutically acceptable salt, where:

L ₁ , L ₂ , L ₃ , L ₄ , L ₅ and L ₆ are the same or different and independently represent —O—, —NH— or - (CH ₂ ) -;

L ₇ , L ₈ , L ₉ and L ₁₀ are the same or different and are independently absent or are - (= O) -;

Y ₁ represents an acid functional group;

Y ₂ and Y ₃ are the same or different and independently represent —OH, —SH or an acid functional group;

Y ₄ represents —OH or —SH;

R ₁ , R ₃ , R ₅ and R ₆ are the same or different and independently represent C _8-13 alkyl; and

R ₂ and R ₄ are the same or different and independently represent C _6-11 alkyl.

2. The GLA compound of claim 1, wherein L ₅ and L _{6 are} both —O— and each of L ₇ , L ₈ , L ₉ and L ₁₀ is —C (= O) -, and the GLA compound has the following formula (II)

(Ii)

3. GLA compound according to claim 2, where each of R ₁ , R ₃ , R ₅ and R ₆ is C _x alkyl, where x is constant and selected from integers from 8 to 13, and R ₂ and R _{4 are} both are C _x-2 alkyl, and the GLA compound has the following formula (III)

(III)

4. GLA compound according to claim 3, where x is selected from integers from 10 to 12.

5. The GLA compound of claim 4, wherein x is 11 and the GLA compound has the following structure (IV)

(Iv)

6. The GLA compound of claim 2, wherein Y ₁ is —OP (= O) (OH) ₂ and each of Y ₂ , Y _3, and Y ₄ is —OH, and GLA compounds have the following formula (V)

(V)

7. The GLA compound of claim 2, wherein L ₁ and L _{3 are} both —O—, and L ₂ and L _{4 are} both —NH—, and the GLA compound has the following formula (VI)

(Vi)

8. The GLA compound of claim 2, wherein Y ₁ is —OP (O) (OH) ₂ , each of Y ₂ , Y ₃ and Y ₄ is —OH, L ₁ and L _{3 are} both —O— , and L ₂ and L _{4 are} both —NH—, and the GLA compound has the following formula (VII)

(Vii)

9. The GLA compound of claim 2, wherein Y ₁ is —OP (O) (OH) ₂ , each of Y ₂ , Y ₃ and Y ₄ is —OH, L ₁ and L ₃ are —O—, L ₂ and L _{4 are} both —NH—, each of R ₁ , R ₃ , R ₅ and R ₆ is C _x alkyl, where x is constant and selected from integers from 8 to 13, and R ₂ and R ₄ both represent C _x-2 alkyl, and the GLA compound has the following formula (VIII)

(Viii)

10. The GLA compound of claim 9, wherein x is 11 and the GLA compound has the following structure (IX)

(Ix)

11. A vaccine composition containing a compound according to any one of claims 1 to 10 in combination with an antigen or with a recombinant expression vector encoding an antigen.

12. The vaccine composition according to claim 11, where the recombinant expression construct is a viral vector.

13. The vaccine composition of claim 12, wherein the viral vector is selected from the group consisting of an adenoviral vector, an adeno-associated viral vector, a herpes virus vector, a lentiviral vector, a poxivirus vector, and a retroviral vector.

14. A method of inducing or enhancing an antigen-specific immune response in a subject, comprising administering to the subject a vaccine composition according to claim 11.

15. A pharmaceutical composition comprising a compound according to any one of claims 1 to 10 and a pharmaceutically acceptable carrier or excipient.

16. A method of stimulating a non-specific immune response in a subject, comprising administering to the subject a pharmaceutical composition according to claim 15.