Synthetic glucopyranosyl lipid adjuvants

• US 9,480,740 B2
• Filed: 03/21/2014
• Issued: 11/01/2016
• Est. Priority Date: 06/05/2009
• Status: Active Grant

• Current Assignee: Infectious Disease Research Institute
• Original Assignee: Infectious Disease Research Institute
• Inventors: Reed, Steven G., Carter, Darrick
• Primary Examiner(s): Mcintosh, III, Traviss C
• Application Number:
  US14/222,481
• Publication Number:
  US 20140322268A1
• Time in Patent Office: 956 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/525 Virus
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2039/575 humoral response
• CPC Class Codes: A61K 31/665 having oxygen as a ring hetero atom, e.g. fosfomycin
• CPC Class Codes: A61K 31/7016 Disaccharides, e.g. lactose, lactulose lactobionic acid A61K31/7032
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/04 Mycobacterium, e.g. Mycobacterium tuberculosis
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61K 39/235 Adenoviridae
• CPC Class Codes: A61K 39/245 Herpetoviridae, e.g. herpes simplex virus
• CPC Class Codes: A61K 39/275 Poxviridae, e.g. avipoxvirus
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07H 15/04 : attached to an oxygen atom of the saccharide radical
• CPC Class Codes: C07H 15/12 : attached to a nitrogen atom of the saccharide radical
• CPC Class Codes: C07H 15/20 : Carbocyclic rings

Abstract

Compounds, particularly, glucopyranosyl lipid adjuvant (GLA) compounds, having the following structure (I) are provided:

or a pharmaceutically acceptable salt thereof, wherein L₁, L₂, L₃, L₄, L₅, L₆, L₇, L₈, L₉, L₁₀, Y₁, Y₂, Y₃, Y₄, R₁, R₂, R₃, R₄, R₅, R₆, are as defined herein. Pharmaceutical compositions, vaccine compositions, and related methods for inducing or enhancing immune responses, are also provided.

Claims

1. A vaccine composition comprising a compound having the following formula, or a pharmaceutically acceptable salt thereof:

2. A vaccine composition comprising a compound having the following formula, or a pharmaceutically acceptable salt thereof:

3. A method for stimulating an immune response in a subject comprising administering to the subject a composition comprising a compound having the following formula, or a pharmaceutically acceptable salt thereof:

4. A method for stimulating an immune response in a subject comprising administering to the subject a composition comprising a compound having the following formula, or a pharmaceutically acceptable salt thereof:

5. A method of eliciting or enhancing an immune response in a subject afflicted with cancer, comprising administering to the subject a composition comprising a compound having the following formula, or a pharmaceutically acceptable salt thereof:

6. A method of eliciting or enhancing an immune response in a subject afflicted with cancer, comprising administering to the subject a composition comprising a compound having the following formula, or a pharmaceutically acceptable salt thereof:

7. A method of eliciting or enhancing an immune response in a subject afflicted with infectious disease, comprising administering to the subject a composition comprising a compound having the following formula, or a pharmaceutically acceptable salt thereof:

8. A method of eliciting or enhancing an immune response in a subject afflicted with infectious disease, comprising administering to the subject a composition comprising a compound having the following formula, or a pharmaceutically acceptable salt thereof:

9. A method of eliciting or enhancing an immune response in a subject afflicted with autoimmune disease, comprising administering to the subject a composition comprising a compound having the following formula, or a pharmaceutically acceptable salt thereof:

10. A method of eliciting or enhancing an immune response in a subject afflicted with autoimmune disease, comprising administering to the subject a composition comprising a compound having the following formula, or a pharmaceutically acceptable salt thereof: