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BR-112013003772-B1 - N-(4-{[4-AMINO-2-BUTYL-1H-IMIDAZO[4,5-C]QUINOLIN-1-YL]OXY}BUTYL) OCTADECANAMIDE COMPOUND, PHARMACEUTICAL COMPOSITION AND USE OF SAID COMPOUND

BR112013003772B1BR 112013003772 B1BR112013003772 B1BR 112013003772B1BR-112013003772-B1

Abstract

LIPID IMMUNE RESPONSE MODIFYING COMPOUND COMPOSITIONS, FORMULATIONS AND METHODS. The compound N-(4-{[4-amino-2-butyl-1H-imidazo{4,5--c}quinolin-1-yl]oxy}butyl) octadecanamide is a useful drug compound for enhancing the immune response and can be used, for example, as a vaccine adjuvant and a cancer treatment.

Inventors

  • PAUL D. WIGHTMAN

Assignees

  • SOLVENTUM INTELLECTUAL PROPERTIES COMPANY

Dates

Publication Date
20260317
Application Date
20110816
Priority Date
20100817

Claims (7)

  1. 1. Compound, CHARACTERIZED by the fact that it has the formula: including any pharmaceutically acceptable salt thereof.
  2. 2. Pharmaceutical composition, CHARACTERIZED in that it comprises a pharmaceutically acceptable carrier and the compound as defined in claim 1, optionally further comprising an antigen.
  3. 3. Pharmaceutical composition, CHARACTERIZED in that it comprises the compound as defined in claim 1, in a formulation comprising liposomes, optionally further comprising an antigen.
  4. 4. Pharmaceutical composition, according to claim 2 or 3, CHARACTERIZED in that the compound and the antigen are: additively mixed in a single composition; or present in separate components of the composition to be administered in combination.
  5. 5. Pharmaceutical composition, according to any one of claims 2 to 4, CHARACTERIZED in that the antigen is a cancer vaccine or a virus vaccine.
  6. 6. Use of a compound having the formula N-(4-{[4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl]oxy}butyl)octadecanamide, or a pharmaceutically acceptable salt thereof, CHARACTERIZED in that it is used as a vaccine adjuvant.
  7. 7. Use according to claim 6, CHARACTERIZED in that the compound is incorporated into a liposome formulation.

Description

Background [001]There has been a significant effort in recent years to discover new drug compounds that act by stimulating certain key aspects of the immune system, as well as by suppressing certain other aspects (see, for example, US patents Nos. 6,039,969 (Tomai et al.) and 6,200,592 (Tomai et al.)). These compounds, here called immune response modifiers (IRMs), appear to act through mechanisms of the basic immune system known as Toll-like receptors (TLRs) to induce selected cytokine biosynthesis, induction of co-stimulatory molecules, and increased antigen presentation capacity. [002]Many MRIs can be useful for treating a wide variety of diseases and conditions. For example, certain MRIs can be useful for treating viral diseases (e.g., human papillomavirus, hepatitis, herpes), neoplasms (e.g., basal cell carcinoma, squamous cell carcinoma, actinic keratosis, melanoma), TH2-mediated diseases (e.g., asthma, allergic rhinitis, atopic dermatitis), and autoimmune diseases. Certain MRIs can also be useful, for example, as vaccine adjuvants. [003]Many known MRIs are derived from imidazoquinoline amines (see, for example, US Patent No. 4,689,338 (Gerster)), but other classes of compounds are also known (see, for example, US Patents Nos. 5,446,153 (Lindstrom et al.); 6,194,425 (Gerster et al.); and 6,110,929 (Gerster et al.); and International Publication No. WO2005/079195 (Hays et al.)). In view of the great therapeutic potential of MRIs in the treatment of a wide variety of diseases and conditions, and despite the important work that has already been done, new compounds that can effectively modulate the immune response, by inducing cytokine biosynthesis or other mechanisms, are still needed. Summary [004]The present invention provides, in one aspect, a novel compound useful for inducing cytokine biosynthesis. The compound (i.e., N-(4-{[4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl]oxy}butyl)octadecanamide) has the following formula (I): [005]Pharmaceutically acceptable salts of the compound may also be used. [006]The compound of Formula I has unexpectedly beneficial properties in terms of biological activity. It is particularly desirable for incorporation into liposome-based formulations. It appears that such formulations are surprisingly effective in enhancing localized immune responses with reduced systemic TNF induction. [007]The ability to induce cytokine biosynthesis in animals makes the compound of formula I useful for treating a variety of conditions such as viral diseases and tumors that respond to such changes in the immune response. Accordingly, the present invention further provides methods of inducing cytokine biosynthesis in an animal, treating a viral infection and/or treating a neoplastic disease in an animal by administering an effective amount of a compound of formula I to the animal. The present invention further provides a method of vaccinating an animal comprising administering an effective amount of a compound of formula I to the animal as a vaccine adjuvant. [008]The invention further provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of formula I. In some embodiments, the pharmaceutical composition also comprises an antigen (e.g., a vaccine). In some embodiments of the pharmaceutical composition, the compound of formula I is incorporated into a homogeneously dispersed formulation. In some embodiments of the pharmaceutical composition, the compound of formula I is incorporated into an emulsified formulation. In some embodiments of the pharmaceutical composition, the compound of formula I is incorporated into an oil-in-water formulation (e.g., formulations comprising soybean oil, TWEEN 80, SPAN 85, and STF). In some embodiments of the pharmaceutical composition, the compound of formula I is incorporated into a liposome-based formulation. [009]Used as a vaccine adjuvant for an antigen vaccine, the compound in formula I enhances the antibody response to the vaccine. It can decrease the amount of antigen vaccine needed to achieve a desirable/therapeutically effective antibody response. For example, it can reduce the amount of vaccine antigen needed by up to 2, 10, 15, 25, 50 times, or enough to be 100 times greater, or more. [0010]As illustrated in part by the non-limiting examples presented herein, the compound of formula I is useful for a wide variety of purposes, including but not limited to such things as a vaccine adjuvant for influenza vaccines. For example, when used as a vaccine adjuvant, the compound of formula I in combination with an influenza vaccine antigen provides protection against H1N1 influenza infection (as well as influenza A, B, and swine flu). In particular, when used as a vaccine adjuvant, the compound of formula I in combination with hemagglutinin antigens provides protection against H1N1 influenza infection. [0011]The compound of formula I induces cytokine production primarily at t