Antiviral linear polymers

Details Antiviral linear polymers Antiviral linear polymers

2001-08-15

2004-05-25

Russel, Jeffrey E. (Department: 1654)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

C525S054200, C530S322000

Reexamination Certificate

active

06740635

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to antiviral agents, and in particular it relates to polyionic, especially polyanionic linear polymers which have been found to have significant antiviral activity, particularly against human immunodeficiency virus (HIV), respiratory syncytial virus (RSV), human influenza virus A and B, Hepatitis B virus (HBV) and other enveloped viruses.
BACKGROUND OF THE INVENTION
It has been established that certain sulfonated polysaccharide compounds have antiviral activity when screened against HIV, however these compounds are relatively unstable and accordingly large amounts of these compounds are required to obtain effective antiviral effects. In addition, many of these compounds, including heparin and dextran sulfate for example, are potent anticoagulants and because of this activity they are not particularly suited for clinical use as antiviral agents.
International Patent Application No. PCT/AU95/00350 (WO 95/34595) discloses a class of antiviral compounds comprising a dendrimer such as a polyarnidoamine or polylysine dendrimer having a plurality of terminal groups, wherein at least one of the terminal groups has an anionic- or cationic-containing moiety bonded or linked thereto, particularly a sulfonic acid-containing, a carboxylic acid-containing or a trimethylammonium-containing moiety.
The present invention provides a new class of antiviral agents based on a particular type of polyionic polymer having a linear “backbone”, which have substantial antiviral activity against HIV1 and HIV2, RSV, HBV and human influenza virus A and B. These compounds are well suited for prophylactic and therapeutic use as antiviral agents in humans.
SUMMARY OF THE INVENTION
According to the present invention, there is provided an antiviral compound comprising a linear noncarbohydrate polymer having a plurality of side chain groups wherein at least one of said side chain groups has an anionic-or cationic-containing moiety bonded or linked thereto.
Particularly preferred antiviral compounds of the present invention are linear polymers having sulfonic acid-containing moieties, carboxylic acid-containing moieties, phosphoric or phosphonic acid-containing moieties, boronic acid-containing moieties, neuraminic or sialic acid-containing moieties or moieties containing neuraminic or sialic acid modified in the 4- or other position thereof, linked to side chain groups thereof.
The compounds of the invention are referred to herein as polyionic polymers, and this term is used throughout this specification to include not only the polymers per se, but also their pharmaceutically or veterinarily acceptable salts, for example the alkaline metal or alkaline earth metal salts such as the sodium, potassium or calcium salts.
DETAILED DESCRIPTION OF THE INVENTION
Preferred polyionic polymers in accordance with the present invention are linear polymers having the general formula I:
wherein:
R is a non-carbohydrate monomer unit forming a linear polymer backbone;
X is an optional linking group on the side chain groups of monomer units R; and
A is an anionic-containing moiety.
Thus, in accordance with the present invention, the preferred linear polymers are polyanionic materials formed by the conjugation of anionic moieties (A) to a linear non-carbohydrate polymer backbone (made up of a plurality of monomer units R), optionally through linking groups (X). The resultant polyanionic linear polymers have a molecular weight range distribution of repeating units to give a desired median range of molecular weight distribution. Desirably, the median range of molecular weight distribution is from 1,000 to 1,000,000, preferably from 10,000 to 600,000.
The monomer unit R is preferably amine or amide moiety, more preferably an amino acid moiety. A particularly preferred monomer unit is a lysine moiety. Poly-L-lysines having various molecular weight ranges are available commercially from Sigma Chemical Company.
The anionic moiety A can be linked to reactive side chain groups on the linear polymer backbone either directly or via a variety of functional linking groups X such as, but not limited to, esters, amides, ethers, thioethers, amines, ureas, thioureas, carbamates and carbonates.
The optional linking group X may also act as a spacer between the polymer and the anionic moiety A, and may consist of an alkyl chain (optionally substituted or branched), an alkoxy, polyalkoxy, alkylthio or polyalcylthio chain (optionally substituted), or an alkenyl, multiple alkenyl, alkynyl or multiple alkynyl chain (optionally substituted). Suitable spacer chains include groups of the formula —(CH
2
)
n
—Z—(CH
2
)
n
—, wherein Z is —CH
2
—, —CH═CH—, —C≡C—, —O— or —S—, and n is an integer of from 1 to 15.
In accordance with the present invention, at least one, and preferably a substantial number, of the reactive side chain groups on the backbone of the linear polymer has an anionic- or cationic-containing moiety covalently bonded thereto. The side chains of the polymer backbone may terminate in amino groups or other functional reactive groups such as OH, SH, or the like, which subsequently can be reacted with the anionic or cationic moieties. Where the side chain groups of the polymer backbone are amine groups, the anionic- or cationic-containing moiety may be linked to the polymer backbone by a variety of functional groups including amide and thiourea linkages. Preferred anionic- or cationic-containing moieties which may be bonded or linked to the side chain groups of the polymer backbone include sulfonic acid-containing moieties, carboxylic acid-containing moieties (including neuraminic and sialic acid-containing moieties and modified neuraminic and sialic acid-containing moieties), boronic acid-containing moieties, phosphoric and phosphonic acid-containing moieties (including esterified phosphoric and phosphonic acid-containing moieties) and trimethylamnonium-containing moieties.
Suitable anionic-and cationic-containing moieties which may be bonded or linked to the amino or other side chain groups of the linear polymers include, by way of example, the following groups (in which n is zero or a positive integer, more particularly n is zero or an integer of from 1 to 20):
In addition to the above, various neuramiric or sialic acid-containing moieties or modified neuraminic or sialic acid-containing moieties may be bonded or linked to the side chain groups in accordance with this invention. These moieties include the various N- and O-substituted derivatives of neuraminic acid, particularly N- and O-acyl derivatives such as N-acetyl, O-acetyl and N-glycolyl derivatives, as well as moieties in which the neuraminic acid group is modified, particularly by substitution in the 4-position, with an amino, amido, cyano, azido or guanidino group.
The polyionic polymers of this invention may be prepared by standard chemical methods which are well known to persons skilled in this art. Suitable methods are described by way of example in the Examples below.
As previously described, the polyionic polymers of the present invention have been found to exhibit significant antiviral activity, particularly against enveloped viruses. Accordingly, these polyionic polymers are useful in prophylactic and therapeutic treatment of viral infections, for example infections by HIV1 and HIV2 and other enveloped viruses including DNA viruses such as Hepatitis B and RNA viruses including flaviviruses such as Hepatitis C, Bovine Viral Diarrhoea Virus and Japanese Encephalitis Virus (JEV). The polyionic polymers of the present invention may also be used in prophylactic or therapeutic treatment against Human Influenza Virus A and B, Rhinoviruses, Corona Viruses, Human Parainfluenza Virus, Respiratory Syncytial Virus (RSV), Varicella Zoster Virus (VZV), Human Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Human Papilloma Virus (HPV), Adenoviruses, Herpes Simplex Virus (HSV) type 1 and 2, Measles Virus and Vesicular Stomatitis Virus (VSV).
Thus, in another aspect the present invention provides a pharmaceutical or veterinary composit

Affiliated with

Also associated with

Rating

Antiviral linear polymers does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Antiviral linear polymers, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antiviral linear polymers will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3256725