Other

Blueberry Therapeutics Limited

The Royal Veterinary College

Rula Zain-luqman

Tecrea Limited

Zain-luqman, Rula

Liam Good

Peter Eigil Nielsen

Rula Zain-Luqman

Helen Bergquist

John Ridden

Kantaraja Chindera

Valentina Gburcik

Michael Davies

Henrik Frydenlund Hansen

Jesper Wengel

Carsten Schou

Olof Gissberg

Birgit Kjaeldgaard Giwercman

Leila Malik

C I Edvard Smith

Eman Zaghloul

Karin Lundin

Pedro Moreno

Frederik Beck

Margit Wissenbach

The present invention relates nanoparticles formed of a polymer and an antifungal agent, wherein the polymer is selected from the group consisting of linear or branched or cyclic polymonoguanide/polyguanidine, polybiguanide, analogues or derivatives thereof, or mixtures thereof. The nanoparticles are particularly suited for the treatment of fungal nail or skin infections.

Composition and methods of treatment

A method for promoting entry of an agent (introduced agent) into a cell, the method comprising the step of complexing the introduced agent in the presence of an entry-promoting agent and then exposing to cells, wherein the entry-promoting agent comprises a linear and/or branched or cyclic polymonoguanide/polyguanidine, polybiguanide, analogue or derivative thereof according to the following Formula 1a & b. The method also provides a means for formation of nanoparticles formed between the entry promoting agent and the introduced agent. wherein: 'n', refers to number of repeating units in the polymer, and n can vary from 2 to 1000, for example from 2 or 5 to 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800 or 900; Gand Gindependently represent a cationic group comprising biguanide or guanidine, wherein L, and Lare directly joined to a Nitrogen atom of the guanide; Land Lare linking groups between the Gand Gcationic groups in the polymer and independently represent an aliphatic group containing C-Ccarbon atoms, for example an alkyl group such as methylene, ethylene, propylene, C, C, C, C, C, Cor C; C-C, -C, -C, -C, -C-C-C, -C, -C, -C-, -C, -C, -Cor -C, alkyl; or a C-C(for example C, C, C, C, C, C, C, C, Cor C; C-C, -C, -C, -C, -C-C, -C, -C, -C, -C, -C, -C, -Cor -C), cycloaliphatic, heterocyclic, aromatic, aryl, alkylaryl, arylalkyl, or oxyalkylene radical; or a polyalkylene radical optionally interrupted by one or more, preferably one, oxygen, nitrogen or sulphur atoms, functional groups or saturated or unsaturated cyclic moiety: N and Gare optional end groups; X can be either present or absent; L, Land X are linking groups between the Gand Gcationic groups in the polymer and independently represent an aliphatic group containing C-Ccarbon atoms, for example an alkyl group such as methylene, ethylene, propylene, C, C, C, C, C, Cor C; C-C, -C, -C, -C, -C-C, -C, -C, -C, -C, -C, -C, -Cor -C, alkyl; or Land Land X can independently be C-C(for example C, C, C, C, C, C, C, C, Cor C; C-C, -C, -C, -C, -C-C, -C, -C, -C, -C, -C, -C, -Cor -C), cycloaliphatic, heterocyclic, aromatic, aryl, alkylaryl, arylalkyl, oxyalkylene radicals; or a polyalkylene radical optionally interrupted by one or more, preferably one, oxygen, nitrogen or sulphur atoms, functional groups as well as saturated or unsaturated cyclic moiety; “G” and “G” are cationic moieties and can be same or different, and at least one of them is a biguanidine moiety or carbamoylguanidine, and the other moiety may be biguanidine or carbamoylguanidine or amine; and cationic moieties Gand Gdo not contain single guanidine groups. The entry-promoting agent may comprise homogeneous or heterogeneous mixture of one or more of agents arising from formulae 1 a and b, for example polyhexamethylene biguanide (PHMB), polyhexamethylene monoguanide (PHMG), polyethylene biguanide (PEB), polytetramethylene biguanide (PTMB), polyethylene hexamethylene biguanide (PEHMB), polymethylene biguanides (PMB), poly(allylbiguanidnio-co-allylamine), poly(N-vinylbiguanide), polyallybiguanide.

Methods for promoting entry of an agent into a cell

The present invention relates to anti-gene oligonucleotides adapted to hybridize to DNA in a HTT gene, which are based on locked nucleic acids, phosphorodiamidate morpholino oligomers, (PMO) or equivalent oligonucleotide analogues comprising a (CAG)sequence, and whose target is a sequence where the majority of the repeats are CAG/CTG, for use in down regulating the expression of the HTT gene, resulting in reduced HTT mRNA and protein levels in afflicted subjects, or in diagnosis, treatment and/or prevention of Huntington's disease, and where the anti-gene oligonucleotides target non-canonical DNA structures, including hairpin and cruciform. The invention also relates to a delivery system comprising said oligonucleotides and said use thereof.

Therapeutic method for huntington's disease

The present invention relates to a topical composition (and methods of producing the such compositions) for the treatment of a fungal infection comprising a polymer capable of forming nanoparticles and an antifungal agent. The invention also relates to novel uses of polyhexamethylene biguanide.

Antifungal topical composition and methods of treatment

The present invention is directed to oligonucleotides based on peptide nucleic acid oligonucleotide or an equivalent oligonucleotide analog, such as morpholino or a locked nucleic acid sequences and the use of such oligonucleotides for the dissociation of higher order structures, including triplex-helix DNA structures, in repeated sequences of DNA in Friedreich's ataxia. The dissociation of such structures may be used in the diagnosis and/or treatment of Friedreich's ataxia. Consequently, the present invention is also directed to a method for diagnosing Friedreich's ataxia and the use of peptide nucleic acid oligonucleotide or an equivalent oligonucleotide analog, such as morpholino or a locked nucleic acid sequences in the treatment of Friedreich's ataxia. Preferably, the oligonucleotides comprise a sequence selected from the group consisting of (GAA), (CTT), (JTT)or a mixed (JTT/CTT)sequence.

Diagnosis and treatment of Friedreich's ataxia

A method for promoting entry of an agent (introduced agent) into a cell, the method comprising the step of complexing the introduced agent in the presence of an entry-promoting agent and then exposing to cells, wherein the entry-promoting agent comprises a linear and/or branched or cyclic polymonoguanide/polyguanidine, polybiguanide, analogue or derivative thereof according to the following Formula 1a & b. The method also provides a means for formation of nanoparticles formed between the entry promoting agent and the introduced agent. wherein: 'n', refers to number of repeating units in the polymer, and n can vary from 2 to 1000, for example from 2 or 5 to 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800 or 900; Gand Gindependently represent a cationic group comprising biguanide or guanidine, wherein L, and Lare directly joined to a Nitrogen atom of the guanide; Land Lare linking groups between the Gand Gcationic groups in the polymer and independently represent an aliphatic group containing C-Ccarbon atoms, for example an alkyl group such as methylene, ethylene, propylene, C, C, C, C, C, Cor C; C-C, -C, -C, -C, -C-C-C, -C, -C0, -C-, -C, -C, -Cor -C, alkyl; or a C-C(for example C, C, C, C, C, C, C, C, Cor C; C-C, -C, -C, -C, -C-C, - C, -C, -C, -C, -C0, -C, -Co or -C), cycloaliphatic, heterocyclic, aromatic, aryl, alkylaryl, arylalkyl, or oxyalkylene radical; or a polyalkylene radical optionally interrupted by one or more, preferably one, oxygen, nitrogen or sulphur atoms, functional groups or saturated or unsaturated cyclic moiety; N and Gare optional end groups; X can be either present or absent; L, Land X are linking groups between the Gand Gcationic groups in the polymer and independently represent an aliphatic group containing C-Ccarbon atoms, for example an alkyl group such as methylene, ethylene, propylene, C, C, C, C, C, Cor C; C-C, -C, -C, -C, -C-C, -C, -C, -C, -C, -C, -C, -Cor -C, alkyl; or Land Land X can independently be C-C(for example C, C, C, C, C, C, C, C, Cor C; C-C, -C, -C, -C, -C-C, -C, -C, -C, -C, -C, -C, -Cor -C), cycloaliphatic, heterocyclic, aromatic, aryl, alkylaryl, arylalkyl, oxyalkylene radicals; or a polyalkylene radical optionally interrupted by one or more, preferably one, oxygen, nitrogen or sulphur atoms, functional groups as well as saturated or unsaturated cyclic moiety; 'G' and &#x201c;G&#x201d; are cationic moieties and can be same or different, and at least one of them is a biguanidine moiety or carbamoylguanidine, and the other moiety may be biguanidine or carbamoylguanidine or amine; and cationic moieties Gand Gdo not contain single guanidine groups. The entry-promoting agent may comprise homogeneous or heterogeneous mixture of one or more of agents arising from formula 1 a and b, for example polyhexamethylene biguanide (PHMB), polyhexamethylene monoguanide (PHMG), polyethylene biguanide (PEB), polytetramethylene biguanide (PTMB), polyethylene hexamethylene biguanide (PEHMB), polymethylene biguanides (PMB), poly(allylbiguanidnio-co-allylamine), poly(N-vinylbiguanide), polyallybiguanide. 

The present invention is directed to oligonucleotides based on peptide nucleic acid oligonucleotide or an equivalent oligonucleotide analogue, such as morpholino or a locked nucleic acid sequences and the use of such oligonucleotides for the dissociation of higher order structures, including triplex-helix DNA structures, in repeated sequences of DNA in Friedreich's ataxia. The dissociation of such structures may be used in the diagnosis and/or treatment of Friedreich's ataxia. Consequently, the present invention is also directed to a method for diagnosing Friedreich's ataxia and the use of peptide nucleic acid oligonucleotide or an equivalent oligonucleotide analogue, such as morpholino or a locked nucleic acid sequences in the treatment of Friedreich's ataxia. Preferably, the oligonucleotides comprise a sequence selected from the group consisting of (GAA), (CTT), (JTT)or a mixed (JTT/CTT)sequence.

Diagnosis and treatment of friedreich's ataxia

Methods of and compositions for killing or inhibiting the growth of a bacteria are disclosed. The methods comprise the use of peptide nucleic acids that are targeted to mRNA and/or rRNA. In certain embodiments, methods include the use of one or more separate antibiotics.

Peptide nucleic acids having antibacterial activity

The present invention relates to novel drugs which may be used in combating infectious micro-organisms, particularly bacteria. More specifically, the invention relates to peptide nucleic acid (PNA) sequences that are modified by conjugating cationic peptides to the PNA moiety in order to obtain novel PNA molecules that exhibit enhanced anti-infective properties.

Modified peptide nucleic acid (PNA) molecules

Methods of and compositions for killing or inhibiting the growth of a bacteria are disclosed. The methods comprise the use of peptide nucleic acid that is targeted to mRNA and/or rRNA. In certain embodiments, methods include the use of one or more separate antibiotics.

Antibacterial and antibiotic methods using peptide nucleic acids and pharmaceutical compositions therefor

Methods of and compositions for killing or inhibiting the growth of a bacteria are disclosed. Methods of determing bacterial gene functions are also disclosed. The methods comprise the use of peptide nucleic acid that is targeted to mRNA and/or rRNA. In certain embodiments, methods include the use of one or more separate antibiotics.

Growing community of inventors

London, United Kingdom

Liam Good